tbuckley/cabot-search huggingface dataset:
Abstract 16563: Impacts of Left Ventricle Filling Index on Myocardial Contractile Performance Before and After Exercise Stress in Hypertensive Patients with a Normal Ejection Fraction
Authors: Yi-Chih Wang, Chih-Chieh Yu, Fu-Chun Chiu, Ruth Klepfer, Kathryn Hilpisch, Juey-Jen Hwang, Ling-Ping Lai, Chia-Ti Tsai, Jiunn-Lee Lin
Journal: Circulation (2010)

Background:  If higher left ventricle (LV) filling index (FI), the indicator of LV filling pressure, would interfere with myocardial contractile adaptation to exercise in hypertensive patients (pts) with a normal ejection fraction (EF) was unknown.   Methods:  A total of 147 hypertensive pts (66±11 years, 60 male) with LVEF > 50 % were classified into low FI [mitral E/Ea (annular early diastolic velocity)] ( 13; 38 pts) groups after echo study. The mean of systolic myocardial velocity (Sm) and standard deviation of time delay from QRS onset to peak Sm (SD-Ts) of 12 LV segments in apical views were measured before and after 6 minutes treadmill exercise by Bruce protocol. N-terminal pro-brain natriuretic peptide (NT-proBNP) was checked.   Results:  Pts with higher FI were older (high FI: 70±9 vs. medium FI: 67±8 vs. low FI: 60±13 years,  p  p =0.01) and a higher pro-BNP level (high FI: 405±710 vs. medium FI: 183±246 vs. low FI: 70±53 pg/ml,  p =0.01), but other clinical aspects were similar. Echo study showed similar LV wall thickness, chamber sizes, and EF among groups, but higher FI was accompanied by expected poorer diastolic indices. Regarding myocardial contractile performance, the mean Sm was lower (high FI: 6.1±1.0 vs. medium FI: 6.4±0.8 vs. low FI: 6.7±1.1 cm/s,  p =0.04), and SD-Ts was greater (high FI: 49±17 vs. medium FI: 41±25 vs. low FI: 33±23 ms,  p  p =0.32). The post-exercise SD-Ts remained stable in low FI group, but aggravated in combined medium and high FI groups (47±22 vs. 43±24 ms,  p =0.02). After adjustment for age and sex, FI > 13 was independently associated with baseline SD-Ts >33 ms (OR=4.8, 95% CI=1.5–16,  p   40 (20% increase) (OR=3.8, 95% CI=1.3–11,  p =0.01) in overall pts.   Conclusion:  Elevated LV FI did not interfere with post-exercise adaptation of myocardial contractile velocity, but was associated with exercise-aggravated ventricular dyssynchrony which could contribute to higher FI-related exercise intolerance in hypertensive pts with heart failure and a normal EF.
Update in Chronic Obstructive Pulmonary Disease 2008
Authors: John D Maclay, Roberto A Rabinovich, William MacNee
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The last year has seen important new information published on chronic obstructive pulmonary disease (COPD), its pathogenesis, systemic effects, exacerbations, and treatment. Several important new COPD research programs have been initiated during the past year, including the Sub-Populations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) program, which will categorize patients on the basis of molecular fingerprinting and will attempt to identify and validate intermediate outcome measures in COPD. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study (1) aims to define clinically relevant COPD subtypes and identify genetic factors and biomarkers that correlate with these COPD subtypes and predict disease progression. In addition, several large research consortia have been established, including the COPD clinical research network and the National Heart, Lung, and Blood Institute–funded lung tissue research consortium (2).
