tbuckley/cabot-search huggingface dataset:
Epidemiological, Clinical, and Biological Characterization of Newly Diagnosed Acute Myeloid Leukemia in Algeria. Report on Behalf of the Algerian Acute Leukemia Study Group
Authors: Bekadja Med Amine, Amina Krim, Rachid Amar Bouhass, Malika Rekab, Yamina bouchakor Moussa, Souad Taoussi, Mohand Tayed Abad, Mohamed Bradai, Mohamed Graine, Hocine AIT ALI, Imene Bouras, Selma Hamdi, Redhouane Ahmed Nacer, Sabrina Akhrouf, Rose-Marie Hamladji, Yasmina Berkouk, Nadia Boudjerra, Meriem Belhani, Samira Zouani, Djamel Saidi, Hadj Touhami, Soraya Boughrira, Fatiha Grifi, Malika Merrouche, Mahdia Saidi, Brahim Benzineb, Naima Mesli, Sihem Kebaili, Noureddine Sidimansour, Mohamed Mohamed Benlazar, Zahia Zouaoui, Mohamed Aberkane, Aissa Bachiri, Faiza Mezhoud, Yamina Ouarlent, Hichem Gaid, Nemra Mehalhal, Mustapha Talbi, Laid Touati, Nordine Lakhdari, Bassima Bendjaballah, Malika Djillali, Salaheddin Belakehal, Khadija Djouadi, Fatima zohra Ardjoun, Mohamed Ramaoun, Nesrine Benyaa, Salim Nekkal, Salima Oukid, Farih Mehdid, Nacer Ait Ameur, Toufik Yachekour, Malek Benakli, Noureddine Metahri, Ali Bazarbachi
Journal: Blood (2018)
Distinct Microrna Profiles in Patients with Essential Thrombocythemia: Clinical and Prognostic Correlation
Authors: Yi-Hao Chiang, Yu-Cheng Chang, Huan-Chau Lin, Ling Huang, Chun-Chia Cheng, Nai-Wen Su, Caleb Gon-Shen Chen, Johnson Lin, Ruey-Kuen Hsieh, Ming-Chih Chang, Yi-Fang Chang, Wei-Ming Chen, Shih-Ting Kang, Yu-Shan Huang, Jian-Yi Lin, Tiffany Wang, Ken-Hong Lim
Journal: Blood (2018)
Abstract 626: Pro-Inflammatory Signaling by Cardiomyocytes Involves Activation of a RhoA Dependent Gene Expression Pathway
Authors: Cameron S Brand, Hoyoung Moon, Joan Heller Brown
Journal: Circulation Research (2019)

Cardiac inflammation, particularly the recruitment of inflammatory cells following injury, precedes cardiac fibrosis. A chronic inflammatory state in the heart increases risk of progression to heart failure. Activation of the small G-protein RhoA occurs in response to cardiac injury, and chronic activation of RhoA has been shown to facilitate maladaptive cardiac fibrosis. We tested the hypothesis that RhoA activation induces early pro-inflammatory signals in the cardiomyocyte which can lead to progression of inflammatory responses and adverse remodeling. Mice were infused with angiotensin-II, an agonist that can activate RhoA signaling and which rapidly induces cardiac inflammation and fibrosis. After one day of infusion, hearts were assessed for RNA levels of various inflammatory genes in wildtype versus cardiomyocyte-specific RhoA knockout mice. A set of genes for pro-inflammatory secreted cytokines associated with macrophage infiltration, including CCL2, IL-6, and IL-1β were upregulated in hearts from control mice infused with angiotensin-II, but these responses were abolished in hearts from RhoA knockouts. These findings indicate that RhoA activation in the cardiomyocyte contributes to the upregulation of these inflammatory signals. Our lab and others have demonstrated the importance of transcriptional responses to RhoA activation, and have shown concomitant downstream activation of the transcriptional co-activators Myocardin-related Transcription Factor A (MRTF-A) and Yes-activated Protein (YAP). With intravenous injection of cardiomyocyte-specific adeno-associated virus serotype 9 (AAV9) expressing Cre recombinase in mice with floxed YAP, we thus tested involvement of YAP in inflammatory gene expression regulated by angiotensin-II activation of RhoA. In summary, we propose that activation of RhoA in the cardiomyocyte facilitates a gene program involved in cardiac inflammatory response, and are examining the role of signaling from cardiomyocytes through MRTF-A and YAP regulated genes for inflammation and immune cell infiltration.
