| 1. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 2. |
- Skinner, Roderick, et al.
(författare)
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Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors : a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium
- 2017
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 18:2, s. 75-90
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Forskningsöversikt (refereegranskat)abstract
- Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.
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| 3. |
- Breznau, Nate, et al.
(författare)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
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Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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| 4. |
- Campo, E, et al.
(författare)
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The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee
- 2022
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 140:11, s. 1229-1253
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Tidskriftsartikel (refereegranskat)abstract
- Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.
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| 5. |
- Hastings-Simon, S R, et al.
(författare)
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Spectral hole-burning spectroscopy in Nd3+: YVO4
- 2008
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 77:12
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Tidskriftsartikel (refereegranskat)abstract
- We present spectral hole-burning measurements on the 879 nm, I-4(9/2) -> F-4(3/2) transition in Nd3+ : YVO4. We observe antiholes in the spectrum along with long lived spectral holes, which demonstrates optical pumping between the ground state Zeeman levels. The spectral holes are narrow (homogeneous linewidth of 63 kHz) at 2.1 K with a 300 mT applied magnetic field. We also perform preliminary spectral tailoring in this material by creating a 40 MHz wide transmission window in the inhomogeneous absorption. These results show the potential of the Zeeman levels in Nd doped materials to be used for spectral tailoring for quantum and classical information processing.
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| 6. |
- Jerkeman, M., et al.
(författare)
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Targeting of B-cell receptor signalling in B-cell malignancies
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 282:5, s. 415-428
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Forskningsöversikt (refereegranskat)abstract
- Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma. In addition, the role of these drugs in diffuse large B-cell lymphoma and marginal zone lymphoma is under investigation, as single agents and in combination with chemotherapy. In CLL, both ibrutinib and idelalisib have an established role as first-line therapy in patients with del(17p), and in MCL, ibrutinib is a standard option for patients relapsing after chemoimmunotherapy. Unexpected toxicities have been encountered when combining these potent new agents with other drugs, including chemotherapy and lenalidomide, and based on this experience the risks and benefits of novel combinations must be evaluated carefully. In this review, we summarize the efficacy and safety results with these inhibitors and discuss novel combinations that are under study and the future role of BCR inhibitors in these disorders.
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| 7. |
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| 8. |
- Niinemets, Ue., et al.
(författare)
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Estimations of isoprenoid emission capacity from enclosure studies: measurements, data processing, quality and standardized measurement protocols
- 2011
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 8:8, s. 2209-2246
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Tidskriftsartikel (refereegranskat)abstract
- The capacity for volatile isoprenoid production under standardized environmental conditions at a certain time (E-S, the emission factor) is a key characteristic in constructing isoprenoid emission inventories. However, there is large variation in published E-S estimates for any given species partly driven by dynamic modifications in E-S due to acclimation and stress responses. Here we review additional sources of variation in E-S estimates that are due to measurement and analytical techniques and calculation and averaging procedures, and demonstrate that estimations of E-S critically depend on applied experimental protocols and on data processing and reporting. A great variety of experimental setups has been used in the past, contributing to study-to-study variations in E-S estimates. We suggest that past experimental data should be distributed into broad quality classes depending on whether the data can or cannot be considered quantitative based on rigorous experimental standards. Apart from analytical issues, the accuracy of E-S values is strongly driven by extrapolation and integration errors introduced during data processing. Additional sources of error, especially in meta-database construction, can further arise from inconsistent use of units and expression bases of E-S. We propose a standardized experimental protocol for BVOC estimations and highlight basic meta-information that we strongly recommend to report with any E-S measurement. We conclude that standardization of experimental and calculation protocols and critical examination of past reports is essential for development of accurate emission factor databases.
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| 9. |
- Niinemets, Ü., et al.
(författare)
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The leaf-level emission factor of volatile isoprenoids: caveats, model algorithms, response shapes and scaling
- 2010
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 7:6, s. 1809-1832
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Tidskriftsartikel (refereegranskat)abstract
- In models of plant volatile isoprenoid emissions, the instantaneous compound emission rate typically scales with the plant's emission potential under specified environmental conditions, also called as the emission factor, ES. In the most widely employed plant isoprenoid emission models, the algorithms developed by Guenther and colleagues (1991, 1993), instantaneous variation of the steady-state emission rate is described as the product of ES and light and temperature response functions. When these models are employed in the atmospheric chemistry modeling community, species-specific ES values and parameter values defining the instantaneous response curves are often taken as initially defined. In the current review, we argue that ES as a characteristic used in the models importantly depends on our understanding of which environmental factors affect isoprenoid emissions, and consequently need standardization during experimental ES determinations. In particular, there is now increasing consensus that in addition to variations in light and temperature, alterations in atmospheric and/or within-leaf CO2 concentrations may need to be included in the emission models. Furthermore, we demonstrate that for less volatile isoprenoids, mono- and sesquiterpenes, the emissions are often jointly controlled by the compound synthesis and volatility. Because of these combined biochemical and physico-chemical drivers, specification of ES as a constant value is incapable of describing instantaneous emissions within the sole assumptions of fluctuating light and temperature as used in the standard algorithms. The definition of ES also varies depending on the degree of aggregation of ES values in different parameterization schemes (leaf- vs. canopy- or region-scale, species vs. plant functional type levels) and various aggregated ES schemes are not compatible for different integration models. The summarized information collectively emphasizes the need to update model algorithms by including missing environmental and physico-chemical controls, and always to define ES within the proper context of model structure and spatial and temporal resolution.
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| 10. |
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| 11. |
- West, Christina E., et al.
