A semantic interoperability approach to support integration of gene expression and clinical data in breast cancer

[Abstract] Introduction. The introduction of omics data and advances in technologies involved in clinical treatment has led to a broad range of approaches to represent clinical information. Within this context, patient stratification across health institutions due to omic profiling presents a complex scenario to carry out multi-center clinical trials. Methods. This paper presents a standards-based approach to ensure semantic integration required to facilitate the analysis of clinico-genomic clinical trials. To ensure interoperability across different institutions, we have developed a Semantic Interoperability Layer (SIL) to facilitate homogeneous access to clinical and genetic information, based on different well-established biomedical standards and following International Health (IHE) recommendations. Results. The SIL has shown suitability for integrating biomedical knowledge and technologies to match the latest clinical advances in healthcare and the use of genomic information. This genomic data integration in the SIL has been tested with a diagnostic classifier tool that takes advantage of harmonized multi-center clinico-genomic data for training statistical predictive models. Conclusions. The SIL has been adopted in national and international research initiatives, such as the EURECA-EU research project and the CIMED collaborative Spanish project, where the proposed solution has been applied and evaluated by clinical experts focused on clinico-genomic studies.Instituto de Salud Carlos III, PI13/02020Instituto de Salud Carlos III, PI13/0028

A Study of the Near-Ultraviolet Spectrum of Vega

UV, optical, and near-IR spectra of Vega have been combined to test our understanding of stellar atmospheric opacities, and to examine the possibility of constraining chemical abundances from low-resolution UV fluxes. We have carried out a detailed analysis assuming Local Thermodynamic Equilibrium (LTE) to identify the most important contributors to the UV continuous opacity: H, H$^{-}$, C I, and Si II. Our analysis also assumes that Vega is spherically symmetric and its atmosphere is well described with the plane parallel approximation. Comparing observations and computed fluxes we have been able to discriminate between two different flux scales that have been proposed, the IUE-INES and the HST scales, favoring the latter. The effective temperature and angular diameter derived from the analysis of observed optical and near-UV spectra are in very good agreement with previous determinations based on different techniques. The silicon abundance is poorly constrained by the UV observations of the continuum and strong lines, but the situation is more favorable for carbon and the abundances inferred from the UV continuum and optical absorption lines are in good agreement. Some spectral intervals in the UV spectrum of Vega that the calculations do not reproduce well are likely affected by deviations from LTE, but we conclude that our understanding of UV atmospheric opacities is fairly complete for early A-type stars.Comment: 13 pages, 9 figures, to be published in Ap

Neoadjuvant in situ vaccination with cowpea mosaic virus as a novel therapy against canine inflammatory mammary cancer

BackgroundInflammatory mammary cancer (IMC), the counterpart of human inflammatory breast cancer (IBC), is the deadliest form of canine mammary tumors. IMC patients lack specific therapy and have poor outcomes. This proof-of-principle preclinical study evaluated the efficacy, safety, and effect on survival of neoadjuvant intratumoral (in situ) empty cowpea mosaic virus (eCPMV) immunotherapy in companion dogs diagnosed with IMC.MethodsTen IMC-bearing dogs were enrolled in the study. Five dogs received medical therapy, and five received weekly neoadjuvant in situ eCPMV immunotherapy (0.2–0.4 mg per injection) and medical therapy after the second eCPMV injection. Efficacy was evaluated by reduction of tumor growth; safety by hematological and biochemistry changes in blood and plasma; and patient outcome by survival analysis. eCPMV-induced immune changes in blood cells were analyzed by flow cytometry; changes in the tumor microenvironment were evaluated by CD3 (T lymphocytes), CD20 (B lymphocytes), FoxP3 (Treg lymphocytes), myeloperoxidase (MPO; neutrophils), Ki-67 (proliferation index, PI; tumor cell proliferation), and Cleaved Caspase-3 (CC-3; apoptosis) immunohistochemistry.ResultsTwo neoadjuvant in situ eCPMV injections resulted in tumor shrinkage in all patients by day 14 without systemic adverse events. Although surgery for IMC is generally not an option, reduction in tumor size allowed surgery in two IMC patients. In peripheral blood, in situ eCPMV immunotherapy was associated with a significant decrease of Treg$^{+}$/CD8$^{+}$ ratio and changes in CD8$^{+}$Granzyme B$^{+}$ T cells, which behave as a lagging predictive biomarker. In the TME, higher neutrophilic infiltration and MPO expression, lower tumor Ki-67 PI, increase in CD3$^{+}$ lymphocytes, decrease in FoxP3$^{+}$/CD3$^{+}$ ratio (p<0.04 for all comparisons), and no changes in CC-3$^{+}$ immunostainings were observed in post-treatment tumor tissues when compared with pretreatment tumor samples. eCPMV-treated IMC patients had a statistically significant (p=0.033) improved overall survival than patients treated with medical therapy.ConclusionsNeoadjuvant in situ eCPMV immunotherapy demonstrated anti-tumor efficacy and improved survival in IMC patients without systemic adverse effects. eCPMV-induced changes in immune cells point to neutrophils as a driver of immune response. Neoadjuvant in situ eCPMV immunotherapy could be a groundbreaking immunotherapy for canine IMC and a potential future immunotherapy for human IBC patients

