A reciclable bifuctional acid-base organocatalyst with ionic liquid character. The role of sites separation and spatial configuration on different condensation reaction

A series of bifunctional organic catalysts containing acid and basic sites with ionic liquid characteristics have been prepared and their catalytic activity and reaction coordinate for aldol and Knoevenagel condensations have been compared. While the only factor controlling catalyst activity for the Knoevenagel condensation was the distance between the acid and base sites, the spatial orientation of the organocatalyst is also key to achieve high activity and selectivity in the Claisen-Schmidt condensation. Mechanistic studies based on theoretical DFT calculations show that the acid-base bifunctional organocatalyst follows a mechanism inspired in natural aldolases for the synthesis of trans-chalcones, being able to produce a large variety of these compounds of industrial interest. The combination of the acid-base pairs within the proper geometry and the ionic liquid nature makes this catalyst active, selective and recyclable.We thank Consolider-Ingenio 2010 (project MULTICAT), Spanish MICINN (Project MAT2006-14274-C02-01), Generalitat Valenciana (Project PROMETEO/2008/130), and Fundacion Areces for financial support.Corma Canós, A.; Boronat Zaragoza, M.; Climent Olmedo, MJ.; Iborra Chornet, S.; Montón Molina, R.; Sabater Picot, MJ. (2011). A reciclable bifuctional acid-base organocatalyst with ionic liquid character. The role of sites separation and spatial configuration on different condensation reaction. Physical Chemistry Chemical Physics. 13(38):17255-17261. https://doi.org/10.1039/c1cp21986cS17255172611338Motokura, K., Tada, M., & Iwasawa, Y. (2008). Acid-Base Bifunctional Catalytic Surfaces for Nucleophilic Addition Reactions. Chemistry - An Asian Journal, 3(8-9), 1230-1236. doi:10.1002/asia.200800126Gröger, H. (2001). 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Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436

Validity of the Walter Reed Visual Assessment Scale to measure subjective perception of spine deformity in patients with idiopathic scoliosis

BACKGROUND: The Walter Reed Visual Assessment Scale (WRVAS) was designed to allow idiopathic scoliosis patients to describe their perception of their deformity. In a previous stduy, the scale has shown good correlation with magnitude of the curve METHODS: The study included 70 patients (60 women and 10 men), mean age 19.4 years (range 12–40), with idiopathic scoliosis. Each patient filled out the WRVAS and the SRS-22 questionnaire. Thoracic and lumbar curve angles were determined in standing X-rays and the largest was named Cobbmax. WRVAS internal consistency was assessed with Cronbach's alpha. Correlation coefficients were calculated between Cobbmax and the various WRVAS questions, and Cobbmax and the SRS-22 scales. The correlation between the WRVAS and SRS-22 was also determined RESULTS: Mean magnitudes were thoracic curve, 36.6° and lumbar curve, 33.2°; average Cobbmax was 37.9°. The mean total WRVAS score was 15.6. Mean scores for the various SRS-22 scales were function 4.6, pain 4.3, self-image 3.7, mental health 4.2, and total score 84.1. Internal consistency for the WRVAS was excellent (Cronbach's alpha, 0.9), and there were no signs of collinearity among the seven questions (tolerance range 0.2–0.5). All the items on the WRVAS correlated significantly with Cobbmax (correlation coefficients, 0.4 to 0.7). The correlation between the total WRVAS and total SRS-22 score was -0.54 (P = .0001) and between WRVAS total score and SRS-22 image domain score was -0.57 (p = 0.0001) CONCLUSION: The WRVAS showed excellent internal consistency and absence of collinearity. There was a highly significant correlation between the results of the test and the magnitude of the deformity. The WRVAS correlated significantly with the SRS-22 image scale. The WRVAS is a valid instrument to assess scoliosis patients perception of their deformit

Polymers from biomass: one pot two-step synthesis of furilydenepropanenitrile derivatives with MIL-100(Fe) catalyst

