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Sarcoma stratification by combined pH2AX and MAP17(PDZK1IP1)levels for a better outcome on doxorubicin plus olaparib treatment

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Signal Transduction and Targeted Therapy 2020年第1期5卷 697-709页

作者： Marco Perez JoséManuel García-Heredia Blanca Felipe-Abrio Sandra Muñoz-Galván Javier Martín-Broto Amancio Carnero Instituto de Biomedicina de Sevilla(IBIS) Hospital Universitario Virgen del RocíoUniversidad de SevillaConsejo Superior de Investigaciones CientíficasSevillaSpain Ciber de Cancer IS Carlos IIIMadridSpain Departamento de Bioquímica Vegetal y Biología Molecular Universidad de SevillaSevillaSpain Departamento de Anatomía Patológica Hospital Universitario Virgen del RocíoSevillaSpain

Sarcomas constitute a rare heterogeneous group of tumors,including a wide variety of histological subtypes.Despite advances in our understanding of the pathophysiology of the disease,first-line sarcoma treatment options are still limited and new treatment approaches are needed.Histone H2AX phosphorylation is a sensitive marker for double strand breaks and has recently emerged as biomarker of DNA damage for new drug development.In this study,we explored the role of H2AX phosphorylation at Ser139 alone or in combination with MAP17 protein,an inducer of DNA damage through ROS increase,as prognostic biomarkers in sarcoma tumors.Next,we proposed doxorubicin and olaparib combination as potential therapeutic strategies against sarcomas displaying high level of both markers.We evaluate retrospectively the levels of pH2AX(Ser139)and MAP17 in a cohort of 69 patients with different sarcoma types and its relationship with clinical and pathological features.We found that the levels of pH2AX and MAP17 were related to clinical features and poor survival.Next,we pursued PARP1 inhibition with olaparib to potentiate the antitumor effect of DNA damaging effect of the DNA damaging agent doxorubicin to achieve an optimal synergy in sarcoma.We demonstrated that the combination of olaparib and doxorubicin was synergistic in vitro,inhibiting cell proliferation and enhancing pH2AX intranuclear accumulation,as a result of DNA damage.The synergism was corroborated in patient-derived xenografts(PDX)where the combination was effective in tumors with high levels of pH2AX and MAP17,suggesting that both biomarkers might potentially identify patients who better benefit from this combined therapy.

关键词： H2AX doxorubicin treatment

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新冠疫情下委内瑞拉保障大学教学活动的教育政策 ——以委内瑞拉中央大学为例

新冠疫情下委内瑞拉保障大学教学活动的教育政策 ...

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作者： Nazarelys blanca Arcila 华东师范大学

学位级别：硕士

新冠肺炎给世界各地的教育系统带来了危机,威胁着人们的受教育权和学习过程的连续性。因此,各国出台了基于网络技术的政策来保证教育。但是,许多国家的技术基础设施并不能够胜任疫情期间在线教育的要求。委内瑞拉制定了“居家上大学（Un... 详细信息

新冠肺炎给世界各地的教育系统带来了危机,威胁着人们的受教育权和学习过程的连续性。因此,各国出台了基于网络技术的政策来保证教育。但是,许多国家的技术基础设施并不能够胜任疫情期间在线教育的要求。委内瑞拉制定了“居家上大学（University at Home,Universidad en Casa）政策,以保证大学部门在新冠大流行期间的运行。本研究以委内瑞拉中央大学为例,探究疫情期间委内瑞拉为保证大学的正常教学活动而实施的“居家上大学”政策,研究目的在于明确委内瑞拉于疫情下的教育政策对保障大学正常教学的作用,借助混沌和复杂理论解释战略性政策帮助优化远程教学的实践效果,提出保证教育权的教育政策建议。研究对委内瑞拉中央大学的管理层（包括3名院长,1名学校主任,1名教职学术协调员,1名学校学术协调员和1名平台专家）进行了半结构性访谈,并采用内容分析方法对这些质性资料进行了归纳分析。研究结果表明,由于线上教育的条件,国家宪法要求的受教育权难以保障,而且政策的制定未征询大学管理者意见。混沌和复杂性理论原则也没有得到合理应用,因为该理论要求适应性、弹性和计划性,但疫情下委内瑞拉的事实并非如此。大学依靠自己的资源来完成教学任务,不乏有一些好的教学实践,诸如学习、信息和协作等。源于线上教学的特性,教学活动也需要更多弹性和分析。总结而言,此项研究考察了疫情期间委内瑞拉如何采取教育保障政策,以保证大学的正常教学,并提供了相关建议。委内瑞拉在疫情期间制定了“居家上大学”的教育保障政策,但政策的实施未取得理想效果。

