tbuckley/cabot-search huggingface dataset:
Abstract 20678: A Systematic Review of World-Wide Characteristics and Management of Patients With ST-Segment Elevation Myocardial Infarction
Authors: Yang Zhan, Thao Huynh
Journal: Circulation (2014)

Background: Management of ST elevation myocardial infarction (STEMI) has made tremendous progresses during the last decades. However, it remains uncertain whether all STEMI patients are receiving optimal care and whether variation in care has any impact on their outcomes. We aim to characterize the contemporary global characteristics, managements, and outcomes of STEMI patients. Methods and Results: We searched EMBASE/MedLINE Ovid for observational data of patients with STEMI. We identified 17 studies enrolling 112 772 patients in 20 countries during the last 5 years (2008-2013). The median age ranged from 54 to 66 years with 13%-33% females. Twelve percent to 39% of patients presented in Killip heart failure class 2-4. In-hospital use of aspirin (ASA), P2Y12 inhibitor/thienopyridines, and systemic anticoagulation was 90-99%, 77-97%, and 61-100% respectively. Reperfusion was provided for 63%-97% of patients. Fibrinolysis was used in 0.7%-66% with a door-to-needle (D2N) time of 28-65 minutes; 12%-74% with D2N &lt;30minutes. Primary percutaneous coronary intervention was performed for 17%-97% with a door-to-balloon (D2B) time of 40-125 minutes; 40%-94% had D2B &lt;90 minutes. Emergency cardiac surgery was performed in 0.4%-8% of patients. Discharge prescriptions included ASA, thienopyridines/P2Y12 inhibitors, beta-blockers, and statins in 85%-99%, 77%-97%, 54%-83%, and 64%-95% respectively. In-hospital outcomes included death (2%-10%), recurrent myocardial infarction (0.4%-5%), stroke (0.2%-1.6%), major bleeding (0.3%-7%). The median hospital stay ranged from 4-6 days. Conclusion: Despite recent progresses in STEMI care, there remains marked heterogeneity in STEMI care and outcomes worldwide that warrants further attention. Identification of gaps to STEMI care and remedial actions may improve the global outcomes of STEMI patients.
Treating In-Hospital Stroke—Reply
Authors: Alexandra P. Saltman, Moira K. Kapral
Journal: JAMA Neurology (2015)

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Is race a prognosticator for survival in metastatic non-small cell lung cancer?
Authors: D. Berz, A. Birnbaum
Journal: Journal of Clinical Oncology (2009)

6610 Background: Available cancer statistics for non-small cell lung cancer (NSCLC) in the US relate mainly to Caucasians and African Americans. NSCLC also represents a major health concern in other US American sub-populations. This study describes ethnic patterns of survival in metastatic NSCLC in eight different racial/ethnic groups. Methods: We analyzed the SEER (surveillance, epidemiology, and end results) program database for cancer specific survival rates in stage IV NSCLC patients who were diagnosed between 1991 and 2004 in the SEER catchment geographic areas. The primary exposure of interest was race. The eight different race groups were non-Hispanic whites, Hispanics, African Americans, American Indians/Alaskan natives, Filipinos, Japanese, Chinese, Hawaiians, and other. The later group consisted mainly of a mix of different Asian subpopulations. We performed uni- and multivariate non-parametrical and parametrical survival analysis and developed a final cox-proportional hazard model controlling for marital status, age at diagnosis, year of diagnosis, gender and histologic type and grade. We tested the proportional hazard assumptions with graphical and modeling methods Results: We identified 39,784 eligible patients. When compared to non-Hispanic whites the risk of death from lung cancer was highest amongst American Indians/Alaskan Natives hazard ratio 1.33(95% CI 1.09–1.62, p = 0.004). For patients with Chinese HR 0.84 (95% CI 0.77–0.91) and Filipino HR 0.80 (95% CI 0.73–0.88) ethnicity the risk of death from lung cancer was significantly lower when compared with non-Hispanic whites. Hispanics HR 1.00 (95% CI 0.94–1.07) and Blacks HR 1.00 (95% CI 0.97–1.04) had about equal hazards of death from stage IV NSCLC as whites. In patients of Japanese and Hawaiian origin a trend towards a lower hazard with HR 0.99(95% CI 0.90–1.08) and HR 0.97(95% CI 0.85–1.09) respectively was identified without reaching statistical significance. Conclusions: Significant racial disparities in the outcome in metastatic NSCLC can be observed in the US. The indigenous populations of the Western hemisphere have the worst outcome and the previously proposed worse outcome of African Americans with NSCLC when compared to non-Hispanic whites could not be confirmed in our study. No significant financial relationships to disclose.
