tbuckley/cabot-search huggingface dataset:
Association of electronic medical record (EMR) QTc alerts with higher mortality within 10 days for patients with blood, lung, GI, and soft tissue cancer.
Authors: Benjamin Aaron Bleiberg, Donglu Xie, Tammy Lightfoot, Joan Reisch, Saad A. Khan
Journal: Journal of Clinical Oncology (2019)

235 Background: Patients with cancer receive many prescriptions associated with QTc interval prolongation. Prognostic implications of drug-induced QTc interactions are unknown. EMR's regularly generate QTc-alerts but their significance or impact is not known. Methods: Using the UTSW tumor registry we identified 14,731 adult cancer patients from 2005-2018 for whom the EMR had generated 16,797 unique alerts for potential QTc drug interactions. We collected patient cancer details, demographics and specific drugs prescribed. After a QTc alert, timing of patient death within a &lt; 365 day period was recorded and analyzed. Prior studies have defined death within 10 days as acute mortality that may be related to QTc prolongation-associated factors. We compared actual deaths that occurred ≤10 days from a QTc alert to expected deaths based on the null hypothesis that deaths ≤10 days were evenly distributed by cancer primary site and would be proportionate to the number of patients in each group; data were analyzed by chi-squared goodness of fit testing. Results: The number of ACTUAL deaths ≤10 days compared to those EXPECTED by the null model varied significantly by cancer site (Table). No mortality differences were noted based on patient demographics, age at first alert, ethnicity, or race. Conclusions: There is a significant association between EMR QTc alerts and higher than expected acute mortality for some cancers, but not universally. In lung, breast, and GI cancer patients who died &lt;365 days of a QTc alert, &gt; 15% died within 10 days of a QTc alert. EMR generated QTc alerts may identify cancer patients who are at imminent risk of death in some cancers but may represent distractions in other types of cancers. [Table: see text]
Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B‐cell lymphoma
Authors: Alex F. Herrera, Andre Goy, Amitkumar Mehta, Radhakrishnan Ramchandren, John M. Pagel, Jakub Svoboda, Shanhong Guan, John S. Hill, Kevin Kwei, Emily A. Liu, Tycel Phillips
Journal: American Journal of Hematology (2019)

