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New horizons for uncommon mutations in non-small cell lung cancer: BRAF, KRAS, RET, MET, NTRK, HER2

World Journal of Clinical Oncology 2022年第4期13卷 276-286页

作者： Maria Eugenia Olmedo Raquel Cervera Luis Cabezon-Gutierrez Yolanda Lage Elena Corral de la Fuente ana gomez rueda1,xabier mielgo-rubio Juan Carlos Trujillo Felipe Counago Department of Medical Oncology Ramon y Cajal University HospitalMadrid 28034Spain Department of Medical Oncology Del Henares University HospitalCoslada 28822MadridSpain Medical Oncology Hospital Universitario de TorrejonTorrejon de Ardoz 28850MadridSpain Medical Oncology Department Hospital Universitario Ramon y CajalMadrid 28034Spain Department of Medical Oncology Foundation Alcorcon University HospitalAlcorcón 28922MadridSpain Department Thoracic Surgery Hospital de la Santa Creu I Sant PauBarcelona 08029CataloniaSpain Department of Surgery Universitat Autonoma de BarcelonaBarcelona 08029CataloniaSpain Department of Radiation Oncology Hospital Universitario Quironsalud MadridPozuelo 28223MadridSpain Department of Radiation Oncology Hospital La LuzMadrid 28003Spain Medicine Department School of Biomedical SciencesUniversidad Europea de MadridMadrid 28670Spain

The 2004 discovery of EGFR mutations,followed by ALK rearrangements,ushered in a targeted therapy era for advanced non-small cell lung cancer(NSCLC).Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with *** the last decade,rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted *** genome studies of lung adenocarcinoma have identified other possible therapeutic targets,including RET,NTRK fusions,c-MET alterations,and activating mutations in KRAS,BRAF,and HER2,all with frequencies greater than 1%.Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical *** review updates the therapeutic arsenal that especially targets those genes.

关键词： BRAF NTRK KRAS MET RET HER2 Non-small cell lung cancer Targeted therapy Uncommon mutations

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AN OPTIMAL CONTROL PROBLEM FOR A LOTKA-VOLTERRA COMPETITION MODEL WITH CHEMO-REPULSION

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Acta Mathematica Scientia 2024年第2期44卷 721-751页

作者： Diana I.HERNÁNDEZ Diego A.rueda-gomez Élder J.VILLAMIZAR-ROA Universidad Industrial de Santander Escuela de MatemáticasA.A.678BucaramangaColombia

In this paper we study a bilinear optimal control problem for a diffusive Lotka-Volterra competition model with chemo-repulsion in a bounded domain of ℝ^(ℕ),N=2,*** model describes the competition of two species in which one of them avoid encounters with rivals through a chemo-repulsion *** prove the existence and uniqueness of weak-strong solutions,and then we analyze the existence of a global optimal solution for a related bilinear optimal control problem,where the control is acting on the chemical ***,we derive first-order optimality conditions for local optimal solutions using the Lagrange multipliers ***,we propose a discrete approximation scheme of the optimality system based on the gradient method,which is validated with some computational experiments.

关键词： Lotka-Volterra chemo-repulsion optimal control optimality conditions

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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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Military Medical Research 2024年第2期11卷 228-267页

作者： Miguel A.Ortega Oscar Fraile-Martinez Cielo García-Montero Sergio Haro Miguel Ángel Álvarez-Mon Diego De Leon-Oliva ana M.gomez-Lahoz Jorge Monserrat Mar Atienza-Pérez David Díaz Elisa Lopez-Dolado Melchor Álvarez-Mon Department of Medicine and Medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal Institute of Sanitary Research(IRYCIS) 28034 MadridSpain Department of Psychiatry and Mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune System Diseases‑Rheumatology Service and Internal Medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this ***(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a *** initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and *** the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are ***,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： Spinal cord injury(SCI) Psychoneuroimmunoendocrinology(PNIE) Secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities

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Emerging bisphenol a replacements(colour developers)in indoor dust from Spain

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Emerging Contaminants 2019年第1期5卷 168-172页

