tbuckley/cabot-search huggingface dataset:
Abstract 810: Structural and Electrophysiological Maturation of Human iPSC-Derived Atrial Cardiomyocytes to Serve as a Platform to Model Atrial Fibrillation
Authors: Olivia T Ly, Seock Won Youn, Grace Brown, Liang Hong, Arvind Sridhar, Meihong Zhang, Erin Lambers, Salman Khetani, Dawood Darbar
Journal: Circulation Research (2019)

Background: Atrial fibrillation (AF), the most globally common arrhythmia requiring treatment, is associated with significant morbidity and mortality. Although antiarrhythmic drugs (AADs) are most commonly used to treat symptomatic AF, AADs are incompletely and unpredictably effective, and fail to target underlying cellular mechanisms of AF. Previously, pluripotent stem cell derived immature atrial cardiomyocytes (iPSC-aCMs) were shown to recapitulate the structural and electrophysiologic (EP) phenotype of AF-linked mutations. However, there are gaps in structural and EP phenotype between immature and mature iPSC-aCMs to successfully evaluate cellular mechanisms. Objective: The goal is to determine optimal condition(s) to enhance maturity of iPSC-aCMs, to establish iPSC-aCMs as a novel platform to model AF in a dish, elucidate cellular mechanisms and molecular pathogenesis, and identify and assess novel, personalized mechanism based therapies. Methods: Conditions used to enhance iPSC-aCMs maturity are 1) different ECMs to culture iPSC-aCMs, 2) patterned ECM to improve alignment and formation of intercellular gap junctions, and 3) treatment with postnatal factors (T3, IGF-1 and dexamethasone; TID). Maturity was assessed with immunofluorescence and EP measurement with patch-clamping and optical voltage analysis. Results were compared to equivalent parameters in adult atrial cardiomyocytes (aCM) and untreated atrial iPSC-CMs. Results: Fibronectin and laminin were ECMs found suitable for long time culture of iPSC-aCMs. Structural maturity (α-actinin and cardiac troponin T) and EP maturity (resting membrane potential [83 ± 3%], APD 90 [67 ± 2.5%], and conduction velocity [59.6 ±3%]) with patterned ECM and TID treatment were significantly improved compared to untreated iPSC-aCMs, and closer to those of adult aCMs. Conclusion: Structural and EP maturity of iPSC-aCMs are significantly enhanced by precise microenvironmental engineering of in-vivo relevant cell-cell, cell-ECM, and cell-soluble factor interactions. Thus, our findings will provide a platform to investigate cellular mechanisms of AF.
Final Analysis of MELISSE, a Large Multicentric Observational Study to Determine Risk Factors of Venous Thromboembolism in Patients with Multiple Myeloma Treated with Immunomodulator Drugs
Authors: Xavier Leleu, Laurent Daley, Philippe Rodon, Cyrille Hulin, Charles Dauriac, Hacini Hacini, Olivier Decaux, Jean-Claude Eisemann, Olivier Fitoussi, Laurent Voillat, Borhane Slama, Ahmad Al Jijakli, Carinne Chaleteix, Régis Costello, Anne Lamblin, Patrick Natta, Jean Paul Fermand, Philippe Moreau
Journal: Blood (2011)
Efficacy of Low-Dose Decitabine in the Early Relapse of AML/MDS after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Xu Guo-Fa, Chen Ting, Liu Huanfeng, Lin Shijia, Lei Gao, Cheng Zhang, Yao Liu, Xi Zhang, Defu Zeng, Kong Peiyan
Journal: Blood (2018)
Abstract 807: Rad Ablation as a Treatment to Target Cardiac Inotropy via L-type Calcium Channel Function
Authors: Brooke Ahern, Bryana Levitan, Sudhakar Veeranki, Mihir Shah, Nemat Ali, Andrea Sebastian, Jiayang Li, Julian E Stelzer, Doug Andres, Jonathan Satin