关键词：居家上大学国家政策学习过程受教育权

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Bigger or long-winged male common crossbills exhibit redder carotenoid-based plumage coloration

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Current Zoology 2023年第2期69卷 165-172页

作者： blanca Fernandez-Eslava Daniel Alonso David Galicia Juan Arizaga Carlos Alonso-Alvarez Biologia Ambiental Universidad de NavarraFacultad de CienciasC/Irunlarrea1 Pamplona31008 NavarraSpain Ornitologia Sociedad de Ciencias de AranzadiZorroagagaina 1120014 DonostiaSan SebastianSpain Ecologia Evolutiva Museo Nacional de Ciencias Naturales(CSiC)Edificio Pinar 2528006 MadridSpain

Carotenoid-based ornaments are often considered reliable(honest)individual condition signals because their expression implies physiological costs unaffordable for low-quality animals(handicap signals).Recently,it has been suggested that efficient cell respiration is mandatory for producing red ketocarotenoids from dietary yellow carotenoids.This implies that red colorations should be entirely unfalsifiable and independent of expression costs(index signals).In a precedent study,male common crossbills,Loxia curvirostra,showing a red plumage reported higher apparent survival than those showing yellowish-orange colors.The plumage redness in this species is due to ketocarotenoid accumulation in feathers.Here,we correlated the male plumage redness(a 4-level visual score:yellow,patchy,orange,and red)and the body morphology in more than 1,ooo adult crossbills captured in 3 Iberian localities to infer the mechanisms responsible for color evolution.A principal component analysis summarized morphometry of 10 variables(beak,wing,tarsus length,etc.).The overall body size(PC1)and the length of flight feathers regarding body size(Pc3)showed significant positive relationships with plumage redness.Plumage redness was barely correlated with bill shape measures,suggesting no constraint in acquiring carotenoids from pine cones.However,large body sizes or proportionally long flying feathers could help carotenoid acquisition via social competition or increased foraging ranges.Proportionally longer flight feathers might also be associated with a specific cell respiration profile that would simultaneously favor flying capacities and enzymatic transformations needed for ketocarotenoid synthesis.Such a phenotypic profile would agree with the hypothesis of ketocarotenoid-based colors acting as individual quality index signals.

关键词： avian carotenoids color and biometrics Loxia genus Mediterranean crossbills resource allocation trade-offs shared pathway hypothesis

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基于相互作用关系的中国省际人口流动研究

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地理研究 2018年第9期37卷 1848-1861页

作者：豆晓 ARELLANO blanca ROCA Josep 山东农业大学城市管理系泰安271018 加泰罗尼亚理工大学建筑学院西班牙巴塞罗那08028

基于2000年、2010年人口普查及2005年、2015年人口抽样调查数据,采用相互作用关系模型计算了中国"人口流动系统"和"单向相互作用关系值"。结果表明:(1)人口流动具有明显的凝聚性,东部地区对流动人口的吸引力依然具有绝对优势;(2)省际人... 详细信息

基于2000年、2010年人口普查及2005年、2015年人口抽样调查数据,采用相互作用关系模型计算了中国"人口流动系统"和"单向相互作用关系值"。结果表明:(1)人口流动具有明显的凝聚性,东部地区对流动人口的吸引力依然具有绝对优势;(2)省际人口流动呈"非对称双向迁移模式",人口回流的趋势已不容忽视;(3)长三角地区逐渐代替珠三角成为新的人口流动中心,人口流动开始北移;(4)中西部地区的人口流动分中心某种意义上已经出现,人口就近转移日渐凸显。将2010-2015年间省际人口流动新规律和特征与1995-2010年进行动态对比,对于制定未来人口和区域发展政策,继续缩小东西部地区之间的差距,最终实现区域协调发展具有重要意义。

关键词：省际人口流动人口流动系统相互作用关系中国

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A Feature-based Convolutional Neural Network（FbCNN） for Reconstruction of Interventional MRI

A Feature-based Convolutional Neural Network（FbCNN） for Re...

