tbuckley/cabot-search huggingface dataset:
Cardiac glycosides are broad-spectrum senolytics
Authors: Ana Guerrero, Nicolás Herranz, Bin Sun, Verena Wagner, Suchira Gallage, Romain Guiho, Katharina Wolter, Joaquim Pombo, Elaine E. Irvine, Andrew J. Innes, Jodie Birch, Justyna Glegola, Saba Manshaei, Danijela Heide, Gopuraja Dharmalingam, Jule Harbig, Antoni Olona, Jacques Behmoaras, Daniel Dauch, Anthony G. Uren, Lars Zender, Santiago Vernia, Juan Pedro Martínez-Barbera, Mathias Heikenwalder, Dominic J. Withers, Jesús Gil
Journal: Nature Metabolism (2019)
What Are Patients' Preferences and Satisfaction Regarding Modes of Administration for the Treatment of Chronic Lymphocytic Leukemia (CLL), Diffuse Large B-Cell Lymphoma (DLBCL), and Follicular Lymphoma (FL)?
Authors: Mark Price, Arliene Ravelo, Elisa Weiss, Peggy Ann Torney, Victor Gonzalez, Maria Sae-Hau, Carol Mansfield, Eydith Comenencia-Ortiz, Miko Cunanan, Anthony Masaquel, Keith L Dawson
Journal: Blood (2018)
Survival of AML Patients Relapsing after Hematopoetic Stem Cell Transplantation: A Single Center Experience
Authors: Pelin Aytan, Mahmut Yeral, Aslı Korur, Cigdem Gereklioglu, Funda Tanrıkulu, Mutlu Kasar, Soner Solmaz, Nurhilal Buyukkurt, Suheyl Asma, Ilknur Kozanoglu, Hakan Ozdogu, Can Boga
Journal: Blood (2018)
Impact of ABO Incompatibility on Engraftment , Transfusion Requirement and Survival after Unrelated Cord Blood Transplantation：a Single Institute Experience in China
Authors: Jiawei Yan, Guangyu Sun, Wen Yao, Lei Zhang, Xiang Wan, Baolin Tang, Xiaoyu Zhu, Kaiyang Ding, Changcheng Zheng, Huilan Liu, Zimin Sun
Journal: Blood (2014)
Successful Empirical Antifungal Therapy of Intravenous Itraconazole with Pharmacokinetic Evidence in Pediatric Cancer Patients Undergoing Hematopoietic Stem Cell Transplantation
Authors: Hyery Kim, Donghoon Shin, Ji Won Lee, Mi Kyoung Jang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn, Kyung-Sang Yu, Hyoung Jin Kang
Journal: Blood (2011)
Abstract 894: Inhibition of Long Noncoding RNA lncExACT1 Induces Physiological Cardiac Hypertrophy and Protects Against Pathological Hypertrophy
Authors: Haobo LI, Xiaojun Liu, Chunyang Xiao, Guoping Li, Ashish Yeri, Anthony Rosenzweig
Journal: Circulation Research (2019)

Long noncoding-RNAs (lncRNAs) are critical regulators of cardiac development as well as pathological hypertrophy and heart failure (HF). However, their roles in exercise-induced physiological hypertrophy are unclear. Here, we used RNAseq to identify a novel class of cardiac lncRNAs that are dynamically regulated by exercise. We call these l ong n on c oding Ex ercise A ssociated C ardiac T ranscripts (lncExACTs). Among them, lncExACT1, a highly conserved lncRNA, is down-regulated in exercised hearts but upregulated in transverse aortic constriction (TAC)-induced pathological hypertrophy and HF. In primary neonatal cardiomyocytes (CMs), transfection of LNA antisense oligonucleotide complementary to lncExACT1 (GapmeR) was sufficient to inhibit lncExACT1 expression and increase CM size with a gene expression pattern consistent with physiological hypertrophy (increased PCG1α and α/βMHC ratio, all p &lt;0.05 vs . control). In contrast, lentiviral overexpression of lncExACT1 in primary CMs induced a pathological gene expression pattern (decreased PCG1α and β/αMHC ratio, with increased ANP and BNP, all p &lt;0.05 vs . control). In vivo, GapmeR treatment for two weeks reduced cardiac lncExACT1 expression (0.5-fold at 2 weeks), increased ventricular wall thickness and fractional shortening (FS, p =0.034 vs . control), increased heart weight to tibial length ratio (HW/TL) and α/βMHC. In contrast, injection of AAV9-lncExACT1 increased cardiac lncExACT1 (6-fold at 5 weeks) increased HW/TL as well as βMHC and ANP. Further, lncExACT1 acted as a sponge for microRNA-222 (a microRNA we previously reported is necessary for physiological cardiac growth) thereby increasing expression of microRNA-222 targets, including p27, a cell cycle inhibitor protein. Moreover, GapmeR injection reduced TAC-induced increase of interventricular septal end diastole (IVSd) and left Ventricular Posterior Wall Dimensions (LVPWd) without affecting FS. We conclude that inhibition of lncExACT1 is sufficient to induce physiological hypertrophy and protect against pathological hypertrophy, while induction of lncExACT1 promotes pathological hypertrophy. lncExACT1 appears to mediate these effects, at least in part, by acting as competing endogenous RNA for microRNA-222.
