tbuckley/cabot-search huggingface dataset:
Quality improvement of lung cancer patient selection using clinic-based spirometry.
Authors: Tony Kin- Ming CL Lam, Reenika Aggarwal, Erin L. Stewart, Katrina Hueniken, Maureen McGregor, Wei Xu, Heidi Schmidt, John Kavanagh, Geoffrey Liu
Journal: Journal of Clinical Oncology (2019)

282 Background: Coordinating lung cancer screening requires risk assessment for patient selection. Optimal selection can reduce costs and improve efficiency of low dose computed tomography (LDCT) screening of lung cancer. This study evaluated clinic-based spirometry as a tool to improve patient selection for lung cancer screening. Methods: Eligibility criteria for three large LDCT screening studies were retrospectively applied to the highest risk patients enrolled in the Princess Margaret Lung Cancer Screening Program who had received clinic-based research spirometry. The three studies were: Danish Lung Cancer Screening Trial (DLST), National Lung Screening Trial (NLST), and the Ontario Lung Cancer Screening Program (OLCS). Lung cancer incidence was compared between those who would were included by the screening study eligibility criteria (Group I), those who were excluded by the eligibility criteria but demonstrated obstruction on spirometry (defined as a Forced Expiratory Volume in 1 Second % Predicted (FEV1%) &lt; 90%) (Group II), and those who did not meet eligibility criteria and had no obstruction (FEV1% ≥90) (Group III). Results: The 321 highest risk participants of the screening program had a mean age of 65 years and were 39% male. The median number of pack years in this group was 39. After undergoing spirometry, this cohort was screened using LDCT for a median of 3.3 years (range 1–8.1 years). Under DLST criteria, Groups I and II had virtually identical lung cancer incidences detected by screening at 13.1% and 13.6% of the individuals screened, respectively; Group III had a substantially lower incidence at 6.3%. Results were similar by NLST criteria where the incidence of screen-detected lung cancer were 13.7% for Groups I, 11.1% for Group II, and 8.6% for Group III. Under OLCS criteria, these values were 13.4% (Group I), 13.5% (Group II), and 8.2% (Group III). Conclusions: Individuals who were excluded from LDCT screening because they lacked other clinical eligibility criteria, but had a FEV1 &lt; 90%, had similar lung cancer incidence as patients who had met screening study eligibility criteria. Coordinating care for screening of at-risk individuals could be improved by incorporating spirometric tools.
Abstract 213: Single-Cell RNA Sequencing Reveals Pathways Dysregulation by a NFATc1 Mutation in Patient-Specific Cardiomyocytes Derived From Inducible Pluripotent Stem Cells
Authors: Natalia S Torres, Karissa Wang, Enrique Coca, Andrew Carey, Colin Maguire, Scott Cho, Martin Tristani-Firouzi
Journal: Circulation Research (2019)

