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| 1 | Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual显示文摘Osteoblasts,which are the bone-forming cells,operate in a hypoxic environment.The transcription factors hypoxia-inducible factor-1α(HIF1)and HIF2 are key mediators of the cellular response to hypoxia.Both are expressed in osteoblasts.HIF1 is known to be a positive regulator of bone formation.Conversely,the role of HIF2 in the control osteoblast biology is still poorly understood.In this study,we used mouse genetics to demonstrate that HIF2 is an inhibitor of osteoblastogenesis and bone mass accrual.Moreover,we provided evidence that HIF2 impairs osteoblast differentiation at least in part,by upregulating the transcription factor Sox9.Our findings constitute a paradigm shift,as activation of the hypoxia-signaling pathway has traditionally been associated with increased bone formation through HIF1.Inhibiting HIF2 could thus represent a therapeutic approach for the treatment of the low bone mass observed in chronic diseases,osteoporosis,or aging. | Christophe Merceron Kavitha Ranganathan Elizabeth Wang Zachary Tata Shreya Makkapati Mohd Parvez Khan Laura Mangiavini Angela Qing Yao Laura Castellini Benjamin Levi Amato J.Giaccia Ernestina Schipani | 2019 | Bone Research2019，7，1： | 7 |
| 2 | 中年成人平均动脉压的体位改变与动脉硬度的关系:Framingham心脏研究显示文摘Torjesen A, Cooper LL, Rong J, Larson MG, Hamburg NM, Levy D, Benjamin EJ, Vasan RS, Mitchell GF. Relations of arterial stiffness with postural change in mean arterial pressure in middle-aged adults:the Framingham heart study. Hyperten- sion,2017,69(4) :685-690.站立位血压稳定调节受损可导致不良结果,包括跌倒、晕厥和定向障碍。平均动脉压(meanarterialpressure,MAP)通常在站立位时增加,然而,站立位MAP增加不足或减少可能导致脑灌注减少。已有研究报道,在动脉硬度增加的老年人中存在体位性低血压,年轻至中年人MAP的体位性改变与动脉硬度的相关性尚未阐明。该研究分析了Framingham心脏研究第3代队列中的受试者3205人(女性1693人,占53%)的直立性血压反应和全面血液动力学数据。 | Torjesen A Cooper LL Rong J Larson MG Hamburg NM Levy D Benjamin EJ Vasan RS Mitchell GF 刘莉 叶鹏 | 2017 | 中华高血压杂志2017，25，3： | 5 |
| 3 | Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification显示文摘Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision may provide palliation,the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone.Based on these clinical observations,we set out to examine the role of vascular signaling in HO.Vascular endothelial growth factor A(VEGFA)has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis.Our findings,using a validated mouse model of HO,demonstrate that HO lesions are highly vascular,and that VEGFA is critical to ectopic bone formation,despite lacking a contribution of endothelial cells within the developing anlagen. | Charles Hwang Simone Marini Amanda KHuber David MStepien Michael Sorkin Shawn Loder Chase APagani John Li Noelle DVisser Kaetlin Vasquez Mohamed AGarada Shuli Li Jiajia Xu Ching-Yun Hsu Paul BYu Aaron WJames Yuji Mishina Shailesh Agarwal Jun Li Benjamin Levi | 2019 | Bone Research2019，7，4： | 4 |
| 4 | 一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。 | Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) | 2009 | 世界临床医学2009，，9： | 2 |
| 5 | Modeling the role of public health education in Ebola virus disease outbreaks in Sudan显示文摘Public involvement in Ebola Virus Disease(EVD)prevention efforts is key to reducing disease outbreaks.Targeted education through practical health information to particular groups and sub-populations is crucial to controlling the disease.In this paper,we study the dynamics of Ebola virus disease in the presence of public health education with the aim of assessing the role of behavior change induced by health education to the dynamics of an outbreak.The power of behavior change is evident in two outbreaks of EVD that took place in Sudan only 3 years apart.The first occurrence was the first documented outbreak of EVD and produced a significant number of infections.The second outbreak produced far fewer cases,presumably because the population in the region learned from the first outbreak.We derive a system of ordinary differential equations to model these two contrasting behaviors.Since the population in Sudan learned from the first outbreak of EVD and changed their behavior prior to the second outbreak,we use data from these two instances of EVD to estimate parameters relevant to two contrasting behaviors.We then simulate a future outbreak of EVD in Sudan using our model that contains two susceptible populations,one being more informed about EVD.Our finding show how a more educated population results in fewer cases of EVD and highlights the importance of ongoing public health education. | Benjamin Levy Christina Edholm Orou Gaoue Roselyn Kaondera-Shava Moatlhodi Kgosimore Suzanne Lenhart Benjamin Lephodisa Edward Lungu Theresia Marijani Farai Nyabadza | 2017 | Infectious Disease Modelling2017，2，3： | 2 |
| 6 | Impact of Atrial Fibrillation on the Risk of Death: The Framingham Heart Study显示文摘 | Emelia J. Benjamin Philip A. Wolf Ralph B. D’Agostino Halit Silbershatz William B. Kannel Daniel Levy | 1998 | Circulation1998，，10： | 2 |
| 7 | Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair显示文摘Macrophage plasticity is critical for normal tissue repair following injury.In pathologic states such as diabetes,macrophage plasticity is impaired,and macrophages remain in a persistent proinflammatory state;however,the reasons for this are unknown.Here,using single-cell RNA sequencing of human diabetic wounds,we identified increased JMJD3 in diabetic wound macrophages,resulting in increased inflammatory gene expression.Mechanistically,we report that in wound healing,JMJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 signaling.However,in the diabetic state,we found that IL-6,a cytokine increased in diabetic wound tissue at later time points post-injury,regulates JMJD3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JMJD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 mechanism.Interestingly,RNA sequencing of wound macrophages isolated from mice with JMJD3-deficient myeloid cells(Jmjd3f/fLyz2Cre+)identified that the STING gene(Tmem173)is regulated by JMJD3 in wound macrophages.STING limits inflammatory cytokine production by wound macrophages during healing.However,in diabetic mice,its role changes to limit wound repair and enhance inflammation.This finding is important since STING is associated with chronic inflammation,and we found STING to be elevated in human and murine diabetic wound macrophages at late time points.Finally,we demonstrate that macrophage-specific,nanoparticle inhibition of JMJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and STING.Taken together,this work highlights the central role of JMJD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds. | Christopher O.Audu William J.Melvin Amrita D.Joshi Sonya J.Wolf Jadie Y.Moon Frank M.Davis Emily C.Barrett Kevin D.Mangum Hongping Deng Xianying Xing Rachel Wasikowski Lam C.Tsoi Sriganesh B.Sharma Tyler M.Bauer James Shadiow Matthew A.Corriere Andrea TObi Steven LKunkel Benjamin Levi Bethany BMoore Johann EGudjonsson Andrew MSmith Katherine A.Gallagher | 2022 | Cellular & Molecular Immunology2022，19，11： | 2 |
| 8 | Changes in Arterial Stiffness and Wave Reflection With Advancing Age in Healthy Men and Women: The Framingham Heart Study显示文摘 | Gary F. Mitchell Helen Parise Emelia J. Benjamin Martin G. Larson Michelle J. Keyes Joseph A. Vita Ramachandran S. Vasan Daniel Levy | 2004 | Hypertension: Journal of the American Heart Association2004，，6： | 2 |
| 9 | Independent risk factors for atrialfibrillation in a populationg-hased cohort: the Framingham heart study显示文摘 | Benjamin E J Levy D Vaziri S M | 1994 | JAMA1994，271，11： | 1 |
| 10 | Prevalence,Clinical features and Prognosis of Diastolic Heart Failure:an Epidemiologic Perspective显示文摘 | Vasan R S Benjamin E J Levy D | 1995 | J Am Coll Cardiol1995，26，7： | 1 |
| 11 | Why is left ventricular hypertrophy so predictive of morbidity and mortality 显示文摘 | Benjamin E J Levy D | 1999 | Am J Mqed Sci1999，317，： | 1 |
| 12 | Independent risk factors for atrial fibrillation in a population - based cohort: Framingham Heart Study 显示文摘 | Benjamin EJ Levy D Vazifi SM | 1994 | JAMA1994，271，11： | 1 |
| 13 | Independent risk factors for atrial fibrillation in a population-based cohort:The framingham heart study显示文摘 | Benjamin EJ Levy D Vaziri SM | 1994 | JAMA1994，271，： | 1 |
| 14 | Disclosing Medical Errors to Patients: Attitudes and Practices of Physicians and Trainees显示文摘 | Lauris C. Kaldjian Elizabeth W. Jones Barry J. Wu Valerie L. Forman-Hoffman Benjamin H. Levi Gary E. Rosenthal | 2007 | Journal of General Internal Medicine2007，，7： | 1 |
| 15 | The epidemiology of ' asymp- tomatic' left ventricular systolic dysfunction: implications for screening显示文摘 | Wang TJ Levy D Benjamin E J | 2003 | Ann Intern Med2003，138，11： | 1 |
| 16 | The Framingham Heart Study显示文摘 | Benjamin EJ Levy D Vaziri SM Independent riskfactors for atrial fibrillation in a population-based cohort | 1994 | JAMA1994，271，11： | 1 |
| 17 | 可用于临床的脂肪组织基础知识概述显示文摘脂肪组织中含有干细胞,这一认识促使我们进一步探索在更广泛的临床状况下利用脂肪和脂肪来源干细胞的可能性。关于脂肪来源干细胞的获取、分离以及分离的脂肪来源干细胞的分化特性的新知识已带来新的研究,这些新研究的研究方向是新的组织工程构建,以及脂肪来源干细胞转化为诱发的多能干细胞。临床上,脂肪移植物和脂肪来源干细胞在美国及全世界范围内的使用急剧增加,同时,以脂肪来源干细胞为基础的治疗方法的安全性和有效性带来的问题也随之增多。当前,FDA还未批准分离的脂肪来源干细胞用于任何临床领域。 | Spencer A. Brown Benjamin Levi Charlotte Lequex Victor W. Wong All Mojallal Michael T. Longaker 魏峰(译) 高景恒(译) 张晨(译) | 2011 | 中国美容整形外科杂志2011，22，7： | 1 |
| 18 | Independent risk factors for atrial fibrillation in a population based cohort (the Framingham Heart Study) 显示文摘 | Benjamin EJ Levy D Vaziri SM | 1994 | JAMA1994，271，11： | 1 |
| 19 | Independent risk factors for atrial fibrillation in a population-based cohort:the framingham heart study显示文摘 | Benjamin EJ Levy D Vaziri SM | | 0，，11： | 1 |
| 20 | Determinants of Doppler indexes of left ventricular diastolic function in normal subjects(the Framingham Heart Study)显示文摘 | Benjamin EJ Levy D Anderson KM | 1992 | Am J Cardiol1992，70，4： | 1 |
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