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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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Assessing the energy saving potential of using adaptive setpoint temperatures:The case study of a regional adaptive comfort model for Brazil in both the present and the future

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Building simulation 2024年第3期17卷 459-482页

作者： Daniel sánchez-garcía david Bienvenido-Huertas Carlos Rubio-Bellido Ricardo Forgiarini Rupp Department of Electrical Engineering University Carlos III of MadridMadridSpain Department of Building simulation ZEROCEM SLSevilleSpain Department of Building Constructions University of GranadaGranadaSpain Department of Building Constructions II University of SevilleSevilleSpain section of Design for sustainability Department of Civil and Mechanical EngineeringTechnical University of DenmarkKgs.LyngbyDenmark

It has been found in recent years that using setpoint temperatures based on adaptive thermal comfort models is a successful method of energy *** studies using adaptive setpoint temperatures incorporate international models from AsHRAE standard 55 and *** study,however,has instead considered a regional Brazilian adaptive comfort *** study investigates the energy demand arising from the use of a local Brazilian comfort model in order to assess the energy implications from the use of the worldwide AsHRAE standard 55 adaptive model and various fixed setpoint *** of Brazil’s climate zones,full air-conditioning,mixed-mode building operating modes,present-day climate change scenarios,and future scenarios—specifically Representative Concentration Pathways(RCP)2.6,4.5,and 8.5 for the years 2050 and 2100—have all been taken into account in building energy *** use of adaptive setpoint temperatures based on the Brazilian local model considering mixed-mode has been found to significantly reduce energy consumption when compared to static setpoint temperatures(average energy-saving values ranging from 52%to 58%)and the AsHRAE 55 adaptive model(average values ranging from 15%to 21%).Considering climate change and the mixed-mode Brazilian model,the overall energy demand for the three groups of climatic zones(annual average outdoor temperatures≤21℃,>21 and≤25℃and>25℃)ranged between 2%decrease and 5%increase,4%and 27%increase,and 13%and 45%increase,*** is concluded as a consequence that setting setpoint temperatures based on the Brazilian local adaptive comfort model is a very efficient energy-saving method.

关键词： adaptive thermal comfort building energy simulation energy efficiency climate change adaptive setpoint temperatures local comfort mode

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Role of climatic variability in shaping intraspecific variation of thermal tolerance in Mediterranean water beetles

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Insect science 2024年第1期31卷 285-298页

作者： susana Pallarés david Garoffolo Belén Rodríguez david sánchez-Fernández Department of Zoology University of SevilleSevilleSpain Faculty of Biology Department of Ecology and HydrologyUniversity of MurciaCampus EspinardoMurciaSpain

The climatic variability hypothesis(CVH)predicts that organisms in more thermally variable environments have wider thermal breadths and higher thermal plasticity than those from more stable ***,due to evolutionary trade-offs,taxa with greater absolute thermal limits may have little plasticity of such limits(trade-off hypothesis).The CVH assumes that climatic variability is the ultimate driver of thermal tolerance variation across latitudinal and altitudinal gradients,but average temperature also varies along such *** explored intraspecific variation of thermal tolerance in three typical Mediterranean saline water beetles(families Hydrophilidae and Dytiscidae).For each species,we compared two populations where the species coexist,with similar annual mean temperature but contrasting thermal variability(continental *** population).We estimated thermal limits of adults from each population,previously acclimated at 17,20,or 25℃.We found species-specific patterns but overall,our results agree with the CVH regarding thermal ranges,which were wider in the continental(more variable)*** the two hydrophilid species,this came at the cost of losing plasticity of the upper thermal limit in this population,supporting the trade-off hypothesis,but not in the dytiscid *** results support the role of local adaptation to thermal variability and trade-offs between basal tolerance and physiological plasticity in shaping thermal tolerance in aquatic ectotherms,but also suggest that intraspecific variation of thermal tolerance does not fit a general pattern among aquatic *** such intraspecific variation could lead to inaccurate predictions of the vulnerability of aquatic insects to global warming.

