tbuckley/cabot-search huggingface dataset:
Abstract 265: Systemic Inflammation and Cardiac Macrophage Infiltration Accompany Stretch-induced Myocardial Injury in Swine Subjected to Transient Pressure Overload
Authors: Brian R Weil, Kristen Kosmerl, Dorcas Nsumbu, Rebeccah Young, Shannon Allen, John M Canty
Journal: Circulation Research (2020)

Objective: Transient pressure overload (TPO) elicits stretch-induced myocyte injury in the absence of ischemia or infarction, but the extent to which this is associated with inflammation is unclear. The present study was designed to assess immune activation after TPO in swine and compare the inflammatory cytokine profile to that observed after myocardial infarction (MI). Methods: Swine received a brief infusion of phenylephrine (18 mg/hr iv; 30-60 min) to induce TPO and were studied for 1 hr (n=5), 3 hr (n=6), or 24 hr (n=6) before analysis of myocardial macrophage gene expression (CD68) via qPCR. Serial blood sampling was performed to assess neutrophil and monocyte counts as well as circulating cardiac troponin I (cTnI), IL-6, TNF-α, and CRP. Cytokine levels were compared to those from a separate group (n=5) subjected to a 60 min LAD occlusion to produce MI. Results: TPO increased circulating cTnI (from 20±5 ng/L to 340±58 ng/L at 3 hr and 1520±616 ng/L at 24 hr; p&lt;0.01) without evidence of infarction. Compared with controls (n=6), swine subjected to TPO exhibited increased CD68 gene expression at 1, 3, and 24 hr ( A ). This was accompanied by a rise in peripheral blood neutrophils and monocytes ( B ) as well as an elevation in circulating IL-6, TNF-α, and CRP that was comparable to that observed after MI ( C ). Conclusion: Myocyte injury following TPO elicits mobilization of neutrophils and monocytes and a rise in circulating inflammatory cytokines comparable to that observed after MI. This is accompanied by an increase in cardiac macrophages and may be an important mechanism by which repetitive episodes of TPO lead to interstitial fibrosis and diastolic dysfunction without anatomic hypertrophy.
Safety of Allogeneic Stem Cell Transplantation after PD-1 Blockade for Patients with Relapsed/Refractory Classical Hodgkin Lymphoma: Focus on Immune-Related Adverse Events
Authors: Anastasiya Beynarovich, Kirill Lepik, Evgenia Borzenkova, Elena Kondakova, Elena Babenko, Nikita P. Volkov, Ivan S. Moiseev, Aleksander Kulagin, Natalia B. Mikhailova, Marina O. Popova
Journal: Blood (2020)
Activity of Decitabine (DAC) Combined with All-Trans Retinoic Acid (ATRA) in Oligoblastic AML: Subgroup Analysis of a Randomized 2x2 Phase II Trial
Authors: Michael Luebbert, Olga Grishina, Claudia Schmoor, Martina Crysandt, Edgar Jost, Felicitas Thol, Michael Heuser, Katharina S. Götze, Richard F. Schlenk, Konstanze Döhner, Helmut R. Salih, Marcus M. Schittenhelm, Gerhard Heil, Carsten Schwaenen, Carsten Mueller-Tidow, Wolfram Brugger, Andrea Kündgen, Ulrich Germing, Maike de Wit, Stephan Kremers, Aristoteles Giagounidis, Sebastian Scholl, Andreas Neubauer, Jürgen Krauter, Gesine Bug, Ralph Wäsch, Heiko Becker, Christoph Rummelt, Annette M. May, Justus Duyster, Arnold Ganser, Björn Hackanson, Hartmut Döhner
Journal: Blood (2020)
Loss of LKB1/<i>STK11</i> Facilitates Leukemic Progression of the Myeloproliferative Neoplasms
Authors: Christian Marinaccio, Praveen K Suraneni, Hamza Celik, Andrew Volk, Jeremy Q. Wen, Te Ling, Terra Lasho, Richard P. Koche, Christopher Famulare, Brady L. Stein, Sandeep Gurbuxani, Ronald Hoffman, Naseema Gangat, Navdeep Chandel, Ross L. Levine, Raajit K. Rampal, Grant Challen, Ayalew Tefferi, John D. Crispino
Journal: Blood (2020)
T(4; 14) Is Not a Poor Prognostic Factor for Newly Diagnosed Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation in New Drug Era
Authors: Chuanying Geng, Guangzhong Yang, Wen Gao, Huijuan Wang, Yanchen Li, Yin WU, Huixing Zhou, Zhiyao Zhang, Yuan Jian, Wenming Chen
Journal: Blood (2020)
Reducing Cytogenetic Testing in the Era of Next Generation Sequencing (NGS); Are We Choosing Wisely?