Molecular mechanism of lung aging in senescence-accelerated mouse (SAM)
Authors: Yiming Yuan, Xiuying Hu, Li Luo, Ming Yang, Zhiguang Su, Xiaoyan Zhang
Journal: European Respiratory Journal (2011)

The SAM strains are a collection of inbred mouse strains developed as models of accelerated aging, and include nine short-lived, the senescence-prone strains (SAMP) and three longer lived control strains designated the senescence-resistant strains (SAMR). The SAMP was suggested as a new murine model of aging lung. However, molecular mechanism of accelerated lung aging remains to be elucidated. By using quantitative real time RT-PCR and western blot, here we show that expression of FOXO, a forkhead transcription factor that acts downstream of the PTEN/PI3K/Akt pathway and a key regulator of stress resistance, metabolism and ageing, was significantly decreased in aged SAMP mice compared to normal aging control SAMR mice. The decreased expression of FOXO gene was correlated with elevation of reactive oxidative species (ROS) and thiobarbituric acid reactive substances (TBARS), reduced mRNA expression levels of superoxide dismutase (SOD2) and catalase, as well as greater mean linear intercept (MLI) in SAMP mice lungs. Based on these findings we concluded that reduced FOXO activity may contribute to accelerated lung aging in this animal model. Given that FOXO proteins play a critical role in maintaining the quiescence and self-renewal capacity in hematopoietic stem cells and neural stem cells, manipulation of FOXO in lung progenitor cells may represent a novel approach to lung regenerative medicine and chronic lung disease such as COPD.
Abstract 18443: Impact of Left Ventricular Hypertrophy on Impaired Coronary Microvascular Dysfunction Determined by Direct Single-Wire Pressure and Flow Velocity Measurement
Authors: Kenichi Tsujita, Kenshi Yamanaga, Naohiro Komura, Kenji Sakamoto, Takashi Miyazaki, Masanobu Ishii, Noriaki Tabata, Tomonori Akasaka, Tomonori Akasaka, Yuichiro Arima, Takamichi Ono, Sunao Kojima, Shinji Tayama, Koichi Kaikita, Seiji Hokimoto, Hiroshige Yamabe, Sunao Nakamura, Hisao Ogawa
Journal: Circulation (2014)

Introduction: Coronary microvascular (MV) dysfunction can be sustained by several pathogenic mechanisms (e.g. functional, structural and extravascular alterations). On the other hand, structural abnormalities (an adverse remodeling of intramural coronary arterioles consisting of vessel wall thickening mainly due to hypertrophy of smooth muscle cells and increased collagen deposition in the tunica media) responsible for coronary MV dysfunction have been consistently documented in patients with hypertrophic cardiomyopathy (HCM) and in those with pathologic left ventricular hypertrophy (LVH). However, there has been no technique that enables direct measurement of coronary MV dysfunction in vivo . Methods: According to transthoracic echocardiographic data, patients without coronary obstruction (&gt;50% diameter) on angiography were divided into 2 groups; LVH (n=17) and non-LVH (n=24). LVH was defined either interventricular septal thickness (IVST) or posterior wall thickness (PWT) thicker &gt;11mm. To evaluate directly coronary MV dysfunction, a velocity-based index of hyperemic MV resistance (hMR) was measured using a dual-sensor (Doppler velocity and pressure)-equipped guidewire, and the guidewire-derived hemodynamic parameters were compared. Results: There were no differences in clinical demographics between the groups except for more common male gender and HCM in LVH group. Although fractional flow reserve was comparable between the 2 groups, coronary flow reserve was significantly impaired (1.96±0.79 vs. 2.55±0.89, p=0.04), and hMR was significantly elevated (2.09±0.79 vs. 1.60±0.50, p=0.04) in LVH group compared with non-LVH group. Older age, worse estimated glomerular filtration rate, and LVH were significantly associated with MV dysfunction (≥median value of hMR [1.7]) in univariate analysis, and left ventricular mass index tended to predict MV dysfunction in multivariate logistic regression analysis (OR, 1.03; 95% CI, 1.00-1.06; p=0.10). Conclusions: Compared with non-LVH patients, MV function was impaired in patients with LVH. In vivo assessment of hMR was a promising index of MV dysfunction in patients without epicardial obstruction to elucidate the pathophysiologic mechanisms underlying coronary MV dysfunction.