Very High Efficacy of Bendamustine, Gemcytabine and Dexamethasone (BGD) in Relapsed/Refractory Classical Hodgkin Lymphoma
Authors: Ryszard Swoboda, Jacek Najda, Katarzyna Dulik, Anna Kwiatkowska-Pamula, Maja Twardosz, Sebastian Giebel
Journal: Blood (2018)
Enhancing the electronic health record to promote and measure adherence to breast cancer clinical pathways.
Authors: Lauren E. Geisel, Helen M. Johnson, Andrew Weil, Mahvish Muzaffar, Nasreen A. Vohra, Phyllis DeAntonio, Katherine H. Mulligan, Chantel L. Morey, Jan H. Wong
Journal: Journal of Clinical Oncology (2019)

322 Background: Clinical pathways are widely accepted tools for improving the quality of cancer care. We developed and implemented, within the electronic health record (EHR), a standardized multidisciplinary breast cancer conference template comprised of NCCN clinical pathway elements, with triggers to promote adherence and measure compliance. Methods: The records of breast cancer patients diagnosed from January 2016 to December 2017 were reviewed. Baseline data on (1) the documentation of clinical stage prior to prospective presentation at multidisciplinary conference, (2) documentation of family history, and (3) functional breast imaging utilization were recorded. EHR enhancements developed throughout 2018 were implemented in January 2019. Post-implementation data were obtained via an EHR query of records from January 2019 to the present. Results: At baseline, 56.5% of new patients (n = 435) had a clinical stage documented appropriately (goal 100%). After the EHR enhancements went live, this rate increased to 76.9% (n = 78 new diagnoses), ranging from 40% for patients with metastatic disease to 85.7% for non-metastatic. Compared with baseline data, EHR-derived data from 149 multidisciplinary conference notes demonstrated relatively stable rates of compliance with the family history and imaging metrics: 94.3% to 93.9% (goal 100%), and 12.8% to 13.4% (goal ≤20%), respectively. In 2019, there were 128 instances of an EHR trigger prompting physicians to review the multidisciplinary conference recommendations. While 89.1% of users responded that they reviewed the note, only 42.1% of these clicked on the link to view it. Conclusions: The EHR is a powerful tool for incorporating clinical pathways into oncology providers’ daily workflow. Quality improvement data can be extracted rapidly and efficiently, which facilitates continuous QI. We observed a notable improvement in documentation of clinical staging prior to multidisciplinary conference after the implementation of the clinical pathways in the EHR. Our first report identified several areas for improvement, which will be the focus of subsequent PDSA cycles.
