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- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 2. |
- Machiela, Mitchell J., et al.
(författare)
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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
- 2016
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:8, s. 1663-1676
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
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| 6. |
- van Leeuwen, A., et al.
(författare)
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How cod shapes its world
- 2008
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Ingår i: Journal of Sea Research. - : Elsevier. - 1385-1101 .- 1873-1414. ; 60:1-2, s. 89-104
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Tidskriftsartikel (refereegranskat)abstract
- Cod stocks in the North West Atlantic and the Baltic Sea have shown similar dynamics in recent decades with a rapid decline in abundance and a lack of stock recovery following a period of large biomass. We explore whether the lack of recovery can be ascribed to an emergent Allee effect, which is a mechanism intrinsic to the community in contrast to explanations involving environmental factors. We formulate a stage-structured biomass model for the cod-sprat interaction in the Baltic Sea, paying special attention to the size-dependent prey preference of differently sized cod. The model predicts that alternative community states can occur under the same environmental conditions, in which cod is either present or absent. In a stable equilibrium with its main prey cod has a strong effect on the prey size distribution, resulting in larger densities of preferred prey sizes for cod than in the absence of any predation. Cod thus shapes its food environment to its own benefit. Furthermore, in response to increased exploitation cod biomass and yield tend to increase unless a stock collapse is imminent. After a cod stock collapse and the consequent drop in predation the prey size distribution becomes stunted and offers too little food for cod to grow and recover. These results are consequences of the indirect effects of predation and harvesting, whereby increased mortality relaxes competition among surviving individuals, leading to an increase in food intake and hence increased somatic growth and reproduction. We review observed community changes following the collapse of the cod stocks in the North West Atlantic and the Baltic Sea in the light of model predictions. In line with our model predictions growth in body size of cod has slowed down after the collapse, despite high densities of prey biomass. Furthermore, estimates of total prey population fecundity in the Baltic Sea identify the emergent Allee effect as a potentially important mechanism contributing to the lack of cod recovery.
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| 9. |
- De Roos, Andre M., et al.
(författare)
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Ontogenetic symmetry and asymmetry in energetics
- 2013
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Ingår i: Journal of Mathematical Biology. - : Springer Science and Business Media LLC. - 0303-6812 .- 1432-1416. ; 66:4-5, s. 889-914
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Tidskriftsartikel (refereegranskat)abstract
- Body size ( biomass) is the dominant determinant of population dynamical processes such as giving birth or dying in almost all species, with often drastically different behaviour occurring in different parts of the growth trajectory, while the latter is largely determined by food availability at the different life stages. This leads to the question under what conditions unstructured population models, formulated in terms of total population biomass, still do a fair job. To contribute to answering this question we first analyze the conditions under which a size-structured model collapses to a dynamically equivalent unstructured one in terms of total biomass. The only biologically meaningful case where this occurs is when body size does not affect any of the population dynamic processes, this is the case if and only if the mass-specific ingestion rate, the mass-specific biomass production and the mortality rate of the individuals are independent of size, a condition to which we refer as "ontogenetic symmetry". Intriguingly, under ontogenetic symmetry the equilibrium biomass-body size spectrum is proportional to 1/size, a form that has been conjectured for marine size spectra and subsequently has been used as prior assumption in theoretical papers dealing with the latter. As a next step we consider an archetypical class of models in which reproduction takes over from growth upon reaching an adult body size, in order to determine how quickly discrepancies from ontogenetic symmetry lead to relevant novel population dynamical phenomena. The phenomena considered are biomass overcompensation, when additional imposed mortality leads, rather unexpectedly, to an increase in the equilibrium biomass of either the juveniles or the adults (a phenomenon with potentially big consequences for predators of the species), and the occurrence of two types of size-structure driven oscillations, juvenile-driven cycles with separated extended cohorts, and adult-driven cycles in which periodically a front of relatively steeply decreasing frequencies moves up the size distribution. A small discrepancy from symmetry can already lead to biomass overcompensation; size-structure driven cycles only occur for somewhat larger discrepancies.
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| 10. |
- de Roos, A. M., et al.
(författare)
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Population and community ecology of ontogenetic development
- 2013
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Most organisms show substantial changes in size or morphology after they become independent of their parents and have to find their own food. Furthermore, the rate at which these changes occur generally depends on the amount of food they ingest. In this book, André de Roos and Lennart Persson advance a synthetic and individual-based theory of the effects of this plastic ontogenetic development on the dynamics of populations and communities. De Roos and Persson show how the effects of ontogenetic development on ecological dynamics critically depend on the efficiency with which differently sized individuals convert food into new biomass. Differences in this efficiency--or ontogenetic asymmetry--lead to bottlenecks in and thus population regulation by either maturation or reproduction. De Roos and Persson investigate the community consequences of these bottlenecks for trophic configurations that vary in the number and type of interacting species and in the degree of ontogenetic niche shifts exhibited by their individuals. They also demonstrate how insights into the effects of maturation and reproduction limitation on community equilibrium carry over to the dynamics of size-structured populations and give rise to different types of cohort-driven cycles.
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