Journal: Circulation Research (2019)

The L-type Ca 2+ channel current (I Ca,L ) provides trigger Ca 2+ to contribute to cardiac contraction. Rad GTPase associates with the L-type Ca 2+ channel (LTCC) and serves as an endogenous inhibitor of LTCC activity. Overexpression of Rad blocks I Ca,L ; absence of Rad increases I Ca,L . Rad attenuates β-adrenergic receptor (β-AR) signaling. Chronic β-AR stimulation associates with Ca 2+ mishandling and can promote signaling that progresses towards heart failure. Early studies of global, constitutive Rad-knockout mice (gRadKO) suggested that elevated Ca 2+ dynamics leads to pathological cardiac hypertrophy; however, Rad is also expressed in non-cardiac tissues. Our objective is to test the hypothesis that increased myocardial I Ca,L via Rad deletion safely enhances cardiac function without driving pathological remodeling. We created a cardiac-restricted inducible Rad knockout mouse (Rad Δ/Δ ). In vivo function was measured with echocardiography. We examined I Ca,L through whole cell configuration of the patch clamp technique, assessed Ca 2+ handling, and sarcomere dynamics. Unlike gRadKO, Rad Δ/Δ showed no elevation of fetal gene program, nor fibrosis, and no change to aortic pressure. Rad Δ/Δ had a sustained increase of inotropy without structural or functional remodeling (EF: Rad Δ/Δ =76 ± 2%, n=16; Rad fl/fl =59 ± 4%, n=7; p=0.001.) I Ca,L was significantly increased, with Rad loss mirroring a β-AR modulated phenotype on basal I Ca,L (max. conductance: Rad Δ/Δ =254 ± 19 pS/pF, n=15; Rad fl/fl =144 ± 12 pS/pF, n=18; p&lt;10 -4 ). Contrary to models of chronic β-AR stimulation, Rad Δ/Δ retained β-AR signaling shown in vivo using isoproterenol, and by preserved phosphorylation of protein regulators of Ca 2+ reuptake and contractility. Rad Δ/Δ cardiomyocytes show enhanced cytosolic Ca 2+ handling (Decay of Ca 2+ transient: Rad Δ/Δ = 0.07 ± 0.003 (F 340 /F 380 )/s, n=67, Rad fl/fl = 0.10 ± 0.005, n=69; p&lt;10 -4 ), increased contractile function, and elevated SERCA2a expression. These new findings challenge the canonical assumption that increased myocardial Ca 2+ necessarily promotes pathology. We conclude that cardiac hypertrophy in gRadKO was caused by non-cardiac tissue effects, and myocardial Rad deletion is a promising cardiac inotropic therapeutic direction.
A Safety Study of the Addition of Omacetaxine to the Standard-of-Care Induction Regimen of Cytarabine and Idarubicin in Newly-Diagnosed AML Patients
Authors: Sonia Christian, Kelley E. Kozma, Stephanie Barath, Ardaman Shergill, Damiano Rondelli, David Peace, Santosh L. Saraf, Annie Lee Oh, Karen Sweiss, Irum Khan, Pritesh Patel, Arkadiusz Dudek, John G. Quigley
Journal: Blood (2018)
Diseases of the small intestine in childhood
Authors: J. T. Harries
Journal: Gut (1980)

chapters on motility.Diet, and psycho- logical aspects, are not considered, and the liver is allotted little more than two chapters.The book has to compete with review articles which appear regularly in the journals.The editors have sought to provide a balance of topics within gastro- enterology, and, as a balanced and thoughtful text, it is the best available.It is a book that will be read with interest by gastroenterologists,
Complement Cascade (CC) Cleavage Fragments - C3a and C5a Anaphylatoxins - As New Unexpected Hypoxia-Related Stimulators of Erythropoiesis.