Microsatellite instability (MSI) due to mutation or epigenetic silencing is associated with increased cytotoxicity to irinotecan (CPT-11) in human colorectal cancer (CRC) cell lines
Authors: E. Vilar, M. Scaltriti, C. Saura, M. Guzman, T. Macarulla, J. Arribas, J. Tabernero
Journal: Journal of Clinical Oncology (2007)

10527 Background: MSI is a phenomenon found in tumor DNA of individuals with dysfunction of the mismatch repair system (MMR). Epigenetic inactivation by promoter hypermethylation of hMLH1 causes 15 to 20% of sporadic CRC. In vitro studies have suggested an increased sensitivity to CPT-11 of MMR-deficient human CRC cell lines. Chemosensitivity evaluation in preclinical models of human CRC cell lines according to the MMR status could help in the design of specific studies in the clinical setting. Methods: We have performed drug cytotoxicity assays to compare sensitivity to CPT-11 in several human CRC cell lines with different MMR gene status that resemble the most common clinical situations in CRC patients. HCT116, HCT15, SW48 and RKO are MSI-High (MSI-H), being HCT116 due to a homozygous nonsense mutation of hMLH1 gene, HCT15 due to MSH6 mutation (both of them similar to hereditary cases) and both SW48 and RKO due to methylation of hMLH1 promoter (as MSI-H sporadic CRC cases). HT29 expresses normal levels of MMR proteins (as microsatellite stable (MSS) CRC cases). Drug concentrations resulting in 50% growth inhibition (IC 50 ) were determined by a curve-fitting analysis and cell cycle analyses in order to characterize the cytotoxicity of cell lines were performed. Results: IC 50 values and 95% confidence intervals (CI) are show in Table 1 . hMLH1-deficient cell lines due to either epigenetic silencing or mutation showed very similar IC 50 and were 5- to 8-fold more sensitive to CPT-11 than the MSS line. hMSH6- deficient cell line HCT15 has sensitivity closer to MSS than MSI cell lines. Treatment with CPT-11 induced a G2/M arrest. Conclusions: Lack of hMLH1 protein due to either genetic alteration or epigenetic silencing correlates with increased sensitivity to CPT-11. MSI-H CRC cell lines are more sensitive to CPT-11 than MSS. Future clinical trials tailoring chemotherapy regimens based on microsatellite status are warranted. [Table: see text] No significant financial relationships to disclose.
