tbuckley/cabot-search huggingface dataset:
Mediterranean Diet and Incidence of Advanced Age-Related Macular Degeneration
Authors: Bénédicte M.J. Merle, Johanna M. Colijn, Audrey Cougnard-Grégoire, Alexandra P.M. de Koning-Backus, Marie-Noëlle Delyfer, Jessica C. Kiefte-de Jong, Magda Meester-Smoor, Catherine Féart, Timo Verzijden, Cécilia Samieri, Oscar H. Franco, Jean-François Korobelnik, Caroline C.W. Klaver, Cécile Delcourt, Soufiane Ajana, Blanca Arango-Gonzalez, Angela Armento, Verena Arndt, Vaibhav Bhatia, Shomi S. Bhattacharya, Marc Biarnés, Anna Borrell, Sebastian Bühren, Sofia M. Calado, Johanna M. Colijn, Audrey Cougnard-Grégoire, Sascha Dammeier, Eiko K. de Jong, Berta De la Cerda, Cécile Delcourt, Anneke I. den Hollander, Francisco J. Diaz-Corrales, Sigrid Diether, Eszter Emri, Tanja Endermann, Lucia L. Ferraro, Míriam Garcia, Thomas J. Heesterbeek, Sabina Honisch, Carel B. Hoyng, Eveline Kersten, Ellen Kilger, Caroline C.W. Klaver, Hanno Langen, Imre Lengyel, Phil Luthert, Cyrille Maugeais, Magda Meester-Smoor, Bénédicte M.J. Merle, Jordi Monés, Everson Nogoceke, Tunde Peto, Frances M. Pool, Eduardo Rodríguez, Marius Ueffing, Karl U. Ulrich Bartz-Schmidt, Elisabeth M. van Leeuwen, Timo Verzijden, Markus Zumbansen, Vassil Vasiliev
Journal: Ophthalmology (2018)
Abstract 536: Targeting PRPK and TOPK for skin cancer prevention and therapy
Authors: Eunmiri Roh, Mee-Hyun Lee, Tatyana A. Zykova, Feng Zhu, Hong-Gyum Kim, Ki Beom Bae, Yong Yeon Cho, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2018)

Abstract Solar ultraviolet (sUV) irradiation is a major environmental carcinogen that can cause inflammation and skin cancer. The costs and morbidity associated with skin cancer are increasing, thus identifying molecules that can help prevent skin carcinogenesis is important. In this study, we identified the p53-related protein kinase (PRPK) as a novel oncogenic protein that is phosphorylated by the T-LAK cell-originated protein kinase (TOPK). Knockdown of TOPK inhibited PRPK phosphorylation and conferred resistance to solar simulated light (SSL)-induced skin carcinogenesis in mouse models. In the clinic, acute SSL irradiation significantly increased epidermal thickness as well as total protein and phosphorylation levels of TOPK and PRPK in human skin tissues. We identified two PRPK inhibitors, FDA-approved rocuronium bromide (Zemuron®) or betamethasone 17-valerate (Betaderm®) that could attenuate TOPK-dependent PRPK signaling. Importantly, topical application of either rocuronium or betamethasone attenuated SSL-induced epidermal hyperplasia, neovascularization and cutaneous squamous cell carcinoma (cSCC) development in SKH1 (Crl: SKH1-Hrhr) hairless mice by inhibiting PRPK activation, and also reduced expression of the proliferation and oncogenesis markers COX-2, cyclin D1 and MMP-9. This study is the first to demonstrate that PRPK- targeted therapy could be useful against sUV-induced cSCC. Citation Format: Eunmiri Roh, Mee-Hyun Lee, Tatyana A. Zykova, Feng Zhu, Hong-Gyum Kim, Ki Beom Bae, Yong Yeon Cho, Ann M. Bode, Zigang Dong. Targeting PRPK and TOPK for skin cancer prevention and therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 536.
Long-Term Outcome of Aortic Dissection With Patent False Lumen
Authors: ArturEvangelista, ArmandoSalas, AidaRibera, IgnacioFerreira-González, HugCuellar, VictorPineda, TeresaGonzález-Alujas, BartBijnens, GaietàPermanyer-Miralda, DavidGarcia-Dorado
Journal: Circulation (2012)