The microenvironmental niche in classic Hodgkin lymphoma is enriched for CTLA-4- positive T-cells that are PD-1-negative
Authors: Sanjay S. Patel, Jason L. Weirather, Mikel Lipschitz, Ana Lako, Pei-Hsuan Chen, Gabriel K. Griffin, Philippe Armand, Margaret A. Shipp, Scott J. Rodig
Journal: Blood (2019)
Perioperative omega-3 fatty acids fail to confer protection in liver surgery: Results of a multicentric, double-blind, randomized controlled trial
Authors: Michael Linecker, Florin Botea, Dimitri Aristotele Raptis, Diana Nicolaescu, Përparim Limani, Ruslan Alikhanov, Pavel Kim, Andrea Wirsching, Philipp Kron, Marcel A. Schneider, Christoph Tschuor, Patryk Kambakamba, Christian Oberkofler, Michelle L. De Oliveira, John Bonvini, Michail Efanov, Rolf Graf, Henrik Petrowsky, Igor Khatkov, Pierre-Alain Clavien, Irinel Popescu
Journal: Journal of Hepatology (2019)
Abstract 341: Efficient Large-scale Sarcomere Tracking (sarctrack) to Assess HCM Variants in iPSC-CMs
Authors: Christopher Toepfer, Arun Sharma, Amanda Garfinkel, Marcelo Cicconet, Radhika Agarwal, Anant Chopra, Christopher Chen, Jonathan Seidman, Christine Seidman
Journal: Circulation Research (2019)

Variants that drive HCM and associated adverse patient outcomes are found in the cardiac sarcomere. These variants range from those that are known to be pathogenic to those that are likely pathogenic or even variants of unknown significance (VUS). CRISPR/Cas-9 engineering has accelerated our ability to generate variants in iPSC to probe changes in cellular function and assess cellular pathogenicity in VUSs. However, iPSC-CMs are not as functionally mature as adult cardiomyocytes. For this reason we have developed a platform to assess contractile function directly at the level of the sarcomere. We use a custom built MatLab algorithm to assess sarcomere length, contraction time, relaxation time, and beat rate of individual sarcomeres within iPSC-CMs. Sarcomeres are visualised using reporter lines that have been engineered with an N-terminal TTN-GFP. We assess the contractile function of thick filament variants in MYH7 and MYBPC3. We show the ability to detect changes in key contractile parameters. This platform allows the screening of pharmacological compounds against these reporter lines with engineered variants.
Abstract 718: Reparative Macrophage Transplantation for Myocardial Repair: A Refinement of Bone Marrow Mononuclear Cell-Based Therapy
Authors: Mihai-Nicolae Podaru, Laura Fields, Satoshi Kainuma, Yuki Ichihara, Mohsin Hussain, Tomoya Ito, Kobayashi Kazuya, Fulvio D'Aquisto, Anthony Mathur, Fiona Lewis, Ken Suzuki
Journal: Circulation Research (2019)

Background: Reparative (alternatively activated or M2-like) macrophages play an important role in post-myocardial infarction (MI) cardiac repair. Transplantation of bone marrow mononuclear cells (BM-MNCs) is an emerging therapy for MI while its therapeutic efficacy in previous clinical trials is not satisfactory. We hypothesized that induced differentiation/polarisation of BM-MNCs to reparative macrophages before transplantation may enhance the effect of BM-MNC transplantation. Purpose: This study aimed to develop a robust in vitro protocol to produce reparative macrophages from BM-MNCs and to establish the pre-clinical proof of concept data for reparative macrophage transplantation for the treatment of MI. Methods &amp; Results: Mouse BM-MNCs were treated with M-CSF plus IL-4, IL-10, TGF-β1 or combinations of these in vitro . The concomitant M-CSF+IL-4 protocol produced the highest rate and number of CD11b + F4/80 + CD206 + macrophages. Expression and secretion of tissue repair-related factors of the produced cells, including IGF-1, TGF-β1, VEGF and IL1-ra, were more extensive compared to BM-MNCs. Then, reparative macrophages, BM-MNCs or PBS only were intramyocardially injected in a mouse MI model. At 4 weeks after treatment, echocardiography demonstrated that reparative macrophage transplantation markedly improved cardiac function (left ventricular ejection fraction; 57.2±1.6%, n=11) compared to both BM-MNC transplantation (48.4±1.3%, n=9) and control group (44.4±2.0%, n=9). Histological studies showed that infarct size was the smallest after reparative macrophage transplantation in association with the greatest tissue repair in the peri-infarct myocardium, including augmented microvascular formation, reduced cardiomyocyte hypertrophy and reduced pathological interstitial fibrosis. It was also found that reparative macrophage transplantation increased host-derived reparative macrophages through TGF-β1 secretion. Conclusion: M-CSF+IL-4 treatment was effective in producing reparative macrophages from BM-MNCs in vitro . Addition of this pre-treatment improved the therapeutic effect of BM-MNC transplantation. Further pre-clinical and clinical development of this advanced cell therapy is warranted.