作者： María Jesús Duenas-Mas ana Ballesteros-gomez Soledad rubio Department of analytical Chemistry Institute of Fine Chemistry and NanochemistryMarie Curie Building AnnexCampus of RabanalesUniversity of Cordoba14071CordobaSpain

Bisphenol A(BPA)and replacements,such as bisphenol S(BPS)and F(BPF)and other substitutes(BPSMAE,D-8 and TGSA)have been recently reported in thermal *** this study,BPA,BPS,BPF;BPS-MAE,D-8 and TGSA were analysed in indoor dust collected in Spain from different microenvironments(living rooms,bedrooms,cars and offices).Levels were compared with those reported in our previous study(shops and other public microenvironments,where frequent use of thermal paper is expected).We investigated the differences between microenvironments,possible correlations between compounds and estimated the ingestion ***-MAE,D-8 and TGSA were present at levels up to 529,128 and 356 ng g^-1,respectively,in all the *** highest levels were measured in cars.

关键词： Bisphenol A Bisphenol F Bisphenol S BPS-MAE D-8 TGSA Indoor dust

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Postoperative radiotherapy in resected non-small cell lung cancer:The never-ending story

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World Journal of Clinical Oncology 2021年第10期12卷 833-844页

作者： Javier Serrano Patricia Calvo Crespo Begoña Taboada ana Alvarez Gonzalez Rafael Garcia García Antonio gomez Caamaño Juan Carlos Trujillo Reyes xabier mielgo-rubio Felipe Couñago Department of Radiation Therapy Clinica Universidad de NavarraMadrid 28027Spain Department of Radiation Oncology Hospital Clínico Universitario Santiago de CompostelaSantiago de Compostela 15706Spain Department of Radiation Oncology HGU Gregorio MarañónMadrid 28007Spain Department of Radiation Oncology Hospital Ruber InternacionalMadrid 28034Spain Department of Radiation Oncology Hospital Clínico Universitario Santiago de CompostelaA Coruña 15706Spain Department of Thoracic Surgery Hospital de La Santa Creu I Sant PauBarcelona 08026Spain Department of Medical Oncology Hospital Universitario Fundación AlcorcónMadrid 28922Spain Department of Radiation Oncology Hospital Universitario Quirónsalud MadridHospital La LuzUniversidad Europea de MadridMadrid 28223Spain

This manuscript collects in a joint and orderly manner the existing evidence at the present time about postoperative treatment with radiotherapy in non-small cell lung *** also systematically reviews the current evidence,the international recommendations in the most relevant guidelines,the most controversial aspects in clinical and pathological staging,the specific technical aspects of radiotherapy treatment,and also collects all the potential risk factors that have been postulated as significant in the prognosis of these patients,evaluating the possibility of segmenting a particularly sensitive subpopulation with a high risk of relapse on which an adjuvant treatment with radiotherapy could have an impact on their clinical ***,currently active trials that aspire to provide more evidence on this topic are reviewed.

关键词： Non-small lung cancer Radiotherapy Postoperative Lung cancer

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Nestling sex ratio is unaffected by individual and population traits in the griffon vulture

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Current Zoology 2023年第3期69卷 227-235页

作者： Guillermo gomez-Lopez Felix Martinez ana Sanz-Aguilar Martina Carrete Guillermo Blanco Department of Evolutionary Ecology National Museum of Natural Sciences(MNCN)Spanish National Research Council(CSiC)Jose Gutierrez Abascal 228006 MadridSpain Escuela Internacional de Doctorado Universidad Rey Juan Carlos(URJC)Tulipan s/n28933 MostolesMadridSpain Animal Demography and Ecology Group Institut Mediterrani d'Estudis Avangats(IMEDEA)Miquel Marques 217020 EsporlesMallorcaSpain Applied Zoology and Conservation Group Universitat de les Illes Balears(UIB)Ctra.De Valldemossa km.7.507122PalmaSpain Department of Physical Chemical and Natural SystemsUniversidad Pablo de Olavide(UPO)Ctra.de Utrera km.141013 SevillaSpain

