Dental pulp pluripotent-like stem cells (DPPSC), a new stem cell population with chromosomal stability and osteogenic capacity for biomaterials evaluation

Background: Biomaterials are widely used to regenerate or substitute bone tissue. In order to evaluate their potential use for clinical applications, these need to be tested and evaluated in vitro with cell culture models. Frequently, immortalized osteoblastic cell lines are used in these studies. However, their uncontrolled proliferation rate, phenotypic changes or aberrations in mitotic processes limits their use in long-term investigations. Recently, we described a new pluripotent-like subpopulation of dental pulp stem cells derived from the third molars (DPPSC) that shows genetic stability and shares some pluripotent characteristics with embryonic stem cells. In this study we aim to describe the use of DPPSC to test biomaterials, since we believe that the biomaterial cues will be more critical in order to enhance the differentiation of pluripotent stem cells. Methods: The capacity of DPPSC to differentiate into osteogenic lineage was compared with human sarcoma osteogenic cell line (SAOS-2). Collagen and titanium were used to assess the cell behavior in commonly used biomaterials. The analyses were performed by flow cytometry, alkaline phosphatase and mineralization stains, RT-PCR, immunohistochemistry, scanning electron microscopy, Western blot and enzymatic activity. Moreover, the genetic stability was evaluated and compared before and after differentiation by short-comparative genomic hybridization (sCGH). Results: DPPSC showed excellent differentiation into osteogenic lineages expressing bone-related markers similar to SAOS-2. When cells were cultured on biomaterials, DPPSC showed higher initial adhesion levels. Nevertheless, their osteogenic differentiation showed similar trend among both cell types. Interestingly, only DPPSC maintained a normal chromosomal dosage before and after differentiation on 2D monolayer and on biomaterials. Conclusions: Taken together, these results promote the use of DPPSC as a new pluripotent-like cell model to evaluate the biocompatibility and the differentiation capacity of biomaterials used in bone regeneration

ACE and CXCL10 as predictive biomarkers in the LEA study

Background: LEA Study (GEICAM/2006-11/GBG51), is a randomized clinical trial comparing bevacizumab in combination with endocrine therapy (ET + B) with endocrine therapy (ET) in postmenopausal women with advanced or metastatic HR-positive/HER2-negative breast cancer (BC) with indication of hormonotherapy as first-line treatment. Patients with secondary hypertension had better progression-free survival (PFS) and overall survival (OS). We have evaluated the role of two hypertension-related biomarkers, Angiotensin-Converting Enzyme (ACE) and Small-Inducible Cytokine B10 (CXCL10) as prognostic and/or predictive biomarkers of benefit to bevacizumab in the first line metastatic disease. Methods: From 380 patients, 266 were included in 33 Spanish sites. Median age was 64 years, 63.5% had measurable disease, 97.4% were metastatic at randomization, 51.5% had visceral disease and 52.6% received previous chemotherapy. PFS was 14.3 months (range 0.8-61.1), OS was 34 months (range 0.8-71.6) and 93 patients had Objective Response (OR). We analyzed 124 plasma samples collected before treatment (52 from ET and 72 from ET + B arms). Circulating levels of ACE and CXCL10 were determined by ELISA. ACE levels of 115ng/ml and 135ng/ml were pre-defined as cutoff values. CXCL10 was explored as a quantitative variable. Results: PFS was 15.1 months (range 1.4-61.1), OS was 31.1 months (range 2.8-61.1) and 40.3% had OR. OR was significantly different between treatment arms (p < 0.001) but not PFS or OS. Median ACE concentration was 130.9ng/ml (range 35.3-315.4). Low ACE (<135ng/ml) had better PFS in the whole population (p = 0.048) and in the ET + B arm (p = 0.041). ACE cutoff of 115 ng/ml was not able to identify any subgroup with better prognosis. Median CXCL10 concentration was 230.3pg/ml (range 15.1-4129.6). A higher expression of CXCL10 was significantly associated with worse OS in the whole population (p < 0.0001) and each treatment arm (p = 0.002 and p = 0.001 in ET and ET + B, respectively). No association with OR were identified neither for ACE nor for CXCL10. Conclusions: ACE levels could be considered a prognostic and a bevacizumab predictive biomarker of PFS. CXCL10 could be prognostic of OS. Confirmatory studies are warranted