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作者： blanca ZUFIRIA GERBOL（?）S 上海交通大学

学位级别：硕士

Real-time interventional MRI（I-MRI）would be very helpful to track the position of the surgical device during MR-guided neurosurgery.This would improve the patient outcome.Specially,in deep brain stimulation（DBS）,the visualization of the surgical procedure in real-time using I-MRI could improve the accuracy of the electrode placement.However,the reconstruction of interventional images using high undersampling rate and fast reconstruction speed for real-time imaging pose a great challenge.We proposed a feature-based convolutional neural network（FbCNN）for reconstructing for reconstructing interventional images from golden-angle radially sampled data,based on recent advances in deep learning（DL）.The reconstruction is composed of two steps: 1)reconstruction of the interventional feature;2)feature refinement and postprocessing.We showed that the interventional feature can be reconstructed with a cascade CNN,using an undersampling of only 5 radially sampled spokes.We obtained a final interventional image from a refined feature and a fully sampled reference image.FbCNN was compared with traditional reconstruction techniques and recent DL-based method,and it was shown that only FbCNN could reconstruct the interventional feature and the final interventional image.Furthermore,FbCNN demonstrated that had the potential in real-time I-MRI applications with a reconstruction time of ～500ms per frame and an acceleration factor of ～80.

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Nutrient drink test: A promising new tool for irritable bowel syndrome diagnosis

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World Journal of Gastroenterology 2019年第7期25卷 837-847页

作者： Fermin Estremera-Arevalo Marta Barcelo blanca Serrano Enrique Rey Department of Gastroenterology Complejo Hospitalario de Navarra Department of Gastroenterolgy Hospital Infanta Leonor Department of Digestive Diseases Hospital Clinico San Carlos Department of Digestive Diseases Hospital Clinico San Carlos and Complutense University

BACKGROUND Irritable bowel syndrome(IBS) is a highly prevalent condition. It is diagnosed on the basis of chronic symptoms after the clinical and/or investigative exclusion of organic diseases that can cause similar symptoms. There is no reproducible noninvasive test for the diagnosis of IBS, and this raises diagnostic uncertainty among physicians and hinders acceptance of the diagnosis by patients.Functional gastrointestinal(GI) syndromes often present with overlapping upper and lower GI tract symptoms, now believed to be generated by visceral hypersensitivity. This study examines the possibility that, in IBS, a nutrient drink test(NDT) provokes GI symptoms that allow a positive differentiation of these patients from healthy subjects.AIM To evaluate the NDT for the diagnosis of IBS.METHODS This prospective case-control study compared the effect of two different nutrient drinks on GI symptoms in 10 IBS patients(patients) and 10 healthy controls(controls). The 500 kcal high nutrient drink and the low nutrient 250 kcal drink were given in randomized order on separate days. Symptoms were assessed just before and at several time points after drink ingestion. Global dyspepsia and abdominal scores were derived from individual symptom data recorded by two questionnaires designed by our group, the upper and the general GI symptomquestionnaires, respectively. Psycho-social morbidity and quality of life were also formally assessed. The scores of patients and controls were compared using single factor analysis of variance test.RESULTS At baseline, IBS patients compared to controls had significantly higher levels of GI symptoms such as gastro-esophageal reflux(P = 0.05), abdominal pain(P =0.001), dyspepsia(P = 0.001), diarrhea(P = 0.001), and constipation(P = 0.001) as well as higher psycho-social morbidity and lower quality of life. The very low incidence of GI symptoms reported by control subjects did not differ significantly for the two test drinks. Compared with the low nutrient drink, IBS patients with the high nutrient

关键词： Irritable bowel syndrome Nutrient drink test Non-invasive Dyspepsia Screening

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Molecular mechanisms contributing to glucocorticoid resistance in lymphoid malignancies

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Cancer Drug Resistance 2019年第3期2卷 647-664页

作者： blanca Scheijen Department of Pathology Radboud University Medical Center and Radboud Institute for Molecular Life SciencesGA 6525Nijmegenthe Netherlands

Despite the introduction of many novel therapies into the clinic to target hematological malignancies,glucocorticoids(GCs)still remain one of the cornerstone drugs in first-line treatment of lymphoid tumors.However,a significant portion of the patients display acquired GC therapy resistance.This review will describe the different molecular mechanisms that contribute to GC resistance in lymphoid tumors.These include suppression of glucocorticoid receptor(GR)expression,activation of cell signaling pathways that modulate GR function,differential recruitment of transcriptional co-regulators,and changes in chromatin accessibility.Many of these mechanisms are interconnected to genetic alterations associated with relapsed disease in lymphoid malignancies.