Abstract This phase 1b/2, multicenter, open‐label study evaluated ibrutinib plus durvalumab in relapsed/refractory follicular lymphoma (FL) or diffuse large B‐cell lymphoma (DLBCL). Patients were treated with once‐daily ibrutinib 560 mg plus durvalumab 10 mg/kg every 2 weeks in 28‐day cycles in phase 1b without dose‐limiting toxicities, confirming the phase 2 dosing. Sixty‐one patients with FL (n = 27), germinal center B‐cell (GCB) DLBCL (n = 16), non‐GCB DLBCL (n = 16), and unspecified DLBCL (n = 2) were treated. Overall response rate (ORR) was 25% in all patients, 26% in patients with FL, 13% in patients with GCB DLBCL, and 38% in patients with non‐GCB DLBCL. Overall, median progression‐free survival was 4.6 months and median overall survival was 18.1 months; both were longer in patients with FL than in patients with DLBCL. The most frequent treatment‐emergent adverse events (AEs) in patients with FL and DLBCL, respectively, were diarrhea (16 [59%]; 16 [47%]), fatigue (12 [44%]; 16 [47%]), nausea (9 [33%]; 12 [35%]), peripheral edema (7 [26%]; 13 [38%]), decreased appetite (8 [30%]; 11 [32%]), neutropenia (6 [22%]; 11 [32%]), and vomiting (5 [19%]; 12 [35%]). Investigator‐defined immune‐related AEs were reported in 12/61 (20%) patients. Correlative analyses were conducted but did not identify any conclusive biomarkers of response. In FL, GCB DLBCL, and non‐GCB DLBCL, ibrutinib plus durvalumab demonstrated similar activity to single‐agent ibrutinib with the added toxicity of the PD‐L1 blockade; the combination resulted in a safety profile generally consistent with those known for each individual agent.
High Level EBV Persistence in the IgM+ IgD+ CD27+ B Cell Subset in Patients with X-Linked Lymphoproliferative Disease Lacking Isotype-Switched Memory B Cells.
Authors: Sridhar Chaganti, Cindy Ma, Andrew Bell, Debbie Croom-Carter, Andrew Hislop, Stuart Tangye, Alan Rickinson
Journal: Blood (2007)
Effect of Tetrandrine and Toremifene on the Reversion of Multidrug Resistance of K562/A02 Cell Line
Authors: Bao-An Chen, Qiu-xia Zhao, Jian Cheng, Feng Gao, Wen-lin Xu, Hui-lin Shen, Jia-hua Ding, Chong Gao, Yun-Yu Sun, Jun Wang, Gang Zhao, Hui-hui Song, Wen Bao, Xin-chen Sun, Hong-yan Cheng, Yu-xia Deng, Guo-hong Li, Li-jie Liu, Wen-ji Chen, Jue-qiong Wang, Peng Yuan, Xiao-ping Pei, Ning-na Chen, Xue-mei Wang
Journal: Blood (2008)
Genotypic and Phenotypic Analysis of Adolescents with Heavy Menstrual Bleeding and Low Von Willebrand Activity - Interim Report of a Multi-Center Study
Authors: Lakshmi Srivaths, Jorge Di Paola, Charles Minard, Sarah H. O'Brien, Allison Wheeler, Shilpa Jain, Mukta Sharma, Roshni Kulkarni, Eric S. Mullins, Margaret V. Ragni, Jennifer Dietrich, Peter A. Kouides
Journal: Blood (2018)
Integrated Genomic and Proteomic Analysis of Murine CLL-like Cells Reveals SF3B1 Mutation to Impact DNA Damage Response and BCR Signaling
Authors: Lili Wang, Shanye Yin, Aina zurita Martinez, Fara Faye Regis, Angela Brooks, Sarah E. M. Herman, Elisa Ten Hacken, Esther Obeng, Dean Campagna, Mark D. Fleming, Benjamin L. Ebert, Adrian Wiestner, Ignaty Leshchiner, Gad Getz, Ruben D. Carrasco, Catherine J. Wu
Journal: Blood (2018)
Exploratory Study of Urine Metabolomics in Sickle Cell Disease Children with Albuminuria in Malawi
Authors: Laila Elsherif, Jonathan Brett Heimlich, Portia Kamthunzi, Pilirani Mafunga, Satish Gopal, Nigel S. Key, Adane Wogu, Andrey Tikunov, Fei Zou, Jeffrey Macdonald, Kenneth I. Ataga
Journal: Blood (2018)
KIR-Ligand Incompatibility Is Not Associated with Relapse Reduction After Double Umbilical Cord Blood Transplantation,
Authors: Alfred L Garfall, Haesook T Kim, Lixian Sun, Vincent T Ho, Philippe Armand, John Koreth, Edwin Alyea, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz, Corey S. Cutler
Journal: Blood (2011)
Abstract 20518: Quantification of Pulsed Operation of Rotary Left ventricular Assist Devices With Wave Intensity Analysis
Authors: Christopher Bouwmeester, Pramod Bonde
Journal: Circulation (2017)

Background: The current generation of left ventricular assist devices (LVADs) provide continuous flow and have the capacity to reduce aortic pulsatility, which may be related to a range of complica...
Transcriptional characterisation of human lung cells identifies novel mesenchymal lineage markers
Authors: Soula Danopoulos, Soumyaroop Bhattacharya, Thomas J. Mariani, Denise Al Alam
Journal: European Respiratory Journal (2019)