2021 Tajogaite eruption records infiltration of crustal fluids within the upper mantle beneath La Palma, Canary Islands

The 2021 Tajogaite eruption at La Palma has represented a unique opportunity to investigate the characteristics of the mantle source feeding modern volcanism in the Canary Islands. With the aim of track the fingerprint of carbon in the local oceanic lithosphere-asthenosphere system, we report the isotopic composition of CO2 (δ13C values versus Vienna Pee Dee Belemnite) in olivine- and clinopyroxene-hosted fluid inclusions (FI) from the 2021 Tajogaite lavas and from lavas/ultramafic xenoliths (olivine-clinopyroxenites, clinopyroxenites, dunites and harzburgites) from the nearby 1677 San Antonio eruption cone/lavas, in an attempt to characterize the origin and evolution of carbon within the local mantle source. Our results indicate that the 2021 and 1677 lavas exhibit δ13C values ranging from −4.94‰ to −2.71‰ and CO2/3He ratios from 3.37 to 6.14 × 109. Ultramafic xenoliths fall in a comparable range of values despite showing higher CO2 concentrations. Our δ13C values fall within the range of carbon isotope results previously reported for the Dos Aguas cold spring located in the Taburiente Caldera (northern La Palma), suggesting an apparent carbon isotope homogeneity at the scale of the entire island. The (relatively narrow) δ13C vs. CO2/3He ratio range of La Palma samples is interpreted to reflect either i) variable extents of open-system degassing of a common mantle endmember having δ13C of ∼1.7‰, or ii) mixing between depleted mantle-like carbon (−6‰ &lt; δ13C &lt; −4‰) and crustal carbon (δ13C = 0‰) endmembers. Both models testify a crustal carbon component recycled in the local mantle. This component, also detected in mantle xenoliths from the neighboring island of El Hierro and the easternmost Lanzarote, indicates a regional characteristic of the mantle beneath the Canary Islands, interpreted as a result of infiltration of carbon-rich melts during past metasomatic events in the local mantle

Star Formation Rate Indicators in Wide-Field Infrared Survey Preliminary Release

With the goal of investigating the degree to which theMIR luminosity in theWidefield Infrared Survey Explorer (WISE) traces the SFR, we analyze 3.4, 4.6, 12 and 22 {\mu}m data in a sample of {\guillemotright} 140,000 star-forming galaxies or star-forming regions covering a wide range in metallicity 7.66 < 12 + log(O/H) < 9.46, with redshift z < 0.4. These star-forming galaxies or star-forming regions are selected by matching the WISE Preliminary Release Catalog with the star-forming galaxy Catalog in SDSS DR8 provided by JHU/MPA 1.We study the relationship between the luminosity at 3.4, 4.6, 12 and 22 {\mu}m from WISE and H\alpha luminosity in SDSS DR8. From these comparisons, we derive reference SFR indicators for use in our analysis. Linear correlations between SFR and the 3.4, 4.6, 12 and 22 {\mu}m luminosity are found, and calibrations of SFRs based on L(3.4), L(4.6), L(12) and L(22) are proposed. The calibrations hold for galaxies with verified spectral observations. The dispersion in the relation between 3.4, 4.6, 12 and 22 {\mu}m luminosity and SFR relates to the galaxy's properties, such as 4000 {\deg}A break and galaxy color.Comment: 10 pages, 3 figure