Syndecan-1 Is Essential for the Myeloma Cell Growth Factor Activity of EGF-Family Ligands in Multiple Myeloma.
Authors: Karène Mahtouk, Friedrich W. Cremer, Thierry Rème, Michel Jourdan, Marion Baudard, Jérome Moreaux, Guilhem Requirand, Geneviève Fiol, John De Vos, Marion Moos, Philippe Quittet, Hartmut Goldschmidt, Jean-Francois Rossi, Dirk Hose, Bernard Klein
Journal: Blood (2005)
Abstract 15890: ACEI and ARB Use Modulates Blood Pressure Response During Initiation of Vascular Endothelial Growth Factor Receptor Inhibition
Authors: Wendy Bottinor, Ali Manouchehri, Megan M Shuey, Eric Farber-Eger, Joe-Elie Salem, Javid J Moslehi, Thomas J Wang, Evan L Brittain
Journal: Circulation (2018)

Introduction: Vascular endothelial growth factor inhibition (VEGFi) in cancer treatment is associated with hypertension. Imbalance between the renin-angiotensin-aldosterone system (RAAS) and VEGF m...
Relapse After Allogeneic Hematopoietic Stem Cell Transplantation in Hematological Malignancies: Factors Impacting Its Occurrence and Treatment Options for a Better Management,
Authors: Mauricette Michallet, Mohamad Sobh, Stephane Morisset, Helene Labussiere, Marie Y. Detrait, Sophie Ducastelle, Fiorenza Barraco, Jihane Fattoum, Nathalie Tedone, Youcef Chelghoum, Giovanna Cannas, Xavier Thomas, Franck E. Nicolini
Journal: Blood (2011)
Abstract 774: Gene-Environment Regulatory Circuit of Right Ventricular Pathology in Cyanotic Congenital Heart Defects
Authors: Zhao Yan, Xuedong Kang, Reshma Biniwale, Fadi Shahoud, Van Arsdell Glen, Fabiola Quintero, Nelson Stanley F, Marlin Touma
Journal: Circulation Research (2019)

Introduction: The phenotypic spectrum of congenital heart defects (CHDs) is contributed by both genetic and environmental factors. Their contributions are profoundly heterogeneous but may operate on common pathways that are not well understood. Elucidating the gene-environment interplays in CHDs pathogenesis is essential to identify chamber specific therapies. Methods: Following the UCLA CHD-BioCore approved protocol, right ventricle outflow tracts (RVOTs) samples were collected from infants with tetralogy of fallot (TOF) or Ventricular Septal Defect (VSD). Total RNA was used for RNA-seq. Systemic hypoxia was induced using hypoxia chamber. Weighted gene network co-expression analysis was performed using R package. Results: Genome-wide transcriptome analysis of RVOT samples from cyanotic and non-cyanotic CHDs uncovers disease-associated differences in gene expression. Co-expression network analysis reveals that individuals with CHDs show diagnosis-specific and environment-specific gene modules. In particular, hypoxia-dependent induction of proliferation and E2F1 dependent cell cycle reprograming are inversely associated with WNT11 signaling in the cyanotic TOF. In addition, epithelial mesenchymal transition (EMT), fibrosis and apoptosis are repressed. Importantly, perinatal hypoxia attenuates the baseline differences between ventricular chambers in neonatal mouse heart. Remarkably, the observed attenuation of ventricular patterning (AVP) genes is more robust in the right ventricle and highly concordant in hypoxemic hearts in mouse and human. Transcriptional dysregulation of the P53 network is a shared hallmark among AVP genes and cyanotic TOF modules. Importantly, P53 network analysis suggests CREB1, a hypoxia sensor, and LEF1, an EMT regulator during cardiogenesis, as potential mediators of hypoxia-Wnt11 circuit. Finally, the data demonstrate that genetic subtypes of TOF may influence hypoxia-induced regulation leading to phenotypic heterogeneity at molecular and cellular levels in cyanotic TOF hearts. Conclusions: Gene-environment interrelations may influence changes in regional gene expression leading to phenotypic heterogeneity at the molecular cellular level in complex cyanotic CHDs.
Abstract 568: Effects of Burn-induced Cardiac Released Factors on Cardiomyocyte and Profiles of Differentially Expressed Cardiac Mitochondrial Proteins Effects of Burn-induced Cardiac Released Factors on Cardiomyocyte and Profiles of Differentially Expressed Cardiac Mitochondrial Proteins
Authors: Jake J Wen, Geetha L Radhakrishnan, Craig Porter, Ravi S Radhakrishnan
Journal: Circulation Research (2019)

Introduction: Previous studies have indicated that cardiac dysfunction worsens in the first 24 hours post burn (pb) and improved over the next 48 hpb. We have found that cardiac mitochondria were damaged at 24 hpb and 24 hpb serum-treatment caused cardiomyocyte’mitochondrial dysfunction. However, the differentially expression of mitochondrial proteins in the early post burn period have still not been explored. Aims: To test if 3 hpb serum-treatment will interfere cardiomyocyte growth/proliferation similar to 24 hpb serum-treatment in vitro ; To identify the cardiac mitochondrial protein expression profile, relating to burn-induced cardiac mit dysfunction. Methods: Male Sprague Dawley rats were randomized into sham control, 3 hpb and 24 hpb groups, with six rats in each group. 60% TBSA burn was induced by immersing in boiling water. In this study, heart function cardiac mit function, and cardiac mitochondrial protein profiles were measured. Burned rat serum were used to test our hypothesis in vitro . Results: Cardiac functions was significantly worse in 3 hpb (Fig 1). Cardiac mitochondrial dysfunction was observed via mit OXPHOS or mit complexes activities after burn. However, no change of CII-driving OXPHOS in 24 hpb and no change of CIII activity in 3 hpb were seen, suggesting that different mechanisms may be involved (Fig.2). Burn-serum treatment increased oxidative stress, apoptosis, and nitrite/nitrate, while decreasing antioxidants and cell proliferation in cardiomyocytes (Fig. 3). Nano LC MS/MS identified 13569 peptides and 1275 proteins from burn-induced heart lysates (Fig.4.A), which were associated with cardiomyopathy (Fig.4.B). Further analysis showed that burn injury induced the alterations of 25 up regulated signaling pathway and 7 down regulated signaling pathway (Fig.5.A). 147 mitochondrial proteins were identified to be differentially expressed after burn. Among the 147 proteins, 32 proteins were continually down-regulated, 37 continually up-regulated. In addition, 16 were first up regulated then down-regulated while38 had the opposite expression perform (Fig.5.B). Conclusions: Burn-induced heart dysfunction is associated with cardiac mitochondrial damage by altering mitochondrial protein expression.
Predictors Of The Post-Thrombotic Syndrome In a Large Cohort Of Patients With Proximal DVT: Secondary Analysis Of The Sox Trial
Authors: Susan R. Kahn, Stan Shapiro, Philip S. Wells, Marc A Rodger, Michael J. Kovacs, David Anderson, Vicky Tagalakis, Adrielle H Houweling, Thierry Ducruet, Susan Solymoss, Marie-José Miron, Erik Yeo, Reginald Smith, Pharm D, Sam Schulman, Jeannine Kassis, Clive Kearon, Isabelle Chagnon, Turnly Wong, Christine Demers, Rajendar Hanmiah, Scott Kaatz, Rita Selby, Suman Rathbun, Sylvie Desmarais, Lucie Opatrny, Thomas L. Ortel, Jeffrey S Ginsberg
Journal: Blood (2013)
Effect of Intravenous and Oral N-Acetylcysteine Treatment in a Patient with Sickle Cell Disease at Disease Baseline
Authors: Hasan Tahsin Ozpolat, Junmei Chen, Xiaoyun Fu, Warren Osborn, Jennie Le, Minhua Ling, Sophie Schmitter, Sarah Ruuska, Dominic W. Chung, Barbara A Konkle, José A. López
Journal: Blood (2018)
IL10-592 CC Genotype In the Donor Is Associated with a Significant Decrease of Relapse Rate and a Significant Increase of Event-Free Survival and Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation In Children with Hematological Malignancies
Authors: Bernd Gruhn, Janine Voigt, Nadine Pfaffendorf-Regler, Ilona Wolff, Felix Zintl, James F. Beck
Journal: Blood (2011)
Neoadjuvant chemoradiation (NCRT) for esophageal (EC) or gastroesophageal junction cancer (GEJC): A Canadian single institution real-world experience using the CROSS trial regimen.
