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Real-World Evidence in Localized Pancreatic: Coping with Uncertainty in Unselected Populations

Journal of Cancer Therapy 2024年第4期15卷 164-178页

作者： María I. Pamies Ramón Diana Ibarra Anguita Paula Rodríguez Payá Alvaro Muñoz Abad David Sánchez García María Valero Revert Beatriz Grau Mirete Mariano Martínez Marín alicia calero amaro Lorena Rodríguez Cazalla Javier Gallego Plazas Medical Oncology Department Elche University Hospital Elche (Alicante) Spain General Surgery Department Elche University Hospital Elche (Alicante) Spain General Surgery Department Vega Baja Hospital Orihuela (Alicante) Spain

Background: Localized pancreatic cancer, including resectable (R), borderline resectable (BR) and locally advanced unresectable disease (LAU), is considered in clinical guidelines for diverse treatment options based on clinical trials in selected populations. Hence, exploring with real world evidence (RWE) clinicians’ preferences for treatment options and their results seems pertinent. Methods: In a set of consecutive patients with localized pancreatic cancer assisted in a third level hospital from January 2013 to December 2022, medical records, symptoms, diagnostic process, distribution between subtypes, and treatment plans, with safety and efficacy results, were assessed. Results: A total of 152 patients with localized disease were included (43.4% R, 21.0% BR, 33.6% LAU). The population characteristics exemplified differences between daily practice and clinical trials. Tumor location and symptoms were as expected. Treatment plan was conditioned by PS or comorbidities in 23.0% of patients. In patients with R disease, surgery followed by different adjuvant chemotherapy (CT) regimes was the antineoplastic treatment of choice (64.8%) with efficacy results (OS 37.5 months;95% CI 18.4 - 56.7), in the range of contemporary standards. The common use of neoadjuvant CT for BR disease (94.4%), with surgery in 50% of them, and its results (OS 30.8 months;95% CI 10.5 - 51.2) reflected current controversies of treatment recommendations and evolution in this scenario. Paliative CT with or without radiotherapy was the standard specific treatment in LAU disease (95.1%) with survival results (PFS: 10.8 months;95% CI 8.8 - 12.7. OS: 20.3 months;95% CI 13.5 - 27.2) that justify the distinct character and the specific study of this entity. Conclusion: RWE for localized pancreatic cancer aroused from the analysis of this population confirms the distinct nature of patients assisted in daily practice, as well as mirrors the complexity of decision making in clinical assumptions in which a

关键词： Real-World Evidence Localized Pancreatic Cancer

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Advances in metabolic engineering of yeasts for the production of fatty acid-derived hydrocarbon fuels

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Green Chemical Engineering 2022年第4期3卷 289-303页

作者： Ran Lu Tian-Qiong Shi Lu Lin Rodrigo Ledesma-amaro Xiao-Jun Ji He Huang State Key Laboratory of Materials-Oriented Chemical Engineering College of Biotechnology and Pharmaceutical EngineeringNanjing Tech UniversityNanjing211816China School of Food Science and Pharmaceutical Engineering Nanjing Normal UniversityNanjing210046China Department of Bioengineering and Imperial College Centre for Synthetic Biology Imperial College LondonLondonSW72AZUnited Kingdom

The reliance of the transport sector on fossil fuels has led to increasing concerns related to sustainability and environmental *** petroleum shortages and global climate change caused by greenhouse gas emissions have given an impetus to the development of renewable and low-carbon energy *** acidderived hydrocarbons are an attractive drop-in biofuel to substitute fossil fuels consumed by the transport sector,especially heavy *** to traditional biofuels such as ethanol and biodiesel,fatty acidderived hydrocarbons have higher energy density and better compatibility with existing storage and transport *** a common microbial platform for biofuel production,yeasts have been engineered to produce fatty acid-derived ***,we attempted to comprehensively review the latest advances in metabolic engineering strategies for the production of fatty acid-derived hydrocarbons in the yeasts Saccharomyces cerevisiae and Yarrowia *** heterologous hydrocarbon synthesis pathways and combinational metabolic engineering strategies have been summarized,followed by a discussion of future research directions for the development of yeasts as industrial hydrocarbon producers.