Using a family-based approach with whole exome sequencing (WES) and custom bioinformatics tools we identified a novel mutation (M527L) in the Nuclear Factor of Activated T-Cells 1 gene (NFATc1). This nonsynonymous heterozygous substitution segregates in an autosomal dominant pattern within a family with a young onset Atrial Fibrillation (AF) phenotype. Patient specific inducible pluripotent stem cell derived-cardiomyocytes (iPSC-CM) from a patient carrying this variant showed abbreviated repolarization resulting in a shorter action potential duration compared to iPSC-CM from a healthy sibling control. Unlike familial monogenic AF where the mutation occurs in an ion channel gene, NFATc1 is a transcription factor that influences expression of multiple genes. Using single-cell RNA sequencing on 30 day post-differentiation iPSC-CM, we identified four subpopulations by K-mean clustering (k=4) of single cell transcriptomes and subsequent marker expression. We then performed gene-annotation enrichment analysis of differentially expressed genes specifically in the mutant (MT) and wild-type (WT) cardiomyocyte (CM) populations, detecting several key functional and pathological cardiac pathways affected in response to the NFATc1 mutation. These included Wnt, NF-kappaB and MAPK signaling, Ca homeostasis and gene categories that have been associated with atrial fibrillation. These results suggest that NFATc1 mutation may play an important role in the pathophysiology of familial atrial fibrillation by its broad impact on gene expression and subsequent pathway regulation.
Long-term follow-up of left ventricular function after angioplasty-reperfused hibernating myocardium in oligosymptomatic patients with coronary disease
Authors: Antonio P. Mansur, Marcus Perin, Whady A. Hueb, Luíz A. M. César, Eulógio E. Martinez, José A. F. Ramires
Journal: Journal of the American College of Cardiology (2002)
Decitabine Combined with FB3 As Conditional Regimen for Elderly Acute Myeloid Leukemia Patient with Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Shichun Gao, Jia Liu, Kong Peiyan, Li Gao, Cheng Zhang, Yao Liu, Hongju Yan, Lidan Zhu, Defu Zeng, Lei Gao, Xi Zhang
Journal: Blood (2018)
Implementation of Combined Storage of the Hematopoietic Cord Blood Cells and Fetal Mesenchymal Stromal Cells (umbilical cord stromal cells, UCSC) from the Same Donors in Warsaw Cord Blood Bank
Authors: Zygmunt Pojda, Eugeniusz K Machaj, Marzena Korczak, Aleksandra Kopera, Paulina Adamczyk-Wojciechowska, Jadwiga Kuczynska-Sicinska, Romuald Debski, Krzysztof Czajkowski, Monika Turkowska
Journal: Blood (2008)
Eradication of Minimal Residual Disease Using Alemtuzumab Consolidation After High-Dose Methyl-Prednisolone Plus Rituximab (HDMP-R) Is Safe, Effective and Induces Long Term Remission in Chronic Lymphocytic Leukemia
Authors: Januario E. Castro, Lina M. Ariza-Serrano, Juan S. Barajas-Gamboa, Julio A. Diaz-Perez, Danelle F. James, Amine Ale-Ali, Thomas J. Kipps
Journal: Blood (2011)
Abstract 608: Long Non Coding RNA Miat Contributes to Cardiac Hypertrophy and Regulates Ribosomal Genes
Authors: He Wang, Zhihua Wang, Yifan Wang, Christopher Rau, Shuxun Ren, Yibin Wang
Journal: Circulation Research (2019)

Cardiac hypertrophy is characterized by elevated protein synthesis and pathological cardiomyocyte enlargement. The mechanisms underlying the stress response in ribosomal remodeling at organelle level during cardiac hypertrophy is not fully established. We have identified a long non-coding RNA, Myocardial Infarction Associated Transcript (MIAT), that is significantly associated with pathological cardiac hypertrophy through a systems genetic analysis. MIAT expression is induced by hypertrophic signal, and silencing of the MIAT gene significantly blocks myocyte hypertrophy in response to hypertrophic stimuli associated with diminished global protein synthesis activities. Furthermore, MIAT inactivation significantly reduces ribosomal genes at mRNA and protein levels, and reduces protein synthesis activity at basal and post-hypertrophic stimulation in vitro and in vivo . Using a MIAT knockout mouse model, we investigated the in vivo pathophysiological impact of MIAT in pressure-overload induced cardiac hypertrophy and heart failure. Remarkably, we find that the MIAT knockout mice show significantly blunted cardiac hypertrophy and preserved cardiac function following pressure-overload. This study highlights a novel mechanism of translational regulation by a lncRNA MIAT. The outcome will expand functional role of lncRNAs in heart diseases and advance our current understanding of the complexity of regulatory circuits in cardiac hypertrophy and heart failure. It will provide novel insights to protein synthesis and ribosomal regulation and reveal potential therapeutic targets for pathological hypertrophy.
Inactivating Gene Alterations of MHC Class II Transactivator CIITA Are Recurrent in Primary Mediastinal B Cell Lymphoma and Hodgkin Lymphoma
Authors: Christian Steidl, Bruce Woolcock, Sanja Rogic, Susana Ben-Neriah, Adele Telenius, Marie Drake, Reiner Siebert, Randy D. Gascoyne
Journal: Blood (2011)
Abstract 154: Human Highly Proliferative Cells Acquire Endothelial Phenotype and Promote Healing After Experimental Myocardial Infarction
Authors: Haifeng Yin, Sergey Ryzhov, Michael P Robich, Reed Quinn, Robert S Kramer, Calvin P Vary, Douglas B Sawyer
Journal: Circulation Research (2019)

