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Journal of Integrative Medicine 2024年第1期22卷 1-11页

作者： Maria Younes Ghady Loubnane Christopher Sleiman sandra Rizk Department of Natural Sciences Lebanese American UniversityByblosLebanon

Tocotrienols are found in a variety of natural sources,like rice bran,annatto seeds and palm oil,and have been shown to have several health-promoting properties,particularly against chronic diseases such as *** incidence of cancer is rapidly increasing around the world,not only a result of continued aging and population growth,but also due to the adoption of aspects of the Western lifestyle,such as high-fat diets and low-physical *** literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers,including breast,lung,ovarian,prostate,liver,brain,colon,myeloma and pancreatic *** findings,along with the reported safety profile of tocotrienols in healthy human volunteers,encourage further research into these compounds’potential use in cancer prevention and *** current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks,such as cellular proliferation,apoptosis,angiogenesis and ***/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive *** an overview of pre-clinical studies,we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.

关键词： Vitamin E Tocotrienols Cancer Molecular mechanism Clinical trials

Targeting KRAS in pancreatic cancer

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Oncology Research 2024年第5期32卷 799-805页

作者： sandra STICKLER BARBARA RATH GERHARD HAMILTON Institute of Pharmacology Medical University of ViennaViennaA-1090Austria

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient *** Kirsten rat sarcoma virus(KRAS)oncogene is mutated in up to 90%of all pancreatic ductal adenocarcinomas(PDACs)and constitutes an attractive target for ***,the most common KRAS mutations in PDAC are G12D(44%),G12V(34%)and G12R(20%)that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung *** G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3%of ***,the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in *** other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor(GEF)Son of Sevenless 1 that drives *** agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.

关键词： Pancreatic cancer PDAC KRAS SOS1 PROTAC

Pandemic punch:SARS-CoV-2 hits pancreas

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1779-1780页

作者： Ninel Azoitei sandra Heller Alexander Kleger Institute of Molecular Oncology and Stem Cell Biology Ulm UniversityUlmGermany Division of Interdisciplinary Pancreatology Clinic of Internal Medicine IUniversity Hospital UlmUlmGermany

The COVID-19 pandemic has profoundly impacted global health systems,revealing the extensive repercussions of SARS-CoV-2 beyond respiratory ***,traditionally considered a respiratory virus,SARS-CoV-2’s showcased the ability to target multiple organ systems including pancreas,an organ crucial for regulating blood sugar levels and aiding digestion.

关键词： pancreas respiratory traditionally

Design multifunctional Mg–Zr coatings regulating Mg alloy bioabsorption

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Journal of Magnesium and Alloys 2024年第4期12卷 1461-1478页

作者： Zohra Benzarti Sandesh Itani JoséDavid Castro sandra Carvalho Ana Sofia Ramos University of Coimbra CEMMPREARISEDepartment of Mechanical EngineeringRua Luís Reis Santos3030-788CoimbraPortugal Laboratory of Multifunctional Materials and Applications(LaMMA) Department of PhysicsFaculty of Sciences of SfaxUniversity of SfaxSoukra Road km 3.5B.P.1171Sfax3000Tunisia

Magnesium(Mg)alloys are widely used for temporary bone implants due to their favorable biodegradability,cytocompatibility,hemocompatibility,and close mechanical properties to ***,rapid degradation and inadequate strength limit their *** overcome this,the direct current magnetron sputtering technique is employed for surface coating in Mg-based alloys using various zirconium(Zr)*** approach presents a promising strategy for simultaneously improving corrosion resistance,maintaining biocompatibility,and enhancing strength without compromising *** leveraging Mg’s inherent biodegradability,it has the potential to minimize the need for secondary surgeries,thereby reducing costs and *** paper is a systematic study aimed at understanding the corrosion mechanisms of Mg–Zr coatings,denoted Mg-xZr(x=0–5 at.%).Zr-doped coatings exhibited columnar growth leading to denser and refined structures with increasing Zr *** analysis confirmed the presence of the Mg(00.2)basal plane,shifting towards higher angles(1.15°)with 5 at.%Zr doping due to lattice parameter changes(i.e.,decrease and increase of“c”and“a”lattice parameters,respectively).Mg–Zr coatings exhibited“liquidphilic”behavior,while Young’s modulus retained a steady value around 80 GPa across all ***,the hardness has significantly improved across all samples’coating,reaching the highest value of(2.2±0.3)GPa for 5 at.%*** testing in simulated body fluid(SBF)at 37℃ revealed a significant enhancement in corrosion resistance for Mg–Zr coatings containing 1.0–3.4 at.%*** with the 5 at.%Zr coating which exhibited a corrosion rate of 32 mm/year,these coatings displayed lower corrosion rates,ranging from 1 to 12 mm/*** synergistic enhancement in mechanical properties and corrosion resistance,achieved with 2.0–3.4 at.%Zr,suggests potential ability for reducing stress shielding and controlled degradation performance,and consequentl

