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Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation

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Bone Research 2018年第1期6卷 83-94页

作者： Heather A.Carey Blake E.Hildreth III jennifer A.Geisler Mara C.Nickel jennifer cabrera Sankha Ghosh Yue jiang jing Yan james Lee Sandeep Makam Nicholas A.Young Giancarlo R.Valiente Wael N.jarjour Kun Huang Thomas j.Rosol Ramiro E.Toribio julia F.Charles Michael C.Ostrowski Sudarshana M.Sharma Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State University Wexner Medical Center College of Veterinary Medicine The Ohio State University Department of Biochemistry and Molecular Biology and Hollings Cancer Center Medical University of South Carolina Division of Rheumatology Immunology and Allergy Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Division of Rheumatology and Immunology Department of Internal Medicine The Ohio State University Wexner Medical Center Department of Biomedical Informatics The Ohio State University Wexner Medical Center

Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(TF)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. Functional genomic analysis indicated PU.1 and MITF orchestrated a TF network essential for OC differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.

关键词： Genome-wide GWASs MITF

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Specific and cross-reactive immune response against Mycobacterium tuberculosis antigens in mice immunized with proteoliposomes from Mycobacterium bovis BCG

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Asian Pacific journal of Tropical Biomedicine 2017年第3期7卷 188-192页

作者： Nadine Alvarez DaymíSerpa Ramlah Kadir Yanely Tirado Reinier Borrero Sonsire Fernández Rubén cabrera Yolanda Valdes Caridad Zayas Reinaldo Acevedo Luis Izquierdo María Elena Sarmiento Mohd-Nor Norazmi joséLuis Pérez Armando Acosta Finlay Institute School of Health Sciences University Sains Malaysia Institute for Research in Molecular Medicine University Sains Malaysia

Objective: To characterize the immunogenicity and the induction of cross-reactive responses against Mycobacterium tuberculosis(M. tuberculosis) of a proteoliposome(PL)from Mycobacterium bovis Bacillus Calmette–Guerin(BCG) with and without alum hydroxide(AL) as adjuvant(PLBCG-AL and PLBCG, respectively) in BALB/c ***: BALB/c mice were inoculated with phosphate buffer solution, BCG, PLBCG and PLBCG-AL. The humoral immunogenicity was determined by ELISA [immunoglobulin G(Ig G), Ig G1 and Ig G2a] and the cellular immunogenicity was evaluated in vivo by delayed type hypersensitivity. The humoral cross-reactive response against M. tuberculosis was determined by Western ***: Sera from animals immunized with PLBCG-AL and PLBCG showed significant increase in specific total Ig G and Ig G1 antibodies and the presence of cross-reactive antibodies against M. tuberculosis antigens, which were more intense with the use of alum as adjuvant. Mice immunized with PLBCG and PLBCG-AL also showed a specific cellular response in ***: The cellular and humoral immunogenicity of PLBCG and the capacity to induce cross-reactive responses against M. tuberculosis is in agreement with the protective capacity previously demonstrated by this vaccine candidate and supports the continuation of its evaluation in further stages.

关键词： BCG Immunogenicity Mycobacterium tuberculosis Proteoliposomes

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uFSHh、pFSH和rFSH在体外受精与卵胞浆内单精子注射妊娠结局的回顾性分析

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宁夏医学杂志 2006年第2期28卷 83-85页

作者：徐仙赵淑梅 Rafael A.cabrera 宁夏医学院附属医院宁夏银川750004 美国弗吉尼亚jones生殖医学研究院弗吉尼亚诺福克23507

目的探讨基因重组和尿卵泡刺激素在体外受精(IVF)和卵胞浆内单精子注射(ICSI)的妊娠结局。方法在促性腺激素释放激素激动剂(GnRHa)长或短方案下,分别应用尿卵泡刺激素(uFSH)、高纯度尿卵泡刺激素(hpFSH)和基因重组卵泡刺激素(rFSH)促排... 详细信息

目的探讨基因重组和尿卵泡刺激素在体外受精(IVF)和卵胞浆内单精子注射(ICSI)的妊娠结局。方法在促性腺激素释放激素激动剂(GnRHa)长或短方案下,分别应用尿卵泡刺激素(uFSH)、高纯度尿卵泡刺激素(hpFSH)和基因重组卵泡刺激素(rFSH)促排卵,回顾性分析1049例实施IVF和ICSI的治疗周期。结果无论在GnRHa长或短方案中,uFSH组和hpFSH组ICSI的受精率较IVF显著降低(P<0.0001),但在rFSH组两者无明显差异;而且各组之间IVF和ICSI的种植率或妊娠率亦无统计学差异。结论在IVF和ICSI周期治疗中,uFSH、hpFSH与rFSH具有等同的胚胎种植率和临床妊娠率。

关键词：卵泡刺激素体外受精卵胞浆内单精子注射种植妊娠

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Efficacy and safety of sphincterotomy with sphincteroplasty using large caliber balloons in the treatment of choledocholithiasis with extraction difficulties

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Open journal of Gastroenterology 2013年第4期3卷 241-248页

作者： R. Uribarrena-Amezaga I. Aured De La Serna I. Calvo-Morillas j. j. Sebastián-Domingo T. cabrera-Chaves M. T. Soria San Teodoro R. Uribarrena-Echebarría Department of Digestive Diseases Miguel Servet University Hospital Zaragoza Spain Department of Digestive Diseases Royo Villanova Hospital Zaragoza Spain

Introduction: Endoscopic retrograde cholangiopan-creatography (ERCP) with endoscopic sphincterotomy (ES) is the most widely used technique for treating choledocholithiasis. In some cases, due to anomalies of the papilla or the presence of large or multiple calculi, additional maneuvers are needed to remove the stones. The present study investigates the efficacy and safety of ES with sphincteroplasty (SP) in the management of choledocholithiasis with extraction difficulties. Patients and Methods: A prospective study was made of 153 patients with choledocholithiasis subjected to ERCP. Fifty-two patients underwent ES with SP, while 101 were subjected only to ES. The two groups were compared in terms of age, gender, percentage cannulation, presence of papilla alterations, large or multiple stones, success in stone removal and complications (acute pancreatitis, bleeding and perforation). In the ES with SP group, we moreover recorded the diameters of the balloons employed (10-18 mm). Results: There were no significant differences between the groups in the stone extraction success rate (94.23% in the ES with SP group versus 97.03% in the ES group) or in the appearance of complications (3.8% in the ES with SP group versus 2.7% in the ES group). The presence of difficult papillae, and of multiple or large stones was significantly greater in the ES with SP group. The diameter of the balloon was not associated with the appearance of complications. Conclusion: Endoscopic sphincterotomy with sphincteroplasty is effective and safe in the treatment of choledocholithiasis with extraction difficulties.

关键词： Choledocholithiasis Endoscopic Sphincterotomy Sphincteroplasty

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代谢综合征、腹型肥胖与老年女性的心血管风险

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世界核心医学期刊文摘(心脏病学分册) 2007年第5期 46-47页

作者： cabrera M.A.S. Gebara O.C.E. Diament j. 马超 Discipline of Geriatrics Department of Internal Medicine State University of Londrina ruaMontese 65- A Londrina Paran 86015020 Brazil

背景:代谢综合征和腹型肥胖是中年女性中心血管疾病的危险因素,但在老年人群中的情况尚不完全清楚。本研究分析了老年女性中代谢综合征和腹型肥胖与心血管事件发生率之间的相关性。方法:对在门诊老年科求医的连续516例60～84岁女性进行... 详细信息

背景:代谢综合征和腹型肥胖是中年女性中心血管疾病的危险因素,但在老年人群中的情况尚不完全清楚。本研究分析了老年女性中代谢综合征和腹型肥胖与心血管事件发生率之间的相关性。方法:对在门诊老年科求医的连续516例60～84岁女性进行了一项前瞻性

关键词：代谢综合征腰臀比腹型肥胖老年女性心血管

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GnRH-a/rFSH促排卵方案下体外受精周期中卵泡期血清黄体生成素水平对分娩率无影响

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世界核心医学期刊文摘（妇产科学分册） 2005年第6期1卷 31-32页

作者： cabrera R.A. Stadtmauer L. Mayer j.F. 李跃萍

To assess the value of serum LH measurements in early and late follicular phase as predictors of ovarian response and IVF outcome in patients treated with recombinant FSH with GnRH agonist (GnRH- a) pituitary down- regulation. Retrospective cohort analysis. Institutional. Women undergoing 157 consecutive IVF cycles suppressed with leuprolide acetate (LA) started in the midluteal phase and stimulated with recombinant FSH. Only women <40 years of age and with a basal cycle day 3 serum FSH ≤ 9 IU/L were included. Serum LH levels were measured on cycle days 3 (D3) and 10 (D10). Delivery rates. Other secondary outcome measures included fertilization rate, clinical pregnancy rate, and parameters of ovarian response (peak E2, number of metaphase II oocytes, and number of ampules of recombinant FSH). No significant differences were found with respect to ovarian response, fertilization rate, and outcome of pregnancy, when three threshold values of D3 and D10 serum LH (1, 1.5, and 2 mIU/mL) were analyzed. In addition, no significant differences were found between conception (n=87) and no conception (n = 71) groups with respect to D3 or D10 LH. Receiver operator characteristic (ROC) analysis showed that neither the serum LH concentration on D3 nor on D10 was able to discriminate between conception and nonconception cycles (area under the curve [AUC]ROC= 0.54, AUCROC= 0.56), or between delivered pregnancies and first trimester pregnancy loss (AUCROC= 0.53, AUCROC = 0.61). The suppressed levels of early and late follicular serum LH in women < 40 years of age with normal ovarian function desensitized with a GnRH- a and treated with recombinant FSH are not predictive of ovarian response, pregnancy, or delivery. These data do not support the use of exogenous LH supplementation in this clinical scenario.

关键词：促排卵方案 GnRH-a/rFSH 体外受精黄体生成素卵泡期卵巢反应性分娩率临床妊娠率卵泡刺激素黄体中期

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Incidentally Discovered HCC (iHCC) in Explant Liver-Histopathologic Features and Clinical Outcome

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journal of Cancer Therapy 2013年第2期4卷 394-398页

作者： Renumathy Dhanasekaran Davinderbir S. Pannu Alpna Limaye Ivan Zendejas Roberto j. Firpi Consuelo Soldevila-Pico Giuseppe Morelli Virginia C. Clark Amitabh Suman David R. Nelson Roniel cabrera Department of Medicine University of Florida Gainesville USA Department of Surgery University of Florida Gainesville USA Division of Gastroenterology Hepatology and Nutrition University of Florida Gainesville USA

Incidentally discovered hepatocellular carcinomas (iHCC) are tumors which are discovered on the explanted liver which were not present on imaging prior to transplant. The natural history, histopathologic characteristics and prognosis of iHCC are not clearly defined. Methods: A retrospective analysis was performed to compare the characteristics of iHCC and established HCC within Milan criteria (eHCC) in patients who underwent liver transplantation at our center between 2000 and 2010. Results: During the study period a total of 975 adult patients were transplanted in our center;124 (12.7%) patients had eHCC and 26 (2.6%) patients had iHCC. A larger number of patients with iHCC (73.1%) had ascites when compared to eHCC (41.3%) (p = 0.035). Patients with iHCC had a higher mean bilirubin (p 0.001) and mean INR (p = 0.05) than patients with eHCC. Around 70% of patients with iHCC had a Model for End Stage Liver Disease (MELD) score greater than 15 at the time of listing while only 25% of patients with eHCC had a MELD greater than 15 at listing (p 0.001).The mean alphafetoprotein (AFP) in patients with iHCC was significantly lower (11.6 ± 16.5) than the patients with eHCC (564.9 ± 2180;p = 0.024). In patients with iHCC, 30.8% had a multiple tumors and 23% had bilobar involvement. The average number of tumors was 1.6 and the cumulative tumor size was 2.1 cm (SD 1.4). The cumulative tumor size in iHCC was significantly smaller than in eHCC (mean 3.9 cm) (p = 0.035). American joint Committee on Cancer (AjCC) T1 tumor stage was found in 58% of patients with iHCC and 48.4% of patients with eHCC (p = 0.829).The median survival was 9.47 years for iHCC (95% CI 7.0 - 11.9) and 8.7 years (95% CI 6.1 - 11.4) for eHCC (p = 0.328). While none of the patients with iHCC had recurrence of HCC, the incidence of recurrence in patients with eHCC was 6.4%. Conclusion: iHCC occurred in patients with more advanced liver disease than eHCC. AFP was usually not elevated in patients with iHCC. The c