关键词： Biofuel Metabolic engineering Fatty acid Hydrocarbon Yeast

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Engineering Yarrowia lipolytica to produce nutritional fatty acids:Current status and future perspectives

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Synthetic and Systems Biotechnology 2022年第4期7卷 1024-1033页

作者： Lizhen Cao Mingxue Yin Tian-Qiong Shi Lu Lin Rodrigo Ledesma-amaro Xiao-Jun Ji State Key Laboratory of Materials-Oriented Chemical Engineering College of Biotechnology and Pharmaceutical EngineeringNanjing Tech UniversityNo.30 South Puzhu RoadNanjing211816People’s Republic of China School of Food Science and Pharmaceutical Engineering Nanjing Normal UniversityNo.1 Wenyuan RoadNanjing210046People’s Republic of China Department of Bioengineering and Imperial College Centre for Synthetic Biology Imperial College LondonLondonSW72AZUnited Kingdom

Due to their vital physiological functions,nutritional fatty acids have great potential as nutraceutical food supplements for preventing an array of diseases such as inflammation,depression,arthritis,osteoporosis,diabetes and *** biosynthesis of fatty acids follows the trend of sustainable development,as it enables green,environmentally friendly and efficient *** a natural oleaginous yeast,Yarrowia lipolytica is especially well-suited for the production of fatty ***,it has a variety of genetic engineering tools and novel metabolic engineering strategies that make it a robust workhorse for the production of an array of value-added *** this review,we summarize recent advances in metabolic engineering strategies for accumulating nutritional fatty acids in ***,including conjugated fatty acids and polyunsaturated fatty *** addition,the future prospects of nutritional fatty acid production using the *** platform are discussed in light of the current progress,challenges,and trends in this ***,guidelines for future studies are also emphasized.

关键词： Yarrowia lipolytica Metabolic engineering Nutritional fatty acids Conjugated fatty acids Polyunsaturated fatty acids

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Remodeling Isoprene Pyrophosphate Metabolism for Promoting Terpenoids Bioproduction

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Engineering 2023年第9期28卷 166-178页

作者： Xianhao Xu Xueqin Lv Shixiu Cui Yanfeng Liu Hongzhi Xia Jianghua Li Guocheng Du Zhaofeng Li Rodrigo Ledesma-amaro Jian Chen Long Liu Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationJiangnan UniversityWuxi 214122China Science Center for Future Foods Ministry of EducationJiangnan UniversityWuxi 214122China Richen Bioengineering Co. Ltd.Nantong 226000China State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China Department of Bioengineering and Centre for Synthetic Biology Imperial College LondonLondon SW72AZUK

Terpenoids are the largest family of natural *** are made from the building block isoprene pyrophosphate(IPP),and their bioproduction using engineered cell factories has received a great deal of *** date,the insufficient metabolic supply of IPP remains a great challenge for the efficient synthesis of *** this work,we discover that the imbalanced metabolic flux distribution between the central metabolism and the IPP supply hinders IPP accumulation in Bacillus subtilis(***).Therefore,we remodel the IPP metabolism using a series of genetically encoded two-input-multioutput(TIMO)circuits that are responsive to pyruvate or/and malonyl-CoA,resulting in an IPP pool that is significantly increased by up to *** a proof-of-concept validation,we design an IPP metabolism remodeling strategy to improve the production of three valuable terpenoids,including menaquinone-7(MK-7,4.1-fold),lycopene(9-fold),andβ-carotene(0.9-fold).In particular,the titer of MK-7 in a 50-L bioreactor reached 1549.6 mg·L^(-1),representing the highest titer reported so ***,we propose a TIMO genetic circuits-assisted IPP metabolism remodeling framework that can be generally used for the synergistic fine-tuning of complicated metabolic modules to achieve the efficient bioproduction of terpenoids.