Diagnostic yield and clinical effects of exome sequencing analysis in patients with early-onset scoliosis
Authors: Sen Zhao, Yuanqiang Zhang, Weisheng Chen, Shengru Wang, Pengfei Liu, Shuyang Zhang, Carol A Wise, James R Lupski, Zhihong Wu, Guixing Qiu, Jianguo Zhang, Nan Wu
Journal: The Lancet (2019)
Abstract 332: Pharmacologic Characterization of the Cardiac Myosin Inhibitor, CK-3773274: A Potential Therapeutic Approach for Hypertrophic Cardiomyopathy
Authors: Darren T Hwee, James J Hartman, Jingying Wang, Yangsong Wu, Julia Schaletzky, Preeti Paliwal, Ken Lee, Khanha D Taheri, Eddie Wehri, Chihyuan Chuang, Bradley P Morgan, Fady I Malik, Eva R Chin
Journal: Circulation Research (2019)

Hypercontractility of the cardiac sarcomere appears to underlie pathological hypertrophy and fibrosis in select genetic hypertrophic cardiomyopathies. Here, we characterize the small molecule, CK-3773274, as a novel cardiac myosin inhibitor that decreases contractility in vitro and in vivo . In bovine cardiac myofibrils, CK-3773274 decreased myosin ATPase activity in a concentration-dependent fashion (IC 50 :1.26 μM). CK-3773274 specifically inhibited myosin activity, as it reduced myosin ATPase activity in a concentration-dependent manner in the absence of other sarcomere proteins, including actin, troponin, and tropomyosin. CK-3773274 (10 μM) reduced fractional shortening by 84% in electrically paced, isolated adult rat cardiomyocytes relative to control without any effect on the calcium transient. The effect of CK-3773274 on cardiac contractility in vivo was assessed in healthy male Sprague Dawley (SD) rats using single oral doses ranging from 0.5 to 4 mg/kg. Fractional shortening (FS) and left ventricular dimensions were determined by echocardiography at select time points over a 24-hour period. One hour after dose administration, CK-3773274 significantly reduced fractional shortening in a dose-related fashion by 20-70% relative to vehicle treatment (FS %: vehicle: 47.9± 1%; 0.5 mg/kg: 39 ± 2%; 4 mg/kg: 15 ± 4%; mean ±SEM, p&lt;0.05 vehicle vs. all doses) without any changes to heart rate. Lastly, the effect of CK-3773274 was evaluated by echocardiography in healthy beagle dogs. Left ventricular ejection fraction (LVEF) was evaluated following single oral doses ranging from 0.75-3 mg/kg over a 48 hour period. 2 hours after dosing, CK-3773274 decreased LVEF in a dose-related fashion by approximately 15-50% relative to vehicle treatment (LVEF vehicle: 74.6 ± 3 %; 0.75 mg/kg: 62.5 ± 3%; 2 mg/kg: 44.9± 3%; 3 mg/kg: 36.8 ± 2%; mean ±SEM, p&lt;0.05 vehicle vs. all doses). In conclusion, CK-3773274 is a novel, small molecule, cardiac myosin inhibitor that reduces cardiac contractility in vitro and in vivo . Cardiac myosin inhibition may be a viable approach to treat the underlying hypercontractility of the cardiac sarcomere in hypertrophic cardiomyopathies.
