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Translational pancreatic cancer research:a comparative study on patient-derived xenograft models

World Journal of gastroenterology 2018年第7期24卷 794-809页

作者： Mercedes Rubio-Manzanares Dorado luis miguel marín gómez Daniel Aparicio Sánchez Sheila Pereira Arenas Juan Manuel Praena-Fernández Juan Jose Borrero martín Francisco Farfán López miguel ángel gómez Bravo Jordi Muntané Relat Javier Padillo Ruiz Department of Hepatobiliary and Pancreatic Surgery Virgen del Rocio University Hospital Oncology Surgery Cell Therapy and Organ Transplantation Group Institute of Biomedicine of Seville (IBiS) Virgen del Rocio University Hospital University of Seville Statistics Methodology and Evaluation of Research Unit Virgen del Rocio University Hospital Pathology Department Virgen del Rocio University Hospital

AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice.METHODS This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUnEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics.COnCLUSIOn In our experience, the faster development andgreatest number o

关键词： Immunohistological analysis Pancreatic cancer Patient-derived xenograft Animal model nude mice

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Optimal Design of Hybrid Microgrid in Isolated Communities of Ecuador

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Journal of Modern Power Systems and Clean Energy 2024年第2期12卷 488-499页

作者： luis A.Pesantes Ruben Hidalgo-León Johnny Rengifo miguel Torres Jorge Aragundi JoséCordova-garcia luis F.Ugarte Facultad de Ingeniería en Electricidad y Computación of Escuela Superior Politécnica del Litoral(ESPOL)University GuayaquilEcuador Department of Electrical Engineering at Universidad Técnica Federico Santa maría SantiagoChile IEEE

In rural territories, the communities use energy sources based on fossil fuels to supply themselves with electricity, which may address two main problems: greenhouse gas emissions and high fuel prices. Hence, there is an opportunity to include renewable resources in the energy mix. This paper develops an optimization model to determine the optimal sizing, the total annual investment cost in renewable generation, and other operating costs of the components of a hybrid microgrid. By running a k-means clustering algorithm on a meteorological dataset of the community under study, the hourly representative values become input parameters in the proposed optimization model. The method for the optimal design of hybrid microgrid is analyzed in six operating scenarios considering:(1) 24-hour continuous power supply;(2) load shedding percentage;(3) diesel power generator(genset) curtailment;(4) the worst meteorological conditions;(5) the use of renewable energy sources including battery energy storage systems(BESSs);and(6) the use of genset. A mathematical programming language(AMPL) tool is used to find solutions of the proposed optimization model. Results show that the total costs of microgrid in the scenarios that cover 100% of the load demand(without considering the scenario with 100% renewables) increase by over 16% compared with the scenario with genset operation limitation. For the designs with power supply restrictions, the total cost of microgrid in the scenario with load shedding is reduced by over 27% compared with that without load shedding.

关键词： Battery energy storage system(BESS) isolated community microgrid renewable energy optimization

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加夫列尔·加西亚·马尔克斯图书馆,巴塞罗那,西班牙

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世界建筑 2024年第5期 76-81页

作者：无 Elena Orte guillermo Sevillano marta Romero Jesús Lopez luis Sierra Ana Patricia Minguito Pablo Corroto maría Abellán Sara Contreras RitaÁlvarez Tabio miguelÁngel Maure Jesús granada(摄影) SUMA建筑设计事务所不详

加布里埃尔·加西亚·马尔克斯图书馆是巴塞罗那的第40座图书馆,也是巴塞罗那30年计划的结晶。该计划旨在建立一个由优秀社区与区域设施组成的密集网络。这座图书馆位于圣马蒂德普罗旺斯区,为53,000人提供服务。关联式建筑图书馆被设计... 详细信息

加布里埃尔·加西亚·马尔克斯图书馆是巴塞罗那的第40座图书馆,也是巴塞罗那30年计划的结晶。该计划旨在建立一个由优秀社区与区域设施组成的密集网络。这座图书馆位于圣马蒂德普罗旺斯区,为53,000人提供服务。关联式建筑图书馆被设计成一座雕塑式实体建筑,让人联想到堆叠的书籍及其折叠的书页。该馆坐落在一处高架广场上,方便周围行人来往。同时,它又在空地上悬挑而出,门廊由现有的树木环绕,形成了一座城市大厅。不同大小及结构的开口定义了其不同立面与周围环境的关系。

关键词：巴塞罗那普罗旺斯周围环境加布里埃尔加西亚·马尔克斯图书馆关联式西班牙

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Functional and patient-reported outcomes of bone-anchored hearing aids (BAHA): A prospective case series study

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Journal of Otology 2023年第1期18卷 7-14页

作者： Catia Azevedo miguel Breda Daniela Ribeiro Fernando Milhazes mar Sergio Vilarinho luis Dias Hospital de Braga BragaPortugal

Objective:The purpose of this study was to evaluate the functional and patient-reported outcomes,and their correlation,after percutaneous bone-anchored hearing aid(BAHA)implantation.Methods:A prospective study was conducted between January 2018 and December 2020 in a tertiary care center.All adult patients who were implanted with a percutaneous BAHA device during this evaluation period were included in the study.Complete auditory function and patients reported outcome measures(PROMs)were assessed in the preoperative period and 6 months after the implant activation.The PROMs included a generic form(Medical Outcome Study 36 Short Form Healthy Survey(MOS SF-36)),and three disease-specific forms(Hearing Handicap Inventory(HHI),Satisfaction with Amplification in Daily Life Scale(SADLS),and Tinnitus Handicap Inventory(THI)).Results:Twenty-two patients with an average age of 53 years were included in the study.The overall functional gain with the BAHA in sound-field pure tone average(PTA)was 29 dB,with no statistically significant differences according to surgical indication(F(3,18)=2.319,p=0.110).The greater the preoperative air-bone gap,the greater the functional gain obtained(r=0.505,pn the PROMs,we found a significant improvement in HHI scores(pnd a significant increase in overall SADLS scores(pneous BAHA devices.We did not verify any statistically significant correlation between functional and PROMs results.Conclusions:The BAHA is a safe and effective alternative hearing rehabilitation option in selected patients.The PROMs results prove patient's overall satisfaction.

关键词： BAHA Hearing loss Implant Hearing results PROMs

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Sarcopenia and Anemia Are Predictors of Poor Prognostic in Cervical Cancer Patients

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Open Journal of Obstetrics and gynecology 2024年第5期14卷 693-704页

作者： Leandro Santos de Araujo Resende Francine Vilela de Amorim miguel Soares Conceição Rodrigo Menezes Jales Patrick nunes Pereira luis Otávio Sarian glauco Baiocchi Sophie Derchain Agnaldo Lopes da Silva Filho Department of gynecology and Obstetrics Botucatu Medical School S&#227o Paulo State University UNESP S&#227o Paulo Brazil Department of Health Sciences University of Sao Francisco S&#227o Paulo Brazil Department of Obstetrics and gynecology School of Medical Science State University of Campinas (UNICAMP) Campinas Brazil Department of gynecologic Oncology AC Camargo Cancer Center Sao Paulo Brazil Department of gynecology and Obstetrics School of Medicine of the Federal University of Minas Gerais Belo Horizonte Brazil

Objective: Evaluate pretreatment sarcopenia and anemia as prognostic factors in women undergoing treatment for cervical cancer (CC) with concurrent chemoradiotherapy (CCRT). Methods: 151 women with CC were analysed in this cohort study. Pretreatment computed tomography (CT) images were analysed to assess skeletal muscle index (SMI). Hazard ratios (HR) and multivariate Cox proportional HR were used to analyse association between low SMI, age, body mass index (BMI), haemoglobin levels, histological type, and International Federation of gynaecology and Obstetrics (FIgO) stage with PFS and OS. Results: A total of 151 patients were included, 53 (35.1%) presented pretreatment sarcopenia;51 (34%) stage I/II and 100 (66%) stage III/IV. Among those patients in advanced stage (III/IV) 37 (70%) (p = 0.28) were sarcopenic at the beginning of treatment. Sarcopenia was associated with worse progression-free survival (PFS) and overall survival (OS) in our cohort [HR 0.97 (p = 0.01)] [HR 0.73 (p = 0.001)], as well as anemia [HR 0.73 (p = 0.001)] [HR 0.78 (p = 0.001)]. Linear regression models indicated that despite showing no association with age, neutrophil or platelet counts, sarcopenia was associated with pretreatment anemia levels (p = 0.01). After a multivariate analysis, only haemoglobin (anemia) and complete CCRT remained associated with PFS and OS. Sarcopenia and anemia were associated with worse PFS and OS in FIgO stage I/II. Conclusion: Pretreatment sarcopenia was significantly associated with low haemoglobin levels. Anemia and incomplete CCRT were independently associated with poor prognosis in women with CC. Pretreatment sarcopenia, as low SMI, was a predictor of poor prognostic in early stages of CC.

关键词： Cervical Cancer Sarcopenia Anemia Chemoradiotherapy

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Management of incidentally discovered appendiceal neuroendocrine tumors after an appendicectomy

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World Journal of gastroenterology 2022年第13期28卷 1304-1314页

作者： Joséluis Muñoz de nova Jorge Hernando miguel Sampedro núñez greissy Tibisay Vázquez Benítez Eva maría Triviño Ibáñez maría Isabel del Olmo garcía Jorge Barriuso Jaume Capdevila Elena martín-Pérez Department of general and Digestive Surgery Hospital Universitario de La PrincesaMadrid 28006Spain Department of Surgery Universidad Autónomade MadridMadrid 28029Spain gastrointestinal and Endocrine Tumor Unit Medical Oncology DepartmentVall d´Hebron University HospitalVall d´Hebron Institute of OncologyBarcelona 08035Spain Department of Endocrinology and nutrition Hospital Universitario de La PrincesaMadrid 28006Spain Department of Pathology Hospital Universitario Puerta de HierroMadrid 28222Spain Department of Pathology Universidad Autónoma de MadridMadrid 28029Spain Department of nuclear Medicine Virgen de las Nieves University HospitalGranada 18014Spain Department of Endocrinology and nutrition Hospital Universitario i Politècnic La FeValencia 46023Spain Division of Cancer Sciences School of Medical SciencesFaculty of BiologyMedicine and HealthUniversity of ManchesterManchester M139PLUnited Kingdom Department of Medical Oncology The Christie NHS Foundation TrustManchester M204BXUnited Kingdom

Appendiceal neuroendocrine tumors(anETs)are an uncommon neoplasm that is relatively indolent in most cases.They are typically diagnosed in younger patients than other neuroendocrine tumors and are often an incidental finding after an appendectomy.Although there are numerous clinical practice guidelines on management of a nETs,there is continues to be a dearth of evidence on optimal treatment.Management of these tumors is stratified according to risk of locoregional and distant metastasis.However,there is a lack of consensus regarding tumors that measure 1-2 cm.In these cases,some histopathological features such as size,tumor grade,presence of lymphovascular invasion,or mesoappendix infiltration must also be considered.Computed tomography or magnetic resonance imaging scans are recommended for evaluating the presence of additional disease,except in the case of tumors smaller than 1 cm without additional risk factors.Somatostatin receptor scintigraphy or positron emission tomography with computed tomography should be considered in cases with suspected residual or distant disease.The main point of controversy is the indication for performing a completion right hemicolectomy after an initial appendectomy,based on the risk of lymph node metastases.The main factor considered is tumor size and 2 cm is the most common threshold for indicating a colectomy.Other factors such as mesoappendix infiltration,lymphovascular invasion,or tumor grade may also be considered.On the other hand,potential complications,and decreased quality of life after a hemicolectomy as well as the lack of evidence on benefits in terms of survival must be taken into consideration.In this review,we present data regarding the current indications,outcomes,and benefits of a colectomy.

