| 11. |
- Apellániz-Ruiz, Maria, et al.
(författare)
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Targeted sequencing reveals low-frequency variants in EPHA genes as markers of paclitaxel-induced peripheral neuropathy.
- 2017
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Ingår i: Clinical Cancer Research. - : American Association of Cancer Research. - 1078-0432 .- 1557-3265. ; 23:5, s. 1227-1235
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/ gene-based analyses were used to compare variant frequencies among neuropathy groups and Cox regression models were used to analyze neuropathy evolution along treatment.RESULTS: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low frequency non-synonymous variants in EPHA6 were present exclusively in patients with high neuropathy and all affected the ligand binding domain. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency non-synonymous variant carriers (HR=14.60, 95%CI=2.33-91.62, P=0.0042) and an independent cohort confirmed an increased neuropathy risk (HR=2.07, 95%CI=1.14-3.77, P=0.017). Combining the series gave an estimated 2.50-fold higher risk of neuropathy (95%CI=1.46-4.31; P=9.1x10(-4)).CONCLUSION: This first study sequencing EPHA genes revealed that low frequency variants in EPHA6, EPHA5 and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHAs neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs.
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| 12. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 13. |
- Bellm, Eric C., et al.
(författare)
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The Zwicky Transient Facility : System Overview, Performance, and First Results
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
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Tidskriftsartikel (refereegranskat)abstract
- The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
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| 14. |
- Blanco-Tourinan, Noel, et al.
(författare)
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The primary root procambium contributes to lateral root formation through its impact on xylem connection
- 2023
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Ingår i: Current Biology. - : CELL PRESS. - 0960-9822 .- 1879-0445. ; 33:9, s. 1716-1727
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Tidskriftsartikel (refereegranskat)abstract
- The postembryonic formation of lateral roots (LRs) starts in internal root tissue, the pericycle. An important question of LR development is how the connection of the primary root vasculature with that of the emerging LR is established and whether the pericycle and/or other cell types direct this process. Here, using clonal analysis and time-lapse experiments, we show that both the procambium and pericycle of the primary root (PR) affect the LR vascular connectivity in a coordinated manner. We show that during LR formation, pro -cambial derivates switch their identity and become precursors of xylem cells. These cells, together with the pericycle-origin xylem, participate in the formation of what we call a "xylem bridge"(XB), which establishes the xylem connection between the PR and the nascent LR. If the parental protoxylem cell fails to differentiate, XB is still sometimes formed but via a connection with metaxylem cells, highlighting that this process has some plasticity. Using mutant analyses, we show that the early specification of XB cells is determined by CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP III) transcription factors (TFs). Subsequent XB cell dif-ferentiation is marked by the deposition of secondary cell walls (SCWs) in spiral and reticulate/scalariform patterns, which is dependent on the VASCULAR-RELATED NAC-DOMAIN (VND) TFs. XB elements were also observed in Solanum lycopersicum, suggesting that this mechanism may be more widely conserved in plants. Together, our results suggest that plants maintain vascular procambium activity, which safeguards the functionality of newly established lateral organs by assuring the continuity of the xylem strands throughout the root system.
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| 15. |
- Bolin, Bryce T., et al.
(författare)
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Characterization of the Nucleus, Morphology, and Activity of Interstellar Comet 2I/Borisov by Optical and Near-infrared GROWTH, Apache Point, IRTF, ZTF, and Keck Observations
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:1
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Tidskriftsartikel (refereegranskat)abstract
- We present visible and near-infrared (NIR) photometric and spectroscopic observations of interstellar object (ISO) 2I/Borisov taken from 2019 September 10 to 2019 December 20 using the GROWTH, the Apache Point Observatory Astrophysical Research Consortium 3.5 m, and the NASA Infrared Telescope Facility 3.0 m combined with pre- and postdiscovery observations of 2I obtained by the Zwicky Transient Facility from 2019 March 17 to 2019 May 5. Comparison with imaging of distant solar system comets shows an object very similar to mildly active solar system comets with an outgassing rate of similar to 10(27)mol s(-1). The photometry, taken in filters spanning the visible and NIR range, shows a gradual brightening trend of similar to 0.03 mag day(-1)since 2019 September 10 UTC for a reddish object becoming neutral in the NIR. The light curve from recent and prediscovery data reveals a brightness trend suggesting the recent onset of significant H2O sublimation with the comet being active with super volatiles such as CO at heliocentric distances >6 au consistent with its extended morphology. Using the advanced capability to significantly reduce the scattered light from the coma enabled by high-resolution NIR images from Keck adaptive optics taken on 2019 October 4, we estimate a diameter for 2I's nucleus of less than or similar to 1.4 km. We use the size estimates of 1I/'Oumuamua and 2I/Borisov to roughly estimate the slope of the ISO size distribution, resulting in a slope of similar to 3.4 1.2, similar to solar system comets and bodies produced from collisional equilibrium.
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| 16. |
- Breeur, Marie, et al.
(författare)
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Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition
- 2022
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations.Methods: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty.Results: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk.Conclusions: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
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| 17. |
- Cea Soriano, Lucía, et al.
(författare)
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Predictors and time trends in clopidogrel and proton pump inhibitor coprescription with low-dose acetylsalicylic acid
- 2012
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 21, s. 463-469
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine trends and predictors of clopidogrel and proton pump inhibitor (PPI) coprescription with low-dose acetylsalicylic acid (ASA) prescribed for secondary cardiovascular or cerebrovascular disease (CVD) prevention in UK primary care. Methods: Patients aged 50-84years who received a first prescription for low-dose ASA for secondary CVD prevention in 2000-2001 (n=10 330) or 2006-2007 (n=8154) were identified in The Health Improvement Network UK primary care database. Clopidogrel or PPI coprescriptions received within 15days after the first low-dose ASA prescription were ascertained. Results: Clopidogrel coprescription with low-dose ASA increased from 1.6% to 25.2% between the two study periods; PPI coprescription increased from 11.6% to 28.3%. Low-dose ASA indications of myocardial infarction [odds ratio (OR) 11.7, 95% confidence interval (CI) 10.2 to 13.4] and unstable angina (OR 1.73, 95%CI 1.09 to 2.75) were positive predictors of clopidogrel coprescription in 2006-2007, relative to chronic ischaemic heart disease. Patients at high risk of upper gastrointestinal bleeding were more likely to receive a PPI than those at lower risk in 2006-2007 (OR 4.36, 95%CI 3.93 to 4.84). In this period, 65.5% of patients who required a clopidogrel coprescription according to guideline recommendations received one, and 44.3% of patients at high risk of upper gastrointestinal bleeding received a PPI. Conclusion: Clopidogrel and PPI coprescription with low-dose ASA increased markedly between 2000-2001 and 2006-2007; however, many patients on low-dose ASA did not receive the recommended coprescriptions at the end of the study period. © 2012 John Wiley & Sons, Ltd.
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