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1Factors predicting poor prognosis in ischemic colitis显示文摘瞄准:决定临床、分析、内视镜的因素与有关是化学家大肠炎(IC ) 严厉。方法:85 个病人的一个总数从 1996 年 1 月在回顾的研究被注册到 2004 年 5 月。有 53 女性和 32 男性(年龄 74.6+/-9.4 年,范围 45-89 年) 。病人作为 IC 被诊断。下列变量包括年龄,性别,从到承认的症状的外观的时间的经期,病历,药,凳子频率,临床的症状和症状被分析,验血(血克和基本生物化学的侧面) ,和内视镜的调查结果。病人们在温和 IC 组和严重 IC 组(外科或死亡) 被划分。质的变量用 chi 平方测试被分析,参量的数据用学生的 t (P<0.05 ) 被分析。结果:温和 IC 组 69 个病人被在于(42 女性和 27 男性,平均年龄 74.7+/-12.4 年) 。严重 IC 组由 16 个病人组成(11 女性和 5 男性,平均 73.8+/-12.4 年的年龄) 。因为麦克匪特斯氏疗法(没有外科) 的失败,一个病人死了, 15 个病人经历了外科(6 在内视镜的诊断以后并且 9 在 peroperatory 以后诊断) 。85 个病人(9.6%) 中的八个死了,其它被跟随在上面作为为 9.6+/-3.5 瞬间的门诊病人。人口统计的数据,病历,药和凳子频率在两个组(P>0.05 ) 是类似的。说正经的有病的病人比稍微有病的病人有更少的便血(37.5% 对 86.9% , P = 0.000 ) 。更多的心悸亢进(45.4% 对 10.1% , P = 0.011 ) 并且假腹膜炎的更高的流行签名(75% 对 5.7% , P = 0.000 ) 当腹的疼痛的存在和紧张在二个组之间是类似的时,在严重 IC 组被观察。当承认时,有严重 IC 的二个病人有吃惊。关于分析数据,更严重有病的病人被发现比略微有病的病人有贫血症和血钠过少(37.5% 对 10.1% , P = 0.014 和 46.6% 对 14.9% , P = 0.012,分别地) 。狭窄是那比在稍微有病的病人更经常出现在严重有病的病人的唯一的内视镜的发现(66.6% 对 17.3% , P = 0.017 ) 。结论:能预言 IC 的差的预后是便血,心悸亢进和假腹膜炎,贫血症和血钠过少和狭窄的缺席的因素。Ramón A■ón Marta Maia Boscá Vicente Sanchiz Joan Tosca Pedro Almela Cirilo Amorós Adolfo Benages 2006World Journal of Gastroenterology2006,12,30:21
2Essential hypertension and oxidative stress:New insights显示文摘Essential hypertension is a highly prevalent pathological condition that is considered as one of the most relevant cardiovascular risk factors and is an important cause of morbidity and mortality around the world. Despite the fact that mechanisms underlying hypertension are not yet fully elucidated,a large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Oxidative stress can be defined as an imbalance between oxidant agents,such as superoxide anion,and antioxidant molecules,and leads to a decrease in nitric oxide bioavailability,which is the main factor responsible for maintaining the vascular tone. Several vasoconstrictor peptides,such as angiotensin Ⅱ,endothelin-1 and urotensin Ⅱ,act through their receptors to stimulate the production of reactive oxygen species,by activating enzymes like NADPH oxidase andxanthine oxidase. The knowledge of the mechanism described above has allowed generating new therapeutic strategies against hypertension based on the use of antioxidants agents,including vitamin C and E,N-Acetylcysteine,polyphenols and selenium,among others. These substances have different therapeutic targets,but all represent antioxidant reinforcement. Several clinical trials using antioxidants have been made. The aim of the present review is to provide new insights about the key role of oxidative stress in the pathophysiology of essential hypertension and new clinical attempts to demonstrate the usefulness of antioxidant therapy in the treatment of hypertension.Jaime González Nicolás Valls Roberto Brito Ramón Rodrigo 2014World Journal of Cardiology2014,6,6:20
3Platelet count/spleen diameter ratio to predict esophageal varices in Mexican patients with hepatic cirrhosis显示文摘AIM:To validate whether the platelet count/spleen size ratio can be used to predict the presence of esophageal varices in Mexican patients with hepatic cirrhosis.METHODS:This was an analytical cross-sectional study to validate the diagnostic test for hepatic cirrhosis and was performed between February 2010 and December 2011.Patients with a diagnosis of hepatic cirrhosis were included and stratified using their ChildPugh score.Biochemical parameters were evaluated,and ultrasound was used to measure the longest diameter of the spleen.The platelet count/spleen diameter ratio was calculated and analyzed to determine whether it can predict the presence of esophageal varices.Upper gastrointestinal endoscopy was used as the gold standard.Sensitivity and specificity,positive and negative predictive values,and positive and negative likelihood ratios were determined,with the cutoff points determined by receiver-operating characteristic curves.RESULTS:A total of 91 patients were included.The mean age was 53.75±12 years;50(54.9%)were men,and 41(45.0%)women.The etiology of cirrhosis included alcohol in 48(52.7%),virally induced in24(26.3%),alcoholism plus hepatitis C virus in three(3.2%),cryptogenic in nine(9.8%),and primary biliary cirrhosis in