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- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Fresard, Laure, et al.
(author)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Journal article (peer-reviewed)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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- Noguchi, S, et al.
(author)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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In: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Journal article (peer-reviewed)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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- Ideguchi, E., et al.
(author)
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Study of high-spin states in 48Ca region induced by secondary fusion reactions
- 2005
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Conference paper (peer-reviewed)abstract
- A new method of in-beam gamma-ray spectroscopy induced by secondary fusion reactions, 37P+9Be and 46Ar+9Be is presented. Low-energy secondary beams of 37P and 46Ar ions of ∼5 MeV/A were developed in order to induce fusion evaporation reactions. Excited states of nuclei in the vicinity of 48Ca, 49-52Ti and 46Ca, were studied by the method as well as β decay of the secondary beam 46Ar. Gamma-gamma coincidence and excitation function analysis were performed to study high-spin states of Ti isotopes.
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| 12. |
- Ideguchi, E, et al.
(author)
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Study of high-spin states in the Ca-48 region by using secondary fusion reactions
- 2005
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In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 25, s. 429-430
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Journal article (peer-reviewed)abstract
- An in-beam gamma-ray spectroscopy study, following a fusion reaction induced by a neutronrich secondary beam, Ar-46 + Be-9, is presented. A low-energy secondary beam of Ar-46 at similar to 5 MeV/A was developed in order to induce fusion reactions. Gamma-gamma coincidence and excitation function analysis was performed to study high-spin states in the vicinity of Ca-48, Ti49-52.
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- Aman, Y, et al.
(author)
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Autophagy in healthy aging and disease
- 2021
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In: Nature aging. - : Springer Science and Business Media LLC. - 2662-8465. ; 1:8, s. 634-650
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Journal article (peer-reviewed)
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- Kuriyama, T., et al.
(author)
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Cellular basis of anti-predator adaptation in a lizard with autotomizable blue tail against specific predators with different colour vision
- 2016
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In: Journal of Zoology. - : Wiley. - 0952-8369 .- 1469-7998. ; 300:2, s. 89-98
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Journal article (peer-reviewed)abstract
- Juveniles of numerous lizard species have a vividly blue-coloured tail that likely serves to deflect predator attacks toward the autotomizable tail rather than the lizard's body. The shades of blue colour in the tails of juvenile Plestiodon latiscutatus lizards vary across populations, most notably among those island populations with different predator assemblages. Here, we determine if this intraspecific variation is associated with the differences in colour vision capabilities of lizard predator species. If associated, it would be evidence for local adaptation of tail colour phenotype – natural selection is maximizing the conspicuousness of the tail to the dominant predator species to increase the chance of successfully deflecting attacks. We also use transmission electron microscopy (TEM) to determine the proximate cellular mechanisms that produce the shades of blue in different populations. We revealed that lizard tails with vivid blue reflectance evolved in communities with either weasel or snake predators, two groups of animals with the ability to detect blue wavelengths. However, lizard tail UV reflectance was much higher in populations with only snake predators; that snakes can detect UV, yet weasels cannot, suggests that high UV reflectance is an adaptation to increase tail conspicuousness specifically to snake predators. Finally, a cryptic brown tail evolved independently on the islands where birds are the primary lizard predator. We suggest that because birds have keen visual acuity; a brown, camouflaged phenotype is more advantageous. We also determined through TEM that the thickness of light reflecting platelets in iridophores, and densities of iridophores and xanthophores, predicted the wavelengths and intensity of light reflected by the lizard tail. For example, blue coloration was produced by selective reflection of short wavelengths of light by the thin light reflecting platelets of the iridophore. Greater iridophore density increased light reflectance, while greater xanthophore density decreased light reflectance.
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| 17. |
- Lue, L. F., et al.