Extreme Starbursts in the Local Universe

The "Extreme starbursts in the local universe" workshop was held at the Insituto de Astrofisica de Andalucia in Granada, Spain on 21-25 June 2010. Bearing in mind the advent of a new generation of facilities such as JWST, Herschel, ALMA, eVLA and eMerlin, the aim of the workshop was to bring together observers and theorists to review the latest results. The purpose of the workshop was to address the following issues: what are the main modes of triggering extreme starbursts in the local Universe? How efficiently are stars formed in extreme starbursts? What are the star formation histories of local starburst galaxies? How well do the theoretical simulations model the observations? What can we learn about starbursts in the distant Universe through studies of their local counterparts? How important is the role of extreme starbursts in the hierarchical assembly of galaxies? How are extreme starbursts related to the triggering of AGN in the nuclei of galaxies? Overall, 41 talks and 4 posters with their corresponding 10 minutes short talks were presented during the workshop. In addition, the workshop was designed with emphasis on discussions, and therefore, there were 6 discussion sessions of up to one hour during the workshop. Here is presented a summary of the purposes of the workshop as well as a compilation of the abstracts corresponding to each of the presentations. The summary and conclusions of the workshop along with a description of the future prospects by Sylvain Veilleux can be found in the last section of this document. A photo of the assistants is included.Comment: worksho

Intermediate snowpack melt-out dates guarantee the highest seasonal grasslands greening in the Pyrenees

In mountain areas, the phenology and productivity of grassland are closely related to snow dynamics. However, the influence that snow melt timing has on grassland growing still needs further attention for a full understanding, particularly at high spatial resolution. Aiming to reduce this knowledge gap, this work exploits 1 m resolution snow depth and Normalized Difference Vegetation Index observations acquired with an Unmanned Aerial Vehicle at a sub-alpine site in the Pyrenees. During two snow seasons (2019–2020 and 2020–2021), 14 NDVI and 17 snow depth distributions were acquired over 48 ha. Despite the snow dynamics being different in the two seasons, the response of grasslands greening to snow melt-out exhibited a very similar pattern in both. The NDVI temporal evolution in areas with distinct melt-out dates reveals that sectors where the melt-out date occurs in late April or early May (optimum melt-out) reach the maximum vegetation productivity. Zones with an earlier or a later melt-out rarely reach peak NDVI values. The results obtained in this study area, suggest that knowledge about snow depth distribution is not needed to understand NDVI grassland dynamics. The analysis did not reveal a clear link between the spatial variability in snow duration and the diversity and richness of grassland communities within the study area

The noble gas signature of the 2021 Tajogaite eruption (La Palma, Canary Islands)

Here, we characterize the temporal evolution of volatiles during the Tajogaite eruption by analyzing the elemental (He-Ar-CO2-N2) and isotopic (He-Ar-Ne) composition of fluid inclusions (FI) in phenocrysts (olivine+pyroxene) identified in erupted lavas. Our 2021 lava samples identify substantial temporal variations in volatile composition. We show that, during the 2021 Tajogaite eruption, the He-CO2-N2 concentrations in FI increased since October 15th; this increase was accompanied by increasing 40Ar/36Ar ratios (from ~300 to &gt;500), and paralleled a major shift in bulk lava chemistry, with increasing Mg contents (Mg#, from 47 to 52 to 55–59), CaO/Al2O3 (from 0.65 to 0.74 to 0.75–0.90), Ni and Cr, and decreasing TiO2, P2O5 and incompatible elements. The olivine core composition also became more forsteritic (from Mg# = 80–81 to Mg# = 84–86). Mineral thermobarometry and FI barometry results indicate that the eruption was sustained by magmas previously stored in at least two magma accumulation zones, at respectively ~6–12 km and 15–30 km, corroborating previous seismic and FI evidence. We therefore propose that the compositional changes seen throughout the eruption can be explained by an increased contribution - since early/mid-October - of more primitive, lessdegassed magma from the deeper (mantle) reservoir. Conversely, Rc/Ra values (3He/4He ratios corrected for atmospheric contamination) remained constant throughout the whole eruption at MORB-like values (7.38 ± 0.22 Ra, 1σ), suggesting an isotopically homogeneous magma feeding source. The Tajogaite He isotope signature is within the range of values observed for the 1677 San Antonio lavas (7.37 ± 0.17Ra, 1σ), but is more radiogenic than the 3He/4He values (&gt;9 Rc/Ra) observed in the Caldera de Taburiente to the north. The 3He/4He ratios (6.75 ± 0.20 Ra, 1σ) measured in mantle xenoliths from the San Antonio volcano indicate a relatively radiogenic nature of the mantle beneath the Cumbre Vieja ridge. Based on these results and mixing modeling calculations, we propose that the homogeneous He isotopic signatures observed in volatiles from the Tajogaite/San Antonio lavas reflect three component mixing between a MORB-like source, a radiogenic component and small additions (6–15%) of a high 3He/4He reservoir-derived (&gt;9Ra) fluid components. The simultaneous occurrence of high 3 He/4 He (&gt;9Ra)- and MORB-like He signatures in northern and southern La Palma is interpreted to reflect smallscale heterogeneities in the local mantle, arising from spatially variable proportions of MORB, radiogenic, and high 3He/4He component