Introduction: The human adult heart contains a subset of mesenchymal cells characterized by high proliferative potential and capability to differentiate into different cell types. We recently demonstrated that a high level of ErbB2 expression is associated with differentiation of human highly proliferative cells (hHiPC) into endothelial cells in vitro. Based on our findings, we hypothesized that ErbB2 high hHiPC play a critical role in early revascularization and repair of injured heart. To test this hypothesis, we performed xenotransplantation of human ERBB2 high hHiPC into mouse hearts and analyzed the phenotype of transplanted cells and cardiac function on day 7 after experimental myocardial infarction (MI). Methods: The effect of ErbB2 high hHiPC was tested in immunodeficient NSG mice. MI was induced by permanent ligation of the left coronary artery. Human ERBB2 high hHiPC (2.5 x 10 5 cells) were injected into the peri-infarct zone immediately after MI. Echocardiography was performed on unsedated mice before and on days 7 after MI. Examination of transplantation efficiency and hHiPC phenotype was performed using flow cytometric analysis of cell suspension obtained from left ventricles (LV). Results: We found that up to 25% of cardiac endothelial cells were represented by cells that originated from hHiPC, as identified by specific expression of human CD31, in mouse LV, on day 7 after MI. The total number of cells expressing mouse or human endothelial cell markers, CD31 and CD105, within non-immune cardiac cell population was higher in mice that received injection of hHiPC compared to control mice (PBS injection) (4.7 vs. 2.9 x 10 5 cells, hHiPC vs. PBS, p= 0.026 ). Echocardiographic analysis revealed that mice which received an injection of ERBB2 high cells demonstrated significantly improved cardiac function compared to control mice injected with PBS (fractional shortening: 21.6% vs. 15.3% for hHiPC vs. PBS, p=0.023 ). Conclusion: ERBB2 high hHiPC survive, undergo endothelial cell differentiation in vivo, and contribute to the pool of cardiac endothelial cells after experimental myocardial infarction. A population of ErbB2 high hHiPC obtained from adult human hearts can be used to improve the revascularization of injured myocardium or other tissues.
Abstract 444: The Phase of Third Harmonic of Radial Pulse Predicts Cardiac Risk in Asymptomatic Patients With Type 2 Diabetes
Authors: Chi-Wei Chang, Kuo-meng Liao, Yi-Ting Chang, Sheng-Hung Wang, Ying-chun Chen, Gin-Chung Wang
Journal: Circulation Research (2019)

Patients with type 2 diabetes (T2DM) have a significantly increased risk of heart disease and adverse cardiac events(ACE). Many of asymptomatic patients with T2DM have myocardial perfusion defects or coronary artery disease and are not recognized by traditional risk factors. The third harmonic of radial pulse has been proved a risk factor for myocardial ischemia. We sought to further investigate if the third harmonic phase of the radial pulse(P3) could be an independent predictor of ACE and cardiac dysfunction in asymptomatic T2DM patients. The study consisted of 1968 asymptomatic T2DM patients who had no history of angina and cardiovascular disease. We conducted the pulse wave measurement at baseline and dived the enrolled patients into quartile groups based on P3 value(&gt;3.2, 3.0 to 3.2, 2.7 to 3.0, and &lt;2.7). Participated patients received an average of 1.8 years of follow-up. To assess the risk of ACE , the primary outcomes were the composite of myocardial infarction, heart failure, and cardiovascular death. To measure the risk of cardiac dysfunction, the secondary outcomes were composed of newly discovered single or multi coronary stenosis, myocardial ischemia, and left ventricular dysfunciton. Cox proportional hazards model were used. Reference to patients with P3&gt;3.2, the hazard ratios(HR) of patients with P3&lt;2.7 were as follows: (1) myocardial infarction(HR, 1.98; 95% CI, 1.32-2.98), heart failure(HR, 1.64; 95% CI, 0.88-3.06), and cardiovascular death(HR, 3.51; 95% CI, 0.73-16.9); (2) Single coronary stenosis(HR, 10.1; 95% CI, 1.29-78.7), multi coronary stenosis(HR, 9.06; 95% CI, 1.15-71.5), myocardial ischemia(HR, 3.05; 95% CI, 1.37-6.80), and low left ventricular ejection fraction(HR, 2.09; 95% CI, 1.13-38.7). The trend analysis further demonstrated that the reducing P3 leads to higher incidence of both primary and secondary composite outcomes(P&lt;0.001). After adjusting for age, gender, smoking, systolic blood pressure, dyslipidemia, duration of diabetes, and Hba1c, P3 was still an independent predictor of ACE and cardiac dysfunction (P trend &lt;0.005). Conclusively, this report suggested that P3 provides independent predictive value for risk assessment of ACE and cardiac dysfunction in asymptomatic patients with T2DM.
Gender medicine and oncology: report and consensus of an ESMO workshop
Authors: A.D. Wagner, S. Oertelt-Prigione, A. Adjei, T. Buclin, V. Cristina, C. Csajka, G. Coukos, U. Dafni, G.-P. Dotto, M. Ducreux, J. Fellay, J. Haanen, A. Hocquelet, I. Klinge, V. Lemmens, A. Letsch, M. Mauer, M. Moehler, S. Peters, B.C. Özdemir
Journal: Annals of Oncology (2019)
Identification of Significant Barriers to Accrual (BtA) to NCI Sponsored Multiple Myeloma – Clinical Trials (MM-CT): A Step towards Improving Accrual to Clinical Trials.
Authors: Matthias Weiss, Susanna Jacobus, Rafat Abonour, Kenneth C. Anderson, Bart Barlogie, Natalie Callander, Edward J. Gorak, Antje Hoering, Robert C. Kane, Michael S Katz, Jeffrey Matous, Glenn M. Mills, James Omel, Robert Z. Orlowski, S. Vincent Rajkumar, Paul G. Richardson, LeeAnn Jensen, Richard F. Little, Morie A Gertz, Nikhil C. Munshi
Journal: Blood (2012)
Risk Factors for Early Mortality in Hemato-Oncological Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia
Authors: Liat Shargian-Alon, Anat Gafter-Gvili, Ofir Wolach, Moshe Yeshurun, Pia Raanani, Dafna Yahav
Journal: Blood (2018)
Analysis of Temporal Trends and Variation in the Use of Defibrillation Testing in Contemporary Practice
Authors: Ryan T. Borne, Tiffany Randolph, Yongfei Wang, Jeptha P. Curtis, Pamela N. Peterson, Frederick A. Masoudi, Amneet Sandhu, Matthew M. Zipse, Kevin Thomas, Valentina Kutyifa, Nihar R. Desai, Yong-Mei Cha, Jonathan C. Hsu, Andrea M. Russo
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Defibrillation testing (DFT) is performed during implantable cardioverter-defibrillator (ICD) implantation to assess the capacity of the device to detect and terminate ventricular arrhythmias. However, DFT can result in complications and omission of its use has been shown to be safe. <h3>Objective</h3> To describe temporal trends and variation in the use of DFT in contemporary practice in the United States. <h3>Design, Setting, and Participants</h3> This multicenter cross-sectional study used data from the National Cardiovascular Data Registry ICD Registry. A total of 499 211 patients from 1794 different facilities undergoing first-time ICD implantation from April 2010 to December 2015 were included. Data analysis was performed from May 20, 2015, to August 15, 2019. <h3>Exposure</h3> Defibrillation testing was assessed using the National Cardiovascular Data Registry ICD Registry. <h3>Main Outcomes and Measures</h3> Defibrillation testing rates and median odds ratios (MORs) were assessed over time. The MOR represents the odds that a randomly selected patient receiving testing at a hospital with high testing rates would be tested compared with if he or she had received care at a hospital with low testing rates. <h3>Results</h3> Of the 499 211 patients from 1794 different facilities included in this analysis, the mean (SD) age of the population was 65.5 (13.4) years and 356 681 patients (71.4%) were men. The use of DFT declined from 71.6% in the first calendar quarter of 2010 to 36.4% in the fourth quarter of 2015 (<i>P</i> &lt; .001). Patients undergoing DFT were more likely than those without testing to have ischemic heart disease (170 569 [58.1%] vs 116 295 [56.6%]), ventricular tachycardia (91 500 [31.2%] vs 58 949 [28.7%]), and less advanced heart failure (New York Heart Association class I and II, 153 188 [52.2%] vs 91 215 [44.4%]) (<i>P</i> &lt; .001 for all). The MOR for the use of defibrillation testing was 3.78 (95% CI, 3.54-4.03) in 2010, increasing to 6.05 (95% CI, 5.61-6.52) in 2015, indicating that by 2015 a randomly selected patient receiving testing at a hospital with high testing rates would have a 6-fold higher odds of being tested than if they had received care at a hospital with low testing rates. <h3>Conclusions and Relevance</h3> Defibrillation testing at the time of ICD placement in the United States may have declined over time; however, institutional variation in its use appears to be marked and increased. This variability in the reduced use of defibrillation testing could reflect differences in individual or institutional cultures of practice.
Abstract 14982: Association Between Industry Payments to Physicians and Device Selection: A Report From the NCDR ICD Registry
Authors: Amarnath Annapureddy, Karl E Minges, Shady Henien, Yongfei Wang, Joseph S Ross, Erica S Spatz, Nihar Desai, Jeptha P Curtis
Journal: Circulation (2018)