Rationale The lung mesenchyme gives rise to multiple distinct lineages of cells in the mature respiratory system, including smooth muscle cells of the airway and vasculature. However, a thorough understanding of the specification and mesenchymal cell diversity in the human lung is lacking. Methods We completed single-cell RNA sequencing analysis of fetal human lung tissues. Canonical correlation analysis, clustering, cluster marker gene identification and t-distributed stochastic neighbour embedding representation was performed in Seurat. Cell populations were annotated using ToppFun. Immunohistochemistry and in situ hybridisation were used to validate spatiotemporal gene expression patterns for key marker genes. Results We identified molecularly distinct populations representing “committed” fetal human lung endothelial cells, pericytes and smooth muscle cells. Early endothelial lineages expressed “classic” endothelial cell markers (platelet endothelial cell adhesion molecule/CD31 and claudin 5), while pericytes expressed platelet-derived growth factor receptor-β, Thy-1 membrane glycoprotein and basement membrane molecules (collagen IV, laminin and proteoglycans). We observed a large population of “nonspecific” human lung mesenchymal progenitor cells characterised by expression of collagen I and multiple elastin fibre genes ( ELN , MFAP2 and FBN1 ). We closely characterised the diversity of mesenchymal lineages defined by α 2 -smooth muscle actin ( ACTA2 ) expression. Two cell populations, with the highest levels of ACTA2 transcriptional activity, expressed unique sets of markers associated with airway or vascular smooth muscle cells. Spatiotemporal analysis of these marker genes confirmed early and persistent spatial specification of airway ( HHIP , MYLK and IGF1 ) and vascular ( NTRK3 and MEF2C ) smooth muscle cells in the developing human lung. Conclusion Our data suggest that specification of distinct airway and vascular smooth muscle cell phenotypes is established early in development and can be identified using the markers we provide.
Long non-coding RNAs identify a subset of luminal muscle-invasive bladder cancer patients with favorable prognosis
Authors: Joep J. de Jong, Yang Liu, A. Gordon Robertson, Roland Seiler, Clarice S. Groeneveld, Michiel S. van der Heijden, Jonathan L. Wright, James Douglas, Marc Dall’Era, Simon J. Crabb, Bas W. G. van Rhijn, Kim E. M. van Kessel, Elai Davicioni, Mauro A. A. Castro, Yair Lotan, Ellen C. Zwarthoff, Peter C. Black, Joost L. Boormans, Ewan A. Gibb
Journal: Genome Medicine (2019)

Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease, and gene expression profiling has identified several molecular subtypes with distinct biological and clinicopathological characteristics. While MIBC subtyping has primarily been based on messenger RNA (mRNA), long non-coding RNAs (lncRNAs) may provide additional resolution.
Analgesic requirement as a predictor of mortality to guide ceilings of care discussions for oncology patients in the emergency room.
Authors: Fiona Paxton-Hall, Zarnie Lwin, Bryan Anthony Chan, William Lukin, Julian Williams, Jaimi Greenslade, Anna Kermond
Journal: Journal of Clinical Oncology (2019)