[EN] Furilydenepropanenitrile derivatives, which are useful as monomers, have been obtained in high yields by coupling the oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-diformylfuran (DFF) and the Knoevenagel condensation of DFF with methylene active compounds in a one pot process. The oxidation step was studied using an Fe containing metal-organic framework (MIL-100(Fe), and Fe(BTC)), a Cu containing MOF (Cu3(BTC)(2)), an Fe exchanged HY zeolite and homogeneous Fe salts in the presence of 2,2,6,6-tetramethylpiperidine- 1-oxide (TEMPO) as a cocatalyst, NaNO2 as an additive and oxygen as the terminal oxidant. The results showed that the synthesized MIL-100(Fe) post treated with NH4F was the most active catalyst achieving 100% HMF conversion with 100% selectivity to DFF and can be reused with good success. Additionally, the catalytic system has been applied to the oxidation of different primary and secondary alcohols to aldehydes and ketones under mild reaction conditions with good success. The second step, the Knoevenagel condensation of the obtained DFF with malononitrile or ethyl cyanoacetate, was performed taking advantage of the basicity of the reaction medium.The Spanish MICINN Project (CTQ-2015-67592-P), Generalitat Valenciana (Prometeo Program), the Severo Ochoa Program and the EU-Japan Project NOVACAM are gratefully acknowledged.Rapeyko, A.; Arias Carrascal, KS.; Climent Olmedo, MJ.; Corma Canós, A.; Iborra Chornet, S. (2017). Polymers from biomass: one pot two-step synthesis of furilydenepropanenitrile derivatives with MIL-100(Fe) catalyst. Catalysis Science & Technology. 7(14):3008-3016. https://doi.org/10.1039/c7cy00463jS30083016714Rosatella, A. A., Simeonov, S. P., Frade, R. F. M., & Afonso, C. A. M. 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Surface Enhanced Raman Scattering and Gated Materials for Sensing Applications: The Ultrasensitive Detection of Mycoplasma and Cocaine

[EN] We present herein a novel combination of gated mesoporous silica nanoparticles (MSNs) and surface-enhanced Raman scattering (SERS) for sensing applications. As a proof-of-concept, we show the design of a system comprising MSNs loaded with crystal violet (CV), a molecule with high Raman cross section acting as SERS reporter, and capped with either a suitable DNA sequence for the detection of Mycoplasma genomic DNA or with an aptamer that selectively coordinates cocaine. In both cases the presence of the corresponding target analyte in solution (i.e., genomic DNA or cocaine) resulted in the release of CV. CV delivery was detected by SERS upon adsorption on gold nanotriangles (AuNTs), which display an efficient electromagnetic field enhancement and a high colloidal stability. By using this novel procedure a limit of detection of at least 30 copies DNA per mL was determined for the detection of Mycoplasma genomic DNA, whereas cocaine was detected at concentrations as low as 10 nm.M.C.-P. acknowledges an FPU Scholarship from the Spanish Ministry of Education, Culture and Sports. L.M.L.- M. acknowledges financial support from the European Research Council (ERC Advanced Grant #267867 Plasmaquo) and the European Union's Seventh Framework Programme (FP7/2007-2013 under Grant Agreement No 312184, SACS). M.O. is grateful to the Universitat Politecnica de Valencia for a FPI-UPV grant. Financial support from the Spanish Government (Project MAT2015-64139-C4-1-R MINECO/FEDER) and the Generalitat Valenciana (Project PROMETEOII/2014/047) is gratefully acknowledged.Oroval, M.; Coronado Puchau, M.; Langer, J.; Sanz-Ortiz, MN.; Ribes, À.; Aznar, E.; Coll Merino, MC.... (2016). Surface Enhanced Raman Scattering and Gated Materials for Sensing Applications: The Ultrasensitive Detection of Mycoplasma and Cocaine. Chemistry - A European Journal. 22(38):13488-13495. https://doi.org/10.1002/chem.201602457S1348813495223