seven(7.6%).Esophageal varices were present in 73(80.2%)patients.Child-Pugh classification,17(18.6%)patients were classified as class A,37(40.6%)as class B,and 37(40.6%)as class C.The platelet count/spleen diameter ratio to detect esophageal varices independent of the grade showed using a cutoff value of≤884.3,had 84%sensitivity,70%specificity,and positive and negative predictive values of 94%and 40%,respectively.CONCLUSION:Our results suggest that the platelet count/spleen diameter ratio may be a useful tool for detecting esophageal varices in patients with hepatic cirrhosis.Alejandro González-Ojeda Gabino Cervantes-Guevara Manuela Chávez-Sánchez Carlos Dávalos-Cobián Susana Ornelas-Cázares Michel Dassaejv Macías-Amezcua Mariana Chávez-Tostado Kenia Militzi Ramírez-Campos Anaís del Rocío Ramírez-Arce Clotilde Fuentes-Orozco 2014World Journal of Gastroenterology2014,20,8:18
4Relative peripheral refraction across 4 meridians after orthokeratology and LASIK surgery显示文摘Background:To characterize the axial and off-axis refraction across four meridians of the retina in myopic eyes before and after Orthokeratology(OK)and LASIK surgery.Methods:Sixty right eyes with a spherical equivalent(M)between−0.75 to−5.25 D(cylinder<−1.00 D)underwent LASIK(n=26)or OK(n=34)to treat myopia.Axial and off-axis refraction were measured with an open-field autorefractometer before and after stabilized treatments.Off-axis measurements were obtained for the horizontal(35°nasal and temporal retina)and vertical(15°superior and inferior retina)meridians,and for two oblique directions(45–225°and 135–315°)up to 20°of eccentricity.The refractive profile was addressed as relative peripheral refractive error(RPRE).Results:OK and LASIK post-treatment results showed an increase of myopic relative refraction at several eccentric locations.At the four meridians evaluated,the M component of the pre-treatment RPRE values was not statistically different(p>0.05)from the post-treatment RPRE within 30°and 20°of the central visual field after LASIK and OK,respectively.These results demonstrated that the treatment zone warrants an optimal central field of vision.Conclusions:The present study gives an overview of RPRE after refractive corneal reshaping treatments(OK and LASIK)across vertical,horizontal and two oblique meridians together.This allows a 3D representation of RPRE at the retina and shows that the myopic shift induced by both treatments is more relevant in horizontal directions.António Queirós Ana Amorim-de-Sousa Daniela Lopes-Ferreira César Villa-Collar Ángel Ramón Gutiérrez JoséManuel González-Méijome 2018Eye and Vision2018,5,1:8
5Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review显示文摘BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.Rogelio González-González Sandra López-Verdín Jesús Lavalle-Carrasco Nelly Molina-Frechero Mario Isiordia-Espinoza Ramón G Carreón-Burciaga Ronell Bologna-Molina 2020World Journal of Clinical Oncology2020,11,1:6
6Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation显示文摘AIM:To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.METHODS:Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy.Laparoscopic surgery was planned after 5-8 wk.Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol.Patients with ypT1-2N0 or ypT3-4 or N+were offered 5-fluorouracil-based adjuvant treatment on an individual basis.An external cohort was used as a reference for the findings.RESULTS:One hundred and seventy six patients were treated with induction chemoradiotherapy and 170underwent total mesorectal excision.Cancer staging of ypT0N0 was achieved in 26/170(15.3%)patients.After a median follow-up of 58.3 mo,patients withypT0N0 had five-year disease-free and overall survival rates of 96%(95%CI:77-99)and 100%,respectively.We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation.The inherent good prognosis of these patients will have implications for clinical trial design and care of patients.CONCLUSION:Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team.Xabier García-Albéniz Rosa Gallego Ralf Dieter Hofheinz Gloria Fernández-Esparrach Juan Ramón Ayuso-Colella Josep Antoni Bombí Carles Conill Miriam Cuatrecasas Salvadora Delgado Angels Ginés Rosa Miquel Mario Pagés Estela Pineda Verónica Pereira Aarón Sosa Oscar Reig Iván Victoria Luis Feliz Antonio María de Lacy Antoni Castells Iris Burkholder Andreas Hochhaus Joan Maurel 2014World Journal of Gastroenterology2014,20,42:5