Authors: Eri Kawata, Benjamin Hedley, Benjamin Chin-Yee, Anargyros Xenocostas, Alejandro Lazo-Langner, Cyrus C. Hsia, Kang Howson-Jan, Ping Yang, Michael Levy, Stephanie Santos, Chris Howlett, Hanxin Lin, Bekim Sadikovic, Ian Chin-Yee
Journal: Blood (2020)
Airway microbiome studies challenge simplistic models of inhaled tobramycin benefit
Authors: Geraint B Rogers
Journal: Thorax (2020)

In 1999, Ramsey and colleagues published the results of a clinical trial of aerosolised tobramycin in cystic fibrosis (CF) to target chronic Pseudomonas aeruginosa infection.1 In keeping with their earlier demonstration of efficacy,2 they reported treatment to be associated with a reduction in P. aeruginosa sputum density and substantial clinical benefit (improved lung function and reduced risk of hospitalisation). Consistent findings were reported in subsequent studies,3 4 leading tobramycin inhaled powder/solution (TIP/S) maintenance therapy to go on to become the most common antibiotic used to treat people with cystic fibrosis (PWCF). While none of these studies related clinical outcome to microbiological impact directly, it is widely assumed that depletion of P. aeruginosa underpins TIP/S benefit.

This presumptive mechanism of TIP/S, and its limitation to those with chronic P. aeruginosa infection, has been challenged by two recent studies. In this issue, Heirali and colleagues report an investigation of the microbial predictors of response to TIP/S in adults with CF.5 16S rRNA gene amplicon sequencing was applied to banked sputum samples from 41 patients with chronic P. aeruginosa infection who had received TIP/S for at least 1 year and from whom sputum samples were available before and after the initiation of therapy. Somewhat unexpectedly, their study determined response to therapy (defined by the absence of a net decrease in forced expiratory volume in one second (FEV1)) to be associated with higher relative abundance of staphylococci …
The Heme Oxygenase-1/Carbon Monoxide Pathway Activates TLR4 Signaling Promoting Bortezomib Resistance in Multiple Myeloma Cells
Authors: Cesarina Giallongo, Grazia Scandura, Alessandro Barbato, Alessandra Romano, Fabrizio Puglisi, Daniela Cambria, Enrico La Spina, Giuseppe Musumeci, Michelino Di Rosa, Concetta Conticello, Giovanni Li Volti, Giuseppe A. Palumbo, Francesco Di Raimondo, Daniele Tibullo
Journal: Blood (2020)
Phase 2 Study Evaluating the Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Mantle Cell Lymphoma Not Previously Treated with a BTK Inhibitor (CITADEL-205)
Authors: Amitkumar Mehta, Marek Trněný, Jan Walewski, Vincent Ribrag, Caroline Dartigeas, Jacob Haaber Christensen, Fabrizio Pane, Guillermo Rodríguez, Michal Taszner, Parameswaran Venugopal, Vittorio Ruggero Zilioli, Fred Zheng, Douglas J DeMarini, Wei Jiang, Pier Luigi Zinzani
Journal: Blood (2020)
Prognostic Impact of Nutritional Status at Diagnosis and Weight Changes in Acute Myeloid Leukemia Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Dominic Brauer, Donata Backhaus, Vladan Vucinic, Dietger Niederwieser, Uwe Platzbecker, Madlen Jentzsch, Sebastian Schwind
Journal: Blood (2020)
A Phase I/II Study of Twice Weekly Ixazomib Plus Pomalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma: Results from Phase I Dose Escalation Cohorts