关键词： acclimation capacity aquatic insects climate change heat coma temperature supercooling point thermal plasticity

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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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Neural Regeneration Research 2024年第3期19卷 542-547页

作者： María Norte-Muñoz david garcía-Bernal Diego garcía-Ayuso Manuel Vidal-sanz Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical *** stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and *** studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional ***,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous ***,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

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Navigating the controversy regarding antibiotic prophylaxis in acute variceal bleeding

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World Journal of Gastroenterology 2024年第18期30卷 2485-2487页

作者： david Aguirre-Villarreal Ignacio garcía-Juárez Department of Gastroenterology and Liver Transplant Unit Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical ***,with recent evidence arguing against antibiotic prophylaxis,the role of this... 详细信息

关键词： Cirrhosis Acute variceal bleeding Antibiotic prophylaxis Endoscopic band ligation spontaneous bacterial peritonitis

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Towards an integrated risk analysis security framework according to a systematic analysis of existing proposals

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Frontiers of Computer science 2024年第3期18卷 199-216页

作者： Antonio sANTOs-OLMO Luis Enrique sÁnchez david G.ROsADO Manuel A.sERRANO Carlos BLANCO Haralambos MOURATIDIs Eduardo FERNÁNDEZ-MEDINA GsyA Research Group University of Castilla-La ManchaCiudad Real 13071Spain Institute for Analytics and Data science University of EssexColchester CO43SQUK Alarcos Research Group University of Castilla-La ManchaCiudad Real 13071Spain IsTR Research group Department of Computer Science and ElectronicsUniversity of CantabriaSantander 39005Spain

The information society depends increasingly on risk assessment and management systems as means to adequately protect its key information *** availability of these systems is now vital for the protection and evolution of ***,several factors have led to an increasing need for more accurate risk analysis *** are:the speed at which technologies evolve,their global impact and the growing requirement for companies to *** analysis processes must consequently adapt to these new circumstances and new technological *** objective of this paper is,therefore,to present the results of an exhaustive analysis of the techniques and methods offered by the scientific community with the aim of identifying their main weaknesses and providing a new risk assessment and management *** analysis was carried out using the systematic review protocol and found that these proposals do not fully meet these new *** paper also presents a summary of MARIsMA,the risk analysis and management framework designed by our research *** basis of our framework is the main existing risk standards and proposals,and it seeks to address the weaknesses found in these *** is in a process of continuous improvement,as is being applied by customers in several European and American *** consists of a risk data management module,a methodology for its systematic application and a tool that automates the process.

关键词： information security management security system security risk assessment and management

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Breaking paradigms: Long non-coding RNAs forming gene fusions with potential implications in cancer

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Genes & Diseases 2024年第3期11卷 311-323页

作者： david sanchez-Marin Macrina Beatriz silva-Cazares Fany Iris Porras-Reyes Rebeca garcia-Roman Alma D.Campos-Parra Posgrado en Ciencias Biologicas Facultad de MedicinaUniversidad Nacional Autonoma de MexicoCiudad de MexicoC.P.04360Mexico Unidad Academica Multidisciplinaria Region Altiplano Universidad Autonoma de San Luis Potost(UASLP)Carretera a Cedral Km 5+600Ejido San Jose de la TrojesMatehualaSan Luis PotosiC.P.78760Mexico servicio de Anatomia Patologica Instituto Nacional de Cancerologia(INCan)Nino JesuisTlalpanCiudaddeMexicoC.P.14080Mexico Instituto de salud Publica Universidad Veracruzana(UV)Av.Dr LuisDr.Castelazo Ayala s/nCol.Industrial AnimasXalapaVeracruzC.P.91190Mexico

Long non-coding RNAs(lncRNAs)are non-coding RNAs longer than 200 nucleotides with dynamic regulatory *** interact with a wide range of molecules such as DNA,RNA,and proteins to modulate diverse cellular functions through several mechanisms and,if deregulated,they can lead to cancer development and ***,it has been described that IncRNAs are susceptible to form gene fusions with mRNAs or other IncRNAs,breaking the paradigm of gene fusions consisting mainly of protein-coding ***,their biological significance in the tumor phenotype is still ***,their recent identification opens a new line of research to study their biological role in tumor-igenesis,and their potential as biomarkers with clinical relevance or as therapeutic *** present study aimed to review the IncRNA fusions identified so far and to know which of them have been associated with a potential *** address the current challenges to deepen their study as well as the reasons why they represent a future therapeutic window incancer.