Varicella zoster virus infection
Authors: Anne A. Gershon, Judith Breuer, Jeffrey I. Cohen, Randall J. Cohrs, Michael D. Gershon, Don Gilden, Charles Grose, Sophie Hambleton, Peter G. E. Kennedy, Michael N. Oxman, Jane F. Seward, Koichi Yamanishi
Journal: Nature Reviews Disease Primers (2015)
O001 : C-salvage: grazoprevir (GZR; MK-5172), elbasvir (EBR; MK-8742) and ribavirin (RBV) for chronic hcv-genotype 1 (GT1) infection after failure of direct-acting antiviral (DAA) therapy
Authors: X. Forns, S. Gordon, E. Zuckerman, E. Lawitz, M. Buti, J. Calleja Panero, H. Hofer, C. Gilbert, J. Palcza, A. Howe, M. DiNubile, M. Robertson, J. Wahl, E. Barr, J. Sullivan-Bolyai
Journal: Journal of Hepatology (2015)
Genomics and drug profiling of fatal TCF3-HLF−positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options
Authors: Ute Fischer, Michael Forster, Anna Rinaldi, Thomas Risch, Stéphanie Sungalee, Hans-Jörg Warnatz, Beat Bornhauser, Michael Gombert, Christina Kratsch, Adrian M Stütz, Marc Sultan, Joelle Tchinda, Catherine L Worth, Vyacheslav Amstislavskiy, Nandini Badarinarayan, André Baruchel, Thies Bartram, Giuseppe Basso, Cengiz Canpolat, Gunnar Cario, Hélène Cavé, Dardane Dakaj, Mauro Delorenzi, Maria Pamela Dobay, Cornelia Eckert, Eva Ellinghaus, Sabrina Eugster, Viktoras Frismantas, Sebastian Ginzel, Oskar A Haas, Olaf Heidenreich, Georg Hemmrich-Stanisak, Kebria Hezaveh, Jessica I Höll, Sabine Hornhardt, Peter Husemann, Priyadarshini Kachroo, Christian P Kratz, Geertruy te Kronnie, Blerim Marovca, Felix Niggli, Alice C McHardy, Anthony V Moorman, Renate Panzer-Grümayer, Britt S Petersen, Benjamin Raeder, Meryem Ralser, Philip Rosenstiel, Daniel Schäfer, Martin Schrappe, Stefan Schreiber, Moritz Schütte, Björn Stade, Ralf Thiele, Nicolas von der Weid, Ajay Vora, Marketa Zaliova, Langhui Zhang, Thomas Zichner, Martin Zimmermann, Hans Lehrach, Arndt Borkhardt, Jean-Pierre Bourquin, Andre Franke, Jan O Korbel, Martin Stanulla, Marie-Laure Yaspo
Journal: Nature Genetics (2015)
Abstract 11877: Novel Method to Quantify the Degree of Fluid Accumulation and Its Prognostic Implication in Patients With Acute Decompensated Heart Failure
Authors: Taiki Sakaguchi, Kaori Yasumura, Hiroki Nishida, Hiroyuki Inoue, Tetsuo Furukawa, Kazuya Shinouchi, Hiroyuki Miura, Koichi Miyazaki, Masao Koide, Haruhiko Abe, Keiji Hirooka, Yukihiro Koretsune, Hideo Kusuoka, Yoshio Yasumura
Journal: Circulation (2014)

Introduction: Fluid accumulation is an important therapeutic target in acute decompensated heart failure (ADHF). Our objective was to develop a non-invasive and repeatable clinical method to quantify the degree of fluid accumulation in ADHF patients, and investigate its prognostic implications. Methods: We measured extracellular water (ECW) volume using bioelectrical impedance analysis (BIA) in 60 control subjects without heart failure (aged 75±7 years). The reliability of the measured values was assessed through comparisons with ECW estimates from Moore’s regression equations based on multiple isotope dilution. We then developed original regression equations to predict ECW values from multivariate analyses that incorporate patient height, body weight, age and sex. ECW values on admission and at discharge in 120 ADHF patients (aged 73±11 years) were measured, and the ratios of measured to predicted ECW values (M/P ratios) were calculated. The primary endpoint was the occurrence of cardiac death or readmission for ADHF. Results: In the control subjects, BIA-measured ECW values correlated with those estimated by Moore’s equations (r 2 =0.72, p&lt;0.001), and showed even stronger correlations with estimates from our equations (r 2 =0.86, p&lt;0.001). In ADHF patients, measured ECW was significantly reduced during hospitalization (15.4±6.2L to 12.1±4.7L, p&lt;0.001), and M/P ratios were approximately 100% at discharge (126±26% to 104±19%, p&lt;0.001). Patients whose M/P ratios remained higher than 100% at discharge showed higher 3-month cardiac death or readmission rates than patients with lower M/P ratios (50% vs 17%, hazard ratio 3.69; 95% confidence interval 1.935-7.048, p&lt;0.001). Conclusions: We successfully quantified the degree of fluid accumulation using BIA, and the predicted ECW estimates from our regression equations can be a treatment goal in ADHF patients. This BIA-guided therapy may provide better clinical outcomes in the management of ADHF.