关键词： neuroendocrine tumors Carcinoid tumor Appendiceal neoplasms Colectomy neoplasm grading Treatment outcome

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DnA Fidelity: Expression of a Monocot Promoter in a Dicot Plant

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American Journal of Plant Sciences 2022年第1期13卷 50-59页

作者： luis maría Suárez-Rodríguez Hugh Mason Joel Ramírez-Cabrera luis Jorge Saucedo miguel Angel gómez-Lim Charles Arntzen Rodolfo López-gómez Instituto de Investigaciones Químico-Biológicas Universidad Michoacana de San Nicolás de Hidalgo Morelia México School of Life Sciences Arizona State University Tempe USA Departamento de genética Cinvestav IPn Campus Irapuato Irapuato México

The knowledge generated from the identification of plant promoters has been very important for plant biotechnology development. The use of promoters in transgenic plants allows a reasonable level of regulating protein expression. With the application of reporter genes, such as gusA (uidA,) the production of a colored protein, β-glucuronidase, can be detected and measured both qualitatively and quantitatively, and the activity of the promoter can be assessed. In this work we use a promoter of an abundant banana fruit protein gene Musa acuminata Acidic Chitinase class III a monocot species, to drive expression of gusA in a dicot species, like tomato. We evaluated the monocot promoter capabilities by localizing and quantifying β-glucuronidase (gUS) expression through fluorometric assays during tomato fruit ripening. Our results suggest that this promoter could be used for specifically strong fruit protein expression in dicot plants.

关键词： Promoter Fruit Ripening Tomato Banana

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MicroRnAs in biliary diseases

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World Journal of gastroenterology 2012年第43期18卷 6189-6196页

作者： Patricia Munoz-garrido Maite garcía-Fernández de Barrena Elizabeth Hijona miguel Carracedo JoséJ g marín luis Bujanda Jesús M Banales Division of Hepatology and gastroenterology Biodonostia Research InstituteDonostia Universitary Hospital20014 San SebastiánSpain Division of Oncology Research Schulze Center for Novel TherapeuticsMayo ClinicRochesterMN 55905United States Division of Hepatology and gastroenterology Biodonostia Research InstituteDonostia Universitary Hospital20014 San SebastiánSpains Department of Liver and gastrointestinal Diseases National Institute for the Study of Liver and Gastrointestinal Diseases(CIBERehdfunded by the Spanish CarlosⅢInstitute)08036 BarcelonaSpain Department of Physiology and Pharmacology Experimental Hepatology and Drug Targeting(HEVEFARM)Biomedical Research Institute of Salamanca(IBSAL)University of Salamanca37008 SalamancaSpain Ikerbasque Basque Foundation for Science48011 BilbaoSpain

Cholangiopathies are a group of diseases primarily or secondarily affecting bile duct cells, and result in cholangiocyte proliferation, regression, and/or transformation. Their etiopathogenesis may be associated with a broad variety of causes of different nature, which includes genetic, neoplastic, immune-associated, infectious, vascular, and drug-induced alterations, or being idiopathic. miRnAs, small non-coding endogenous RnAs that post-transcriptionally regulate gene expres sion, have been associated with pathophysiological processes in different organs and cell types, and are postulated as potential targets for diagnosis and therapy. In the current manuscript, knowledge regarding the role of miRnAs in the development and/or progression of cholangiopathies has been reviewed and the most relevant findings in this promising field of hepatology have been highlighted.