Fertility and Gonadal Function After Treatment of Early Unfavorable Hodgkin Lymphoma (HL): An Analysis of the German Hodgkin Study Group (GHSG)
Authors: Karolin Behringer, Indra Thielen, Horst Mueller, Helen Goergen, Angelika Eibl, Johannes Rosenbrock, Teresa Halbsguth, Katrin S. Reiners, Volker Diehl, Andreas Engert, Peter Borchmann
Journal: Blood (2011)
Angiopoietin-Like Proteins Stimulate HSC Development Through Direct Interaction With Notch
Authors: Michelle I Lin, Emily Price, Sonja Boatman, Eirini Trompouki, Sruthi Satishchandran, Charles W Carspecken, Audrey Uong, Anthony DiBiase, Jon C. Aster, Richard M. White, Leonard I. Zon
Journal: Blood (2013)
Safety and Activity of Lenalidomide and Rituximab in Previously Untreated Marginal Zone Lymphoma: Subgroup Analysis and Long-Term Follow-up of an Open-Label Phase II Trial
Authors: Melody R Becnel, Loretta Nastoupil, R. Eric Davis, F. B. Hagemeister, Michelle A. Fanale, Luis Fayad, Jason R. Westin, Michael Wang, Yasuhiro Oki, Linda Claret, Sheryl G Forbes, Lei Feng, Felipe Samaniego, Sattva S. Neelapu, Nathan Fowler
Journal: Blood (2017)
Abstract 946: Aberrant Activation of Nitric Oxide Synthase 1 in the Heart Accelerates Diastolic Dysfunction Though Protein S-nitrosylation
Authors: Somy Yoon, Mira Kim, Yongsook Kim, Youngkeun Ahn, Hyun Kook, Gwang Hyeon Eom
Journal: Circulation Research (2019)

Heart failure refers to an inappropriate blood supply to the periphery. Among subtype of heart failure, pathophysiology and effective therapeutic strategy of systolic heart failure is well established. However, molecular mechanism and specific regimens for diastolic heart failure (DHF) still remains unclear. Here we propose nitric oxide synthase (NOS) 1 mediated exacerbation of DHF and therapeutic potential for novel therapeutics. We screened alteration of posttranslational modifications in DHF which were induced either by SAUNA (SAlty drinking water/Unilateral Nephrectomy/Aldosterone) model or transverse aortic constriction (TAC) model and observed that protein S-nitrosylation was dramatically increased. Total RNA sequencing revealed that transcription amount of NOS1 was aberrantly increased in DHF, whereas NOS2 or NOS3 was not changed. Either non-selective NOS inhibitor or specific NOS1 inhibitor effectively blocked diastolic dysfunction. To elucidate the molecular target of S-nitrosylation, we performed biotin switch assay and requested protein sequencing which were newly appeared in the presence of GSNO. Among novel signal, we identified and confirmed that Histone deacetylase (HDAC) 2 was target molecule of NOS1. HDAC2 cysteine 262 and cysteine 274 were responsible residue of NOS1-mediated S-nitrosylation. We generated knock-in mice carrying S-nitrosylation defect HDAC2 mutant, HDAC2 C262A/C274A (2CA). HDAC2 2CA knock-in mice underwent SAUNA surgery or TAC and diastolic function of those mice was measured by early diastole (E) and mitral valve annulus movement (E’). When compared to wild type littermates, the diastolic function assessed by E/E’ ratio in HDAC2 2CA knock-in mice were relatively well conserved both in SAUNA- and TAC-induced DHF model. Survival rate after TAC operation was also dramatically ameliorated in HDAC2 2CA knock-in mice. Taken together, we proposed novel molecular axis, NOS1/S-NO HDAC2, accelerating diastolic dysfunction and which implicated notable molecular target for treatment of DHF patients.
A New Approach to Predict the Chance of Infectious Complications Following Autologous Hematopoietic Stem Cell Transplantation: Mannose-Binding Lectin ELISA
Authors: Zita Radnay, Miklos Udvardy, Attila Kiss, Maria Papp, Laszlo Rejto, Jolan Harsfalvi, Tamas Masszi, Robert Szasz, Peter Batar, Gyula Remenyi, Bela Telek
Journal: Blood (2011)
Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms
Authors: Hyung-lok Chung, Michael F. Wangler, Paul C. Marcogliese, Juyeon Jo, Thomas A. Ravenscroft, Zhongyuan Zuo, Lita Duraine, Sina Sadeghzadeh, David Li-Kroeger, Robert E. Schmidt, Alan Pestronk, Jill A. Rosenfeld, Lindsay Burrage, Mitchell J. Herndon, Shan Chen, Amelle Shillington, Marissa Vawter-Lee, Robert Hopkin, Jackeline Rodriguez-Smith, Michael Henrickson, Brendan Lee, Ann B. Moser, Richard O. Jones, Paul Watkins, Taekyeong Yoo, Soe Mar, Murim Choi, Robert C. Bucelli, Shinya Yamamoto, Hyun Kyoung Lee, Carlos E. Prada, Jong-Hee Chae, Tiphanie P. Vogel, Hugo J. Bellen
Journal: Neuron (2020)
Delayed Cytomegalovirus (cmv) Infection Following Hematopoietic Cell Transplantation (HCT): City of Hope (COH) Experience.