Integrative genetic analysis of mouse and human AML identifies cooperating disease alleles
Authors: Megan A. Hatlen, Kanika Arora, Vladimir Vacic, Ewa A. Grabowska, Willey Liao, Bridget Riley-Gillis, Dayna M. Oschwald, Lan Wang, Jacob E. Joergens, Alan H. Shih, Franck Rapaport, Shengqing Gu, Francesca Voza, Takashi Asai, Benjamin G. Neel, Michael G. Kharas, Mithat Gonen, Ross L. Levine, Stephen D. Nimer
Journal: The Journal of Experimental Medicine (2015)

t(8;21) is one of the most frequent chromosomal abnormalities observed in acute myeloid leukemia (AML). However, expression of AML1-ETO is not sufficient to induce transformation in vivo. Consistent with this observation, patients with this translocation harbor additional genetic abnormalities, suggesting a requirement for cooperating mutations. To better define the genetic landscape in AML and distinguish driver from passenger mutations, we compared the mutational profiles of AML1-ETO-driven mouse models of leukemia with the mutational profiles of human AML patients. We identified TET2 and PTPN11 mutations in both mouse and human AML and then demonstrated the ability of Tet2 loss and PTPN11 D61Y to initiate leukemogenesis in concert with expression of AML1-ETO in vivo. This integrative genetic profiling approach allowed us to accurately predict cooperating events in t(8;21)(+) AML in a robust and unbiased manner, while also revealing functional convergence in mouse and human AML.
Generation of a double transgenic humanized neonatal Fc receptor (FcRn)/albumin mouse to study the pharmacokinetics of albumin-linked drugs
Authors: Dorthe Viuff, Filipa Antunes, Leslie Evans, Jason Cameron, Hans Dyrnesli, Birgitte Thue Ravn, Magnus Stougaard, Kader Thiam, Birgitte Andersen, Søren Kjærulff, Kenneth A. Howard
Journal: Journal of Controlled Release (2015)
P0698 : Quercetin modifies lipid droplet morphology and impairs hepatitis C viral life-cycle steps from assembly to replication steps
Authors: A. Rojas, S. Clement, J.A. Del Campo, M. Lemasson, M. Garcia -Valdecasas, L. Rojas, A. Gil-Gomez, I. Ranchal, J. Bautista, A.R. Rosenberg, F. Negro, M. Romero-Gomez
Journal: Journal of Hepatology (2015)
Visualizing estrogen receptor-α-expressing neurons using a new ERα-ZsGreen reporter mouse line
Authors: Kenji Saito, Yanlin He, Xiaofeng Yan, Yongjie Yang, Chunmei Wang, Pingwen Xu, Antentor Othrell Hinton, Gang Shu, Likai Yu, Qingchun Tong, Yong Xu
Journal: Metabolism (2015)
Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance
Authors: Milica Vukovic, Amelie V. Guitart, Catarina Sepulveda, Arnaud Villacreces, Eoghan O'Duibhir, Theano I. Panagopoulou, Alasdair Ivens, Juan Menendez-Gonzalez, Juan Manuel Iglesias, Lewis Allen, Fokion Glykofrydis, Chithra Subramani, Alejandro Armesilla-Diaz, Annemarie E.M. Post, Katrin Schaak, Deniz Gezer, Chi Wai Eric So, Tessa L. Holyoake, Andrew Wood, Dónal O'Carroll, Peter J. Ratcliffe, Kamil R. Kranc
Journal: The Journal of Experimental Medicine (2015)