Authors: Omar Nadeem, Clifton C Mo, Jacob P. Laubach, Giada Bianchi, Robert Redd, Peter Barth, Trevor J. Bayliss, Vaishali Sanchorawala, Leyla Shune, Alexandra Distaso, Virginia Dalton, Adam S Sperling, Laura Amweg, Mary McKenney, Kathleen Colson, Ella L Millard, Isabella Hou, Alexandra Savell, Kelly Masone, Nikhil C. Munshi, Irene M. Ghobrial, Kenneth Anderson, Paul G. Richardson
Journal: Blood (2020)
Targeting Oncoproteins with a Positive Selection Assay for Protein Degraders
Authors: Sagar Koduri, Adam C. Wang, Mette Ishoey, Joshiawa Paulk, Xiaoxi Liu, Isaac Harris, Jennifer Endress, Benjamin L. Lampson, Christopher J. Ott, James Bradner, Jeffrey A. Medin, Sara J Buhrlage, William Kaelin
Journal: Blood (2020)
Real World Observational Study Using Clonoseq® Next Generation Sequencing in Hematologic Malignancies: The 'Watch' Registry
Authors: Krish Patel, Neil Bailey, Cristina J. Gasparetto, Tomer Mark, Bijal Shah, Jakub Svoboda, Michael A. Thompson, Heidi Simmons, Mark Schliekelman, Allison P. Jacob, Lance Baldo, John M. Pagel
Journal: Blood (2020)
Abstract 369: Infarct Macrophage Secretome Factors Regulate Neutrophil Degranulation
Authors: Michael Daseke, William Kalusche, Elizabeth Flynn, Shelby Konfrst, Merry L Lindsey
Journal: Circulation Research (2020)

Following myocardial infarction (MI), the left ventricle undergoes wound healing that begins withan intense inflammatory response to recruit leukocytes to the infarcted region. Infiltratedneutrophils degranulate, releasing a series of proteases including matrix metalloproteinase(MMP)-9 into the extracellular space. Macrophages also infiltrate into the infarct region, and wehypothesized that the macrophage may secrete factors that regulate neutrophil degranulation.Stimulating bone marrow derived neutrophils from C57BL/6J mice (3-6 month old male) withphorbol myristate acetate (PMA) induced degranulation, as evidenced by release of MMP-9.Co-stimulation with MI day 1 macrophage secretome (10% by volume) reduced PMA-induceddegranulation of MMP-9 by 8-fold (p&lt;0.0014). Transcriptomic analysis of day 1 MI macrophagesrevealed galectin-3, vimentin, fibronectin, and murinoglobulin-1 were highly expressed.Examination of the day 1 MI macrophage secretome also showed high expression of vimentinand fibronectin. To further unmask signaling connections, neutrophils were co-stimulated withPMA and day 1 MI macrophage secretome, along with blocking antibodies for the 4 proteinsindividually. Galectin-3 inhibition promoted the macrophage secretome effect, whilemurinoglobulin-1 inhibition reversed the macrophage secretome effect. Neutrophil stimulationwith recombinant galectin-3 showed no additive effect with PMA on MMP-9 release, suggestingthat galectin-3 works through the protein kinase C signaling pathway to induce neutrophildegranulation. Neither Vimentin inhibition nor stimulation had an effect on neutrophildegranulation Overall, our results uncovered a role for galectin-3 and fibronectin in inducingneutrophil degranulation while murinoglobulin-1 may be a potent inhibitor of degranulation. Theday 1 MI macrophage therefore secretes both factors that promote as well as factors thattemper neutrophil degranulation. The balance of these factors determines the net effect of themacrophage secretome on neutrophil degranulation.
Morphologic Leukemia-Free State in Acute Myeloid Leukemia Is Sufficient for Successful Allogeneic Hematopoietic Stem Cell Transplant
Authors: Cindy M. Pabon, Zhiguo Li, Therese Hennig, Carlos De Castro, Jadee Neff, Mitchell E. Horwitz, Thomas W. Leblanc, Gwynn D. Long, Richard D. Lopez, Anthony D. Sung, Nelson J. Chao, Cristina Gasparetto, Stefanie Sarantopoulos, Donna B. Adams, Harry P. Erba, David A Rizzieri
Journal: Blood (2020)
Antidepressant use and breast cancer risk
Authors: Chloe Chien, Christopher I. Li, Susan R. Heckbert, Kathleen E. Malone, Janet R. Daling
Journal: Cancer Research (2005)

3222  Background: Antidepressants are among the most commonly prescribed drugs in the United States. Laboratory studies suggest that because certain antidepressants increase prolactin levels that they may also increase breast cancer risk. However, human studies evaluating use of antidepressants in relation to breast cancer risk have yielded inconsistent results. Methods: A population-based case-control study consisting of 975 breast cancer cases 65-79 years of age diagnosed from 1997-1999 and 1,007 age and residence-matched controls was conducted in western Washington State. Detailed information on antidepressant use was obtained through a structured in-person interview for each subject. Logistic regression was performed to analyze the relationship between antidepressant use and breast cancer risk. Results: Overall, there was no apparent association between ever use of antidepressants and breast cancer risk (odds ratio [OR] =1.2, 95% confidence interval [95% CI]: 0.9-1.6). When evaluated separately, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), and triazolopyridines were also each not associated with breast cancer risk. First-degree family history of breast cancer modified the association between antidepressant use and breast cancer risk (p
Impact of immunosuppressive therapy on the severity of COVID-19 in solid organ transplant recipients
Authors: Marco Merli, Luisa Pasulo, Giovanni Perricone, Giovanna Travi, Roberto Rossotti, Valeriana Giuseppina Colombo, Riccardo De Carlis, Stefania Chiappetta, Maria Cristina Moioli, Enrico Minetti, Maria Frigerio, Luciano Gregorio De Carlis, Luca Belli, Stefano Fagiuoli, Massimo Puoti
Journal: Journal of Infection (2020)
AB0007 The distribution of hla-drb1 alleles in the russian population with protracted rheumatoid arthritis (ra)
Authors: LA Taukumova, IA Gousseva
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The objective was to assess the distribution and possible associations of HLA-DRB1 alleles in the Russian population with long standing rheumatoid arthritis. <h3>Methods</h3> Forty four patients (pts) with RA (2 males, 42 females, mean age 53.3 ± 10.85 yr. and mean disease duration 12.9 ± 7.71 yr. and 135 controls were typed for HLA-DRB1 alleles using PCR based molecular techniques. Radiological outcome was measured by scoring X-rays of the hands and feet using the standard radiographs of Larsen (Larsen score). Patients were stratified by RF status and the results were analysed using the Fisher exact test. <h3>Results</h3> The frequency of individuals with DRB1*04 (p &lt; 0.00001) was significantly higher, DRB1*05 (p &lt; 0.04) and *07 (p &lt; 0.006) were lower in the pts in compare with the controls. HLA-DRB1*04 proved to be significantly increased in seropositive pts (p &lt; 0.038). RF(+) pts with homozygous status for HLA-DRB1*04 (p &lt; 0.04) had significantly higher radiological score (p &lt; 0.05). <h3>Conclusion</h3> Protracted RA in the Russian population is characterised by high frequency HLA-DRB1*04 and low distribution DRB1*05 and DRB1*07. In RF(+) RA pts there was association between the presence DR4 and radiological severity.
Subgroup Analyses of Elderly Patients Aged ≥ 70 Years in MAGNIFY: A Phase IIIb Interim Analysis of Induction R2 Followed By Maintenance in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
Authors: Frederick Lansigan, David Jacob Andorsky, Morton Coleman, Abdulraheem Yacoub, Jason M. Melear, Suzanne R. Fanning, Kathryn S. Kolibaba, Christopher M. Reynolds, Grzegorz S. Nowakowski, Mecide Gharibo, Erin Ahn, Ju Li, Mathias J. Rummel, Jeff P Sharman
Journal: Blood (2020)
Intratumoral CpG, Local Radiation, and Oral Ibrutinib Combine to Produce Effective <i>in Situ</i> Vaccination in Patients with Low-Grade B-Cell Lymphoma
Authors: Tanaya Shree, Michael S. Khodadoust, Debra K. Czerwinski, Matthew J. Frank, Sara Beygi, Steven R. Long, Brock Martin, Ronald Levy
Journal: Blood (2020)
Multimodal imaging of bacterial-host interface in mice and piglets with <i>Staphylococcus aureus</i> endocarditis
Authors: Peter Panizzi, Marvin Krohn-Grimberghe, Edmund Keliher, Yu-Xiang Ye, Jana Grune, Vanessa Frodermann, Yuan Sun, Charlotte G. Muse, Kaitlyn Bushey, Yoshiko Iwamoto, Mandy M. T. van Leent, Anu Meerwaldt, Yohana C. Toner, Jazz Munitz, Alexander Maier, Georgios Soultanidis, Claudia Calcagno, Carlos Pérez-Medina, Giuseppe Carlucci, Kay P. Riddell, Sharron Barney, Glenn Horne, Brian Anderson, Ashoka Maddur-Appajaiah, Ingrid M. Verhamme, Paul E. Bock, Gregory R. Wojtkiewicz, Gabriel Courties, Filip K. Swirski, William R. Church, Paul H. Walz, D. Michael Tillson, Willem J. M. Mulder, Matthias Nahrendorf
Journal: Science Translational Medicine (2020)

Multimodal intravital microscopy and PET imaging of S. aureus endocarditis can monitor adjuvant immunotherapy in mice and pigs.
GENDER IN SMALL-CELL LUNG CANCER (SCLC): AN ANALYSIS OF CHEMOTHERAPY TRIALS FROM THE MANCHESTER LUNG CANCER GROUP (MLCG) AND THE UK MEDICAL RESEARCH COUNCIL CLINICAL TRIALS UNIT (MRC CTU)
Authors: P. Wheatley-Price, C. Ma, L. F. Ashcroft, M. Nankivell, R. J. Stephens, S. C. White, P. Lorigan, N. Thatcher, F. H. Blackhall, F. A. Shepherd
Journal: Annals of Oncology (2008)
Impact of Deletion6q23 Identified By FISH in Patients with Chronic Lymphocytic Leukemia
Authors: Hadiyah Y. Audil, Paul J. Hampel, Daniel L. Van Dyke, Sara J. Achenbach, Kari G Rabe, Stephanie A. Smoley, Timothy G. Call, Wei Ding, Min Shi, Curtis A. Hanson, Yucai Wang, Eli Muchtar, Amber B. Koehler, Susan M. Schwager, Jose F. Leis, Esteban Braggio, Susan L. Slager, Neil E. Kay, Saad S. Kenderian, Sameer A. Parikh
Journal: Blood (2020)
Abstract 259: Dysregulation of AMP-activated Protein Kinase-alpha Isoforms in Left Ventricular Myocardium of Dogs With Chronic Heart Failure
Authors: Ramesh C Gupta, Vinita Singh-Gupta, Hani N Sabbah
Journal: Circulation Research (2020)

Background: The adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) plays critical roles in regulating cellular growth and metabolism and is activated when cellular ATP levels decrease. The heterotrimeric structure of AMPK consists of a catalytic alpha (α) subunit and regulatory beta (β) and gamma (γ) subunits. The two isoforms of the catalytic α subunit have different cellular localization: AMPKα1 is predominantly found in the non-nuclear fraction and AMPKα2 is found in both the nuclear and the non-nuclear fractions. Both AMPKα isoforms reside in cardiomyocytes, increased expression of AMPKα1 during stress can trigger an increased inflammatory state whereas AMPKα2 has recently been recognized as a regulator of mitophagy, the selective degradation of damaged mitochondria by autophagy. Dysregulation in AMPKα1 and AMPKα2 has been reported in explanted failed human hearts. This study tested the hypothesis that mRNA and protein expression levels of AMPKα1 increase and that of AMPKα2 decrease in LV myocardium of dogs with chronic heart failure (HF) produced by microembolization. Methods: RNA was extracted