Authors: Sidra Khalid, Wilma M. Hopman, Beatrice Preti, Anna T. Tomiak, Kiran Virik
Journal: Journal of Clinical Oncology (2019)

25 Background: NCRT followed by surgery per the CROSS trial regimen is an accepted standard of care in the treatment of EC and GEJC. When treatments are used in the real-world setting, there are often patient, treatment and potential outcome differences compared to the original clinical trial. The study aim was to assess the real-world application and outcomes of the CROSS trial protocol. Methods: A retrospective chart review was undertaken of 83 patients (pts) with EC or GEJC who were treated from June 2012 to June 2018 with CRT. 65 pts were with NCRT intent to proceed to surgery. Pts’ demographics, clinical, pathological, treatment and surgical characteristics were assessed and exploratory analyses were conducted to review these factors and outcomes. Analyses included Chi-square, t-tests and Kaplan-Meier. Results: For pts who underwent NCRT (n = 65): median age was 68 yrs (range 52-80), male 79%, adenocarcinoma 82%, median (m) tumor length 5 cm, GERD 43%, clinical stage II/III 95%, and BMI &gt; 30 in 37%. 80% completed CRT with RT ≥ 41.4 Gy; of these 88% had ≥ 50.4 Gy. Delay/interruption in chemotherapy occurred in 46% and in RT 37%. Pts who underwent surgery were younger (p = 0.04) and weighed more (p = 0.05). mOS was 37 months (M) v 14 M in those who started CRT ≤ 8 weeks (w) from diagnosis v &gt; 8 w (p = 0.10). The median time from CRT to surgery was 8.9 w. 40 pts had surgery with a complete response in 38% and a R0 resection in 98%. Postoperative major and minor complications occurred in 67%. Those &lt; 75 yrs v ≥ 75 yrs had a mOS of 32 M v 15 M respectively (log rank p = 0.46). 25 pts did not get surgery; 28% was due to death/progression. Pts who proceeded to surgery had a mOS of 35 M v 12 M in pts who did not go to surgery (log rank p = 0.002). Further correlative outcome data will be presented. Conclusions: Real-world data in our center showed patient, tumor and treatment differences compared to the CROSS trial protocol. Despite the broadening of eligibility and treatment criteria, survival in a single institution setting is maintained with trimodality therapy compared to NCRT alone. Real-world data is of value in the assessment of therapeutic validity of clinical trial data.
The VLA-4 Integrin Is Constitutively Activated in a Subset of CD49d-Expressing CLL: A Relationship with the Autonomous BCR-Mediated Signaling?
Authors: Erika Tissino, Tamara Bittolo, Dania Benedetti, Riccardo Bomben, Gabriela Forestieri, Eva Szenes, Andrea Haerzschel, Enrico Santinelli, Maria Francesca Rossi, Alexandre Chigaev, Larry A. Sklar, Francesco Zaja, Pietro Bulian, Giovanni Francesco D'Arena, Annalisa Chiarenza, Francesco Di Raimondo, Gabriele Pozzato, Davide Rossi, Giovanni Del Poeta, Tanja N. Hartmann, Antonella Zucchetto, Valter Gattei
Journal: Blood (2018)
Sustained Depletion of B-Cells by a Humanized, Fc-Engineered Anti-CD20 Antibody, AME-133v, in Patients with Relapsed Follicular Lymphoma
Authors: Jennifer Wayne, Kristen N. Ganjoo, Andres Forero, Brad Pohlman, Sven de Vos, Susan P. Carpenter, James E Wooldridge, Shashidhara Marulappa, Vinay Jain
Journal: Blood (2011)