188 Background: Discussing an oncology patient’s ceiling of care in the emergency room (ER) is a high-stakes and time-pressured challenge. Discussions and consensus for ceilings are warranted when patients are acutely unwell with sepsis. We explored whether daily oral morphine equivalent (OME) was predictive of outcome and could therefore assist in ceiling of care decision making or advanced resuscitation planning (ARP). Methods: Oncology patients presenting with infection or sepsis to a quaternary hospital ER between October 2008 and April 2011 were included. Hospital electronic databases and medical records were manually reviewed to extract data on patient demographics, OME at time of presentation to ER, illness severity (SOFA scores), whether patients had a pre-existing formalised ARP vs acute ARP documented within the ER and 90-day mortality from ER presentation. Descriptive statistics were reported. Results: A total of 91 patients were identified with median age 64 years, 60% were male, 62% were undergoing palliative-intent treatment and 70% were receiving first-line chemotherapy. There were 54 patients taking no analgesia (OME 0) and 37 patients with an OME &gt; 0. Of the 37 patients with OME &gt; 0, 6 patients (16.2%) had an ARP documented in the ER. A further 14 patients with OME &gt; 0 had an ARP documented at some point during their admission. The median total SOFA scores for patients with OME &gt; 0 was 3 and OME of 0 was also 3. The 90- day mortality from ER presentation was higher for patients with an OME &gt; 0 compared to those with an OME of 0 (Chi-square = 5.02, p = 0.03). There were 15/37 patients (40.5%) with an OME &gt; 0 who were deceased within 90 days compared with 10/54 patients (18.5%) with an OME of 0. Conclusions: Patients with higher OME use at ER presentation had poorer outcomes and this may be useful to guide clinicians in ceilings of care decisions. Daily OME should signal a need for timely, formalised advanced care planning with patients and their treating oncologists.
Unrelated Cord Blood Transplantation Using Myeloablative Conditioning Regimen for Adults with Acute Myeloid Leukemia in First Complete Remission. A Survey by EUROCORD and the Acute Leukemia Working Party of the EBMT
Authors: Annalisa Ruggeri, Myriam Labopin, Guillermo Sanz, Josep-Maria Ribera, Anne Sirvent, Alessandro Rambaldi, Renato Cunha, Fernanda Volt, Eliane Gluckman, Chantal Kenzey, Mohamad Mohty, William Arcese, Vanderson Rocha
Journal: Blood (2011)
The Impact of Cytogenetics on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Survey from the Acute Leukemia Working Party (ALWP) of EBMT
Authors: Monica Poiani, Myriam Labopin, Dietrich W. Beelen, Johanna Tischer, Jürgen Finke, Arne Brecht, Edouard Forcade, Arnold Ganser, Jakob R. Passweg, Helene Labussiere-Wallet, Ibrahim Yakoub-Agha, Kerstin Schäfer-Eckart, Nicolaus Kroeger, Bruno Lioure, Annalisa Ruggeri, Jordi Esteve, Arnon Nagler, Mohamad Mohty
Journal: Blood (2018)
Thalidomide (THAL) and Lenalidomide (LEN)-Associated Venous Thromboembolism (VTE): Optimal Prophylaxis Strategies Remain Elusive
Authors: June M. McKoy, Dustin B Liebling, Alfred W. Rademaker, Bing Bing Weitner, Beatrice J. Edwards, Steven M. Belknap, Andrew Thurston, Monica Boen, Katrina-Marie E Tulas, Judith M McKoy-Bent, Jowella Pineda, Dennis P. West
Journal: Blood (2012)
Phase 2 Study Of Early Discharge and Outpatient Management Of Adult Patients Following Intensive Induction Chemotherapy For MDS and Non-APL AML
Authors: Jennifer E. Vaughn, Morgan A. Powell, Kelda M. Gardner, Megan Othus, Rajeev Rajendra, Donnelle Rizutto, Pamela S. Becker, Paul C. Hendrie, Andrei R. Shustov, Siobán B. Keel, Vivian G. Oehler, Terry B. Gernsheimer, Janis L. Abkowitz, Elihu H. Estey, Roland B. Walter
Journal: Blood (2013)
Abstract 370: A Novel Algorithm for the Collective Integration of Single Cell Rna-seq During Embryogenesis
Authors: Wuming Gong, Bhairab N Singh, Satyabrata Das, Mary G Garry, Daniel J Garry
Journal: Circulation Research (2019)

Background: Single cell RNA-seq (scRNA-seq) over specified time periods has been widely used to dissect the cell populations during mammalian embryogenesis. Integrating such scRNA-seq data from different developmental stages and from different laboratories is critical to comprehensively define and understand the molecular dynamics and systematically reconstruct the lineage trajectories. Methods: Here, we describe a novel algorithm to integrate heterogenous temporal scRNA-seq datasets and to preserve the global developmental trajectories. scNCA not only successfully corrected the batch effects, but also preserved the global structure of gene expression. For both balanced and imbalanced synthetic scRNA-seq data, we found that scNCA had significantly better performance of batch correction than mnnCorrect and Seurat alignment, on mixing cells from different batches, revealing the global trajectories, and bringing together the cells from the same lineage. Results: We applied this algorithm and approach to integrate 3,387 single cells from seven heterogenous temporal scRNA-seq datasets, and reconstructed the cell atlas of early mouse cardiovascular development from E6.5 to E9.5. Using this integrated atlas, we identified an Etv2 downstream target, Ebf1 , as an important transcription factor for mouse endothelial development. Conclusions: In summary, we presented scNCA as a novel tool to correct the batch effect of temporal scRNA-seq. We used scNCA to integrate 3,387 single cells from seven heterogenous temporal scRNA-seq datasets of mouse early cardiovascular development , and identified an Etv2 downstream target, Ebf1 , as an important transcription factor for mouse endothelial development. We provide the R/TensorFlow implementation of scNCA at https://github.com/gongx030/scNCA. The integrated mouse early cardiovascular development data can be explored at https://heartmap.umn.edu/scNCA.
Implanted Monitor Alerting to Reduce Treatment Delay in Patients With Acute Coronary Syndrome Events
Authors: David R. Holmes, Mitchell W. Krucoff, Chris Mullin, Ghiath Mikdadi, Dale Presser, David Wohns, Andrew Kaplan, Allen Ciuffo, Arthur L. Eberly, Bruce Iteld, David R. Fischell, Tim Fischell, David Keenan, M. Sasha John, C. Michael Gibson
Journal: Journal of the American College of Cardiology (2019)
Abstract 713: Engineering Complex Tissue Mechanical Environment for Cardiac Microtissues Derived From Human Induced Pluripotent Stem Cells
Authors: Zhen Ma, Chenyan Wang, Sangmo Koo, Costas Grigoropoulos
Journal: Circulation Research (2019)