TMOD-46. cMyc OVEREXPRESSION INDUCES CHOROID PLEXUS TUMOURS THROUGH MODULATION OF INFLAMMATORY PATHWAYS
Authors: Ashirwad Merve, Silvia Marino
Journal: Neuro-Oncology (2017)

Choroid plexus tumours (CPTs) account for up to 20% of brain tumours in children under 2 years of age. They can spread along the neuraxis and can recur after treatment. Little is known about the molecular mechanisms underlying their formation and only one high fidelity mouse model of p53-deficient CPTs is available. c-Myc is a proto-oncogene deregulated in various malignancies, including paediatric brain tumours. Here, we conditionally overexpressed c-Myc in neural progenitor cells to assess its role in brain tumour pathogenesis. We show that c-Myc overexpression increased proliferation of neural progenitor cells both in vitro and in vivo during brain development while at the same time inducing apoptosis in a dosage-dependent manner. Neural progenitor cell-derived brain tumours did not develop in these mice. Interestingly though, a high incidence (84%) of CPTs was observed in the compound mutant mice. We used a publicly available gene expression dataset of 40 human CPTs to assess the translational value of this novel mouse model. We show that a proportion of human CPTs expressed c-Myc and this discovery platform revealed a specific molecular signature of this CPT subgroup associated with inflammatory pathways, including TNF, Interleukins and Cytokine-Cytokine receptor pathways. An independent cohort of 42 human CPT (Brain UK) was used to validate overexpression of c-Myc in these tumours. 43% of cases overexpressed c-Myc and in these cases the CD3+ T-lymphocyte and the CD68+ macrophage infiltrates were increased. Deregulation of inflammatory pathways and increased intratumoural inflammation were found also in the mouse CPT model. Overexpression of c-Myc identifies a proportion of human CPTs, which can be modelled by overexpressing c-Myc in chroroid plexus cells. The underlying pathogenetic mechanism is mediated by c-Myc induced pro-inflammtory role in the murine model, which reflects the histopathological phenotype observed in human c-Myc overexpressing CPTs.
Clinical Correlates, Prognostic Impact and Survival Outcomes in Chronic Myelomonocytic Leukemia Patients with Myeloproliferative Neoplasm Associated-Driver Mutations
Authors: Prateek Pophali, Terra L. Lasho, Christy Finke, Pedro Horna, Rhett P. Ketterling, Naseema Gangat, Kebede H. Begna, Abhishek A. Mangaonkar, Animesh Pardanani, Ayalew Tefferi, Mrinal M. Patnaik
Journal: Blood (2018)
Abstract 3729: Novel radiation mitigators and anticancer drugs
Authors: Robert H. Schiestl, Yelena Rivina, Michael Davoren
Journal: Cancer Research (2016)

Abstract The possibility of a radiation disaster from a nuclear detonation or accident has existed for over 50 years and spawned much of the basic research in radiobiology in the 1950-60s. The recent Fukushima accident was yet another reminder that there remains a dire need to develop novel therapies against radiation-induced toxicities. Here we report on the development of two novel radiation countermeasure therapies: CJ010 and Yel002. These small, biologically active, drug-like molecules were uncovered in the DEL high throughput assay reducing radiation-induced cyto- and geno-toxicity in yeast. Radiation-modulating activity was further confirmed in yeast plate-based DEL Assay: addition of either CJ010 or Yel002 to irradiated cultures reduced cell death and genomic instability. Further, the compounds increases survival to 75% in vivo following an LD100/30 dose of ionizing radiation (IR) with the first therapeutic injection administered 24 hours post exposure followed by injections at 48,72,96, and 120 hours. Additionally, treatment with Yel001 an analog of CJ010 and Yel002 compounds reduces radiation-induced leukemia from 90% to to 50% and 40% respectively. Of note, treatment with either Yel001 or Yel002 reduced spontaneous leukemia rate from 10% to 0%. Treatment with Yel002 following IR accelerates the recovery of the hematopoietic cells after sub-lethal exposures. In addition, treatment with Yel002 reduces EMS, MMS, UV, radioactive iodine, cigarette smoke extract as well as nitrogen mustard induced toxicity as well as genotoxicity showing a broad application spectrum. It also prolongs live of cells in a senescence assay. In addition Atm deficient mice live 16 weeks longer with weekly injection of Yel002 which is about 12 years in human life expectancy. In addition, Yel002 complements a zebrafish model of Diamond Blackfan Anemia. It works in yeast, CHO cells, different human cells, mice and zebrafish. Toxicity has not been observed in neither in vitro or in vivo administrations. Overall, Yel compounds have much potential as stockpile therapies for radiation-induced lethality and cancer: they are highly effective when administered up to 24hours post exposure, they reduce radiation-induce sequelae such as leukemia, and appear to have an acceptable toxicity profile. Citation Format: Robert H. Schiestl, Yelena Rivina, Michael Davoren. Novel radiation mitigators and anticancer drugs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3729.
Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease
Authors: Abhinav Sharma, Adrian Coles, Nishant K. Sekaran, Neha J. Pagidipati, Michael T. Lu, Daniel B. Mark, Kerry L. Lee, Hussein R. Al-Khalidi, Udo Hoffmann, Pamela S. Douglas
Journal: Journal of the American College of Cardiology (2019)
Retrospective Analysis of Treatment Patterns and Effectiveness of Palbociclib and Subsequent Regimens in Metastatic Breast Cancer
Authors: Jing Xi, Aabha Oza, Shana Thomas, Foluso Ademuyiwa, Katherine Weilbaecher, Rama Suresh, Ron Bose, Mathew Cherian, Leonel Hernandez-Aya, Ashley Frith, Lindsay Peterson, Jingqin Luo, Jairam Krishnamurthy, Cynthia X. Ma
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors are now the standard of care for hormone receptor-positive (HR+), HER2-negative (HER-) metastatic breast cancer (MBC). However, guidelines are lacking regarding their optimal sequencing with other available agents. This study examines physician practice patterns and treatment outcomes of palbociclib and subsequent therapies in a real-world setting. Methods: A retrospective chart review was conducted for consecutive patients with MBC who received palbociclib between February 2015 and August 2017 at the Alvin J. Siteman Cancer Center. Kaplan-Meier method was used to generate time-to-event curves and estimate median progression-free survival (mPFS). Log-rank test was used to compare differences. Results: A total of 200 patients, with a median age of 59.4 years and a follow-up of 19.5 months, were included. Palbociclib was most frequently combined with letrozole (73.5%), followed by fulvestrant (25%), anastrozole (1%), and tamoxifen (0.5%). Most patients received palbociclib in the endocrine-resistant setting (n=42, n=50, and n=108 in the first-, second-, and subsequent-line settings, respectively), and the fraction of patients receiving palbociclib as first- or second-line therapy increased in recent months (P=.0428). mPFS was 20.7, 12.8, and 4.0 months with palbociclib administered in the first-, second-, and subsequent-line settings, respectively (P<.0001). Incidences of grade 3/4 neutropenia (41.5%) and dose reductions (29%) were comparable to reports in the literature. Among patients whose disease progressed on palbociclib (n=104), the most frequent next-line treatment was capecitabine (n=21), followed by eribulin (n=16), nab-paclitaxel (n=15), and exemestane + everolimus (n=12). mPFS with hormone therapy alone or in combination with targeted agents (n=32) after first-, second-, and subsequent-line palbociclib was 17.0, 9.3, and 4.2 months, respectively (P=.04). mPFS with chemotherapy (n=70) was not reached, 4.7, and 4.1 months after first-, second-, and subsequent-line palbociclib, respectively (P=.56). Conclusions: Palbociclib is effective for HR+/HER2- MBC in real-world practice. Hormone therapy alone or in combination with targeted agents remains an effective option after palbociclib progression.
Safety and Efficacy of Combined Peptide Receptor Radionuclide Therapy and Liver Selective Internal Radiation Therapy in a Patient With Metastatic Neuroendocrine Tumor
Authors: Marco Maccauro, Giulia Anna Follacchio, Carlo Spreafico, Jorgelina Coppa, Ettore Seregni
Journal: Clinical Nuclear Medicine (2019)

Nuclear medicine treatments of well-differentiated neuroendocrine tumors (NETs) are gaining increasing acceptance among clinicians. Peptide receptor radionuclide therapy (PRRT) is an effective systemic treatment, providing a significant survival benefit and improving patients' quality of life. Locoregional selective internal radiation therapy (SIRT) is a safe and effective treatment for unresectable NET liver metastases, providing good local tumor control and symptomatic relief. Few reports in literature examine the sequential use of PRRT and SIRT in metastatic NET. We report the case of a metastatic NET patient treated with sequential PRRT-SIRT achieving a long disease control interval without cumulative toxicity issues.
Phenobarbital‐Induced Liver Injury With Nodal Angiomatosis
Authors: Li‐Ting Cheng, Matthew M. Yeh, Chun‐Chi Lu
Journal: Hepatology (2019)

1Department of Internal MedicineTri‐Service General Hospital, National Defense Medical CenterTaipeiTaiwan 2Department of PathologyUniversity of Washington School of MedicineSeattleWA 3Department of MedicineUniversity of Washington School of MedicineSeattleWA 4Division of Rheumatology/Immunology and Allergy, Department of Internal MedicineTri‐Service General Hospital, National Defense Medical CenterTaipeiTaiwan *Address Correspondence and Reprint Requests to: Chun‐Chi Lu, M.D., Ph.D. Department of Pathology, University of Washington 1959 NE Pacific Street Seattle, WA 98195 E‐mail: [email protected] Tel: +886 2 87927135
High risk of heart failure associated with desmoglein‐2 mutations compared to plakophilin‐2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia
Authors: Alexis Hermida, Véronique Fressart, Francoise Hidden‐Lucet, Erwan Donal, Vincent Probst, Jean‐Claude Deharo, Philippe Chevalier, Didier Klug, Nicolas Mansencal, Etienne Delacretaz, Pierre Cosnay, Patrice Scanu, Fabrice Extramiana, Dagmar I. Keller, Stephanie Rouanet, Philippe Charron, Estelle Gandjbakhch
Journal: European Journal of Heart Failure (2019)
National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2016
Authors: Tanja Y. Walker, Laurie D. Elam-Evans, James A. Singleton, David Yankey, Lauri E. Markowitz, Benjamin Fredua, Charnetta L. Williams, Sarah A. Meyer, Shannon Stokley
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents routinely receive tetanus, diphtheria, and acellular pertussis vaccine (Tdap), meningococcal conjugate vaccine (MenACWY), and human papillomavirus (HPV) vaccine (1) at age 11-12 years. ACIP also recommends catch-up vaccination with hepatitis B vaccine, measles, mumps, and rubella (MMR) vaccine, and varicella vaccine for adolescents who are not up to date with childhood vaccinations. ACIP recommends a booster dose of MenACWY at age 16 years (1). In December 2016, ACIP updated HPV vaccine recommendations to include a 2-dose schedule for immunocompetent adolescents initiating the vaccination series before their 15th birthday (2). To estimate adolescent vaccination coverage in the United States, CDC analyzed data from the 2016 National Immunization Survey-Teen (NIS-Teen) for 20,475 adolescents aged 13-17 years.* During 2015-2016, coverage increased for ≥1 dose of Tdap (from 86.4% to 88.0%) and for each HPV vaccine dose (from 56.1% to 60.4% for ≥1 dose). Among adolescents aged 17 years, coverage with ≥2 doses of MenACWY increased from 33.3% to 39.1%. In 2016, 43.4% of adolescents (49.5% of females; 37.5% of males) were up to date with the HPV vaccination series, applying the updated HPV vaccine recommendations retrospectively.† Coverage with ≥1 HPV vaccine dose varied by metropolitan statistical area (MSA) status and was lowest (50.4%) among adolescents living in non-MSA areas and highest (65.9%) among those living in MSA central cities.§ Adolescent vaccination coverage continues to improve overall; however, substantial opportunities exist to further increase HPV-associated cancer prevention.
Abstract 3966: GenomeSpace: An environment for frictionless bioinformatics
Authors: Michael Reich, John Liefeld, Helga Thorvaldsdottir, Marco Ocana, Eliot Polk, DK Jang, Jill Mesirov
Journal: Cancer Research (2012)

Abstract Over the past several years, cancer genome characterization initiatives such as The Cancer Genome Atlas and the Tumor Sequencing Project have produced an explosion of genomic data. The pace of data production has recently increased with the adoption of next-generation sequencing technologies and large-scale data production efforts to discover the breadth of genomic variation in humans. Comprehensive analysis of these datasets requires the coordinated use of Web-based applications and data repositories, desktop analysis tools and visualizers, and single-purpose algorithms. However, the effort required to transfer data between tools, convert between data formats, and manage results often prevents researchers from utilizing the wealth of methods available to them. Many integrative genomics and translational “bench to bedside” discoveries are possible with combinations of existing tools, but the necessary transitions between them puts them out of the reach of most researchers. GenomeSpace, http://www.genomespace.org, is an environment that brings together diverse computational tools, enabling scientists without programming skills to easily combine their capabilities. It aims to offer a common space to create, manipulate and share an ever-growing range of genomic analysis tools. GenomeSpace features support for cloud-based data storage and analysis, multi-tool analytic workflows, automatic conversion of data formats, and ease of connecting new tools to the environment. A set of six “GenomeSpace-enabled” seed tools developed by collaborating organizations provides a comprehensive platform for the analysis of cancer data: Cytoscape (UCSD), Galaxy (Penn State University), GenePattern (Broad Institute), Genomica (Weitzmann Institute), Integrative Genomics Viewer (Broad Institute), and the UCSC Genome Browser (UCSC). We show how researchers can use GenomeSpace to effortlessly combine the capabilities of all of these tools in several cancer research scenarios. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3966. doi:1538-7445.AM2012-3966