Authors: Alexandra Schaible, Allison Mays, Can-Lan Sun, Liton Francisco, Lennie Wong, Jon Sharp, Lester Laddaran, Stephen Forman, John Zaia, Sanjeet Dadwal, Smita Bhatia
Journal: Blood (2008)
Development of Expert-Level Automated Detection of Epileptiform Discharges During Electroencephalogram Interpretation
Authors: Jin Jing, Haoqi Sun, Jennifer A. Kim, Aline Herlopian, Ioannis Karakis, Marcus Ng, Jonathan J. Halford, Douglas Maus, Fonda Chan, Marjan Dolatshahi, Carlos Muniz, Catherine Chu, Valeria Sacca, Jay Pathmanathan, Wendong Ge, Justin Dauwels, Alice Lam, Andrew J. Cole, Sydney S. Cash, M. Brandon Westover
Journal: JAMA Neurology (2019)

Interictal epileptiform discharges (IEDs) in electroencephalograms (EEGs) are a biomarker of epilepsy, seizure risk, and clinical decline. However, there is a scarcity of experts qualified to interpret EEG results. Prior attempts to automate IED detection have been limited by small samples and have not demonstrated expert-level performance. There is a need for a validated automated method to detect IEDs with expert-level reliability.To develop and validate a computer algorithm with the ability to identify IEDs as reliably as experts and classify an EEG recording as containing IEDs vs no IEDs.A total of 9571 scalp EEG records with and without IEDs were used to train a deep neural network (SpikeNet) to perform IED detection. Independent training and testing data sets were generated from 13 262 IED candidates, independently annotated by 8 fellowship-trained clinical neurophysiologists, and 8520 EEG records containing no IEDs based on clinical EEG reports. Using the estimated spike probability, a classifier designating the whole EEG recording as positive or negative was also built.SpikeNet accuracy, sensitivity, and specificity compared with fellowship-trained neurophysiology experts for identifying IEDs and classifying EEGs as positive or negative or negative for IEDs. Statistical performance was assessed via calibration error and area under the receiver operating characteristic curve (AUC). All performance statistics were estimated using 10-fold cross-validation.SpikeNet surpassed both expert interpretation and an industry standard commercial IED detector, based on calibration error (SpikeNet, 0.041; 95% CI, 0.033-0.049; vs industry standard, 0.066; 95% CI, 0.060-0.078; vs experts, mean, 0.183; range, 0.081-0.364) and binary classification performance based on AUC (SpikeNet, 0.980; 95% CI, 0.977-0.984; vs industry standard, 0.882; 95% CI, 0.872-0.893). Whole EEG classification had a mean calibration error of 0.126 (range, 0.109-0.1444) vs experts (mean, 0.197; range, 0.099-0.372) and AUC of 0.847 (95% CI, 0.830-0.865).In this study, SpikeNet automatically detected IEDs and classified whole EEGs as IED-positive or IED-negative. This may be the first time an algorithm has been shown to exceed expert performance for IED detection in a representative sample of EEGs and may thus be a valuable tool for expedited review of EEGs.