Authors: Janina Ratajczak, Marcin Wysoczynski, Bogdan Machalinski, Anna Janowska-Wieczorek, Mariusz Z. Ratajczak
Journal: Blood (2007)
Targeting Lewis Y-Positive Multiple Myeloma and Acute Myeloid Leukemia with Gene-Modified T Cells Demonstrating Memory Phenotype
Authors: Stefan Peinert, David S. Ritchie, Dirk Hoenemann, Simon J. Harrison, Preethi Guru, Michael H. Kershaw, Amanda Shin, Mark J. Smyth, Joseph A. Trapani, Andrew M Scott, Glenn A Cartwright, Fiona E Smyth, Barbara E Power, Phillip K. Darcy, Peter Gambell, David Westerman, Paul Neeson, H. Miles Prince
Journal: Blood (2008)
A Single Nucleotide Polymorphism Of Growth Factor Independence 1 (GFI136N) is a Novel Prognostic Marker For The Progression Of Myelodysplastic Syndrome To Acute Myeloid Leukemia
Authors: Lars C. Michel, Lacramioara Botezatu, Judith Hönes, Damien Grapton, Charles Vadnais, Ulrich Germing, Uwe Platzbecker, Amos Zeller, Andre Görgens, Bernd Giebel, Thomas Schroeder, Roland Rudolph, Ulla von Verschuer, Jana Sengpiel, Bert A. Van der Reijden, Joop H. Jansen, Rainer Haas, Gerhard Ehninger, Tarik Moroy, Ulrich Duehrsen, Cyrus Khandanpour
Journal: Blood (2013)
Evaluation Of Multidrug Resistance (MDR) Functional Activity and Expression Levels Of P-Glycoprotein and MDR Related Protein-1 For The Prediction Of Treatment Failure In Chronic Myeloid Leukemia Patients
Authors: Sang Hyuk Park, Chan-Jeoung Park, Dae-Young Kim, Bo-Ra Lee, Young Jin Kim, Young-Uk Cho, Seongsoo Jang, Hyun-Sook Chi
Journal: Blood (2013)
The Oncology Evaluation Center: Implementation of a same-day evaluation and treatment center to avoid unnecessary ED visits.
Authors: Lindsey Zinck, Suzanne McGettigan, Jennifer Braun, Abbey Walsh, Lauren Cullen
Journal: Journal of Clinical Oncology (2019)

81 Background: Oncology patients have high rates of both Emergency Department (ED) visits and readmissions. The Hematology-Oncology Division at this urban, 776-bed academic medical center established the Oncology Evaluation Center (OEC) to provide cancer patients with prompt ambulatory evaluation for new symptoms that may otherwise lead to ED visits and unplanned admissions. With new therapeutic options associated with unique complications, the OEC Advanced Practice Providers are knowledgeable in providing care to this high-risk population. ED providers can lack oncology-specific training, comfort, and confidence when caring for cancer patients, resulting in sub-optimal care. Methods: A retrospective review of the chief complaints (CC) of oncology patients presenting to the ED was conducted. Using Plan Do Study Act methodology, in 2016 the OEC was opened to provide same day evaluations and interventions to patients with symptoms related to their cancer diagnosis, their treatment, or their comorbidities. Inclusion and exclusion criteria were developed to ensure appropriate referrals to the OEC. A hospital awareness campaign launched to promote OEC referrals, including educational sessions at multidisciplinary tumor boards. Additionally, two Lean Six Sigma trained infusion RNs led initiatives to promote OEC utilization. Results: The OEC resulted in quick evaluation and intervention for oncology patients. The most common CC are pain, dehydration, fever, nausea/vomiting, and fatigue. Of the 2721 patients seen to date in the OEC, 72% were discharged to home. According to survey results, 81% of oncology providers agree that if the OEC were not in existence, patients referred to the OEC would be referred to the ED. Oncology readmission rates have decreased from 14% (2016) to 12% (2018). Conclusions: The OEC has proven to be an innovative solution for prompt evaluation and ambulatory treatment of cancer patients with complications. This is a valuable component of comprehensive patient-focused care, resulting in ED visit and readmission avoidance. The OEC is an effective low cost, high reward programmatic strategy to expand access to care while improving patient experience.
Domain-Focused CRISPR-Cas9 Screen Identifies Hri Kinase As a Regulator of Fetal Hemoglobin in Adult Human Erythroid Cells
Authors: Jeremy D. Grevet, Nicole Hamagami, Xianjiang Lan, Laavanya Sankaranarayanan, Saurabh Bhardwaj, Carolyne Face, David Posocco, Osheiza Abdulmalik, