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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 Efficient Real Space Method for Orbital-Free Density-Functional Theory

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Communications in Computational Physics 2007年第2期2卷 334-357页

作者： Carlos J.Garcıa-cervera Department of Mathematics University of CaliforniaSanta BarbaraCA 93106USA.

We consider the Thomas-Fermi-von Weizsacker energy functional,with the Wang-Teter correction,and present an efficient real space method for Orbital-Free Density Functional *** is proved that the energy minimizer satisfies a second order quasilinear elliptic equation,even at the points where the electron density *** information is used to construct an efficient energy minimization method for the resulting constrained problem,based on the truncated Newton method for unconstrained *** Wang-Teter kernel is analyzed,and its behavior in real space at short and far distances is determined.A second order accurate discretization of the energy is obtained using finite *** efficiency and accuracy of the method is illustrated with numerical simulations in an Aluminium FCC lattice.

关键词： Density functional theory truncated Newton method constrained optimization.

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Neutrophils in chronic inflammatory diseases

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Cellular & Molecular Immunology 2022年第2期19卷 177-191页

作者： Andrea Herrero-cervera Oliver Soehnlein Ellinor Kenne Institute for Experimental Pathology Center for Molecular Biology of InflammationWestfälische Wilhelms-Universität MünsterMünsterGermany Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden.

Chronic inflammation is a component of many disease conditions that affect a large group of individuals *** inflammation is characterized by persistent,low-grade inflammation and is increased in the aging *** are normally the first responders to acute inflammation and contribute to the resolution of ***,in chronic inflammation,the role of neutrophils is less well understood and has been described as either beneficial or detrimental,causing tissue damage and enhancing the immune *** evidence suggests that neutrophils are important players in several chronic diseases,such as atherosclerosis,diabetes mellitus,nonalcoholic fatty liver disease and autoimmune *** review will highlight the interaction of neutrophils with other cells in the context of chronic inflammation,the contribution of neutrophils to selected chronic inflammatory diseases,and possible future therapeutic strategies.

关键词： Chronic Inflammation Disease Neutrophil Neutrophil extracellular traps

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A Remark on "An Efficient Real Space Method for Orbital-Free Density-Functional Theory"

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Communications in Computational Physics 2008年第4期3卷 968-972页

作者： Carlos J.Garcia-cervera Mathematics Department University of CaliforniaSanta BarbaraCA 93106USA

In this short note we clarify some issues regarding the existence of minimizers for the Thomas-Fermi-von Weiszacker energy functional in orbital-free density functional theory,when the Wang-Teter corrections are inclu... 详细信息

关键词： Density functional theory Thomas-Fermi constrained optimization

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Genetic variants of innate immune receptors and infections after liver transplantation

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World Journal of Gastroenterology 2014年第32期20卷 11116-11130页

作者： Gemma Sanclemente Asuncion Moreno Miquel Navasa Francisco Lozano Carlos cervera Department of Infectious Diseases Hospital Clinic of BarcelonaIDIBAPS University of Barcelona Liver Transplant Unit Hospital Clinic of Barcelona IDIBAPS University of Barcelona Immunology Hospital Clinic of BarcelonaIDIBAPS University of Barcelona

Infection is the leading cause of complication after liver transplantation, causing morbidity and mortality in the first months after surgery. Allograft rejection is mediated through adaptive immunological responses, and thus immunosuppressive therapy is necessary after transplantation. In this setting, the presence of genetic variants of innate immunity receptors may increase the risk of post-transplant infection, in comparison with patients carrying wild-type alleles. Numerous studies have investigated the role of genetic variants of innate immune receptors and the risk of complication after liver transplantation, but their results are discordant. Tolllike receptors and mannose-binding lectin are arguably the most important studied molecules; however, many other receptors could increase the risk of infection after transplantation. In this article, we review the published studies analyzing the impact of genetic variants in the innate immune system on the development of infectious complications after liver transplantation.

关键词： Innate immunity Genetic variants Single nucleotide polymorphisms Liver transplantation Post-transplant infections Toll-like receptors Mannose-binding lectin

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Sequential Multiscale Modeling Using Sparse Representation

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Communications in Computational Physics 2008年第10期4卷 1025-1033页

作者： Carlos J.Garcıa-cervera Weiqing Ren Jianfeng Lu Weinan E Mathematics Department University of CaliforniaSanta BarbaraCA 93106USA Courant Institute of Mathematical Sciences New York UniversityNew YorkNY 10012USA Program in Applied and ComputationalMathematics Princeton UniversityPrincetonNJ 08544USA Department of Mathematics and PACM Princeton UniversityPrincetonNJ 08544USA

The main obstacle in sequential multiscale modeling is the pre-computation of the constitutive relationwhich often involvesmany independent *** constitutive relation of a polymeric fluid is a function of six variables,even after making the simplifying assumption that stress depends only on the rate of *** such a function is usually considered too *** the value of sequential multiscale modeling is often limited to“parameter passing”.Here we demonstrate that sparse representations can be used to drastically reduce the computational cost for precomputing functions of many *** strategy dramatically increases the efficiency of sequential multiscale modeling,making it very competitive in many situations.

关键词： Multiscale modeling sparse grids

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The Study of Carbamoyl Phosphate Synthetase 1 Deficiency Sheds Light on the Mechanism for Switching On/Off the Urea Cycle

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Journal of Genetics and Genomics 2015年第5期42卷 249-260页

作者： Carmen Díez-Fernández José Gallego Johannes H?berle Javier cervera Vicente Rubio Institute for Biomedicine of Valencia of the Spanish Research Council Medical School of the Catholic University of Valencia University Children's Hospital Zurich and Children's Research Center Centre for Biomedical Networking Research on Rare Diseases of the Carlos Ⅲ Health Institute

Carbamoyl phosphate synthetase i （CPS1） deficiency （CPS1D） is an inborn error of the urea cycle having autosomal （2q34） recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPS1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPS1 deficiency that map in the 20-kDa C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPS 1, N-acetyl- L-glutamate （NAG）, is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPS1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-L- glutamate （a registered drug, the analog of NAG）. Our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the 134-~4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPS1.

关键词： Urea cycle diseases Inborn errors Hyperammonemia Site-directed mutagenesis Restrained molecular dynamics Allosteric regulation Carbamoyl phosphate synthetase 1 Enzyme

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Visions of the 21st Century City:Nature Integrated into Urban Design

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China Today 2024年第7期73卷 35-37页

作者： ROSA cervera Catedra China a Spanish association

In this era of urban expansion and rapid growth of densely populated cities,it is crucial to ask ourselves how urban models may be improved,so as to create cities that both fulfill their essential functions and enhanc... 详细信息

关键词： Urban urban emotional

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Optimizing nutrition in hepatic cirrhosis:A comprehensive assessment and care approach

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World Journal of Gastroenterology 2024年第10期30卷 1313-1328页

作者： Osvely Mendez-Guerrero Anaisa Carranza-Carrasco Luis Alberto Chi-cervera Aldo Torre Nalu Navarro-Alvarez Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Clínica de Especialidades Gastrointestinales y Hepáticas Hospital Star MedicaMerida 97133YucatanMexico Molecular Biology Universidad Panamericana School of MedicineCampus MéxicoMexico City 03920Mexico Department of Surgery University of Colorado Anschutz Medical CampusDenverCO 80045United States

Cirrhosis is considered a growing cause of morbidity and mortality,which represents a significant public health ***,there is no effective treatment to reverse *** primarily centers on addressing the underlying liver condition,monitoring,and managing portal hypertension-related complications,and evaluating the potential for liver transplantation in cases of decompensated cirrhosis,marked by rapid progression and the emer-gence of complications like variceal bleeding,hepatic encephalopathy,ascites,malnutrition,and ***,a prevalent complication across all disease stages,is often underdiagnosed in cirrhosis due to the complexities of nutritional assessment in patients with fluid retention and/or obesity,despite its crucial impact on *** emphasis has been placed on the collaboration of nutritionists within hepatology and Liver transplant teams to deliver compre-hensive care,a practice that has shown to improve *** review covers appropriate screening and assessment methods for evaluating the nutritional status of this population,diagnostic approaches for malnutrition,and context-specific nutrition *** also discusses evidence-based recommendations for supplementation and physical exercise,both essential elements of the standard care provided to cirrhotic patients.

关键词： Cirrhosis Nutritional diagnosis Treatment Diet Guidelines

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Comparison of Mineral Contents in Three Different Tobacco Formulations

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Biomedical and Environmental Sciences 2017年第1期30卷 52-58页

作者： HOUAS Ikram TEYEB Hassen Arancha ROCHINA-MARCO DOUKI Wahiba NAJJAR Mohamed Fadhel GAHA Lotfi cervera MariaLuisa DE LA GUARDIA Miguel Research Laboratory 'Vulnerability to Psychotic Disorders LR 05 ES 10' Department of Psychiatry Faculty of Medicine University of Monastir Monastir 5000 Tunisia Biochemistry and Toxicology Laboratory Monastir University Hospital Monastir 5000 Tunisia Department of Analytical Chemistry University of Valencia Burjassot 46100 Spain

We identified and quantified a variety of mineral elements in 18 tobacco samples purchased from a Tunisian market. In total, 25 mineral elements have been measured in cigarettes, water pipe tobacco, and smokeless tobacco using inductively coupled plasma-optical emission spectroscopy following microwave-assisted digestion. Statistical analyses were performed using SPSSTM, version 18.0. The lowest concentrations of all studied elements were observed in water pipe tobacco. Significantly higher concentrations of Al, Fe, Mg, Na, Ca, Cr, and Co were found in smokeless tobacco, while cigarettes brands contained the highest concentrations of K, Mn, Ni, Ba, and Sr. There was no significant difference between the mineral contents of local and foreign cigarettes and conventional and light cigarettes. Our findings demonstrated that local smokeless tobacco appears to be the most hazardous tobacco type. The concentration of minerals in light cigarettes was not significantly different from the concentration in conventional cigarettes.

关键词： Comparison of Mineral Contents in Three Different Tobacco Formulations

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