7Is it possible to stop nucleos(t)ide analogue treatment in chronic hepatitis B patients?显示文摘Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus(HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen(HBs Ag), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBs Ag loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBs Ag seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure aclose follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBe Ag(+) cases, have proven useless in HBe Ag(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups.Elia Moreno-Cubero Robert T Sánchez del Arco Julia Pena-Asensio Eduardo Sanz de Villalobos Joaquín Míquel Juan Ramón Larrubia 2018World Journal of Gastroenterology2018,24,17:5
8Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer’s disease and dementia with Lewy bodies显示文摘Background:Because of the increasing life expectancy in our society,aging-related neurodegenerative disorders are one of the main issues in global health.Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline.Among these diseases,Alzheimer’s disease(AD)and dementia with Lewy bodies(DLB)are the most common types of degenerative dementia.Although both show specific features,an important neuropathological and clinical overlap between them hampers their correct diagnosis.In this work,we identified molecular biomarkers aiming to improve the misdiagnosis between both diseases.Methods:Plasma extracellular vesicles(EVs)-from DLB,AD and healthy controls-were isolated using size-exclusion chromatography(SEC)and characterized by flow cytometry,Nanoparticle Tracking Analysis(NTA)and cryo-electron microscopy.Next Generation Sequencing(NGS)and related bibliographic search was performed and a selected group of EV-associated microRNAs(miRNAs)was analysed by qPCR.Results:Results uncovered two miRNAs(hsa-miR-451a and hsa-miR-21-5p)significantly down-regulated in AD samples respect to DLB patients,and a set of four miRNAs(hsa-miR-23a-3p,hsa-miR-126-3p,hsa-let-7i-5p,and hsamiR-151a-3p)significantly decreased in AD respect to controls.The two miRNAs showing decreased expression in AD in comparison to DLB provided area under the curve(AUC)values of 0.9 in ROC curve analysis,thus suggesting their possible use as biomarkers to discriminate between both diseases.Target gene analysis of these miRNAs using prediction online tools showed accumulation of phosphorylation enzymes,presence of proteasome-related proteins and genes involved in cell death among others.Conclusion:Our data suggest that plasma-EV associated miRNAs may reflect a differential profile for a given dementia-related disorder which,once validated in larger cohorts of patients,could help to improve the differential diagnosis of DLB versus AD.Ana Gámez-Valero Jaume Campdelacreu Dolores Vilas Lourdes Ispierto Ramón Reñé RamiroÁlvarez MPilar Armengol Francesc E.Borràs Katrin Beyer 2019Translational Neurodegeneration2019,8,1:4
9Accuracy of Magnetic Resonance Enterography in Assessing Response to Therapy and Mucosal Healing in Patients With Crohn’s Disease显示文摘Ingrid Ordás Jordi Rimola Sonia Rodríguez José M. Paredes María J. Martínez-Pérez Esther Blanc Juan A. Arévalo Marta Aduna Montserrat Andreu Alexander Radosevic Anna M. Ramírez-Morros Susana Pinó Marta Gallego Aranzazu Jauregui-Amezaga Elena Ricart Julián 2013Gastroenterology2013,,:3
10Hepatic Expression of CXC Chemokines Predicts Portal Hypertension and Survival in Patients With Alcoholic Hepatitis显示文摘Marlene Dominguez Rosa Miquel Jordi Colmenero Montserrat Moreno Joan–Carles García–Pagán Jaime Bosch Vicente Arroyo Pere Ginès Juan Caballería Ramón Bataller 2009Gastroenterology2009,,5:3
11Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma显示文摘AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.Borja Hernández-Breijo Jorge Monserrat Sara Ramírez-Rubio Eva P Cuevas Diana Vara Inés Díaz-Laviada M Dolores Fernández-Moreno Irene D Román Javier P Gisbert Luis G Guijarro 2011World Journal of Gastroenterology2011,17,34:2