Background—Patent false lumen in aortic dissection has been associated with poor prognosis. We aimed to assess the natural evolution of this condition and predictive factors. Methods and Results—One hundred eighty-four consecutive patients, 108 surgically treated type A and 76 medically treated type B, were discharged after an acute aortic dissection with patent false lumen. Transesophageal echocardiography was performed before discharge, and computed tomography was performed at 3 months and yearly thereafter. Median follow-up was 6.42 years (quartile 1 to quartile 3: 3.31–10.49). Forty-nine patients died during follow-up (22 type A, 27 type B), 31 suddenly. Surgical or endovascular treatment was indicated in 10 type A and 25 type B cases. Survival free from sudden death and surgical-endovascular treatment was 0.90, 0.81, and 0.46 (95% CI, 0.36–0.55) at 3, 5, and 10 years, respectively. Multivariate analysis identified baseline maximum descending aorta diameter (hazard ratio [HR]: 1.32 [1.10–1.59]; P=0.00...
P53 protein overexpression in de novo acute myeloid leukemia patients with normal diploid karyotype correlates with <i>FLT3</i> internal tandem duplication and worse relapse‐free survival
Authors: Rita Assi, Hatice D. Gur, Sanam Loghavi, Sergej N. Konoplev, Marina Konopleva, Naval Daver, Mehrnoosh Tashakori, Tapan Kadia, Mark Routbort, Alireza Salem, Rashmi Kanagal‐Shamanna, Andres Quesada, Elias J. Jabbour, Steven M. Kornblau, L. Jeffrey Medeiros, Hagop Kantarjian, Joseph D. Khoury
Journal: American Journal of Hematology (2018)

Abstract Although ~50% of acute myeloid leukemia (AML) patients have a normal diploid karyotype by conventional cytogenetics at diagnosis, this patient subset has a variable disease course and outcome. Aberrant overexpression of the p53 protein is usually associated with TP53 alterations and a complex karyotype, but the prevalence and impact of p53 overexpression in AML with diploid cytogenetics is unknown. We examined 100 newly diagnosed AML patients to evaluate the impact of p53 expression status quantified in bone marrow core biopsy samples using immunohistochemistry and computer‐assisted image analysis. A total of 24 patients had p53 overexpression defined as 3+ staining intensity in ≥5% of cells; this finding correlated with lower platelet counts ( P = .002), absence of CD34 expression in blasts ( P = .009), higher bone marrow blast counts ( P = .04), and a higher frequency of FLT3 internal tandem duplication ( P = .007). Overexpression of p53 independently predicted for shorter leukemia‐free survival in patients who underwent allogeneic stem cell transplantation by univariate ( P = .021) and multivariate analyses ( P = .004). There was no correlation between MDM2 and p53 protein expression in this cohort. We conclude that p53 expression evaluated by immunohistochemistry in bone marrow biopsy specimens at the time of AML diagnosis may indicate distinct clinical characteristics in patients with normal diploid cytogenetics and is a potentially valuable tool that can enhance risk‐stratification.
Abstract 1739: Tumor extracellular vesicles are required for tumor-associated macrophage programming
Authors: Daniel C. Rabe, Jiyoung Lee, Felicia Rustandy, Marsha R. Rosner
Journal: Cancer Research (2018)

Abstract Triple-negative breast cancers (TNBC) are highly infiltrated by tumor-associated macrophages (TAMs) that promote tumor growth, survival, metastasis and therapeutic resistance. Although cytokines such as CCL5 have been implicated in TAM recruitment to TNBC tumors, the mechanism by which tumor cells educate TAMs is not understood. Here we show that tumor extracellular vesicles (EVs) are both necessary and sufficient for programming TAMs toward a pro-metastatic phenotype. The mechanism involves CCL5 regulation of tumor EVs, which activate TLR2 and TLR3, leading to secretion of a common set of cytokines that further stimulate tumor cell invasion and metastasis as well as alter the tumor microenvironment. Cytokine expression is significantly correlated to CCL5 expression and up-regulated in TNBC patient tumors. These results demonstrate for the first time that tumor EVs are key mediators of TAM education, phenocopy the pro-metastatic and drug resistant state of the tumors to TAMs, and illustrate the potential clinical relevance of these findings to TNBC patients. Citation Format: Daniel C. Rabe, Jiyoung Lee, Felicia Rustandy, Marsha R. Rosner. Tumor extracellular vesicles are required for tumor-associated macrophage programming [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1739.
Abstract 4506: Loss of SIRT1 alters the secretome of breast cancer cells by impairing lysosomal integrity
Authors: Arash Latifkar, Lu Ling, Xiaoyu Zhang, Claudia Fischbach, Hening Lin, Richard Cerione, Marc Antonyak
Journal: Cancer Research (2018)