Variation in offspring sex ratios is a central topic in animal demography and population *** studies have focused on bird species with marked sexual dimorphism and multiple-nestling broods,where the offspring sex ratio is often biased due to different individual or environmental ***,biases in offspring sex ratios have been far less investigated in monomorphic and single-egg laying species,and few studies have evaluated long-term and large-scale variations in the sex ratio of nestling ***,we explore individual and environmental factors potentially affecting the secondary sex ratio of the monomorphic griffon vulture Gyps *** used information collected at three breeding nuclei from central Spain over a 30-year period(1990–2020)to analyse the effects of nestling age,parental age,breeding phenology,conspecific density,population reproductive parameters,and spatial and temporal variability on nestling *** ratio did not differ from parity either at the population or the nuclei *** significant between-year differences were detected,even under highly changing conditions of food availability associated with the mad-cow *** found that tree nesting breeders tend to have more sons than daughters,but as this nesting behavior is rare and we consequently have a small sample size,this issue would require additional *** further research is needed to assess the potential effect of breeder identity on nestling sex ratio,this study contributes to understanding the basic ecology and population dynamics of Griffon Vultures,a long-lived species with deferred maturity and low fecundity,whose minor deviations in the offspring sex ratio might imply major changes at the population level.

关键词： offspring sex ratio nestling sex Gyps fulvus monomorphism mad-cow crisis demography

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Influence of Pt/Ru anodic ratio on the valorization of ethanol by PEM electrocatalytic reforming towards value-added products

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Journal of Energy Chemistry 2021年第5期30卷 264-275页

作者： Alberto Rodriguez-gomez Fernando Dorado Antonio de Lucas-Consuegra ana Raquel de la Osa Chemical Engineering Department Faculty of Chemical Sciences and TechnologyUniversity of Castilla-La Mancha13071 Ciudad RealSpain

The ethanol electro-reforming process was studied over PtRu/C catalysts synthesized by the modified polyol method with different *** particular,this work reports the influence of anodic Pt:Ru ratio(5:1,2:1 and 1:2)on the organic product distribution(acetaldehyde,acetic acid and ethyl acetate)and pure hydrogen generation at different current densities operation *** characterization of the catalysts was made by X-ray diffraction(XRD),temperature-programmed reduction(TPR)and N_(2) adsorption-desorption *** patterns showed that Ru is introduced into the Pt structure,forming an alloy between both ***,the degree of alloy was higher by increasing the Ru *** TPR profiles Pt was found to be properly reduced while Ru was both in metallic state and forming *** electrochemical behaviour of each catalyst towards ethanol electroreforming process was investigated through electrochemical techniques in a half cell and a single proton exchange membrane(PEM)cell *** intermediate Pt:Ru ratio was found to result in high current density and electrochemical surface area(ECSA)values along with lower amounts of adsorbed ***,Ru addition seems to diminish the degree of degradation of the *** on characterization and in agreement with essays carried out in a PEM cell at mild conditions(80℃ and 1 atm),PtRu/C 2:1 anode provided the best electrocatalytic results in terms of current density(740 mA cm^(-2)),hydrogen production and selectivity toward acetic acid(up to 15%apart from acetaldehyde and ethyl acetate)while requiring the lowest energy consumption.

关键词： Ethanol electro-reforming PEM cell Pt:Ru anodic ratio Hydrogen production Value-added liquid product distribution

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Effect of Wavelength on Metrological Characteristics of Non-Holographic Fiber Specklegram Sensor

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Photonic Sensors 2015年第1期5卷 1-5页

作者： Victor H. ARISTIZABAL Alejandro HOYOS Edgar rueda Nelson D. gomez Jorge A. gomez Grupo de Sistemas en Operaciones y Desarrollo Aplicado -SODA- Universidad Cooperativa de Colombia Cll 50A#41-40 Medellin Colombia Grupo de Fisica Basica y Aplicada Politecnico Colombiano Jaime Isaza Cadavid Cra 48 #7-151 Medellin Colombia Grupo de Optica y Fotonica Instituto de Fisica Universidad de Antioquia Cll 70No. 52-21 Medellin Colombia Grupo de lnvestigacion en Automatica Electronica y Ciencias Computacionales-AE&CC- Instituto Tecnologico Metropolitano - lnstitucion Universitaria Cll 54A #30-01 Medellin Colombia

In this paper, we report some results about the effects of varying the wavelength in a structure of a non-holographic fiber specklegram sensor. In these arrangements, the speckle pattern produced by a multi-mode optical fiber is coupled to the asingle-mode optical fiber with lower numerical aperture, which produces a filtering effect that can be used as an optical transduction mechanism. The influence of the wavelength on the sensor performance is evaluated by changing the laser wavelength, and a strong effect on the linearity and reproducibility of its response is found. Lasers emitting at 1310nm, 1550nm, and 1625nm are used.