关键词： Mg-Zr coatings Magnetron sputtering Nanoindentation Corrosion resistance Bone implants

Immunotherapy combinations and chemotherapy sparing schemes in first line non-small cell lung cancer

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World Journal of Clinical Oncology 2021年第12期12卷 1182-1192页

作者： María Sereno Oliver Higuera Patricia Cruz Castellanos sandra falagan Xabier Mielgo-Rubio Juan Carlos Trujillo-Reyes Felipe Couñago Medical Oncology Department Hospital Universitario Infanta SofíaSan Sebastián de los Reyes 28702MadridSpain Medical Oncology Department Hospital Universitario La PazMadrid 28046Spain Medical Oncology Department Hospital Universitario Fundación AlcorcónAlcorcón 28922MadridSpain Department of 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 Quirónsalud MadridPozuelo de Alarcón 28223MadridSpain Department of Radiation Oncology Hospital La LuzMadrid 28003Spain Medicine Department School of Biomedical SciencesUniversidad Europea de MadridVillaviciosa de Odón 28670MadridSpain

In recent years,studies have explored different combinations of immunotherapy and *** rationale behind these is the improved survival outcomes of new immunologic therapies used in first-line-treatment of advanced non-small cell lung ***,for the most-studied combinations of anti-programed death-1(PD-1)/programed death ligand-1(PD-L1)with the addition of platinumbased chemotherapy,recent research is investigating whether combining different immunologic antitumoral mechanisms of action,such as anti-PD-1/PD-L1 and anti-CTLA-4,or anti-PD-L1 and anti-TIGIT,with or without chemotherapy,can improve efficacy outcomes compared with more classical combinations,or compared with standard chemotherapy ***,we present the data of the main randomized studies that have evaluated these combinations,focusing on the basic rationale behind the different combinations,and the efficacy and tolerability data available to date.

关键词： Immunotherapy combinations Anti-programmed cell death protein Antiprogrammed cell death ligand 1 anti-TIGIT anti-CTLA-4 Combo Non-small cell lung cancer

Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

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Cancer Biology & Medicine 2020年第2期17卷 444-457页

作者： Juan Moreno-Rubio Santiago Ponce Rosa Alvarez Maria Eugenia Olmedo sandra falagan Xabier Mielgo Fatima Navarro Patricia Cruz Luis Cabezon-Gutierrez Carlos Aguado Gonzalo Colmenarejo Marta Munoz-Fernandez de Leglaria Ana Belen Enguita Maria Cebollero Amparo Benito Isabel Alemany Carolina del Castillo Ricardo Ramos Ana Ramirez de Molina Enrique Casado Maria Sereno Ana Ramirez de Molina1 Enrique Casado5Maria Sereno5 XIMDEA Food InstituteCEI UAM+CSICMadrid 28702Spain 12 de Octubre University Hospital Madrid 28041Spain Gregorio Maranon University Hospital Madrid 28009Spain Ramon y Cajal University Hospital Madrid 28034Spain Infanta Sofia University Hospital San Sebastian De Los ReyesMadrid 28702Spain Fundacion Alcorcon University Hospital AlcorconMadrid 28922Spain Prlncipe de Asturias University Hospital Alcala De HenaresMadrid 28805Spain La Paz University Hospital Madrid 28046Spain University Hospital of Torrejon Torrejon De ArdozMadrid 28850Spain Clinico San Carlos University Hospital Madrid 28040Spain Parque Cientifico de Madrid Foundation Madrid 28049Spain

Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with *** are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the *** this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular ***:In the first step,we conducted a clinical-pathological characterization of the ***,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the ***:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of *** obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)***,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

关键词： Long-term survivors non-small cell lung cancer surfactant proteins

Quasilinear elliptic problems with exponential growth via the Nehari manifold method: Existence of nonnegative and nodal solutions

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Acta Mathematica Sinica,English Series 2024年

作者： Giovany FIGUEIREDO sandra Moreira Ricardo Ruviaro Address Departamento de Matematica Universidade de Brasilia Departamento de Matematica e Informatica Universidade Estadual do Maranhao Departamento de Matematica Universidade de Brasilia

In this paper we will be concerned with the problem -Δu-1/2Δ(a（x）u2)u+V（x）u=f（u）,x∈R2，where V is a potential continuous and f : R → R is a superlinear continuous function with exponential subcritical or exponential critical growth. We use as a main tool the Nehari manifold method in order to show existence of nonnegative solutions and existence of nodal solutions. Our results complement the classical result of solutions for quasilinear Schrodinger equations via the Nehari method due to Jia-quan Liu, Ya-qi Wang and Zhi-Qiang Wang in the sense that in this article we are considering nonlinearity of the exponential type.