Abstract 705: Synergistic Activation of the Cardiac Enhancer Landscape During Cardiac Reprogramming
Authors: Glynnis A Garry, Hisayuki Hashimoto, Zhaoning Wang, Huanyu Zhou, Ning Liu, Rhonda Bassel-Duby, Eric N Olson
Journal: Circulation Research (2019)

Direct cardiac reprogramming of fibroblasts to cardiomyocytes is an attractive therapeutic strategy to restore cardiac function following injury. The cardiac transcription factors Gata4, Mef2c, and Tbx5 are sufficient to directly reprogram fibroblasts to a cardiac fate and their cardiogenic activity is enhanced by the addition of Hand2 and Akt1. However, the mechanisms by which these transcription factors orchestrate this cell fate conversion remains elusive. To understand the mechanistic basis of cardiac reprogramming, we performed a genome-wide analysis of cardiogenic transcription factor binding sites and enhancer activation throughout cardiac reprogramming. We found that cardiogenic transcription factors act cooperatively by co-occupying regulatory elements enriched with Mef2 binding sites during cardiac reprogramming. Importantly, these transcription factors when overexpressed in isolation are incapable of activating reprogramming enhancer elements. Further, we discovered that the early reprogramming enhancer landscape most closely resembles that of the neonatal heart. Acquisition of enhancers associated with cardiac maturation occurred at later stages in reprogramming, with addition of Hand2 and Akt1 augmenting activation of this more mature enhancer landscape. Additionally, we constructed a cardiac reprogramming gene regulatory network which demonstrated downregulation of the EGF receptor signaling pathway. We found that inhibition of EGF receptor signaling augments reprogramming toward the cardiac phenotype. Our findings demonstrate that cardiac reprogramming is coordinated by synergistic transcriptional activation across a broad landscape of cardiac enhancers and define the epigenetic landscape of the cardiac phenotype.
Tiotropium add-on therapy reduces seasonal peaks of asthma worsening in adults with symptomatic severe asthma
Authors: J. Mark FitzGerald, Roland Buhl, Thomas B. Casale, Branko Jugovic, Liliana Zaremba-Pechmann, David M.G. Halpin
Journal: European Respiratory Journal (2019)

<b>In adults with symptomatic severe asthma despite inhaled corticosteroid/long-acting β<sub>2</sub>-agonist therapy, tiotropium add-on therapy reduces seasonal peaks of asthma worsening, providing a year-round benefit</b>http://bit.ly/2m4LGuH
Mixed-methods research to evaluate a novel patient-centered cancer care coordination instrument.
Authors: Izumi Okado, Kevin Cassel, Ian Pagano, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2019)

280 Background: Effective care coordination (CC) is a critical component of high-quality cancer care; however, efforts to improve cancer care coordination are hampered by limited patient-centered measures. This mixed-methods research reports on patients’ feedback and the utility of a novel care coordination instrument (CCI) designed to assess cancer care coordination. Methods: 7 focus group discussions were conducted with 68 cancer patients receiving active therapy to evaluate validity of the CCI. Subsequently, the CCI was modified and administered to additional 200 cancer patients derived from community-based private and hospital clinics. The CCI is a 29-item, multiple-choice questionnaire and includes subscales that evaluate CC in 3 domains (Communication, Navigation, Operational) across 4 areas of CC (patient-physician; between providers; during inpatient-to-ambulatory care transitions; during transitions across phases of care). Results: Qualitative analysis of focus group discussions demonstrated that the CCI has good face and content validity. Content analysis identified the following themes: Survey, Education/Knowledge, Navigator, Communication, Support, Access, Providers, and Team. Questions with unclear wording or high proportions of not applicable or missing responses were refined or removed. Results of the revised survey indicated that the CCI is able to distinguish patient- and practice characteristics associated with optimal/poor CC. Specifically, cancer types (leukemia, myeloma) and having a patient navigator predicted high overall patients’ ratings of CC ( p &lt; .05). Marginally significant differences were found for practice setting ( p = .085). A multiple regression model with all predictors entered simultaneously revealed that the presence of a family/friend caregiver significantly predicted better CC ( p &lt; .001); however, the benefits of a patient navigator were no longer significant. Conclusions: This study demonstrates the utility of the CCI for assessing patients’ perspectives of cancer CC. Use and integration of this instrument in oncology practices/clinics can identify areas of potential interventions for CC improvement and lead to a better quality of care.