Análisis intrarregional de la estructura económica en la región Centro-norte de México

Problem: The need for an intra-regional analysis of the North-Central region of Mexico, as the region with the highest economic growth in the country, to answer the research question: how are the states of the North-Central region of Mexico distributing their economic activities? Objectives: to carry out an intra-regional analysis to know how the states of the North Central region of Mexico distribute their economic activities and the way in which they use their resources. Materials and methods: Intraregional analysis techniques were used for the development of the research. The first was the location coefficient to evaluate the level of concentration of the sectors of the region's economy; the second technique is the territorial association coefficient, which helps to make comparisons from the perspective of geographic distribution. Results: The main results in the region in terms of concentration within the economy in the period 2015-2019 are shown, in addition to the existing disparities in terms of territorial association in that period. Discussion: the research highlights the need for the analysis of disparities at the territorial level and the need for the use of local government analysis tool, as well as the importance of applying regional analysis techniques in the evaluation of territories. Conclusions: Intra-regional analysis techniques represent an essential instrument in the diagnosis and evaluation of the states of the Mexican Republic and can be applied to different indicators that allow improving the analysis of the situation of each territory. Contribution / originality: The contribution of the research lies in obtaining the description of the behavior of the gross value added of the primary, secondary and tertiary sectors of the North Central region of Mexico. In addition, from the calculation of coefficients it is possible to analyze the concentration of economic activities in the region.Problemática: la necesidad de un análisis intrarregional de la región Centro-norte de México, al ser la región de mayor crecimiento económico en el país, que permita dar respuesta al interrogante de investigación: ¿cómo se distribuyen las actividades económicas los estados de la región Centro-norte de México? Objetivos: realizar un análisis intrarregional para conocer cómo los estados de la región Centro-norte de México distribuyen sus actividades económicas y la manera en la que emplean sus recursos. Materiales y métodos: para el desarrollo de la investigación se utilizaron las técnicas de análisis intrarregional. La primera fue el coeficiente de localización para evaluar el nivel de concentración de los sectores de la economía de la región, la segunda técnica es el coeficiente de asociación territorial que ayuda a realizar comparaciones desde la perspectiva de la distribución geográfica. Resultados: se muestran los principales resultados en la región en cuanto a la concentración dentro de la economía en el período 2015-2019, además de las disparidades existentes en lo referente a la asociación territorial en ese período. Discusión: en la investigación se resalta la necesidad del análisis de las disparidades a nivel territorial y la necesidad del uso de herramienta de análisis de los gobiernos locales, así como la importancia de aplicar las técnicas de análisis regional en la evaluación de los territorios. Conclusiones: las técnicas de análisis intrarregional representan un instrumento esencial en el diagnóstico y evaluación de los estados de la república mexicana y pueden ser aplicadas a diversos indicadores que permitan mejorar el análisis de la situación de cada territorio. Contribución / originalidad: la contribución de la investigación radica en obtener la descripción que tiene el comportamiento del valor agregado bruto de los sectores primario, secundario y terciario de la región Centro-norte de México. Además, a partir del cálculo de coeficientes se puede analizar la concentración de las actividades económicas en la región

Studying the present, understanding the past

Actuopaleontology is an essential discipline to understand the fossil record. It uses the present as a key to understand the past. Actualistic paleontology has been largely used in a vast array of paleontological fields such as ichnology, paleoart or functional morphology. Given its relevance in current and past paleontological studies, here we examine the advantages of this discipline, focusing in four recent works. In them, the study of contemporary groups allows us to know better if it is possible: to know how reliable is amber when studying extinct arthropods communities; to make trophic inferences about extinct elasmobranchs by dental microwear analysis; to reconstruct the morphology of certain fishes depending on its ecological niche or to find the type of flight in extinct birds considering their humerus morphology

MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma

MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients