Synthesis of Tri- and Tetrasubstituted Alkenyl Boronates from Alkynes

The synthesis of organoboron compounds have attracted the attention of the synthetic community. In particular, molecules with C(sp(2))-B bonds enable the transformation to new C-C or C-heteroatom bonds by well-established methodologies. Alkenyl boronates have the possibility for further conversion of the boron moiety or functionalization of the double bond. This review gives an overview on the recent methodologies for the selective preparation of the challenging highly substituted alkenyl boronates from alkynes.Ministerio de Ciencia e InnovaciónComunidad de MadridUniversidad de Alcal

Imposing exclusion limits on new physics with machine-learned likelihoods

Machine-Learned Likelihood (MLL) is a method that, by combining modern machine-learning techniques with likelihood-based inference tests, allows estimating the experimental sensitivity of high-dimensional data sets. Here we extend the MLL method by including the exclusion hypothesis tests and study it first on a toy model of multivariate Gaussian distributions, where the true probability distribution functions are known. We then apply it to a case of interest in the search for new physics at the LHC, in which a ′ boson decays into lepton pairs, comparing the performance of MLL for estimating 95% CL exclusion limits with respect to the prospects reported by ATLAS at 14 TeV with a luminosity of 3 ab−1.Fil: Arganda Carreras, Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: de Los Rios, Martín Emilio. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Perez, Andres Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Sandá Seoane, Rosa María. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; Españ

One-Pot (3 + 2) Cycloaddition-Isomerization-Oxidation of 2,2,2-Trifluorodiazoethane and Styryl Derivatives

A facile access to5-aryl-3-trifluoromethylpyrazoles has been developedby a one-pot (3 + 2) cycloaddition-isomerization-oxidationsequence employing 2,2,2-trifluorodiazoethane and styryl derivatives.A broad variety of functional groups and good yields are achievedunder mild conditions. Additionally, the functionalization of 3-trifluoromethylpyrazoleswas studied. DFT calculations of the cycloaddition transition stateenergies are consistent with the experimentally observed reactivity.Ministerio de Ciencia e InnovaciónInstituto de Salud Carlos IIIComunidad de Madri

Inhibition of mitochondrial fission by Drp-1 blockade by short-term leptin and Mdivi-1 treatment improves white adipose tissue abnormalities in obesity and diabetes

Background: Obesity and type 2 diabetes are chronic diseases characterized by insulin resistance, mitochondrial dysfunction and morphological abnormalities. Objective: We have investigated if dysregulation of mitochondrial dynamics and biogenesis is involved in an animal model of obesity and diabetes. Methods: The effect of short-term leptin and mdivi-1 – a selective inhibitor of Drp-1 fission-protein – treatment on mitochondrial dynamics and biogenesis was evaluated in epididymal white adipose tissue (WAT) from male ob/ob mice. Results: An increase in Drp-1 protein levels and a decrease in Mfn2 and OPA-1 protein expression were observed with enhanced and sustained mitochondrial fragmentation in ob/ob mice compared to wt C57BL/6 animals (p < 0.05). The content of mitochondrial DNA and PGC-1α mRNA expression –both parameters of mitochondrial biogenesis– were reduced in ob/ob mice (p < 0.05). Treatment with leptin and mdivi-1 significantly increased mitochondrial biogenesis, improved fusion-to-fission balance and attenuated mitochondrial dysfunction, thus inducing white-to-beige adipocyte transdifferentiation. Measurements of glucose and lipid oxidation in adipocytes revealed that both leptin and mdivi-1 increase substrates oxidation while in vivo determination of blood glucose concentration showed decreased levels by 50% in ob/ob mice, almost to the wt level. Conclusions: Pharmacological targeting of Drp-1 fission protein may be a potential novel therapeutic tool for obesity and type 2 diabetes.Fil: Finocchietto, Paola Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Perez, Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Blanco, Guillermo Armando C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Miksztowicz, Verónica Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Marotte, Clarisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Morales, C.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Peralta, Jorge Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Berg, G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Fisiopatologia y Bioquimica Clinica.; ArgentinaFil: Poderoso, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Poderoso, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Carreras, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

The Low Incidence of Viral Hepatitis Reactivation Among Subjects on Immunotherapy Reduces the Impact of Suboptimal Screening Rate