Generation of an Immortalized Erythroid Progenitor Cell Line Directly from Peripheral Blood Mononuclear Cells without Using Mobilized CD34+ Cells
Authors: Abhirup Bagchi, Aneesha Nath, Vignesh Rajendiran, Madhavi Maddali, Ekta Jajodia, Mohankumar Kumarasamypet Murugesan, Yukio Nakamura, Alok Srivastava, Shaji Ramachandran Velayudhan
Journal: Blood (2018)
Rationale and design of the European multicentre study on Stem Cell therapy in IschEmic Non‐treatable Cardiac diseasE (SCIENCE)
Authors: Christina Paitazoglou, Martin W. Bergmann, Bojan Vrtovec, Steven A.J. Chamuleau, Bas van Klarenbosch, Wojtek Wojakowski, Aleksandra Michalewska‐Włudarczyk, Mariann Gyöngyösi, Annette Ekblond, Mandana Haack‐Sørensen, Kai Jaquet, Karsten Vrangbæk, Jens Kastrup
Journal: European Journal of Heart Failure (2019)

Abstract Aims Ischaemic heart failure (IHF) patients have a poor prognosis even with current guideline‐derived therapy. Intramyocardial injections of autologous or allogeneic mesenchymal stromal cells might improve cardiac function leading to better clinical outcome. Methods The SCIENCE (Stem Cell therapy in IschEmic Non‐treatable Cardiac diseasE) consortium has initiated a Horizon 2020 funded multicentre phase II study in six European countries. It is a double‐blind, placebo‐controlled trial testing the safety and efficacy of allogeneic Cardiology Stem Cell Centre Adipose‐derived Stromal Cells (CSCC_ASC) from healthy donors or placebo in 138 symptomatic IHF patients. Main inclusion criteria are New York Heart Association class II–III, left ventricular ejection fraction &lt; 45% and N‐terminal pro‐B‐type natriuretic peptide levels &gt; 300 pg/mL. Patients are randomized in a 2:1 pattern to receive intramyocardial injections of either CSCC_ASC or placebo. CSCC_ASC and placebo treatments are prepared centralized at Rigshospitalet in 5 mL vials as an off‐the‐shelf product. Vials are distributed to all clinical partners and stored in nitrogen vapour tanks ready to be used directly after thawing. A total of 100 × 10 6 CSCC_ASC or placebo are injected directly into viable myocardium in the infarct border zone using the NOGA XP system (BDS, Cordis, Johnson &amp; Johnson, USA). Primary endpoint is a centralized core‐laboratory assessed change in left ventricular end‐systolic volume at 6‐month follow‐up measured by echocardiography. The trial started in January 2017, 58 patients were included and treated until July 2018. Conclusion The SCIENCE trial will provide clinical data on efficacy and safety of intramyocardial cell therapy of allogeneic adipose‐derived stromal cells from healthy donors in patients with IHF.
Claudia Jakubzick: Work hard, play hard
Authors: Stephanie Houston
Journal: The Journal of Experimental Medicine (2019)

Claudia Jakubzick will be an Associate Professor at Dartmouth in the Department of Microbiology and Immunology working on immune homeostasis and how the immune system can recognize and target precancerous cells. She started her own laboratory at National Jewish Health in 2014, becoming a tenure-track Assistant Professor and an Associate Professor in 2017, and will relocate to Dartmouth mid-2019. She is also a member of the American Association of Immunologists' Minority Affairs Committee. We contacted Claudia to find out about her career in science.
Influenza Vaccination Coverage Among Health Care Personnel — United States, 2016–17 Influenza Season
Authors: Carla L. Black, Xin Yue, Sarah W. Ball, Rebecca Fink, Marie A. de Perio, A. Scott Laney, Walter W. Williams, Megan C. Lindley, Samuel B. Graitcer, Peng-Jun Lu, Rebecca Devlin, Stacie M. Greby
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The Advisory Committee on Immunization Practices (ACIP) recommends that all health care personnel (HCP) receive an annual influenza vaccination to reduce influenza-related morbidity and mortality among HCP and their patients and to reduce absenteeism among HCP (1-4). To estimate influenza vaccination coverage among HCP in the United States during the 2016-17 influenza season, CDC conducted an opt-in Internet panel survey of 2,438 HCP. Overall, 78.6% of survey respondents reported receiving vaccination during the 2016-17 season, similar to reported coverage in the previous three influenza seasons (5). Vaccination coverage continued to be higher among HCP working in hospitals (92.3%) and lower among HCP working in ambulatory (76.1%) and long-term care (LTC) (68.0%) settings. As in previous seasons, coverage was highest among HCP who were required by their employer to be vaccinated (96.7%) and lowest among HCP working in settings where vaccination was not required, promoted, or offered on-site (45.8%). Implementing workplace strategies found to improve vaccination coverage among HCP, including vaccination requirements or active promotion of on-site vaccinations at no cost, can help ensure that HCP and patients are protected against influenza (6).