关键词： Incidental HCC Recurrence Survival

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Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19

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World journal of Gastroenterology 2022年第37期28卷 5444-5456页

作者： Ricardo Ulises Macías-Rodríguez Alberto Adrián Solís-Ortega Victoria j Ornelas-Arroyo Astrid Ruiz-Margáin Maria Sarai González-Huezo Nestor A Urdiales-Morán Berenice M Román-Calleja juan M Mayorquín-Aguilar joséA González-Regueiro Alejandro Campos-Murguía Israel Vicente Toledo-Coronado Mónica Chapa-Ibargüengoitia Bernardo Valencia-Peña Carlos Fernando Martínez-cabrera Nayelli C Flores-García Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Department of Gastroenterology Centro Médico ISSEMYMToluca 52140Mexico Department of Radiology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is associated with complications and mortality in patients with coronavirus disease 2019(COVID-19).However,there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD,despite its high *** dehydrogenase,aspartate aminotransferase and alanine aminotransferase have been used as markers of liver ***,we propose an index based on lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and *** To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases(aspartate aminotransferase/alanine aminotransferase)in patients with COVID-19 and MAFLD[liver fibrosis and nutrition(LNF)-COVID-19 index].METHODS In this retrospective cohort study,two cohorts from two different tertiary centers were *** first was the derivation cohort to obtain the score cutoffs,and the second was the validation *** included hospitalized patients with severe COVID-19 and *** steatosis was evaluated by computed tomography *** under the receiver operating characteristic(ROC)curve analysis and survival analysis were *** In the derivation cohort,44.6%had MAFLD;ROC curve analysis yielded a LFN-COVID-19 index>1.67 as the best cutoff,with a sensitivity of 78%,specificity of 63%,negative predictive value of 91%and an area under the ROC curve of *** the multivariate analysis,the LFN-COVID-19 index>1.67 was independently associated with the development of acute kidney injury(odds ratio:1.8,95%confidence interval:1.3-2.5,P<0.001),orotracheal intubation(odds ratio:1.9,95%confidence interval:1.4-2.4,P<0.001),and death(odds ratio:2.86,95%confidence interval:1.6-4.5,P<0.001)in both *** LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19,which

关键词： COVID-19 Metabolic associated fatty liver disease Lactate dehydrogenase Transaminases Prognosis Nonalcoholic fatty liver disease

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乳代用品对仔猪生长的影响

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国外畜牧学（猪与禽） 2007年第4期27卷 4-6页

作者：方正锋（译）方如君（校） Rafael cabrera 不详美国明尼苏达州Marshall Ralco营养公司

如果管理得当，给哺乳期的仔猪补充乳可获得多方面的好处。为获得高断奶窝重而对母猪进行高繁殖性能和高营养需求的选择已使饲喂现代的母猪品种成为商业化养猪场中技术最先进的工作。如果青年母猪要达到200～250kg体重时它才算完全体成... 详细信息

如果管理得当，给哺乳期的仔猪补充乳可获得多方面的好处。为获得高断奶窝重而对母猪进行高繁殖性能和高营养需求的选择已使饲喂现代的母猪品种成为商业化养猪场中技术最先进的工作。如果青年母猪要达到200～250kg体重时它才算完全体成熟，那么当体重为125～145kg时就进行配种以及动员体内储备哺乳10～11头仔猪的事实已经成为青年母猪的一个沉重负担。

关键词：仔猪生长哺乳期代用品青年母猪营养需求繁殖性能断奶窝重养猪场

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跨入21世纪的智利

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拉丁美洲研究 2005年第2期27卷 12-14页

作者：巴勃罗·卡夫雷拉 ,刘承军拉美所

里卡多·拉戈斯总统,21世纪第一位智利总统,将以各个领域里的成就于2006年3月结束其任期.任职期间,他引导国家沿着具有深远意义的战略规划前进,使智利人民能够满怀信心地放眼21世纪的航程.

关键词：智利全球化经济自由贸易协定拉戈斯

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