关键词： Glucocorticoid receptor therapy resistance acute lymphoblastic leukemia non-Hodgkin lymphoma multiple myeloma

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Suitability and limitations of mesenchymal stem cells to elucidate human bone illness

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World Journal of Stem Cells 2019年第9期11卷 578-593页

作者： Izaskun Mitxitorena Arantza Infante blanca Gener Clara I Rodríguez Stem Cells and Cell Therapy Laboratory Biocruces Bizkaia Health Research InstituteCruces University HospitalBarakaldo 48903BizkaiaSpain Service of Genetics Biocruces Bizkaia Health Research InstituteCruces University HospitalBarakaldo 48903BizkaiaSpain Centre for Biomedical Network Research on Rare Diseases Instituto de Salud Carlos IIIMadrid 28005Spain

Functional impairment of mesenchymal stem cells(MSCs),osteoblast progenitor cells,has been proposed to be a pathological mechanism contributing to bone disorders,such as osteoporosis(the most common bone disease)and other rare inherited skeletal dysplasias.Pathological bone loss can be caused not only by an enhanced bone resorption activity but also by hampered osteogenic differentiation of MSCs.The majority of the current treatment options counteract bone loss,and therefore bone fragility by blocking bone resorption.These socalled antiresorptive treatments,in spite of being effective at reducing fracture risk,cannot be administered for extended periods due to security concerns.Therefore,there is a real need to develop osteoanabolic therapies to promote bone formation.Human MSCs emerge as a suitable tool to study the etiology of bone disorders at the cellular level as well as to be used for cell therapy purposes for bone diseases.This review will focus on the most relevant findings using human MSCs as an in vitro cell model to unravel pathological bone mechanisms and the application and outcomes of human MSCs in cell therapy clinical trials for bone disease.

关键词： Mesenchymal stem cells Bone illness Osteoporosis Osteogenesis Osteoanabolic therapies In vitro cell models Cell therapy

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Emotional evaluation of lighting in university classrooms:A preliminary study

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Frontiers of Architectural Research 2018年第4期7卷 600-609页

作者： Nuria Castilla Carmen Llinares Fabio Bisegna Vicente blanca-Gimenez Dpto.Construcciones Arquitectonicas Universitat Politecnica de ValenciaCamino de Veras/nValencia 46022Spain Instituto de Investigacion e Innovacion en Bioingenieria i3BUniversitat Politecnica de ValenciaCamina de Veras/nValencia 46022Spain Dept.of Astronautical Electrical and Energetic Engineering (DIAEE)SAPIENZA University of RomeVia Eudossiana 18Rome 00184Italy

In educational environments an improvement in the quality of interior lighting has a direct benefit in increasing productivity and alertness of students and teachers, as well as very important implications for the energy efficiency of the education facilities but when a replacement with different lighting is analyzed, research may be tarnished by users’ pre-formed opinions, influenced by manufacturers and advertising. Consequently, it is necessary to understand the users’ point of view, even before of being subjected to any change in the lighting stimulus.Based on the Kansei Engineering framework, the general objective of this paper is to evaluate and compare the subjective evaluation of students’ pre-formed opinions to lighting provided by two types of lamps (fluorescent and LED). The subjective assessment of 427 university students has been compared over four years. The results show significant differences in students’ subjective evaluation. This finding highlights the existence of symbolic or functional attributes of the usefulness perceived by the student that could influence on investigations in which different types of lighting are compared.

关键词： Kansei engineering Lighting Fluorescent LED Subjective assessment University classroom

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Beta-blockers and physical frailty in patients with endstage liver disease

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World Journal of Gastroenterology 2018年第33期24卷 3770-3775页

作者： Selena Z Kuo blanca Lizaola Hilary Hayssen Jennifer C Lai Division of Gastroenterology/Hepatology Department of Medicine University of CaliforniaSan Francisco

AIM To investigate beta-blocker(BB) use in patients with cirrhosis and determine their effects on physical frailty and overall survival.METHODS Adult outpatients with cirrhosis listed for liver transplantation underwent testing of physical frailty using the performance-based Liver Frailty Index, comprised of chair stands, grip strength, and balance testing, as well as self-reported assessments of exhaustion and physical activity. BB use was assessed from medical chart review. Univariable and multivariable logistic regression were performed to determine BB use and their association with measures of physical frailty. Competing risk analyses were performed to determine the effect of BB use on wait-list mortality, as defined by death or delisting for being too sick for transplant.RESULTS Of 344 patients, 35% were female, median age was 60, median model for end stage liver disease was 15, and 53% were prescribed a BB. Compared to those not on BB, patients on BB were similar except for percentage female(25% vs 46%; P < 0.001) and BMI(29 vs 28; P = 0.008). With respect to tests of physical frailty, BB use was not associated with increased odds of frailty(by the Liver Frailty Index), exhaustion, or low physical activity. BB use was, however, significantly associated with a decreased adjusted risk of mortality(SHR 0.55; P = 0.005).CONCLUSION In patients with cirrhosis awaiting liver transplantation, BB use is not associated with physical frailty. We confirmed the known survival benefits with BB use, and concerns about adverse effects should not deter their utilization when indicated.

关键词： Beta-blockers Cirrhosis End-stage liver disease Frailty

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