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- 2017
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Journal article (peer-reviewed)
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| 2. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 3. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 4. |
- Lindblad-Toh, Kerstin, et al.
(author)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Journal article (peer-reviewed)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 5. |
- Godoy, Patricio, et al.
(author)
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
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In: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
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Research review (peer-reviewed)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
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| 6. |
- Petri, Michelle, et al.
(author)
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Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus
- 2012
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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:8, s. 2677-2686
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Journal article (peer-reviewed)abstract
- Objective The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. Methods The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Results Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). Conclusion The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or antidouble-stranded DNA antibodies.
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| 7. |
- Wang, Kate N., et al.
(author)
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Proton Pump Inhibitors and Infection-Related Hospitalizations Among Residents of Long-Term Care Facilities : A Case-Control Study
- 2019
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In: Drugs & Aging. - : Springer Science and Business Media LLC. - 1170-229X .- 1179-1969. ; 36:11, s. 1027-1034
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Journal article (peer-reviewed)abstract
- Objective Our objective was to investigate associations between proton pump inhibitor (PPIs) use and infection- related hospitalizations among residents of long-term care facilities ( LTCFs).Methods This was a case-control study of residents aged = 65 years admitted to hospital between July 2013 and June 2015. Residents admitted for infections (cases) and falls or fall-related injuries (controls) were matched for age (+/- 2 years), sex, and index date of admission (+/- 6 months). Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between PPI use and infection-related hospitalizations. Analyses were adjusted for age, sex, polypharmacy, diabetes, heart failure, chronic obstructive pulmonary disease, myocardial infarction, cerebrovascular accident, and concomitant use of cancer and immunosuppressant medications. Subgroup analyses were performed for high- and low/moderate-intensity PPIs and for respiratory and non-respiratory infections. Logistic regression was used to compare the odds of infection- related hospitalizations among users of high- and low/moderate-intensity PPIs.Results Overall, 181 cases were matched to 354 controls. Preadmission PPI use was associated with infection-related hospitalizations (aOR 1.66; 95% CI 1.11-2.48). In subgroup analyses, the association was apparent only for respiratory infections (aOR 2.26; 95% CI 1.37-3.73) and high-intensity PPIs (aOR 1.93; 95% CI 1.23-3.04). However, the risk of infection-related hospitalization was not significantly higher among users of high- versus low/moderate-intensity PPIs (aOR 1.25; 95% CI 0.74-2.13).Conclusion Residents who use PPIs may be at increased risk of infection-related hospitalizations, particularly respiratory infections. Study findings provide further support for initiatives to minimize unnecessary PPI use in the LTCF setting.
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| 8. |
- Wang, Kate N., et al.
(author)
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Statin use and fall-related hospitalizations among residents of long-term care facilities : A case-control study
- 2020
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In: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 14:4, s. 507-514
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Journal article (peer-reviewed)abstract
- BACKGROUND: Statins are associated with muscle-related adverse events, but few studies have investigated the association with fall-related hospitalizations among residents of long-term care facilities (LTCFs).OBJECTIVE: The objective of the study is to investigate whether statin use is associated with fall-related hospitalizations from LTCFs.METHODS: A case-control study was conducted among residents aged >= 65 years admitted to hospital from 2013 to 2015. Cases (n = 332) were residents admitted for falls and fall-related injuries. Controls (n = 332) were selected from patients admitted for reasons other than cardiovascular and diabetes. Cases and controls were matched 1:1 by age (+/- 2 years), index date of admission (+/- 6 months), and sex. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression, after considering for history of falls, hypertension, dementia, functional comorbidity index, polypharmacy (>= 9 regular preadmission medications), and fall-risk medications. Subanalyses were performed for individual statins, dementia, and statin intensity.RESULTS: Overall, 43.1% of cases and 27.1% of controls used statins. Statins were associated with fall-related hospitalizations (aOR = 2.24, 95% CI 1.56-3.23), in particular simvastatin (aOR = 2.26, 95% CI 1.22-4.20) and atorvastatin (aOR = 2.08, 95% CI 1.33-3.24). Statins were associated with fall-related hospitalizations in residents with (aOR = 2.34, 95% CI 1.33-4.11) and without dementia (aOR = 2.30, 95% CI 1.46-3.63). There was no association between statin intensity and fall-related hospitalizations (aOR = 0.78, 95% CI 0.43-1.40).CONCLUSION: This study suggests a possible association between statin use and fall-related hospitalizations among residents living in LTCFs. However, there was minimal evidence for a relationship between statin intensity and fall-related hospitalizations. Further research is required to substantiate these hypothesis-generating findings.
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