关键词： Cancer Genefusions IncRNAs ncRNAs Therapy

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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-sanchis Pedro AAvila-López Iva Tic david Valle-garcía Marta Ribalta-Vilella Luis Labrador Deb Ranjan Banerjee Ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRs UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(sAMP8)control mice and sAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the sAMP8 group treated with G9a inhibitor than in the sAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG sAMP8

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Effect of Ultraviolet Radiation on Hsp70 Protein Expression in HaCaT Cells

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World Journal of Nuclear science and Technology 2024年第1期14卷 59-71页

作者： sergio Hugo sánchez Rodríguez Jesús Rodríguez Vergil Manuel Venancio Muñoz Juárez Kevin said Ramírez Dávila Luis Martín garcía Ortiz Germán Flores Cortés Luz Elena Vidales Rodríguez Jesús Adrián López david Alejandro garcía López Laboratorio de Biología Celular y Neurobiología Unidad Académica de Ciencias Biológicas Universidad Autónoma de Zacatecas Zacatecas México Laboatorio de Bacterias y Hongos Filamentosos Unidad Académica de Ciencias Biológicas Universidad Autónoma de Zacatecas Zacatecas México Laboratorio de MicroRNAs Unidad Académica de Ciencias Biológicas Universidad Autónoma de Zacatecas Zacatecas México

Ultraviolet radiation by its wavelength is divided into: UVA, UVB and UVC. Only UVA and UVB manage to penetrate the ozone layer, but due to anthropological activities, all of them are capable of interacting with humans to a greater or lesser extent, and can generate adverse effects such as cellular stress when interacting with intra-and extracellular biomolecules. The skin is the first organ in contact with UV radiation, and the stress it generates can be analyzed by the expression of a bioindicator of cellular damage such as Hsp70. Therefore, the objective of the project was: to determine the effect of UVA, UVB and UVC radiation on HaCaT epithelial cells, by analyzing the expression of Hsp70. Materials and methods: HaCaT cells were cultured in vitro, which were irradiated with UVA, UVB and UVC light at different doses, to subsequently determine the degree of Hsp70 expression by Immunodetection by PAGE-sDs and Western Blot. Results: Basal expression of Hsp70 was observed in no irradiated HaCaT cells. When HaCaT cells were irradiated with UVA, UVB, UVC, an increase in this Hsp70 protein was observed. With UVA, a higher degree of expression was observed at a time of 30 minutes of irradiation. With UVB the highest expression shifted to a time of 20 minutes. With UVC, overexpression was observed after 10 minutes. Conclusion: UV radiation generates cellular stress on HaCaT cells, evaluated by the stress bioindicator Hsp70. According to the wavelength of UV radiation, those that have a shorter wavelength have a greater potential for cellular damage, such as UVC.

关键词： Ultraviolet A Light (UVA) Ultraviolet B Light (UVB) Ultraviolet C Light (UVC) Heat shock Protein 70 (Hsp70) HaCaT

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Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

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World Journal of Diabetes 2024年第4期15卷 758-768页

作者： Enriqueta Muñoz-Islas Edgar david santiago-sanMartin Eduardo Mendoza-sánchez Héctor Fabián Torres-Rodríguez Laura Yanneth Ramírez-Quintanilla Christopher Michael Peters Juan Miguel Jiménez-Andrade Unidad Académica Multidisciplinaria Reynosa-Aztlán Universidad Autónoma de TamaulipasReynosa 88740TamaulipasMexico Department of Anesthesiology Wake Forest University School of MedicineWinston SalemNC 27101United States

BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain *** To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with *** GDM was induced by *** of streptozotocin(sTZ)in ICR mouse *** 12 wk old,fasting blood glucose levels were determined in *** 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for *** quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal *** Offspring mice born from sTZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated ***,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control ***,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control *** GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

关键词： Gestational diabetes mellitus Immunohistochemistry Confocal microscopy Pancreas Offspring

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