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- Apellániz-Ruiz, Maria, et al.
(author)
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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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In: Clinical Cancer Research. - : American Association of Cancer Research. - 1078-0432 .- 1557-3265. ; 23:5, s. 1227-1235
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Journal article (peer-reviewed)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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| 2. |
- Cristóbal, Lara, et al.
(author)
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Free anterolateral thigh flap and masseter nerve transfer for reconstruction of extensive periauricular defects : Surgical technique and clinical outcomes
- 2017
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In: Microsurgery. - : John Wiley & Sons. - 0738-1085 .- 1098-2752. ; 37:6, s. 479-486
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Journal article (peer-reviewed)abstract
- BACKGROUND: Radical tumor ablation in the periauricular area often results in extensive soft tissue defects, including facial nerve sacrifice, bone and/or dura defects. Reconstruction of these defects should aim at restoring facial reanimation, wound closure, and facial and neck contours. We present our experience using free anterolateral thigh flap (ALT) in combination with masseter nerve to facial nerve transfer in managing complex defects in the periauricular area.METHODS: Between 2011 and 2015 six patients underwent a combined procedure of ALT flap reconstruction and masseter nerve transfer, to reconstruct extensive, post tumor resection, periauricular defects. The ALT flap was customized according to the defect. For smile restoration, the masseter nerve was transferred to the buccal branch of the facial nerve. If the facial nerve stump was preserved, interposition of nerve grafts to the zygomatic and frontal branches was performed to provide separate eye closure. The outcomes were analyzed by assessing wound closure, contour deformity, symmetry of the face, and facial nerve function.RESULTS: There were no partial or total flap losses. Stable wound closure and adequate volume replacement in the neck was achieved in all cases, as well as good facial tonus and symmetry. The mean follow-up time of clinical outcomes was 16.8 months. Smile restoration was graded as good or excellent in four cases, moderate in one and fair in one.CONCLUSION: Extensive periauricular defects following oncologic resection could be adequately reconstructed in a combined procedure of free ALT flap and masseter nerve transfer to the facial nerve for smile restoration.
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| 3. |
- Fernández-Gago, Rocío, et al.
(author)
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Thawing boar semen in the presence of seminal plasma improves motility, modifies subpopulation patterns and reduces chromatin alterations.
- 2017
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In: Reproduction, fertility, and development. - : CSIRO PUBLISHING. - 1031-3613. ; 29:8, s. 1576-1584
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Journal article (peer-reviewed)abstract
- Seminal plasma could have positive effects on boar semen after thawing. In the present study we investigated changes in the motility and chromatin structure in spermatozoa over 4h incubation (37°C) of boar semen thawed in the presence of 0%, 10% or 50% seminal plasma from good-fertility boars. Cryopreserved doses were used from seven males, three of which were identified as susceptible to post-thawing chromatin alterations. Motility was analysed by computer-aided sperm analysis every hour, and data were used in a two-step clustering, yielding three subpopulations of spermatozoa (slow non-linear, fast non-linear, fast linear). Chromatin structure was analysed using a sperm chromatin structure assay and flow cytometry to determine the DNA fragmentation index (%DFI) as a percentage, the standard deviation of the DFI (SD-DFI) and the percentage of high DNA stainability (%HDS), indicating chromatin compaction. Thawing without seminal plasma resulted in a rapid loss of motility, whereas seminal plasma helped maintain motility throughout the incubation period and preserved the subpopulation comprising fast and linear spermatozoa. The incidence of chromatin alterations was very low in samples from non-susceptible males, whereas samples from males susceptible to post-thawing chromatin alterations exhibited marked alterations in%DFI and%HDS. Seminal plasma partly prevented these alterations in samples from susceptible males. Overall, 50% seminal plasma was the most efficient concentration to protect motility and chromatin. Some changes were concomitant with physiological events reported previously (e.g., semen thawed with 50% seminal plasma increased the production of reactive oxygen species and yielded higher fertility after AI). Thawing in the presence of seminal plasma could be particularly useful in the case of samples susceptible to post-thawing chromatin damage.
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| 4. |
- Gupta, Alok C., et al.
(author)
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Multiband optical variability of the blazar OJ 287 during its outbursts in 2015-2016
- 2017
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 465:4, s. 4423-4433
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Journal article (peer-reviewed)abstract
- We present recent optical photometric observations of the blazar OJ 287 taken during 2015 September-2016 May. Our intense observations of the blazar started in 2015 November and continued until 2016 May and included detection of the large optical outburst in 2015 December that was predicted using the binary black hole model for OJ 287. For our observing campaign, we used a total of nine ground-based optical telescopes of which one is in Japan, one is in India, three are in Bulgaria, one is in Serbia, one is in Georgia, and two are in the USA. These observations were carried out in 102 nights with a total of similar to 1000 image frames in BVRI bands, though the majority were in the R band. We detected a second comparably strong flare in 2016 March. In addition, we investigated multiband flux variations, colour variations, and spectral changes in the blazar on diverse time-scales as they are useful in understanding the emission mechanisms. We briefly discuss the possible physical mechanisms most likely responsible for the observed flux, colour, and spectral variability.
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