Previous studies of hiPSC-based cardiac tissue models mainly focused on uniform tissue mechanical environment, which is not sufficient to recapitulate the complex and heterogeneous tissue mechanical environment that would lead to cardiac contractile dysfunction. To create a 3D cardiac tissue model with nonuniform mechanical environment, we have developed state-of-art laser-based 3D bioprinting technology to fabricate “mechanical hybrid” scaffolds comprised of layers of parallel aligned high-aspect-ratio (100:1) fibers.We fabricated the double-hybrid (DH) scaffolds with “1:1 thin-thick” design by positioning the thin fibers (5 μm, low stiffness) next to the thick fiber (10 μm, high stiffness) to create a mismatch region in the center ( Fig. A ). The entire microtissue had to self-balance the force generation between high and low stiffness for synchronized contraction ( Fig. B ). This resulted in tissue hypertrophy at the high stiffness side with larger tissue cross-section comparing to low stiffness side ( Fig. C ). We also determined the local contractile velocities from each segment of the microtissues at different spatial locations, which showed a trend of exponential decay on the contractile velocities from edge to center ( Fig. D ). The difference in the decay rate between thick side of the DH scaffolds (DH-K) and thin side of the DH scaffolds (DH-N) indicated the contractile imbalance on the two sides of the entire microtissues. We also calculated the force output of the cardiac microtissues on DH-K side, which showed a HCM-like diastolic dysfunction comparing to the force output from single scaffolds with thick fibers ( Fig. E ).
Aldosterone Stimulates Neutrophils Leading To Increased β-Glucuronidase, Protein Disulfide Isomerase and Myeloperoxidase Secretion
Authors: Arelys Ramos-Rivera, Alicia Rivera, Enrique D. Machado-Fiallo, Josue A. Benabe-Carlo, Gregory N. Prado, Jose R Romero
Journal: Blood (2013)
Abstract 426: Single Cell RNA-seq Analysis of Dynamic LIF Control of Adipose Derived Stem Cells Transition to Cardiomyocytes
Authors: Jiayi Yao, Jiayi Yao
Journal: Circulation Research (2019)

Heart failure continues to be a leading cause of human mortality worldwide and is the consequence of various forms of myocardial injuries that compromise the pumping ability of the heart. Cellular fate transition through manipulation of modifying factors holds great promise for large-scale production of cardiomyocytes required for therapy and for revealing principles of gene regulation in the process. In this study, we found leukemia inhibitory factor (LIF) acts directly on adipose derived cells to induce cardiomyogenesis by JAK/STAT3. LIF induces adipose-cardiac transdifferentiation in adipose derived stem cells, which exhibits morphology and function typical of beating cardiomyocytes. However, the cell population in adipose tissue that generates cardiomyocyte is not from adipocytes or stromal cells, as examined by Cre-Loxp system and FACs. Here, using single cell RNA sequencing, we identified a cell population in adipose tissue that undergoes a gradual and simultaneous switch form relatively quiescent fate to proliferate cardiomyocyte like cells. By trajectory alignment, we compared the gene expression kinetics across fresh adipose cells and LIF induced cardiac transition process to identify crucial genes involved in the transition. Our findings may provide a better understanding of the mechanism underlying LIF-induced adipose-cardiac transdifferentiation, therefore reveal new therapeutic strategies for the treatment of myocardial injuries, and provide crucial information for regenerative medicine.
Intraoperative Parathyroid Hormone Measurement vs Indocyanine Green Angiography of Parathyroid Glands in Prediction of Early Postthyroidectomy Hypocalcemia
Authors: Pablo Moreno Llorente, José Manuel Francos Martínez, Arantxa García Barrasa
Journal: JAMA Surgery (2019)