Leukemogenesis occurs under hypoxic conditions within the bone marrow (BM). Knockdown of key mediators of cellular responses to hypoxia with shRNA, namely hypoxia-inducible factor-1α (HIF-1α) or HIF-2α, in human acute myeloid leukemia (AML) samples results in their apoptosis and inability to engraft, implicating HIF-1α or HIF-2α as therapeutic targets. However, genetic deletion of Hif-1α has no effect on mouse AML maintenance and may accelerate disease development. Here, we report the impact of conditional genetic deletion of Hif-2α or both Hif-1α and Hif-2α at different stages of leukemogenesis in mice. Deletion of Hif-2α accelerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9. Notably, the accelerated initiation of AML caused by Hif-2α deletion is further potentiated by Hif-1α codeletion. However, established LSCs lacking Hif-2α or both Hif-1α and Hif-2α propagate AML with the same latency as wild-type LSCs. Furthermore, pharmacological inhibition of the HIF pathway or HIF-2α knockout using the lentiviral CRISPR-Cas9 system in human established leukemic cells with MLL-AF9 translocation have no impact on their functions. We therefore conclude that although Hif-1α and Hif-2α synergize to suppress the development of AML, they are not required for LSC maintenance.
Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review
Authors: Ganesh Raghu, Valeria C. Amatto, Jürgen Behr, Susanne Stowasser
Journal: European Respiratory Journal (2015)

Idiopathic pulmonary fibrosis (IPF) is associated with a fatal prognosis and manifests in patients over 60 years old who may have comorbidities. The prevalence and impact of comorbidities on the clinical course of IPF is unclear.This systematic literature review examined the prevalence of comorbidities and mortality associated with comorbidities in IPF patients. Relevant observational studies published in English from January 1990 to January 2015 identified via MEDLINE and EMBASE were included; bibliographies of articles were also searched.Among the 126 studies included, prevalence of pulmonary hypertension (PH) was 3-86%, 6-91% for obstructive sleep apnoea, 3-48% for lung cancer and 6-67% for chronic obstructive pulmonary disease (COPD). Nonrespiratory comorbidities included ischaemic heart disease (IHD) (3-68%) and gastro-oesophageal reflux (GER) (0-94%). Mortality was highest among patients with IPF and lung cancer. Most studies assessed relatively small samples of patients with IPF.PH, COPD, lung cancer, GER and IHD are significant comorbidities; differences in IPF severity, case definitions and patient characteristics limited the comparability of findings. The identification and prompt treatment of comorbidities may have a clinically significant impact on overall outcome that is meaningful for patients with IPF.
Achievement Of a MR5.0 Within the Randomized CML-Study IV: Feasibility, Differences Between Treatment Arms, and Prognostic Implications
Authors: Martin C. Müller, Michael Lauseker, Rüdiger Hehlmann, Benjamin Hanfstein, Christian Dietz, Philipp Erben, Alice Fabarius, Ulrike Proetel, Susanne Schnittger, Stefan W. Krause, Jörg Schubert, Hermann Einsele, Mathias Hänel, Jolanta Dengler, Christiane Falge, Lothar Kanz, Andreas Neubauer, Michael Kneba, Frank Stegelmann, Michael Pfreundschuh, Cornelius F. Waller, Karsten Spiekermann, Gabriela M. Baerlocher, Markus Pfirrmann, Joerg Hasford, Wolf-Karsten Hofmann, Andreas Hochhaus, Susanne Saussele
Journal: Blood (2013)