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- Razis, E., et al.
(author)
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Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force
- 2022
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In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 7:3
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Journal article (peer-reviewed)abstract
- Background: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. Patients and methods: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. Results: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. Conclusions: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.
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- Söderquist, Pär, et al.
(author)
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Admixture between released and wild game birds: a changing genetic landscape in European mallards (Anas platyrhynchos)
- 2017
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In: European Biophysics Journal. - : Springer Verlag (Germany). - 0175-7571 .- 1432-1017. ; 63
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Journal article (peer-reviewed)abstract
- Disruption of naturally evolved spatial patterns of genetic variation and local adaptations is a growing concern in wildlife management and conservation. During the last decade, releases of native taxa with potentially non-native genotypes have received increased attention. This has mostly concerned conservation programs, but releases are also widely carried out to boost harvest opportunities. The mallard, Anas platyrhynchos, is one of few terrestrial migratory vertebrates subjected to large-scale releases for hunting purposes. It is the most numerous and widespread duck in the world, yet each year more than three million farmed mallard ducklings are released into the wild in the European Union alone to increase the harvestable population. This study aimed to determine the genetic effects of such large-scale releases of a native species, specifically if wild and released farmed mallards differ genetically among subpopulations in Europe, if there are signs of admixture between the two groups, if the genetic structure of the wild mallard population has changed since large-scale releases began in the 1970s, and if the current data matches global patterns across the Northern hemisphere. We used Bayesian clustering (Structure software) and Discriminant Analysis of Principal Components (DAPC) to analyze the genetic structure of historical and present-day wild (n = 171 and n = 209, respectively) as well as farmed (n = 211) mallards from six European countries as inferred by 360 single-nucleotide polymorphisms (SNPs). Both methods showed a clear genetic differentiation between wild and farmed mallards. Admixed individuals were found in the present-day wild population, implicating introgression of farmed genotypes into wild mallards despite low survival among released farmed mallards. Such cryptic introgression would alter the genetic composition of wild populations and may have unknown long-term consequences for conservation.
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- Szczepankiewicz, Olga, et al.
(author)
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N-Terminal Extensions Retard Aβ42 Fibril Formation but Allow Cross-Seeding and Coaggregation with Aβ42.
- 2015
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 137:46, s. 14673-14685
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Journal article (peer-reviewed)abstract
- Amyloid β-protein (Aβ) sequence length variants with varying aggregation propensity coexist in vivo, where coaggregation and cross-catalysis phenomena may affect the aggregation process. Until recently, naturally occurring amyloid β-protein (Aβ) variants were believed to begin at or after the canonical β-secretase cleavage site within the amyloid β-protein precursor. However, N-terminally extended forms of Aβ (NTE-Aβ) were recently discovered and may contribute to Alzheimer's disease. Here, we have used thioflavin T fluorescence to study the aggregation kinetics of Aβ42 variants with N-terminal extensions of 5-40 residues, and transmission electron microscopy to analyze the end states. We find that all variants form amyloid fibrils of similar morphology as Aβ42, but the half-time of aggregation (t1/2) increases exponentially with extension length. Monte Carlo simulations of model peptides suggest that the retardation is due to an underlying general physicochemical effect involving reduced frequency of productive molecular encounters. Indeed, global kinetic analyses reveal that NTE-Aβ42s form fibrils via the same mechanism as Aβ42, but all microscopic rate constants (primary and secondary nucleation, elongation) are reduced for the N-terminally extended variants. Still, Aβ42 and NTE-Aβ42 coaggregate to form mixed fibrils and fibrils of either Aβ42 or NTE-Aβ42 catalyze aggregation of all monomers. NTE-Aβ42 monomers display reduced aggregation rate with all kinds of seeds implying that extended termini interfere with the ability of monomers to nucleate or elongate. Cross-seeding or coaggregation may therefore represent an important contribution in the in vivo formation of assemblies believed to be important in disease.
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