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[PMID]: 25438849
[Au] Autor:Radhakrishnan K; Haworth KJ; Peng T; McPherson DD; Holland CK
[Ad] Address:Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA. Electronic address: radhakki@mail.uc.edu....
[Ti] Title:Loss of echogenicity and onset of cavitation from echogenic liposomes: pulse repetition frequency independence.
[So] Source:Ultrasound Med Biol;41(1):208-21, 2015 Jan.
[Is] ISSN:1879-291X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Echogenic liposomes (ELIP) are being developed for the early detection and treatment of atherosclerotic lesions. An 80% loss of echogenicity of ELIP has been found to be concomitant with the onset of stable and inertial cavitation. The ultrasound pressure amplitude at which this occurs is weakly dependent on pulse duration. It has been reported that the rapid fragmentation threshold of ELIP (based on changes in echogenicity) is dependent on the insonation pulse repetition frequency (PRF). The study described here evaluates the relationship between loss of echogenicity and cavitation emissions from ELIP insonified by duplex Doppler pulses at four PRFs (1.25, 2.5, 5 and 8.33 kHz). Loss of echogenicity was evaluated on B-mode images of ELIP. Cavitation emissions from ELIP were recorded passively on a focused single-element transducer and a linear array. Emissions recorded by the linear array were beamformed, and the spatial widths of stable and inertial cavitation emissions were compared with the calibrated azimuthal beamwidth of the Doppler pulse exceeding the stable and inertial cavitation thresholds. The inertial cavitation thresholds had a very weak dependence on PRF, and stable cavitation thresholds were independent of PRF. The spatial widths of the cavitation emissions recorded by the passive cavitation imaging system agreed with the calibrated Doppler beamwidths. The results also indicate that 64%-79% loss of echogenicity can be used to classify the presence or absence of cavitation emissions with greater than 80% accuracy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review

  2 / 1867450 MEDLINE  
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[PMID]: 25438846
[Au] Autor:Bader KB; Gruber MJ; Holland CK
[Ad] Address:Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA. Electronic address: kenneth.bader@uc.edu.
[Ti] Title:Shaken and stirred: mechanisms of ultrasound-enhanced thrombolysis.
[So] Source:Ultrasound Med Biol;41(1):187-96, 2015 Jan.
[Is] ISSN:1879-291X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The use of ultrasound and microbubbles as an effective adjuvant to thrombolytics has been reported in vitro, ex vivo and in vivo. However, the specific mechanisms underlying ultrasound-enhanced thrombolysis have yet to be elucidated. We present visual observations illustrating two mechanisms of ultrasound-enhanced thrombolysis: acoustic cavitation and radiation force. An in vitro flow model was developed to observe human whole blood clots exposed to human fresh-frozen plasma, recombinant tissue-type plasminogen activator (0, 0.32, 1.58 or 3.15 µg/mL) and the ultrasound contrast agent Definity (2 µL/mL). Intermittent, continuous-wave ultrasound (120 kHz, 0.44 MPa peak-to-peak pressure) was used to insonify the perfusate. Ultraharmonic emissions indicative of stable cavitation were monitored with a passive cavitation detector. The clot was observed with an inverted microscope, and images were recorded with a charge-coupled device camera. The images were post-processed to determine the time-dependent clot diameter and root-mean-square velocity of the clot position. Clot lysis occurred preferentially surrounding large, resonant-sized bubbles undergoing stable oscillations. Ultraharmonic emissions from stable cavitation were found to correlate with the lytic rate. Clots were observed to translate synchronously with the initiation and cessation of the ultrasound exposure. The root-mean-square velocity of the clot correlated with the lytic rate. These data provide visual documentation of stable cavitation activity and radiation force during sub-megahertz sonothrombolysis. The observations of this study suggest that the process of clot lysis is complex, and both stable cavitation and radiation force are mechanistically responsible for this beneficial bio-effect in this in vitro model.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 1867450 MEDLINE  
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[PMID]: 25308943
[Au] Autor:Wang S; Mauldin FW; Klibanov AL; Hossack JA
[Ad] Address:Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA....
[Ti] Title:Ultrasound-based measurement of molecular marker concentration in large blood vessels: a feasibility study.
[So] Source:Ultrasound Med Biol;41(1):222-34, 2015 Jan.
[Is] ISSN:1879-291X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Ultrasound molecular imaging has demonstrated efficacy in pre-clinical studies for cancer and cardiovascular inflammation. However, these techniques often require lengthy protocols because of waiting periods or additional control microbubble injections. Moreover, they are not capable of quantifying molecular marker concentration in human tissue environments that exhibit variable attenuation and propagation path lengths. Our group recently investigated a modulated acoustic radiation force-based imaging sequence, which was found to detect targeted adhesion independent of control measurements. In the present study, this sequence was tested against various experimental parameters to determine its feasibility for quantitative measurements of molecular marker concentration. Results indicated that measurements obtained from the sequence (residual-to-saturation ratio, Rresid) were independent of acoustic pressure and attenuation (p > 0.13, n = 10) when acoustic pressures were sufficiently low. The Rresid parameter exhibited a linear relationship with measured molecular marker concentration (R(2) > 0.94). Consequently, feasibility was illustrated in vitro, for quantification of molecular marker concentration in large vessels using a modulated acoustic radiation force-based sequence. Moreover, these measurements were independent of absolute acoustic reflection amplitude and used short imaging protocols (3 min) without control measurements.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review

  4 / 1867450 MEDLINE  
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[PMID]: 25419708
[Au] Autor:Byrareddy SN; Kallam B; Arthos J; Cicala C; Nawaz F; Hiatt J; Kersh EN; McNicholl JM; Hanson D; Reimann KA; Brameier M; Walter L; Rogers K; Mayne AE; Dunbar P; Villinger T; Little D; Parslow TG; Santangelo PJ; Villinger F; Fauci AS; Ansari AA
[Ad] Address:Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA....
[Ti] Title:Targeting α4ß7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.
[So] Source:Nat Med;20(12):1397-400, 2014 Dec.
[Is] ISSN:1546-170X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:α4ß7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4ß7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4ß7 reduces mucosal transmission of SIV in macaques.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/nm.3715

  5 / 1867450 MEDLINE  
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[PMID]: 25401693
[Au] Autor:Hashizume R; Andor N; Ihara Y; Lerner R; Gan H; Chen X; Fang D; Huang X; Tom MW; Ngo V; Solomon D; Mueller S; Paris PL; Zhang Z; Petritsch C; Gupta N; Waldman TA; James CD
[Ad] Address:Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA....
[Ti] Title:Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma.
[So] Source:Nat Med;20(12):1394-6, 2014 Dec.
[Is] ISSN:1546-170X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3. Here we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy for treating K27M-expressing brainstem glioma.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/nm.3716

  6 / 1867450 MEDLINE  
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[PMID]: 25401692
[Au] Autor:Gascon E; Lynch K; Ruan H; Almeida S; Verheyden JM; Seeley WW; Dickson DW; Petrucelli L; Sun D; Jiao J; Zhou H; Jakovcevski M; Akbarian S; Yao WD; Gao FB
[Ad] Address:Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA....
[Ti] Title:Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia.
[So] Source:Nat Med;20(12):1444-51, 2014 Dec.
[Is] ISSN:1546-170X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Neurodegenerative diseases, such as frontotemporal dementia (FTD), are often associated with behavioral deficits, but the underlying anatomical and molecular causes remain poorly understood. Here we show that forebrain-specific expression of FTD-associated mutant CHMP2B in mice causes several age-dependent neurodegenerative phenotypes, including social behavioral impairments. The social deficits were accompanied by a change in AMPA receptor (AMPAR) composition, leading to an imbalance between Ca(2+)-permeable and Ca(2+)-impermeable AMPARs. Expression of most AMPAR subunits was regulated by the brain-enriched microRNA miR-124, whose abundance was markedly decreased in the superficial layers of the cerebral cortex of mice expressing the mutant CHMP2B. We found similar changes in miR-124 and AMPAR levels in the frontal cortex and induced pluripotent stem cell-derived neurons from subjects with behavioral variant FTD. Moreover, ectopic miR-124 expression in the medial prefrontal cortex of mutant mice decreased AMPAR levels and partially rescued behavioral deficits. Knockdown of the AMPAR subunit Gria2 also alleviated social impairments. Our results identify a previously undescribed mechanism involving miR-124 and AMPARs in regulating social behavior in FTD and suggest a potential therapeutic avenue.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/nm.3717

  7 / 1867450 MEDLINE  
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[PMID]: 25401691
[Au] Autor:Wang GX; Zhao XY; Meng ZX; Kern M; Dietrich A; Chen Z; Cozacov Z; Zhou D; Okunade AL; Su X; Li S; Blüher M; Lin JD
[Ad] Address:Life Sciences Institute and Department of Cell &Developmental Biology, University of Michigan Medical Center, Ann Arbor, Michigan, USA....
[Ti] Title:The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis.
[So] Source:Nat Med;20(12):1436-43, 2014 Dec.
[Is] ISSN:1546-170X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Brown fat activates uncoupled respiration in response to cold temperature and contributes to systemic metabolic homeostasis. To date, the metabolic action of brown fat has been primarily attributed to its role in fuel oxidation and uncoupling protein 1 (UCP1)-mediated thermogenesis. Whether brown fat engages other tissues through secreted factors remains largely unexplored. Here we show that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family of extracellular ligands, is highly expressed in adipose tissues, enriched in brown fat and markedly increased during brown adipocyte differentiation. Adipose tissue Nrg4 expression was reduced in rodent and human obesity. Gain- and loss-of-function studies in mice demonstrated that Nrg4 protects against diet-induced insulin resistance and hepatic steatosis through attenuating hepatic lipogenic signaling. Mechanistically, Nrg4 activates ErbB3 and ErbB4 signaling in hepatocytes and negatively regulates de novo lipogenesis mediated by LXR and SREBP1c in a cell-autonomous manner. These results establish Nrg4 as a brown fat-enriched endocrine factor with therapeutic potential for the treatment of obesity-associated disorders, including type 2 diabetes and nonalcoholic fatty liver disease (NAFLD).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/nm.3713

  8 / 1867450 MEDLINE  
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[PMID]: 25362254
[Au] Autor:Kikuchi R; Nakamura K; MacLauchlan S; Ngo DT; Shimizu I; Fuster JJ; Katanasaka Y; Yoshida S; Qiu Y; Yamaguchi TP; Matsushita T; Murohara T; Gokce N; Bates DO; Hamburg NM; Walsh K
[Ad] Address:1] Molecular Cardiology and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA. [2] Department of Medical Technique, Nagoya University Hospital, Nagoya, Aichi, Japan....
[Ti] Title:An antiangiogenic isoform of VEGF-A contributes to impaired vascularization in peripheral artery disease.
[So] Source:Nat Med;20(12):1464-71, 2014 Dec.
[Is] ISSN:1546-170X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Peripheral artery disease (PAD) generates tissue ischemia through arterial occlusions and insufficient collateral vessel formation. Vascular insufficiency in PAD occurs despite higher circulating levels of vascular endothelial growth factor A (VEGF-A), a key regulator of angiogenesis. Here we show that clinical PAD is associated with elevated levels of an antiangiogenic VEGF-A splice isoform (VEGF-A165b) and a corresponding reduction in levels of the proangiogenic VEGF-A165a splice isoform. In mice, VEGF-A165b expression was upregulated by conditions associated with impaired limb revascularization, including leptin deficiency, diet-induced obesity, genetic ablation of the secreted frizzled-related protein 5 (Sfrp5) adipokine and transgenic overexpression of Wnt5a in myeloid cells. In a mouse model of PAD, delivery of VEGF-A165b inhibited revascularization of ischemic hind limbs, whereas treatment with an isoform-specific neutralizing antibody reversed impaired revascularization caused by metabolic dysfunction or perturbations in the Wnt5a-Sfrp5 regulatory system. These results indicate that inflammation-driven expression of the antiangiogenic VEGF-A isoform can contribute to impaired collateralization in ischemic cardiovascular disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/nm.3703

  9 / 1867450 MEDLINE  
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[PMID]: 25474588
[Au] Autor:Wang JZ; Zhang Y; Dong L; Li L; Srimani PK; Yu PS
[Ti] Title:G-Bean: an ontology-graph based web tool for biomedical literature retrieval.
[So] Source:BMC Bioinformatics;15 Suppl 12:S1, 2014 Nov 6.
[Is] ISSN:1471-2105
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Currently, most people use NCBI's PubMed to search the MEDLINE database, an important bibliographical information source for life science and biomedical information. However, PubMed has some drawbacks that make it difficult to find relevant publications pertaining to users' individual intentions, especially for non-expert users. To ameliorate the disadvantages of PubMed, we developed G-Bean, a graph based biomedical search engine, to search biomedical articles in MEDLINE database more efficiently. METHODS: G-Bean addresses PubMed's limitations with three innovations: (1) Parallel document index creation: a multithreaded index creation strategy is employed to generate the document index for G-Bean in parallel; (2) Ontology-graph based query expansion: an ontology graph is constructed by merging four major UMLS (Version 2013AA) vocabularies, MeSH, SNOMEDCT, CSP and AOD, to cover all concepts in National Library of Medicine (NLM) database; a Personalized PageRank algorithm is used to compute concept relevance in this ontology graph and the Term Frequency - Inverse Document Frequency (TF-IDF) weighting scheme is used to re-rank the concepts. The top 500 ranked concepts are selected for expanding the initial query to retrieve more accurate and relevant information; (3) Retrieval and re-ranking of documents based on user's search intention: after the user selects any article from the existing search results, G-Bean analyzes user's selections to determine his/her true search intention and then uses more relevant and more specific terms to retrieve additional related articles. The new articles are presented to the user in the order of their relevance to the already selected articles. RESULTS: Performance evaluation with 106 OHSUMED benchmark queries shows that G-Bean returns more relevant results than PubMed does when using these queries to search the MEDLINE database. PubMed could not even return any search result for some OHSUMED queries because it failed to form the appropriate Boolean query statement automatically from the natural language query strings. G-Bean is available at http://bioinformatics.clemson.edu/G-Bean/index.php. CONCLUSIONS: G-Bean addresses PubMed's limitations with ontology-graph based query expansion, automatic document indexing, and user search intention discovery. It shows significant advantages in finding relevant articles from the MEDLINE database to meet the information need of the user.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/1471-2105-15-S12-S1

  10 / 1867450 MEDLINE  
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[PMID]: 25474487
[Au] Autor:Cui L; Poon J; Poon SK; Chen H; Gao J; Kwan P; Fan K; Ling Z
[Ti] Title:An improved independent component analysis model for 3D chromatogram separation and its solution by multi-areas genetic algorithm.
[So] Source:BMC Bioinformatics;15 Suppl 12:S8, 2014 Nov 6.
[Is] ISSN:1471-2105
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: The 3D chromatogram generated by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) has been researched widely in the field of herbal medicine, grape wine, agriculture, petroleum and so on. Currently, most of the methods used for separating a 3D chromatogram need to know the compounds' number in advance, which could be impossible especially when the compounds are complex or white noise exist. New method which extracts compounds from 3D chromatogram directly is needed. METHODS: In this paper, a new separation model named parallel Independent Component Analysis constrained by Reference Curve (pICARC) was proposed to transform the separation problem to a multi-parameter optimization issue. It was not necessary to know the number of compounds in the optimization. In order to find all the solutions, an algorithm named multi-areas Genetic Algorithm (mGA) was proposed, where multiple areas of candidate solutions were constructed according to the fitness and distances among the chromosomes. RESULTS: Simulations and experiments on a real life HPLC-DAD data set were used to demonstrate our method and its effectiveness. Through simulations, it can be seen that our method can separate 3D chromatogram to chromatogram peaks and spectra successfully even when they severely overlapped. It is also shown by the experiments that our method is effective to solve real HPLC-DAD data set. CONCLUSIONS: Our method can separate 3D chromatogram successfully without knowing the compounds' number in advance, which is fast and effective.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/1471-2105-15-S12-S8


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