关键词： Terpenoids Genetic circuits Bacillus subtilis Isoprene pyrophosphate

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Messages on the Path

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疯狂英语（初中天地） 2008年第10期 66-67页

作者： Corey amaro

There is a message in each step on the path. Gathered in the bold stones and softened by the moss, Rising to meet you in the leaf that sprouts from the crack,

关键词： Messages on the Path

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Characterization of the Topography and Wettability of English Weed Leaves and Biomimetic Replicas

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Journal of Bionic Engineering 2014年第3期11卷 346-359页

作者： Pedro Miguel Matos Pereira Ana Sofia Moita Gabriel amaro Monteiro Duarte Miguel Franca Prazeres IBB - Institute for Biotechnology and Bioengineering Centre for Biological and Chemical Engineering Department of Bioengineering Instituto Superior Tecnico Universidade de Lisboa Av. Rovisco Pals 1049-001 Lisboa Portugal IN+ - Center for Innovation Technology and Policy Research Instituto Superior T~cnico Universidade de Lisboa Av. Rovisco Pais 1049-001 Lisboa Portugal

The topography and wettability of the underside of English weed （Oxalis pes-caprae） leaves and of their biomimetic replicas are investigated. Polyvinyl siloxane molds were cast from the leaves and then filled with an epoxy pre-polymer to produce replicas. The particular topographical structures of leaves and replicas were evaluated by optical microscopy and Scanning Electron Microscopy （SEM） analysis. The static wettability of leaves and replicas was assessed by contact angle measurements, while the dynamic wettability was characterized by estimating contact angle hysteresis and studying the dynamic behavior of impacting water droplets. A smooth glass slip and its replica were used as control surfaces. The replica moulding method used was able to transfer the characteristic pattern of irregular 100 μm - 200 μm × 60 μm convex papillae interspersed with stomata of the original leaf to the epoxy replicas. The static contact angle of 143°± 3° and the contact angle hysteresis of 2~ indicate that the underside of the English weed leaf is close to superhydrophobic. The lower contact angles （130° ± 4°） and higher hysteresis （31°） observed for the replica when compared with the original leaves were associated to an inaccurate replication of the chemistry and structures of the three-dimensional wax projections covering the plant surface. Also, trichomes in the original leaves could not be accurately reproduced due to their flexibility and fragility. Differences in wetting behavior were also evident from droplet impact experiments, with rebound regimes prevailing in the original leaves and regimes characterized by higher adhesion and larger dissipation predominating in the replicas. Nevertheless, the morphological features of the leaf transferred to the replica were sufficient to promote a clear hydrophobic behavior of the replica when compared with the smooth epoxy reference surface.

关键词： biomimetic surfaces oxalis pes-caprae English weed replica molding wettability micro-topography

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GIS-based study of the evolution of the IGN's strong motion network of mainland Spain and the balearics

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Geodesy and Geodynamics 2021年第4期12卷 279-287页

作者： Jose-Lazaro amaro-Mellado Daniel Anton Juan-Manuel Alcalde Instituto Geografico Nacional Servicio Regional en AndaluciaSeville 41013Spain Departamento de Ingenierfa Grafica Universidad de SevillaSeville 41092Spain Research Group TEP970:Innovacion Tecnoldgica Sistemas de Modelado 3D y Diagnosis Energetica en Patrimonio y Edificacidn'Departamento de Expresion Grafica e Ingenieria en la EdificacionEscuela Tecnica Superior de Ingenieria de EdificacionUniversidad de Sevilla4A Reina Mercedes AvenueSeville 41012Spain The Creative and Virtual Technologies Research Laboratory School of ArchitectureDesign and the Built EnvironmentNottingham Trent University50 Shakespeare StreetNottingham NG14FQUK Escuela Superior de Ingenieria y Tecnologia Universidad Intemacional de La Rioja737 La Paz AvenueLogrono 26006Spain Instituto Geografico Nacional Red Sismica NacionalMadrid 28003Spain

In some countries with seismicity,an adequate detection network is essential to assess seismic *** Instituto Geografico Nacional(National Geographic Institute/IGN)of Spain manages a strong motion network distributed throughout the whole country and an earthquake detection network composed of velocity *** paper aims at studying the development of the strong motion network of the Spanish National Seismic Network(focusing on mainland Spain and the Balearics)in the last three decades.A Geographic Information System(GIS)has been implemented to integrate the attributes from the IGN’s database concerning the earthquake catalogue,seismograph and accelerometer networks,which enabled to analyse the data and map the distribution of detection equipments in the *** irregularly distributed Spanish strong motion network was greatly expanded from 1990 to *** the past decade,it developed at a slower rate,but more modern technology was implemented.