Delta excitation in K^+-nucleus collisions

We present calculations for \Delta excitation in the (K^+,K^+) reaction in nuclei. The background from quasielastic K^+ scattering in the \Delta region is also evaluated and shown to be quite small in some kinematical regions, so as to allow for a clean identification of the \Delta excitation strength. Nuclear effects tied to the \Delta renormalization in the nucleus are considered and the reaction is shown to provide new elements to enrich our knowledge of the \Delta properties in a nuclear medium.Comment: 11 pages, 6 figures, LaTe

Health-related quality of life with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor–positive metastatic breast cancer: Patient-reported outcomes in the PEARL study

Background: The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. This analysis compared patient-reported outcomes. Patients and methods: The PEARL quality of life (QoL) population comprised 537 patients, 268 randomised to palbociclib/ET (exemestane or fulvestrant) and 269 to capecitabine. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 and EQ-5D-3L questionnaires. Changes from the baseline and time to deterioration (TTD) were analysed using linear mixed-effect and stratified Cox regression models, respectively. Results: Questionnaire completion rate was high and similar between treatment arms. Significant differences were observed in the mean change in global health status (GHS)/QoL scores from the baseline to cycle 3 (2.9 for palbociclib/ET vs. -2.1 for capecitabine (95% confidence interval [CI], 1.4–8.6; P = 0.007). The median TTD in GHS/QoL was 8.3 months for palbociclib/ET versus 5.3 months for capecitabine (adjusted hazard ratio, 0.70; 95% CI, 0.55–0.89; P = 0.003). Similar improvements for palbociclib/ET were also seen for other scales as physical, role, cognitive, social functioning, fatigue, nausea/vomiting and appetite loss. No differences were observed between the treatment arms in change from the baseline in any item of the EQ-5D-L3 questionnaire as per the overall index score and visual analogue scale. Conclusion: Patients receiving palbociclib/ET experienced a significant delay in deterioration of GHS/QoL and several functional and symptom scales compared with capecitabine, providing additional evidence that palbociclib/ET is better tolerated. Trial registration number: NCT02028507 (ClinTrials.gov). EudraCT study number: 2013-003170-27. © 2021 The Author(s

Mapping the ionized gas of the metal-poor HII galaxy PHL 293B with MEGARA

Here we report the first spatially resolved spectroscopic study for the galaxy PHL293B using the high-resolution GTC/MEGARA IFU. PHL293B is a local, extremely metal-poor, high ionization galaxy. This makes PHL 293B an excellent analogue for galaxies in the early Universe. The MEGARA aperture (~12.5''x 11.3'') covers the entire PHL 293B main body and its far-reaching ionized gas. We created and discussed maps of all relevant emission lines, line ratios and physical-chemical properties of the ionized ISM. The narrow emission gas appears to be ionized mainly by massive stars according to the observed diganostic line ratios, regardless of the position across the MEGARA aperture. We detected low intensity broad emission components and blueshifted absorptions in the Balmer lines (H$\alpha$,H$\beta$) which are located in the brightest zone of the galaxy ISM. A chemically homogeneity, across hundreds of parsecs, is observed in O/H. We take the oxygen abundance 12+log(O/H)=7.64 $\pm$ 0.06 derived from the PHL293B integrated spectrum as the representative metallicity for the galaxy. Our IFU data reveal for the first time that the nebular HeII4686 emission from PHL 293B is spatially extended and coincident with the ionizing stellar cluster, and allow us to compute its absolute HeII ionizing photon flux. Wolf-Rayet bumps are not detected excluding therefore Wolf-Rayet stars as the main HeII excitation source. The origin of the nebular HeII4686 is discussed.Comment: 14 pages, 9 Figures, 3 Tables; Accepted for publication in MNRA

Self energies of the pion and the delta isobar from the ^3He(e,e'pi^+)^3H reaction