关键词：小分子RnA 疾病 miRnA 胆道细胞类型发病机理免疫相关调控基因

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narcea—an unknown,ancient cultivated rose variety from northern Spain

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Horticulture Research 2020年第1期7卷 2217-2228页

作者： maría-Carmen martínez José-luis Santiago Susana Boso Pilar gago InmaculadaÁlvarez-Acero maría-Estela De Vega miguel martínez-Bartolomé RafaelÁlvarez-nogal Pilar Molíst Matteo Caser Valentina Scariot Daniel gómez-garcía Misión Biológica de galicia(CSIC) Carballeira 8Salcedo 36143 PontevedraSpain Instituto de Ciencia y Tecnología de Alimentos y nutrición(CSIC)(Spain) C/JoséAntonio Novais 1028040 MadridSpain Departamento de Biología Molecular-Área de Biología Celular Universidad de LeónCampus de Vegazana s/n24071 LeónSpain grupo neurolamb Biología funcional y Ciencias de la SaludUniversidad de Vigo(Spain)36310 As Lagoas-MarcosendeSpain Department of Agricultural Forest and Food SciencesUniversity of TorinoLargo Paolo Braccini 210095 GrugliascoTurinItaly Instituto Pirenaico de Ecología(CSIC) Dpto.Conservación de Ecosistemas NaturalesAvda.Montaña S/NZaragoza50016 ZaragozaSpain

The present work reports the discovery and the complete characterisation of an ancient cultivated rose variety found growing in a private garden in the southwest of the Principality of Asturias(northern Spain).The variety is here given the name narcea.The majority of roses currently cultivated belong to the so-called group of‘Modern Roses’,all of which were obtained after 1867 via artificial crosses and improvement programmes.All are destined for ornamental use.Until the 19th century,the great majority of the many ancient cultivated roses in Europe were used in perfumery and cosmetics,or had medicinal uses.Rosa damascena and Rosa centifollia are still grown and used by the French and Bulgarian perfume industries.The Asturian Massif of the Cantabrian Mountain Range provides a natural habitat for some 75%of the wild members of the genus Rosa,but until now there was no evidence that this area was home to ancient cultivated roses.A complete botanical description is here provided for a discovered ancient rose.It is also characterised according to a series of sequence tagged microsatellite sites,and its agronomic features are reported.In addition,a histological description(optical and scanning electronic microscope studies)of the petals is offered,along with an analysis of the volatile compounds present in these organs as determined by solid phase microextraction and gas chromatography-mass spectroscopy.The results reveal the uniqueness of this ancient type of rose and suggest it may be of interest to the perfume industry.

关键词： ancient southwest majority

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Time-expanded phase-sensitive optical time-domain reflectometry

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Light(Science & Applications) 2021年第3期10卷 443-454页

作者： miguel Soriano-Amat Hugo F.martins Vicente Duran luis Costa Sonia martin-Lopez miguel gonzalez-Herraez maria R.Fernandez-Ruiz Departamento de Electronica Universidad de AlcalaEscuela Politecnica Superior28805 MadridSpain Instituto deóptica"Daza de Valdes" IO-CSICC/Serrano 12128006 MadridSpain gROC-UJI Institute of New Imaging TechnologiesUniversity Jaume112071 CastellonSpain

Phase-sensitive optical time-domain reflectometry(CDOTDR)is a well-established technique that provides spatiotemporal measurements of an environmental variable in real time.This unique capability is being leveraged in an everincreasing number of applications,from energy transportation or civil security to seismology.To date,a wide number of different approaches have been implemented,providing a plethora of options in terms of performance(resolution,acquisition bandwidth,sensitivity or range).However,to achieve high spatial resolutions,detection bandwidths in the gHz range are typically required,substantially increasing the system cost and complexity.Here,we present a novel OOTDR approach that allows a customized time expansion of the received optical traces.Hence,the presented technique reaches cm-scale spatial resolutions over t km while requiring a remarkably low detection bandwidth in the MHz regime.This approach relies on the use of dual-comb spectrometry to interrogate the fibre and sample the backscattered light.Random phase-spectral coding is applied to the employed combs to maximize the signal-to-noise ratio of the sensing scheme.A comparison of the proposed method with alternative approaches aimed at similar operation features is provided,along with a thorough analysis of the new trade-offs.Our results demonstrate a radically novel high-resolution OOTDR scheme,which could promote new applications in metrology,borehole monitoring or aerospace.

关键词： optical phase expanded

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