This study compares the efficacy of intraoperative parathyroid hormone measurement vs indocyanine green angiography of parathyroid glands in predicting early postthyroidectomy hypocalcemia.
Abstract 118: Reduced Cardiac Transmembrane Protein 65 Resulted in Dilated Cardiomyopathy and Progressive Cardiac Fibrosis <i>in vivo</i>
Authors: Allen C Teng, Liyang Gu, Michelle Di Paola, Meena Fatah, Diptendu Chatterjee, Thomas Kislinger, Robert Hamilton, Anthony O Gramolini
Journal: Circulation Research (2019)

Intercalated discs (ICDs) are unique and functionally indispensible to the heart, but its structural organization remains less understood. Previously, we showed that an ICD-bound transmembrane protein 65 (Tmem65) was required for Connexin 43 (Cx43) localization in cultured mouse neonatal cardiomyocytes, and that reduced Tmem65 was associated with a decrease and internalization of Cx43, and impaired electrical conduction between neighboring cardiomyocytes. Here, we investigated the role of Tmem65 in vivo by injecting CD1 mice with recombinant adeno-associated virus 9 (rAAV9) harboring Tmem65 (or scrambled) shRNA. Quantitative polymerase chain reactions and immunoblots confirmed greater than 90% reduction in Tmem65 expression in mouse ventricles compared to control samples. Immunoblots and immunofluorescence showed reduced and internalized Cx43 in Tmem65 knockdown (KD) hearts compared to controls, respectively. Kaplain-Meier survival plot showed that all Tmem65 KD mice died within 7 weeks (&gt; 50% death 3 weeks post viral injection), whereas no death was seen in control mice. Tmem65 KD mice developed eccentric hypertrophic cardiomyopathy in 3 weeks and dilated cardiomyopathy with severe cardiac fibrosis in 7 weeks as confirmed by H&amp;E and Masson’s Trichrome staining. Echocardiography also confirmed ventricular dilatation and showed a 60% reduction in cardiac output (19.27±1.46 mL/min in control vs. 6.63±0.52 mL/min in Tmem65 KD mice, p&lt;0.01, n = 6 per group) at 7 weeks. Transmission electron microscopy showed an altered ICD pattern and disorganized myofibril structure in Tmem65 KD ventricles while control tissues had smooth ICDs and organized myofibers. Together, these findings suggest a critical role of Tmem65 in maintaining cardiac ICD and myofibers and loss of Tmem65 leads to cardiomyopathy in vivo .
All-Trans Retinoic Acid Improves Outcome in Younger Adult Patients with Nucleophosmin-1 Mutated Acute Myeloid Leukemia – Results of the AMLSG 07-04 Randomized Treatment Trial
Authors: Richard F. Schlenk, Konstanze Döhner, Jürgen Krauter, Verena I. Gaidzik, Peter Paschka, Michael Heuser, Thomas Kindler, Michael Lübbert, Hans Martin, Helmut R. Salih, Andrea Kuendgen, Heinz A. Horst, Marie von Lilienfeld-Toal, Katharina Götze, David Nachbaur, Mohammed Wattad, Claus-Henning Köhne, Walter Fiedler, Martin Bentz, Gerald Wulf, Gerhard Held, Bernd Hertenstein, Hans-Günther Mergenthaler, Hans Salwender, Mathias J. Rummel, Aruna Raghavachar, Axel Benner, Brigitte Schlegelberger, Arnold Ganser, Hartmut Döhner
Journal: Blood (2011)