and sodium dodecyl sulfate (SDS)-extract homogenate prepared from LV tissue of 6 dogs with microembolization-induced HF and 6 normal (NL) dogs. mRNA expression of AMPKα1 and AMPKα2 was measured using real-time PCR and normalized to GAPDH. Protein expression of AMPKα1 and AMPKα2 was measured by Western blotting and normalized to GAPDH. Bands were quantified in densitometric units (du). Results: mRNA and protein levels of GAPDH, used as internal control, were similar between NL and HF dogs. In HF dogs, mRNA expression of AMPKα2 was reduced by 5.09 fold and protein levels were reduced by 2.08 fold (1.02 ± 0.09 vs. 2.12 ± 0.18 du, p&lt;0.05) compared to NL dogs. In HF dogs, AMPKa1 mRNA and protein levels were increased 5.67 fold and 2.09 fold (0.67 ± 0.10 vs. 0.32 ± 0.03 du, p&lt;0.05), respectively compared to NL dogs. Conclusions: The results indicate that in LV myocardium of dogs with chronic HF, mRNA and protein levels for AMPKα1 are upregulated while AMPKα2 levels are downregulated compared to NL dogs. This AMPK isoform shift can trigger abnormalities of mitochondrial respiration and turnover that contribute to an abnormal energetic state characteristic of the failing heart.
Impact of Gain and Amplification of 1q in Newly Diagnosed Multiple Myeloma Patients Receiving Carfilzomib-Based Treatment in the Forte Trial
Authors: Mattia D'Agostino, Marina Ruggeri, Sara Aquino, Nicola Giuliani, Maddalena Arigoni, Massimo Gentile, Martina Olivero, Iolanda Donatella Vincelli, Andrea Capra, Chiara Mussatto, Antonio Ledda, Paola Tacchetti, Caterina Musolino, Claudia Cellini, Francesca Patriarca, Stelvio Ballanti, Raffaele Calogero, Pellegrino Musto, Mario Boccadoro, Francesca Gay
Journal: Blood (2020)
Abstract 377: The Role of Impaired Lymphatic Drainage in Cardiac Transplantation
Authors: Sydney C Ginn, Lanfang Wang, Rebecca D Levit
Journal: Circulation Research (2020)

Functional lymphatic drainage inherently modulates cardiac function by maintaining the immune response and tissue-fluid homeostasis. During cardiac transplantation, the lymphatic collecting vessels are severed at the time of heart excision and not surgically reconstructed in the recipient. The consequence resulting from impaired lymphatic drainage in transplanted hearts is unknown. We hypothesize disruption of lymphatic drainage potentiates chronic inflammation by impeding the egress of immune cells and pro-inflammatory cytokines out of the myocardium exacerbating transplant rejection. Methods: Banked human allograft biopsies were utilized to retrospectively evaluate lymphatic differences between patients that did and did not develop chronic transplant rejection from 1 week to 5 years after surgery. Immunofluorescence staining permitted quantification of normalized lymphatic vessel number and area throughout the lifespan of each cardiac allograft (n=24). Autopsy patients with non-cardiac related fatalities served as controls to delineate normal cardiac lymphatic distribution (n=6). Results: Patients without chronic rejection displayed an initial presence of lymphatic vasculature that steadily declined (n=12), while patients with chronic rejection exhibited a delayed increase in lymphatic development (n=12). Conclusions: These data show significant differences in lymphatic area between patients with and without chronic transplant rejection at critical timepoints, suggesting delayed lymphangiogenesis may correlate with rejection. Translational Impact: These preliminary human data support further investigation into lymphatic-modifying therapeutics to prolong the life of cardiac allografts.
Role of Hypercoagulable Studies in Cryptogenic Stroke: A Retrospective Study
Authors: Amulya Prakash, Sindhuja Korem, Sindhura Inkollu, Haresh Gandhi, Farrukh Iqbal, Peter Abaskhroun, Julio Pernia, Juan Rojas, Vinit Singh, Doantrang T. Du
Journal: Blood (2020)