Cancer; Checkpoint inhibitors; Hepatitis BCáncer; Inhibidores del punto de control; Hepatitis BCàncer; Inhibidors del punt de control; Hepatitis BBackground and Aims: Immunotherapy with immune checkpoint inhibitors (ICIs) is a pillar of many advanced tumors. However, there is scarce data concerning the rate of viral hepatitis screening in this population or the risk of viral reactivation. Methods: Retrospective–prospective study that includes all patients who began ICIs between January/2019 and December/2020 in a University Hospital. Data on viral hepatitis screening prior to the beginning of ICIs were collected. In subjects lacking information, serological tests were requested prospectively. Among HBsAg, anti-HBc, or anti-HCV positive subjects, reactivation was prospectively assessed. Results: During the 2-year period of study, 595 subjects received ICIs (61.2% male, mean age 63 years). The most prevalent cancers found were 35.5% lung cancer, 12.1% melanoma, and 8.2% head and neck; ICIs schemes were mainly anti-PD1 (65.7%), followed by anti-PD-L1 (19.2%), and combined therapy (13.6%). Prior to immunotherapy, anti-HCV screening was performed in 462 (77.6%) subjects, HBsAg in 462 (77.6%), anti-HBc in 335 (56.3%), and the complete screening in 328 (55.1%). The anti-HBc screening was more frequently ordered among patients treated with concomitant systemic therapy (p = 0.003), especially in the case of chemotherapy (p = 0.015), though HCV screening was more commonly performed in concomitant therapies different from chemotherapy (p = 0.001). Serological tests were completed prospectively in those alive, leading to an overall prevalence for anti-HCV of 3.5%, HBsAg at 1.3%, and anti-HBc of 15.2%. HCV-RNA was detected in 2/19 (both patients with hepatocellular carcinoma), HBV-DNA in 4/7 HBsAg positive, and in 1/75 anti-HBc positive subject. Five out of the 7 HBsAg carriers and 1/75 anti-HBc+ subjects (due to concomitant antiretroviral therapy) received antiviral prophylaxis. Neither cases of HBV reactivation nor changes in HCV viral load were observed. Discussion: HBV and HCV screening prior to immunotherapy is suboptimal. Though the rate of viral hepatitis reactivation seems extremely low, efforts should be made to optimize viral hepatitis screening prior to immunotherapy for the selection of candidates for either antiviral prophylaxis or periodical follow-up

Valoración de los alumnos de la Unidad docente HU 12 de Octubre- HU Infanta Cristina sobre la implantación de la docencia y evaluación online con utilización del campus virtual en asignaturas teóricas y prácticas

La docencia en el Grado de Medicina se ha producido tradicionalmente mediante métodos presenciales, tanto en lo que se refiere a impartir clases magistrales o seminarios, como en lo referente a la experiencia clínica de los alumnos con pacientes reales o simulados. Sin embargo, la situación epidemiológica actual, con la pandemia producida por el covid-19, ha precipitado que durante los cursos académicos 2019-20 y 2020-21 se hayan comenzado a utilizar métodos de enseñanza virtual, con un profesorado y alumnado sin a penas conocimiento ni experiencia previa. Por estos motivos, se ha realizado una evaluación de la opinión de los alumnos sobre la docencia teórica online, la actividad práctica virtual, los exámenes on line o las características de la docencia práctica en un ambiente de pandemia

Molecular markers of endometrial carcinoma detected in uterine aspirates.

Endometrial cancer (EC) is the most frequent of the invasive tumors of the female genital tract. Although usually detected in its initial stages, a 20% of the patients present with advanced disease. To date, no characterized molecular marker has been validated for the diagnosis of EC. In addition, new methods for prognosis and classification of EC are needed to combat this deadly disease. We thus aimed to identify new molecular markers of EC and to evaluate their validity on endometrial aspirates. Gene expression screening on 52 carcinoma samples and series of real-time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and noncarcinoma uterine aspirates were performed to identify and validate potential biomarkers of EC. Candidate markers were further confirmed at the protein level by immunohistochemistry and Western blot. We identified ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2 and DCN as differentially expressed in ECs. Furthermore, the differential expression of these biomarkers in primary endometrial tumors is correlated to their expression level in corresponding uterine fluid samples. Finally, these biomarkers significantly identified EC with area under the receiver-operating-characteristic values ranging from 0.74 to 0.95 in uterine aspirates. Interestingly, analogous values were found among initial stages. We present the discovery of molecular biomarkers of EC and describe their utility in uterine aspirates. These findings represent the basis for the development of a highly sensitive and specific minimally invasive method for screening ECs