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Towards trustworthy multi-modal motion prediction:Holistic evaluation and interpretability of outputs

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CAAI Transactions on Intelligence Technology 2024年第3期9卷 557-572页

作者： sandra Carrasco Limeros Sylwia Majchrowska Joakim Johnander Christoffer Petersson MiguelÁngel Sotelo David Fernández Llorca Computer Engineering Department Polytechnic SchoolUniversity of AlcalaMadridSpain AI Sweden GothenburgSweden Zenseact AB GothenburgSweden Department of Electrical Engineering Linköping UniversityLinköpingSweden Chalmers University of Technology GothenburgSweden European Commission Joint Research CentreSevilleSpain

Predicting the motion of other road agents enables autonomous vehicles to perform safe and efficient path *** task is very complex,as the behaviour of road agents depends on many factors and the number of possible future trajectories can be consid-erable(multi-modal).Most prior approaches proposed to address multi-modal motion prediction are based on complex machine learning systems that have limited ***,the metrics used in current benchmarks do not evaluate all aspects of the problem,such as the diversity and admissibility of the *** authors aim to advance towards the design of trustworthy motion prediction systems,based on some of the re-quirements for the design of Trustworthy Artificial *** focus is on evaluation criteria,robustness,and interpretability of ***,the evaluation metrics are comprehensively analysed,the main gaps of current benchmarks are identified,and a new holistic evaluation framework is ***,a method for the assessment of spatial and temporal robustness is introduced by simulating noise in the perception *** enhance the interpretability of the outputs and generate more balanced results in the proposed evaluation framework,an intent prediction layer that can be attached to multi-modal motion prediction models is *** effectiveness of this approach is assessed through a survey that explores different elements in the visualisation of the multi-modal trajectories and *** proposed approach and findings make a significant contribution to the development of trustworthy motion prediction systems for autono-mous vehicles,advancing the field towards greater safety and reliability.

关键词： autonomous vehicles evaluation interpretability multi-modal motion prediction robustness trustworthy AI

High-resolution multi-scale air pollution system:Evaluation of modelling performance and emission control strategies

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Journal of Environmental Sciences 2024年第3期137卷 65-81页

作者： Diogo Lopes Joana Ferreira sandra Rafael Ka In Hoi Xin Li Yuan Liu Ka-Veng Yuen Kai Meng Mok Ana Isabel Miranda Department of Environment and Planning&CESAM University of AveiroAveiroPortugal Department of Civil&Environmental Engineering Faculty of Science and TechnologyUniversity of MacaoMacao SARChina

A high percentage of the world's population lives in areas where air pollutant concentrations exceed the World Health Organization *** work aims to develop and test,a high-resolution multi-scale air pollution modelling system by integrating a set of adequate *** system is able to provide detailed air pollutant concentrations in urban areas and support air quality management strategies through a better identification of different atmospheric *** also allows furthering the design and assessment of air pollution control measures for a specific *** evaluate its performance and suitability,the system was applied to the Macao Special Administrative Region(SAR),China,one of the most densely populated areas on earth,during a winter period when this area is affected by high levels of Particulate Matter(PM).Although the developed system tends to underestimate the PM concentrations,it revealed a good performance in reproducing the temporal and spatial air pollution *** exceedances of the Chinese air quality standards were calculated and high population exposure to PM pollution was *** tested urban atmospheric emission reduction scenarios have shown air quality improvements,indicating that emission reduction measures at urban level should focus on the domestic ***,it is crucial to implement joint pollution prevention strategies with neighbouring regions to improve the air quality in Macao *** approach developed in this work can support policymakers in defining new strategies to reduce atmospheric pollution in urban areas.

关键词： Urban areas High-resolution emission inventory Particulate matter Population exposure

Jacob's Room:A New Form fora New Novel

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Journal of Foreign Languages and Cultures 2024年第1期8卷 80-91页

作者： sandra Guardini VASCONCELOS University of São Paulo

This article discusses the impact of the Post-Impressionist Exhibition that Roger Fry organized in London in 1910 on Virginia Woolf's ideas on the *** dissatisfaction with the state of the genre finds expression in her diary and in her criticism of the work of the Edwardian ***'s Room(1922),her first truly experimental novel,deploys some of the painterly techniques that the post-impressionist painters and vanguard movements of the 1910s *** represents a decisive step in her search for a new form for a new novel.

关键词： Jacob's Room Virginia Woolf essay experimental novel painting post-impressionism