(författare)
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Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life : a randomized controlled trial
- 2017
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Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 82:1, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human milk is rich in osteopontin (OPN), which has immunomodulatory functions. METHODS: In a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing similar to 50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group. RESULTS: The F130 group had increased T-cell proportions compared with the SF (P = 0.036, average effect size 0.51) and F65 groups (P = 0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (P=0.001, average effect size 0.59) and F130 (P=0.006, average effect size 0.50) groups, but were comparable among the formula groups. CONCLUSION: OPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at similar to 50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.
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| 12. |
- Xiao, Wenming, et al.
(författare)
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Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1141-1150
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Tidskriftsartikel (refereegranskat)abstract
- Recommendations are given on optimal read coverage and selection of calling algorithm to maximize the reproducibility of cancer mutation detection in whole-genome or whole-exome sequencing. Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
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| 13. |
- Afzelius, M., et al.
(författare)
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Proposal for a coherent quantum memory for propagating microwave photons
- 2013
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 15, s. Art. no. 065008-
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Tidskriftsartikel (refereegranskat)abstract
- We describe a multi-mode quantum memory for propagating microwave photons that combines a solid-state spin ensemble resonantly coupled to a frequency tunable single-mode microwave cavity. We first show that high efficiency mapping of the quantum state transported by a free photon to the spin ensemble is possible both for strong and weak coupling between the cavity mode and the spin ensemble. We also show that even in the weak coupling limit unit efficiency and faithful retrieval can be obtained through time reversal inhomogeneous dephasing based on spin echo techniques. This is possible provided that the cavity containing the spin ensemble and the transmission line are impedance matched. We finally discuss the prospects for an experimental implementation using a rare-earth doped crystal coupled to a superconducting resonator.
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| 14. |
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| 15. |
- Donovan, Sharon M., et al.
(författare)
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Bovine Osteopontin Modifies the Intestinal Transcriptome of Formula-Fed Infant Rhesus Monkeys to Be More Similar to Those That Were Breastfed
- 2014
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Ingår i: Journal of Nutrition. - 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA : American Society for Nutrition. - 0022-3166 .- 1541-6100. ; 144:12, s. 1910-1919
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteopontin (OPN) is a multifunctional protein found in human milk at high concentration.Objective: The impact of supplemental bovine OPN on growth, body composition, and the jejunal transcriptome was assessed.Methods: Newborn rhesus monkeys were randomly assigned to be breastfed (n = 4) or to receive formula [formula fed (FF), n = 6] or formula supplemented with 125 mg/L of bovine OPN (bOPN, n = 6) for 3 mo. Jejunal mRNA was extracted and subjected to microarray analysis.Results: Growth was similar among all the treatment groups, but breastfed monkeys were similar to 25% leaner at 3 mo. Pairwise comparisons demonstrated that 1017 genes were differentially expressed between breastfed and FF groups, 217 between breastfed and bOPN groups, and 119 between FF and bOPN groups. The data were also analyzed with the use of weighted gene coexpression network analysis, which revealed 6 modules of coexpressed genes that differed among the 3 treatments. Nearly 50% of genes were assigned to one module in which breastfed differed from FF and bOPN expression was intermediate. This module was enriched for genes related to cell adhesion and motility, cytoskeletal remodeling, wingless and integration site signaling, and neuronal development. Most of these canonical pathways centered on integrins, which are receptors for OPN.Conclusions: The intestinal transcriptome of breastfed and FF monkeys differs, but bovine OPN at levels similar to human milk shifts gene expression profiles to be more similar to breastfed monkeys.
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| 16. |
- Niinemets, Ue., et al.
(författare)
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The emission factor of volatile isoprenoids: stress, acclimation, and developmental responses
- 2010
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 7:7, s. 2203-2223
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Tidskriftsartikel (refereegranskat)abstract
- The rate of constitutive isoprenoid emissions from plants is driven by plant emission capacity under specified environmental conditions (E-S, the emission factor) and by responsiveness of the emissions to instantaneous variations in environment. In models of isoprenoid emission, E-S has been often considered as intrinsic species-specific constant invariable in time and space. Here we analyze the variations in species-specific values of E-S under field conditions focusing on abiotic stresses, past environmental conditions and developmental processes. The reviewed studies highlight strong stress-driven, adaptive (previous temperature and light environment and growth CO2 concentration) and developmental (leaf age) variations in E-S values operating at medium to long time scales. These biological factors can alter species-specific E-S values by more than an order of magnitude. While the majority of models based on early concepts still ignore these important sources of variation, recent models are including some of the medium- to long-term controls. However, conceptually different strategies are being used for incorporation of these longer-term controls with important practical implications for parameterization and application of these models. This analysis emphasizes the need to include more biological realism in the isoprenoid emission models and also highlights the gaps in knowledge that require further experimental work to reduce the model uncertainties associated with biological sources of variation.
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| 17. |
- Staudt, Matthias, 1977, et al.
(författare)
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Coupling of an erbium spin ensemble to a superconducting resonator
- 2012
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 1361-6455 .- 0953-4075. ; 45:12, s. Art. no. 124019-
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Tidskriftsartikel (refereegranskat)abstract
- A quantum coherent interface between optical and microwave photons can be used as a basic building block within a future quantum information network. The interface is envisioned as an ensemble of rare-earth ions coupled to a superconducting resonator, allowing for coherent transfer between optical and microwave photons. Towards this end, we have realized a hybrid device coupling a Er3+-doped Y2SiO5 crystal in a superconducting coplanar waveguide cavity. We observe a collective spin coupling of 4 MHz and a spin linewidth of down to 75 MHz.
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