Introduction: The Sunshine Act requires public disclosure of payments from biomedical manufacturers to physicians. Early reports indicated that cardiologists were among the specialists who received...
A Case Report of Refractory Immune Thrombocytopenia (ITP) Following Reduced Intensity Conditioning (RIC) Hematopoietic Cell Transplantation (HCT) for Myelodysplastic Syndrome (MDS) Successfully Treated with Off-Label Use of Daratumumab
Authors: Yazan Migdady, Ridhi Gupta, Asiri Ediriwickrema, Francisco Socola, Sally Arai, Beth A Martin
Journal: Blood (2018)
Targeting Proteases in Cystic Fibrosis Lung Disease. Paradigms, Progress, and Potential
Authors: Michael C. McKelvey, Sinéad Weldon, Daniel F. McAuley, Marcus A. Mall, Clifford C. Taggart
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Cystic fibrosis (CF) is the most common life-limiting hereditary condition of Caucasian populations and is characterised by chronic airways inflammation driving progressive structural lung damage.Despite tremendous advances in the treatment of CF and concomitant increased life expectancy for patients, chronic lung disease remains the main cause of morbidity and mortality among CF patients.While universal restoration of cystic fibrosis transmembrane conductance regulator activity remains a future hope, novel therapies aimed at reducing or preventing chronic airways inflammation and progressive structural lung damage are required.It is well-established that proteolytic enzymes are important in the CF lung beyond the basic turnover of proteins and intracellular degradation of pathogens.When secreted, these enzymes play key roles in extracellular substrate modification implicated in important biological processes such as matrix and airway remodelling, goblet cell metaplasia and mucus hypersecretion, immune cell recruitment and dysregulation of epithelial ion channels.Importantly, the burden of proteases in the CF lung is significantly elevated, overwhelming the endogenous antiprotease shield.Indeed, free protease activity has emerged as a major risk factor of the onset and progression of bronchiectasis and lung function decline in patients with CF.Recent research has highlighted the importance of new players such as cathepsin S and matrix metalloprotease-12, as well as the membrane-associated activity of key proteases such as neutrophil elastase on the surface of neutrophils.Here, we review the current knowledge and emerging concepts of the role of host proteases in the pathogenesis of CF lung disease and their potential as therapeutic targets.
Outcome Of Patients With HTLV-1 Associated Adult T-Cell Leukemia/Lymphoma (ATL) Who Have Undergone Stem Cell Transplantation: A Retrospective Study Of The EBMT Lymphoma Working Party
Authors: Ali Bazarbachi, Kate Cwynarski, Ariane Boumendil, Herve Finel, Paul Fields, Kavita Raj, Arnon Nagler, Mohamad Mohty, Anna Sureda, Peter Dreger, Olivier Hermine
Journal: Blood (2013)
Allogeneic Stem Cell Transplantation Overcomes Negative Impact on Relapse Rate and Progression Free Survival in 294 Non-Remission AML Patients with Adverse Cytogenetic Abnormalities Other Than Monosomal or Complex Karyotype
Authors: Mitsuhiro Yuasa, Michiho Ebihara, Daisuke Kaji, Kosei Kageyama, Aya Nishida, Shinsuke Takagi, Hisashi Yamamoto, Go Yamamoto, Yuki Asano-Mori, Atsushi Wake, Akiko Yoneyama, Shigeyoshi Makino, Naoyuki Uchida, Shuichi Taniguchi
Journal: Blood (2018)
Does Methotrexate Affect Transplant Outcomes? Transplant Related Mortality (TRM), Engraftment, Graft Vs. Host Disease (GvHD), Overall Survival (OS) and Event Free Survival (EFS) in 142 Consecutive Pediatric Cord Blood Transplants (CBT) At Children's Memorial Hospital (CMH)
Authors: Morris Kletzel, Mebhoob Merchant, Nazneen Merchant, Alfred Rademaker, Reggie Duerst, Sonali Chaudhury, Jennifer Schneiderman, William T. Tse
Journal: Blood (2011)
Christopher Dobson: chemist whose work on proteins advanced research into neurodegenerative diseases
Authors: Rebecca Wallersteiner
Journal: BMJ (2019)