Russian Experience of Bosutinib Use in Chronic Myeloid Leukemia Patients in Routine Clinical Practice
Authors: Vasily Shuvaev, Olga Vinogradova, Irina Martynkevich, Novitskaya Natalya, Mikhail Fominykh, Svetlana Tsareva, Dzhariyat Shikhbabaeva, Maria Pankrashkina, Mikhail Chernikov, Nikolay Sharkunov, Irina Zotova, Vera Udaleva, Ekaterina Motyko, Sergei Voloshin
Journal: Blood (2018)
Abstract 922: Cardiac-specific Deletion of Orai3 Channel Causes Dilated Cardiomyopathy
Authors: Salvatore Mancarella, Samuel Kamatham
Journal: Circulation Research (2019)

Background: Calcium (Ca2+) signalling is a vital regulator of cardiac myocyte function. Defective cellular calcium handling is widely recognized as a significant patho-physiological event in the contractile dysfunction of the failing heart. Orai3 is a newly discovered calcium channels that participate in the voltage-independent calcium currents in the mycardium. However, its role in the heart remain uncharacterized. Methods and Results: Here, we show that disruption of Orai3 function in murine cardiomyocytes leads to decompensated dilated cardiomyopathy. Echocardiographic analysis supported by histological examinations revealed that 4-month-old Orai3 knockout (KO) mice have signs of dilated cardiomyopathy denoted by a loss of EF and a thinner left ventricular posterior wall and septum, with significant fibrosis, whereas in the younger animals only a thinner septum could be observed. In both genders, most mice died within six months after birth. Myocardial samples that underwent electron microscopy and immunohistochemical analysis showed myofilament changes in Orai3 KO mice with misexpression of cardiac contractile proteins and profound sarcomere disarray. Transverse aortic constriction (TAC) was used as a chronic stressor on the younger mice to determine whether the ability to compensate against a pathologic insult is compromised in the Orai3 KO heart. Orai3 KO mice presented with significantly reduced systolic function and ventricular dilation that deteriorated into congestive HF within 4 weeks post-surgery, while constricted WT hearts remained well-adapted throughout. Conclusions: Thus, our results identify Orai3 critical role in adult cardiac function and demonstrate a novel cardioprotective role of Orai3 against cardiac pressure overload-induced heart failure.
Examining the Outcomes of Watchful Waiting (WW) Among US Patients with Advanced Stage Follicular Lymphoma (FL)
Authors: Rajni Sinha, Michelle Byrtek, Nutan J. DeJoubner, Ajay K. Nooka, Michael Taylor, James R Cerhan, Jonathan Friedberg, Ryan M Ziemiecki, Jamie H. Hirata, Brian K Link, Christopher R Flowers
Journal: Blood (2011)
Peripheral blood leukocyte telomere length is associated with survival of sepsis patients
Authors: Shuo Liu, Chunxue Wang, Gary Green, Hanjing Zhuo, Kathleen D. Liu, Kirsten N. Kangelaris, Antonio Gomez, Alejandra Jauregui, Kathryn Vessel, Serena Ke, Carolyn Hendrickson, Michael A. Matthay, Carolyn S. Calfee, Lorraine B. Ware, Paul J. Wolters
Journal: European Respiratory Journal (2019)

Shorter peripheral blood leukocyte (PBL) telomere length (TL) has been associated with poor outcomes in various chronic lung diseases. Whether PBL-TL is associated with survival from critical illness was tested in this study. We analysed data from a prospective observational cohort study of 937 critically ill patients at Vanderbilt University Medical Center (VUMC). PBL-TL was measured using quantitative PCR of DNA isolated from PBLs. Findings were validated in an independent cohort of 394 critically ill patients with sepsis admitted to the University of California San Francisco (UCSF). In the VUMC cohort, shorter PBL-TL was associated with worse 90-day survival (adjusted hazard ratio (aHR) 1.3, 95% CI 1.1–1.6 per 1 kb TL decrease; p=0.004); in subgroup analyses, shorter PBL-TL was associated with worse 90-day survival for patients with sepsis (aHR 1.5, 95% CI 1.2–2.0 per 1 kb TL decrease; p=0.001), but not trauma. Although not associated with development of acute respiratory distress syndrome (ARDS), among ARDS subjects, shorter PBL-TL was associated with more severe ARDS (OR 1.7, 95% CI 1.2–2.5 per 1 kb TL decrease; p=0.006). The associations of PBL-TL with survival (adjusted HR 1.6, 95% CI 1.2–2.1 per 1 kb TL decrease; p=0.003) and risk for developing severe ARDS (OR 2.5, 95% CI 1.1–6.3 per 1 kb TL decrease; p=0.044) were validated in the UCSF cohort. Short PBL-TL is strongly associated with worse survival and more severe ARDS in critically ill patients, especially patients with sepsis. These findings suggest that telomere dysfunction may contribute to outcomes from critical illness.