Escriure Biologia a la Universitat

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Long-term anticoagulation in secondary ischemic stroke prevention: The prospective multicenter RESTAIC registry

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up. Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change. Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence. Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence.This study was supported by grants from the Foundation for Biomedical Research of La Paz University Hospital (PI 1131

MoS2 photoelectrodes for hydrogen production: Tuning the S-vacancy content in highly homogeneous ultrathin nanocrystals

Tuning the electrocatalytic properties of MoS2 layers can be achieved through different paths, such as reducing their thickness, creating edges in the MoS2 flakes, and introducing S-vacancies. We combine these three approaches by growing MoS2 electrodes by using a special salt-assisted chemical vapor deposition (CVD) method. This procedure allows the growth of ultrathin MoS2 nanocrystals (1-3 layers thick and a few nanometers wide), as evidenced by atomic force microscopy and scanning tunneling microscopy. This morphology of the MoS2 layers at the nanoscale induces some specific features in the Raman and photoluminescence spectra compared to exfoliated or microcrystalline MoS2 layers. Moreover, the S-vacancy content in the layers can be tuned during CVD growth by using Ar/H2 mixtures as a carrier gas. Detailed optical microtransmittance and microreflectance spectroscopies, micro-Raman, and X-ray photoelectron spectroscopy measurements with sub-millimeter spatial resolution show that the obtained samples present an excellent homogeneity over areas in the cm2 range. The electrochemical and photoelectrochemical properties of these MoS2 layers were investigated using electrodes with relatively large areas (0.8 cm2). The prepared MoS2 cathodes show outstanding Faradaic efficiencies as well as long-term stability in acidic solutions. In addition, we demonstrate that there is an optimal number of S-vacancies to improve the electrochemical and photoelectrochemical performances of MoS2PID2021-126098OB-I00, PID2020-116619GA-C22, TED2021-131788A-I00, SI3/PJI/2021-0050

TOI-431/HIP 26013: A super-Earth and a sub-Neptune transiting a bright, early K dwarf, with a third RV planet

We present the bright (Vmag = 9.12), multiplanet system TOI-431, characterized with photometry and radial velocities (RVs). We estimate the stellar rotation period to be 30.5 ± 0.7 d using archival photometry and RVs. Transiting Exoplanet Survey Satellite (TESS) objects of Interest (TOI)-431 b is a super-Earth with a period of 0.49 d, a radius of 1.28 ± 0.04 R, a mass of 3.07 ± 0.35 M, and a density of 8.0 ± 1.0 g cm-3; TOI-431 d is a sub-Neptune with a period of 12.46 d, a radius of 3.29 ± 0.09 R, a mass of 9.90+1.53-1.49 M, and a density of 1.36 ± 0.25 g cm-3. We find a third planet, TOI-431 c, in the High Accuracy Radial velocity Planet Searcher RV data, but it is not seen to transit in the TESS light curves. It has an Msin i of 2.83+0.41-0.34 M, and a period of 4.85 d. TOI-431 d likely has an extended atmosphere and is one of the most well-suited TESS discoveries for atmospheric characterization, while the super-Earth TOI-431 b may be a stripped core. These planets straddle the radius gap, presenting an interesting case-study for atmospheric evolution, and TOI-431 b is a prime TESS discovery for the study of rocky planet phase curves.Fil: Osborn, Ares. University of Warwick; Reino UnidoFil: Armstrong, David J. University of Warwick; Reino UnidoFil: Cale, Bryson. George Mason University; Estados UnidosFil: Brahm, Rafael. Universidad Adolfo Ibañez; Chile. Instituto de Astrofísica; ChileFil: Wittenmyer, Robert A. University Of Southern Queensland; AustraliaFil: Dai, Fei. Division Of Geological And Planetary Sciences; Estados UnidosFil: Crossfield, Ian J. M. University of Kansas; Estados UnidosFil: Bryant, Edward M. University of Warwick; Reino UnidoFil: Adibekyan, Vardan. Universidad de Porto; PortugalFil: Cloutier, Ryan. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Collins, Karen A. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Delgado Mena, E.. Universidad de Porto; PortugalFil: Fridlund, Malcolm. Leiden University; Países Bajos. Chalmers University of Technology; SueciaFil: Hellier, Coel. Keele University; Reino UnidoFil: Howell, Steve B. NASA Ames Research Center; Estados UnidosFil: King, George W. University of Warwick; Reino UnidoFil: Lillo Box, Jorge. Consejo Superior de Investigaciones Científicas. Centro de Astrobiología; EspañaFil: Otegi, Jon. Universidad de Ginebra; Suiza. Universitat Zurich; SuizaFil: Sousa, S.. Universidad de Porto; PortugalFil: Stassun, Keivan G. Vanderbilt University; Estados UnidosFil: Matthews, Elisabeth C. Universidad de Ginebra; Suiza. Massachusetts Institute of Technology; Estados UnidosFil: Ziegler, Carl. University of Toronto; CanadáFil: Ricker, George. Massachusetts Institute of Technology; Estados UnidosFil: Vanderspek, Roland. Massachusetts Institute of Technology; Estados UnidosFil: Latham, David W. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Seager, S.. Massachusetts Institute of Technology; Estados UnidosFil: Winn, Joshua N.. University of Princeton; Estados UnidosFil: Jenkins, Jon M. NASA Ames Research Center; Estados UnidosFil: Acton, Jack S. University of Leicester; Reino UnidoFil: Addison, Brett C. University Of Southern Queensland; AustraliaFil: Diaz, Rodrigo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentin

YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC. Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples. Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

TOI-332 b : a super dense Neptune found deep within the Neptunian desert

To date, thousands of planets have been discovered, but there are regions of the orbital parameter space that are still bare. An example is the short period and intermediate mass/radius space known as the “Neptunian desert”, where planets should be easy to find but discoveries remain few. This suggests unusual formation and evolution processes are responsible for the planets residing here. We present the discovery of TOI-332 b, a planet with an ultra-short period of 0.78 d that sits firmly within the desert. It orbits a K0 dwarf with an effective temperature of 5251 ± 71 K. TOI-332 b has a radius of 3.20+ 0.16 −0.12 R⊕, smaller than that of Neptune, but an unusually large mass of 57.2 ± 1.6 M⊕. It has one of the highest densities of any Neptune-sized planet discovered thus far at 9.6+ 1.1 −1.3 g cm−3 . A 4-layer internal structure model indicates it likely has a negligible hydrogen-helium envelope, something only found for a small handful of planets this massive, and so TOI-332 b presents an interesting challenge to planetary formation theories. We find that photoevaporation cannot account for the mass loss required to strip this planet of the Jupiter-like envelope it would have been expected to accrete. We need to look towards other scenarios, such as high-eccentricity migration, giant impacts, or gap opening in the protoplanetary disc, to try and explain this unusual discovery

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Escriure Biologia a la Universitat

Aquest projecte ha rebut un ajut Interlingua de la Generalitat de Catalunya.Guia que ajuda els destinataris (professorat i alumnat) a comunicar-se, sobretot per escrit, en la seva disciplina acadèmica; biologia en aquest cas