St John’s College, Cambridge

Christopher Dobson, master of St John’s College, Cambridge, whose work on proteins advanced research into diseases such as Parkinson’s and Alzheimer’s, died at the Royal Marsden Hospital, Surrey, at the age of 69.

Born in Rinteln, Germany, the son of Arthur Dobson, an army officer, and Mabel, nee Pollard, Christopher Dobson was educated at Hereford Cathedral Junior School, Abingdon School (where he was a rowing cox), and Keble College, Oxford, where he took a first in chemistry before going on to take a DPhil at Merton College. Both his parents were originally from Bradford in Yorkshire and had left school aged 14. He had two elder siblings, Graham and Gillian. Because of his father’s postings, Dobson’s early life was fairly nomadic. “He grew up in Nigeria in the formative part of his childhood, which created a lifelong fascination with different cultures,” said his son, William. He first wanted to be an architect but owing to “inspirational science teachers” at Abingdon, he instead chose to study chemistry at university.

Dobson devoted his life to researching diseases such as Parkinson’s and Alzheimer’s and understanding the chemical processes that disrupt the production of healthy proteins and instead trigger their aggregation into toxic clumps. He became one of the world’s leading experts on protein “folding” and “aggregation,” and its links to neurodegenerative conditions. “Alzheimer’s disease is a new ‘plague,’ already affecting 40 million people worldwide,” he said. “It’s one of a group of non-infectious diseases that terrifies us.”

In 1906 …
B0 Vs. Non-B0 Genotype: Differences in Non-Transfusion-Dependent Thalassemia Patients
Authors: Alessia Pepe, Laura Pistoia, Domenico Maddaloni, Teodosio Grippo, Monica Benni, Leonardo Sardella, Maria Grazia Sanna, Giovanni Giugno, Giulia Guerrini, Aurelio Maggio, Stefania Renne, Massimiliano Missere, Vincenzo Positano, Antonella Meloni
Journal: Blood (2018)