Abstract Sirtuin 1 (SIRT1) is an NAD-dependent deacetylase implicated in processes ranging from lifespan promotion to tumor suppression. To probe its role as a tumor suppressor, we knocked down SIRT1 in breast cancer cells. This resulted in the decreased expression of one of the subunits comprising the multi-subunit vacuolar-type H+ ATPase (V-ATPase), which is responsible for the acidification of lysosomes and thus essential for proper lysosomal protein degradation. The impairment in lysosomal function led to a marked reduction in the number of multivesicular bodies (MVBs) targeted for lysosomal degradation, and a corresponding increase in MVBs fusing with the plasma membrane to release their content. Specifically, SIRT1 reduction increased the secretion of exosomes containing unique cargo and the release of soluble hydrolases that typically reside in the lysosome, producing a breast cancer cell secretome that strongly promotes cell invasion and survival. Citation Format: Arash Latifkar, Lu Ling, Xiaoyu Zhang, Claudia Fischbach, Hening Lin, Richard Cerione, Marc Antonyak. Loss of SIRT1 alters the secretome of breast cancer cells by impairing lysosomal integrity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4506.
The Collaterals of the Coronary Arteries in Normal and Pathologic Hearts
Authors: Giorgiobaroldi, Orestemantero, Giuseppescomazzoni
Journal: Circulation Research (1956)

The collateral vessels of normal and pathologic hearts were studied by making plastic casts of the coronary vessels. The normal heart possesses conspicuous coronary anastomoses. The localization, the development and to a certain extent, the incidence was studied. The maximum increase in collateral vessels was observed in cases of coronary narrowing; a less pronounced increase was found in conditions of chronic hypoxemia.
Biased Inference of Selection Due to GC-Biased Gene Conversion and the Rate of Protein Evolution in Flycatchers When Accounting for It
Authors: Paulina Bolívar, Carina F Mugal, Matteo Rossi, Alexander Nater, Mi Wang, Ludovic Dutoit, Hans Ellegren
Journal: Molecular Biology and Evolution (2018)

The rate of recombination impacts on rates of protein evolution for at least two reasons: it affects the efficacy of selection due to linkage and influences sequence evolution through the process of GC-biased gene conversion (gBGC). We studied how recombination, via gBGC, affects inferences of selection in gene sequences using comparative genomic and population genomic data from the collared flycatcher (Ficedula albicollis). We separately analyzed different mutation categories ("strong"-to-"weak," "weak-to-strong," and GC-conservative changes) and found that gBGC impacts on the distribution of fitness effects of new mutations, and leads to that the rate of adaptive evolution and the proportion of adaptive mutations among nonsynonymous substitutions are underestimated by 22-33%. It also biases inferences of demographic history based on the site frequency spectrum. In light of this impact, we suggest that inferences of selection (and demography) in lineages with pronounced gBGC should be based on GC-conservative changes only. Doing so, we estimate that 10% of nonsynonymous mutations are effectively neutral and that 27% of nonsynonymous substitutions have been fixed by positive selection in the flycatcher lineage. We also find that gene expression level, sex-bias in expression, and the number of protein-protein interactions, but not Hill-Robertson interference (HRI), are strong determinants of selective constraint and rate of adaptation of collared flycatcher genes. This study therefore illustrates the importance of disentangling the effects of different evolutionary forces and genetic factors in interpretation of sequence data, and from that infer the role of natural selection in DNA sequence evolution.
Abstract 17383: Total Left Ventricular Unloading with Impella® during Ischemia Reperfusion Minimizes Infarct Size, Preserves Left Ventricular Function and Prevents Chronic Heart Failure
Authors: TakamoroKakaino, KeitaSaku, TakahiroArimura, TakuyaAkashi, AkikoNishizaki, YasuhiroOga, MasatakaIkeda, TakuyaKishi, TomomiIde, KenjiSunagawa
Journal: Circulation (2014)

Background: Despite marked advances of revascularization, acute myocardial infarction (MI) remains a major cause of chronic heart failure (CHF). Since excessive oxygen demand relative to supply is the fundamental mechanism of ischemia, we previously demonstrated, using a conventional left ventricular assist device (VAD), that total left ventricular (LV) unloading markedly reduced the MI size in ischemia reperfusion (IR) model through minimizing the myocardial oxygen consumption in acute experiment. The purpose of this investigation was to examine if the transvascular VAD, Impella®, could totally unload LV during IR and preserve LV function in chronic phase. Methods: We allocated 15 dogs into 3 groups, Sham (n=4), IR (n=6) and IR+Impella® (n=5). In IR and IR+Impella®, we ligated the left anterior descending artery for 180min through a left thoracotomy and then reperfused. In IR+Impella®, we introduced Impella® through the left subclavian artery from 60 min after the beginning of ischemia to 90 min after re...
Multiple Abnormalities in Glucose and Energy Metabolism and Coordinated Changes in Levels of Adiponectin, Cytokines, and Adhesion Molecules in Subjects With Metabolic Syndrome
Authors: UrpuSalmenniemi, EijaRuotsalainen, JussiPihlajamäki, IlkkaVauhkonen, SakariKainulainen, KariPunnonen, EskoVanninen, MarkkuLaakso
Journal: Circulation (2004)

Background— Detailed metabolic defects in glucose and energy metabolism and abnormalities in a variety of cardiovascular risk factors are largely unknown in subjects with the metabolic syndrome. Methods and Results— We characterized the metabolic syndrome in 119 nondiabetic offspring of diabetic probands. Cardiovascular risk factors, including cytokines and adhesion molecules, were measured. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and indirect calorimetry; intra-abdominal fat and subcutaneous fat were assessed by CT; and maximal oxygen consumption was measured with a bicycle ergometer test. By applying factor analysis, we identified a single factor, the metabolic syndrome factor, from the following variables: 2-hour glucose, fasting insulin, body mass index, waist, HDL cholesterol, triglycerides, and mean blood pressure. Subjects with the highest factor score were defined as having the metabolic syndrome. During hyperinsulinemia, the highest factor score was associated wi...
Abstract IA04: Mitotic progression connects DNA damage to activation of antitumor immune responses
Authors: Roger A. Greenberg
Journal: Clinical Cancer Research (2018)

Abstract Inflammatory gene expression following genotoxic cancer therapy is well documented, yet the events underlying its induction remain poorly understood. Inflammatory cytokines modify the tumor microenvironment by recruiting immune cells and are critical for both local and systemic (abscopal) tumor responses to radiotherapy. An enigmatic feature of this phenomenon is its delayed onset (days), in contrast to the acute DNA damage responses that occur in minutes to hours. Such dichotomous kinetics implicate additional rate limiting steps that are essential for DNA-damage induced inflammation. Here, we show that cell cycle progression through mitosis following DNA double-strand breaks (DSBs) leads to the formation of micronuclei, which precede activation of inflammatory signaling and are a repository for the pattern recognition receptor cGAS. Inhibiting progression through mitosis or loss of pattern recognition by cGAS-STING impaired interferon signaling and prevented the regression of abscopal tumors in the context of ionizing radiation and immune checkpoint blockade in vivo. These findings implicate temporal modulation of the cell cycle as an important consideration in the context of therapeutic strategies that combine genotoxic agents with immune checkpoint blockade. Citation Format: Roger A. Greenberg. Mitotic progression connects DNA damage to activation of antitumor immune responses. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA04.
Protease Nexin-1 Interacts With Thrombomodulin and Modulates Its Anticoagulant Effect
Authors: Marie-ChristineBouton, LaurenceVenisse, BenjaminRichard, CécilePouzet, VéroniqueArocas, MartineJandrot-Perrus
Journal: Circulation Research (2007)

The endothelial cell membrane glycoprotein thrombomodulin (TM) plays a critical role in the regulation of coagulation. TM is an essential cofactor in protein C activation by thrombin, and a direct inhibitor of thrombin-induced platelet activation and fibrinogen clotting. Protease nexin-1 (PN-1) is a serpin synthesized and secreted by a variety of cells including endothelial cells. PN-1 bound to the cell surface through interactions with glycosaminoglycans, is an efficient inhibitor of thrombin and controls thrombin-induced cell responses. An investigation of the interaction of PN-1 with TM using purified proteins and cultured human aortic endothelial cells was performed. Purified PN-1 was observed to bind to purified TM in a concentration-dependent manner. Double immunofluorescence studies indicated that PN-1 and TM were colocalized at the endothelial cell surface from which they were coprecipitated. Pretreatment of the cells with chondroitinase ABC greatly decreased the amount of the PN-1 associated to T...
Generation of Anti-Hirudin Antibodies in Heparin-Induced Thrombocytopenic Patients Treated With R-Hirudin
Authors: XuehongSong, GünterHuhle, LianchunWang, UrsulaHoffmann, JobHarenberg
Journal: Circulation (1999)

Background—Hirudin is a small protein with strong thrombin inhibition that may be antigenic. The generation and disappearance of anti-hirudin antibodies were investigated in patients with heparin-induced thrombocytopenia who were treated with recombinant hirudin (r-hirudin) for ≥5 days. Methods and Results—The IgA, IgE, IgG, and IgM isotypes of anti-hirudin antibodies were determined by ELISA before and after the start of r-hirudin therapy. A total of 56% of patients (13 of 23) developed ≥1 antibody isotype during therapy. No IgE antibodies were generated. IgA, IgG, and IgM antibodies were detected in 30% (7 of 23), 52% (12 of 23), and 17% (4 of 23) of patients, respectively. Four patients generated only IgG, 2 patients developed either IgM or IgG and IgM, 5 patients IgG and IgA, and 2 patients IgG, IgM, and IgA antibodies. IgM antibodies disappeared within 8 days of the cessation of r-hirudin. IgA and IgG antibodies disappeared within 1 year in all but 1 patient. Binding of purified IgG to r-hirudin in I...
Bundle-Branch Block in a General Male Population
Authors: PeterEriksson, Per-OlofHansson, HenryEriksson, MikaelDellborg
Journal: Circulation (1998)

Background—Interest in bundle-branch block has focused primarily on its role as a predictor of mortality and coexisting cardiovascular diseases. Previous studies of prevalence, correlation to cardiovascular disease, and mortality have produced conflicting results. Methods and Results—We studied a random-sampled population of 855 men who were 50 years old in 1963 and followed them up for 30 years with repeated examinations. Men who developed bundle-branch block were studied with regard to cumulative incidence, relationship with cardiovascular disease/risk factors, and survival. The prevalence of bundle-branch block increases from 1% at age 50 years to 17% at age 80 years, resulting in a cumulative incidence of 18%. No significant relationship with ischemic heart disease or mortality was found. Men who would develop bundle-branch block had a bigger heart volume at age 50 years and developed diabetes mellitus and congestive heart disease during follow-up more often than control subjects. Conclusions—Bundle-b...
Abstract 5654: Fully automated tissue classification by imaging mass spectrometry, moving towards a hundred samples a day
Authors: Emrys A. Jones, Richard Chapman, Emmy Hoyes, Lukasz Migas, Fiona Henderson, Steven Pringle, James Langridge, Adam McMahon
Journal: Cancer Research (2018)

Abstract Desorption electrospray ionisation mass spectrometry is a surface analysis technique that can rapidly analyse the lipid and metabolite composition of a tissue section. By moving the tissue under the analysis probe, a chemical map of the sample can be generated in a matter of minutes. As has been shown in the literature 1,2, each tissue type or disease state has its own characteristic molecular fingerprint, therefore, using histologically annotated databases of these molecular profiles these maps can be classified using machine learning approaches. With the increased rate of analysis made possible by recent technological advances, the timeframes of a single sample makes automation an attractive proposition. With a slide loading system and a range of software solutions, up to two hundred slides can be queued for analysis. Each will be loaded in turn onto the analysis stage, the location of the tissue section determined with optically directed object detection algorithms, and the analysis started. During the analysis the information from each pixel is projected into the classification model and colour coded by designated tissue type. Applications of this approach that have been demonstrated from a research perspective are the analysis of serial sections of drug dosed spheroids and tumour xenografts for studying the chemical heterogeneity of these systems in three dimensions, in the latter case allowing comparison with other imaging modalities such as MRI and PET. Initial studies will also be presented which will investigate the use of the system for the classification of large cohorts of unknown tissues with subsequent comparison to histological classification by conventional methodologies.l 1. Calligaris, D.Caragacianu, D.Liu, et al; PNAS, 2014, 111, 15185-15189 2. Guenther, S., Muirhead, L.J., et al, Cancer Res, 2015, 75, 1828-1837 Citation Format: Emrys A. Jones, Richard Chapman, Emmy Hoyes, Lukasz Migas, Fiona Henderson, Steven Pringle, James Langridge, Adam McMahon. Fully automated tissue classification by imaging mass spectrometry, moving towards a hundred samples a day [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5654.
Abstract 19407: The Utility of IVUS-Guided PCI Especially in Terms of Mortality in a Community Based Data: In Acute Coronary Syndrome From Japanese Multicenter (KICS) Registry
Authors: Takayoshi Yamashita, Kenji Sakamoto, Ryota Sato, Suguru Nagamatsu, Noriaki Tabata, Koichi Kaikita, Kenichi Tsujita
Journal: Circulation (2017)

Introduction: Although intravascular ultrasound (IVUS) has been widely used in clinical settings. Lately, favorable results of IVUS-guided percutaneous coronary intervention (PCI), compared with An...