12Susceptibility Genetic Variants Associated With Colorectal Cancer Risk Correlate With Cancer Phenotype显示文摘Anna Abulí Xavier Bessa Juan Ramón González Clara Ruiz–Ponte Alejandro Cáceres Jenifer Mu?oz Victoria Gonzalo Francesc Balaguer Ceres Fernández–Rozadilla Dolors González Luisa de Castro Juan Clofent Luís Bujanda Joaquín Cubiella Josep M a Re?é Juan Diego 2010Gastroenterology2010,,3:2
13外科减肥手术后高血压缓解和复发的预测因素显示文摘目前,只有很少量研究涉及外科减肥手术后高血压得到缓解和复发的影响因素,没有可用于预测高血压复发相关因素的信息。该研究的目的是评估在外科减肥手术后第1年和第3年里高血压的缓解情况和复发率,并寻找可能的预测因素。Benaiges D Sagué M Flores-Le Roux JA Pedro-Botet J Ramón JM Villatoro M Chillarón JJ Pera M Más A Grande L Goday A 陈云 2016中华高血压杂志2016,24,9:2
14Characterisation by SPME–GC–MS of the volatile profile of a Spanish soft cheese P.D.O. Torta del Casar during ripening显示文摘Francisco José Delgado José González-Crespo Ramón Cava Jesús García-Parra Rosario Ramírez 2009Food Chemistry2009,,1:2
15Evaluation of hepatocellular carcinoma using SonoVue, a second generation ultrasound contrast agent: correlation with cellular differentiation显示文摘Carlos Nicolau Violeta Catalá Ramón Vilana Rosa Gilabert Luis Bianchi Manel Solé Mario Pagés Concepció Brú 2004European Radiology2004,,6:2
16Prediction of the cetane number of biodiesel using artificial neural networks and multiple linear regression显示文摘Ramón Piloto-Rodríguez Yisel Sánchez-Borroto Magin Lapuerta Leonardo Goyos-Pérez Sebastian Verhelst 2013Energy Conversion and Management2013,,:2
17Measurement planning for circular cross-section tunnels using terrestrial laser scanning显示文摘Ramón Argüelles-Fraga Celestino Ordó?ez Silverio García-Cortés Javier Roca-Pardi?as 2013Automation in Construction2013,,:2
18Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis显示文摘Pere Ginès Juan Uriz Blas Calahorra Guadalupe Garcia–Tsao Patrick S. Kamath Luis Ruiz Del Arbol Ramón Planas Jaime Bosch Vicente Arroyo Juan Rodés 2002Gastroenterology2002,,6:2
19sTWEAK is a marker of early haematoma growth and leukoaraiosis in intracerebral haemorrhage显示文摘Objective To study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis(LA)and the soluble tumour necrosis factor-like weak inducer of apoptosis(sTWEAK)in patients with intracerebral haemorrhage(ICH).Methods This is a retrospective observational study of patients with nontraumatic ICH.Clinical and biochemical parameters were analysed.sTWEAK levels were measured by ELISA.LA was analysed in the hemisphere without haemorrhage to avoid interference with the acute injury.The main endpoint was the haematoma growth evaluated by the difference in volume between the second and the initial neuroimage.Poor functional outcome,defined as a modified Rankin Scale>2 at 3 months,was considered as secondary endpoint.Receiver operating characteristic curve analysis was performed to stablish the best cut-off for sTWEAK levels associated with haematoma growth.Results We included 653 patients with ICH in our analysis(71.1±11.9 years,44%women).Haematoma growth was observed in 188 patients(28.8%).sTWEAK levels≥5600 pg/mL predicted ICH growth with a sensitivity of 84%and a specificity of 87%.sTWEAK levels≥5600 pg/mL and the presence of LA were associated with haematoma growth(OR:42.46;(CI 95%22.67 to 79.52)and OR:2.73(CI 95%1.39 to 5.34),respectively).Also,the presence of LA(OR:4.31(CI 95%2.89 to 6.42))and the interaction between ICH growth and sTWEAK(OR:2.23(CI 95%1.40 to 3.55))were associated with poor functional outcome at 3 months.Conclusion sTWEAKs,together with the presence and grade of LA,are biomarkers able to predict ICH growth and poor functional outcome in patients with ICH.Andrés da Silva-Candal Iria López-Dequidt Manuel Rodriguez-Yañez PauloÁvila-Gómez JoséManuel Pumar JoséCastillo Tomás Sobrino Francisco Campos Ramón Iglesias-Rey Pablo Hervella 2021Stroke & Vascular Neurology2021,6,4:2
20Maintenance treatment with Pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study显示文摘Emilio Alba Manuel Ruiz-Borrego Mireia Margelí álvaro Rodríguez-Lescure Pedro Sánchez-Rovira Amparo Ruiz Jose Ramón Mel-Lorenzo Manuel Ramos-Vázquez Nuria Ribelles Elisa Calvo Antonio Casado Antonia Márquez David Vicente José Angel García-Sáenz Miguel Mar 2010Breast Cancer Research and Treatment2010,,1:2
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