关键词： Optical sensing speckle sensor optical fiber sensor mechanical perturbation sensor

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Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment

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World Journal of Gastroenterology 2017年第25期23卷 4538-4547页

作者： Paloma Munoz de rueda José Manuel Fuentes RodríguezRosa Quiles Pérez ana Gila Medina ana Belén Martínálvarez Jorge Casado Ruíz ángeles Ruíz Extremera Javier Salmerón Research Support Unit San Cecilio University Hospital of Granada Instituto de Investigación Biosanitaria CIBERehd Instituto de Salud Carlos III Unit for Clinical Management of Digestive Diseases San Cecilio University Hospital of Granada Granada University

To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODSSequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTSFor both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.

关键词： Interferon-based therapy Interferon-free therapy Chronic hepatitis C NS5A region Sustained virological response Number of mutations

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Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2

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Journal of Molecular Cell Biology 2014年第4期8卷 299-311页

作者： Lucia Garcia-Guerra Rocio Vila-Bedmar Marta Carrasco-Rando Marta Cruces-Sande Mercedes Martin ana Ruiz-gomez Mar Ruiz-gomez Margarita Lorenzo Sonia Fernandez-Veledo Federico Mayor Jr. Cristina Murga Iria Nieto-Vazquez Department of Biochemistry and Molecular Biology II School of Pharmacy Complutense University 28040 Madrid Spain CIBER de Diabetes y Enfermedades Metab61icas Asociadas (CIBERDEM) 08017 Barcelona Spain Instituto de Investigaciones Biomedicas Alberto Sols (CSIC-UAM) 28029 Madrid Spain CIBER de enfermedades neurodegenerativas (CIBERNED) 28049 Madrid Spain Departament of Molecular Biology and Centro de Biologia Molecular Severo Ochoa (CSIC-UAM) 28049 Madrid Spain Instituto de Investigacion Sanitaria la Princesa 28006 Madrid Spain Centro de Biologia Molecular Severo Ochoa (UAM-CSIC) 28049 Madrid Spain Hospital Universitari de Tarragona Joan XXIII. IISPV. Universitat Rovira i Virgili 43007 Tarragona Spain

G protein-coupled receptor kinase 2 （GRK2） is an important serine/threonine-kinase regulating different membrane receptors and intraceUular proteins. Attenuation of Drosophila Gprk2 in embryos or adult flies induced a defective differentiation of somatic muscles, loss of fibers, and a flightless phenotype. In vertebrates, GRK2 hemizygous mice contained less but more hypertrophied skeletal muscle fibers than wild-type littermates. In C2C12 myoblasts, overexpression of a GRK2 kinase-deficient mutant （K220R） caused precocious differentiation of ceUs into immature myotubes, which were wider in size and contained more fused nuclei, while GRK2 overexpression blunted differentiation. Moreover, p38MAPK and Akt pathways were activated at an earlier stage and to a greater extent in K220R-expressing cells or upon kinase downregulation, while the activation of both kinases was impaired in GRK2-overexpressing cells. The impaired differentiation and fewer fusion events promoted by enhanced GRK2 levels were recapitulated by a p38MAPK mutant, which was able to mimic the inhibitory phosphorylation of p38MAPK by GRK2, whereas the blunted differentiation observed in GRK2-expressing clones was rescued in the presence of a constitutively active upstream stimulator of the p38MAPK pathway. These results suggest that balanced GRK2 function is necessary for a timely and complete myogenic process.

关键词： GRK2 p38MAPK Akt skeletal muscle myogenesis

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