(author)
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Age-Dependent Relationship Between Plasma A beta 40 and A beta 42 and Total Tau Levels in cognitively Normal Subjects
- 2019
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In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 11
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Journal article (peer-reviewed)abstract
- Both amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with Alzheimer's disease (AD). However, the constituents of these hallmarks, amyloid beta (A beta) 40, A beta 42, and total Tau (t-Tau), have been detected in the blood of cognitively normal subjects by using an immunomagnetic reduction (IMR) assay. Whether these levels are age-dependent is not known, and their interrelation remains undefined. We determined the levels of these biomarkers in cognitively normal subjects of different age groups. A total of 391 cognitively normal subjects aged 23-91 were enrolled from hospitals in Asia, Europe, and North America. Healthy cognition was evaluated by NIA-AA guidelines to exclude subjects with mild cognitive impairment (MCI) and AD and by cognitive assessment using the Mini Mental State Examination and Clinical Dementia Rating (CDR). We examined the effect of age on plasma levels of A beta 40, A beta 42, and t-Tau and the relationship between these biomarkers during aging. Additionally, we explored age-related reference intervals for each biomarker. Plasma t-Tau and A beta 42 levels had modest but significant correlations with chronological age (r = 0.127, p = 0.0120 for t-Tau; r = -0.126, p = 0.0128 for A beta 42), ranging from ages 23 to 91. Significant positive correlations were detected between A beta 42 and t-Tau in the groups aged 50 years and older, with Rho values ranging from 0.249 to 0.474. Significant negative correlations were detected between A beta 40 and t-Tau from age 40 to 91 (r ranged from -0.293 to -0.582) and between A beta 40 and A beta 42 in the age groups of 30-39 (r = -0.562, p = 0.0235), 50-59 (r = -0.261, p = 0.0142), 60-69 (r = -0.303, p = 0.0004), and 80-91 (r = 0.459, p = 0.0083). We also provided age-related reference intervals for each biomarker. In this multicenter study, age had weak but significant effects on the levels of A beta 42 and t-Tau in plasma. However, the age group defined by decade revealed the emergence of a relationship between A beta 40, A beta 42, and t-Tau in the 6th and 7th decades. Validation of our findings in a large-scale and longitudinal study is warranted.
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| 20. |
- Pham, M. K., et al.
(author)
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Certified Reference Material IAEA-446 for radionuclides in Baltic Sea seaweed
- 2014
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In: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043 .- 1872-9800. ; 87, s. 468-474
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Journal article (peer-reviewed)abstract
- A Certified Reference Material (CRM) for radionuclides in seaweed (Fucus vesiculosus) from the Baltic Sea (IAEA-446) is described and the results of the certification process are presented. The K-40, Cs-132, U-234 and Pu239+240 radionuclides were certified for this material, and information values for 12 other radionuclides (Sr-90, Tc-99, Pb-210 (Po-210), Ra-226, Ra-228, Th-228, Th-230, Th-232, U-235, U-238, Pu-239 and Pu-240) are presented. The CRM can be used for Quality Assurance/Quality Control of analysis of radionuclides in seaweed and other biota samples, as well as for development and validation of analytical methods, and for training purposes. (C) 2013 Elsevier Ltd. All rights reserved.
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| 23. |
- Wilson, R., et al.
(author)
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Improved dendroclimatic calibration using blue intensity in the southern Yukon
- 2019
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In: The Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 29:11, s. 1817-1830
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Journal article (peer-reviewed)abstract
- In north-western North America, the so-called divergence problem (DP) is expressed in tree ring width (RW) as an unstable temperature signal in recent decades. Maximum latewood density (MXD), from the same region, shows minimal evidence of DP. While MXD is a superior proxy for summer temperatures, there are very few long MXD records from North America. Latewood blue intensity (LWB) measures similar wood properties as MXD, expresses a similar climate response, is much cheaper to generate and thereby could provide the means to profoundly expand the extant network of temperature sensitive tree-ring (TR) chronologies in North America. In this study, LWB is measured from 17 white spruce sites (Picea glauca) in south-western Yukon to test whether LWB is immune to the temporal calibration instabilities observed in RW. A number of detrending methodologies are examined. The strongest calibration results for both RW and LWB are consistently returned using age-dependent spline (ADS) detrending within the signal-free (SF) framework. RW data calibrate best with June-July maximum temperatures (Tmax), explaining up to 28% variance, but all models fail validation and residual analysis. In comparison, LWB calibrates strongly (explaining 43-51% of May-August Tmax) and validates well. The reconstruction extends to 1337 CE, but uncertainties increase substantially before the early 17th century because of low replication. RW-, MXD- and LWB-based summer temperature reconstructions from the Gulf of Alaska, the Wrangell Mountains and Northern Alaska display good agreement at multi-decadal and higher frequencies, but the Yukon LWB reconstruction appears potentially limited in its expression of centennial-scale variation. While LWB improves dendroclimatic calibration, future work must focus on suitably preserved sub-fossil material to increase replication prior to 1650 CE.
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