关键词： Strong motion Accelerometer network Spanish national seismic network Earthquake catalogue GIS

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Network of GRAS transcription factors in plant development,fruit ripening and stress responses

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Horticulture Research 2023年第12期10卷 286-303页

作者： Catarina Neves Beatriz Ribeiro Rute amaro Jesús Expósito Jérôme Grimplet Ana Margarida Fortes BioISI-Biosystems and Integrative Sciences Institute Faculty of SciencesUniversity of LisbonCampo Grande1749-016 LisboaPortugal Centro de Investigación y Tecnología Agroalimentaria de Aragón(CITA) Departamento de Ciencia VegetalGobierno de AragónAvda.Montañana 93050059 ZaragozaSpain Instituto Agroalimentario de Aragón-IA2(CITA-Universidad de Zaragoza) Calle Miguel Servet 17750013 ZaragozaSpain

The plant-specific family of GRAS transcription factors has been wide implicated in the regulation of transcriptional reprogramming associated with a diversity of biological functions ranging from plant development processes to stress *** analyses of GRAS transcription factors supported by in silico structural and comparative analyses are emerging and clarifying the regulatory networks associated with their biological *** this review,a detailed analysis of GRAS proteins’structure and biochemical features as revealed by recent discoveries indicated how these characteristics may impact subcellular location,molecular mechanisms,and *** issues associated with GRAS classification into different subfamilies in diverse plant species even in the presence of robust genomic resources are discussed,in particular how it affects assumptions of biological *** into the mechanisms driving evolution of this gene family and how genetic and epigenetic regulation of GRAS contributes to subfunctionalization are ***,this review debates challenges and future perspectives on the application of this complex but promising gene family for crop improvement to cope with challenges of environmental transition.

关键词： function GRAS plant

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DelEnsembleElec:Computing Ensemble-Averaged Electrostatics Using DelPhi

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Communications in Computational Physics 2013年第1期13卷 256-268页

作者： Lane W.Votapka Luke Czapla Maxim Zhenirovskyy Rommie E.amaro Department of Chemistry and Biochemistry University of CaliforniaSan DiegoLa JollaCalifornia 92093USA Computational Biophysics and Bioinformatics Department of PhysicsClemson UniversityClemsonSC 29634USA

A new VMD plugin that interfaces with DelPhi to provide ensemble-averaged electrostatic calculations using the Poisson-Boltzmann equation is *** general theory and context of this approach are discussed,and examples of the plugin interface and calculations are *** new tool is applied to systems of current biological interest,obtaining the ensemble-averaged electrostatic properties of the two major influenza virus glycoproteins,hemagglutinin and neuraminidase,from explicitly solvated all-atom molecular dynamics *** differences between the ensemble-averaged electrostatics and those obtained from a single structure are examined in detail for these examples,revealing how the plugin can be a powerful tool in facilitating the modeling of electrostatic interactions in biological systems.

关键词： DelEnsembleElec ensemble-averaged electrostatics Poisson Boltzmann equation DelPhi molecular dynamics influenza glycoproteins

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Preparation of a ε-caprolactonic diterpenoid derivate by unexpected oxidative cleavage/lactonization of 2-oxoaustroeupatol

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Natural Products and Bioprospecting 2022年第1期12卷 265-269页

作者： Pablo A.Chacón-Morales Juan M.amaro-Luis Luis Beltrán Rojas Fermín Rémi Jacquet Denis Deffieux Laurent Pouységu Stéphane Quideau Natural Products Laboratory Department of ChemistryFaculty of ScienceUniversity of Los AndesMérida 5101Venezuela Research Institute Faculty of Pharmacy and BioanalysisUniversity of Los AndesMérida 5101Venezuela ISM(CNRS-UMR 5255) Univ.Bordeaux351 cours de la Libération33405 Talence CedexFrance

From aerial parts of Austroeupatorium inulifolium was isolated the ent-nor-furano triol labdane austroeupatol *** compound 1 was treated with IBX showing an unexpected selectivity at the potentially oxidizable sites of the sub-strate yielding the 2-oxoaustroeupatol(2)and 2,19-dioxoaustroeupatol(3).The treatment of 2 with sodium periodate yields a heterocyclic derivative(ε-caprolactone derivate 4)formed by oxidative cleavage and unexpected intramo-lecular attack of the hydroxymethylene(C-19)oxygen to the ketonic carbon(C-2).A plausible mechanistic pathway for the obtention of compound 4 is proposed.

关键词： Oxidative cleavage Austroeupatol NaIO4 IBX Lactonization NMR

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