In a kinematically complete experiment at the Mainz microtron MAMI, pion angular distributions of the $^3$He(e,e'$\pi^+)^3$H reaction have been measured in the excitation region of the $\Delta$ resonance to determine the longitudinal ($L$), transverse ($T$), and the $LT$ interference part of the differential cross section. The data are described only after introducing self-energy modifications of the pion and $\Delta$-isobar propagators. Using Chiral Perturbation Theory (ChPT) to extrapolate the pion self energy as inferred from the measurement on the mass shell, we deduce a reduction of the $\pi^+$ mass of $\Delta m_{\pi^+} = (-1.7^{+ 1.7}_{- 2.1})$ MeV/c$^2$ in the neutron-rich nuclear medium at a density of $\rho = (0.057^{+ 0.085}_{- 0.057})$ fm$^{-3}$. Our data are consistent with the $\Delta$ self energy determined from measurements of $\pi^0$ photoproduction from $^4$He and heavier nuclei.Comment: Elsart, 12 pages and 4 figures, Correspondent: Professor Dr. Dr. h.c. mult. Achim Richter, [email protected], submitted to Phys. Rev. Let

MEGADES: MEGARA Galaxy Discs Evolution Survey. Data Release I: central fields

The main interest of the Science Team for the exploitation of the MEGARA instrument at the 10.4m Gran Telescopio Canarias (GTC hereafter) is devoted to the study of nearby galaxies, with focus on the research of the history of star formation, and chemical and kinematical properties of disc systems. We refer to this project as MEGADES: MEGARA Galaxy Discs Evolution Survey. The initial goal of MEGADES is to provide a detailed study of the inner regions of nearby disc galaxies, both in terms of their spectrophotometric and chemical evolution, and their dynamical characterisation, by disentangling the contribution of in-situ and ex-situ processes to the history of star formation and effective chemical enrichment of these regions. In addition, the dynamical analysis of these inner regions naturally includes the identification and characterization of galactic winds potentially present in these regions. At a later stage, we will extend this study further out in galactocentric distance. The first stage of this project encompasses the analysis of the central regions of a total of 43 nearby galaxies observed with the MEGARA Integral Field Unit for 114 hours, including both Guaranteed Time and Open Time observations. In this paper we provide a set of all the processed data products available to the community and early results from the analysis of these data regarding stellar continuum, ionized and neutral gas features.Comment: Accepted for publication in Astronomy & Astrophysic

Theoretical study of lepton events in the atmospheric neutrino experiments at SuperK

Super-Kamiokande has reported the results for the lepton events in the atmospheric neutrino experiment. These results have been presented for a 22.5kT water fiducial mass on an exposure of 1489 days, and the events are divided into sub-GeV, multi-GeV and PC events. We present a study of nuclear medium effects in the sub-GeV energy region of atmospheric neutrino events for the quasielastic scattering, incoherent and coherent pion production processes, as they give the most dominant contribution to the lepton events in this energy region. We have used the atmospheric neutrino flux given by Honda et al. These calculations have been done in the local density approximation. We take into account the effect of Pauli blocking, Fermi motion, Coulomb effect, renormalization of weak transition strengths in the nuclear medium in the case of the quasielastic reactions. The inelastic reactions leading to production of leptons along with pions is calculated in a $\Delta$- dominance model by taking into account the renormalization of $\Delta$ properties in the nuclear medium and the final state interaction effects of the outgoing pions with the residual nucleus. We present the results for the lepton events obtained in our model with and without nuclear medium effects, and compare them with the Monte Carlo predictions used in the simulation and the experimentally observed events reported by the Super-Kamiokande collaboration.Comment: 23 pages, 13 figure

Latin Americans and Caribbeans in Europe. A cross-country analysis

With the beginning of the 21st century, there has been an acceleration of migratory flows from Latin America and the Caribbean (LAC) to Europe. As a result, and despite the negative impact of the economic crisis, 4.6 million Latin American and Caribbean immigrants reside in Europe, half of them in Spain. This article analyses the recent evolution of these migratory flows, their territorial distribution, and their demographic profiles according to the 2011 European census data disseminated by a new tool -the Census Hub- implemented by the European Statistical System. The analysis shows the existence of a high LAC immigrant concentration in Spain and in certain European cities, a marked young and feminized demographic profile, a great variety of educational levels and a different insertion in each European labour market, although many LAC immigrants work in low-skill occupations, being overqualified and underemployed in most of the countries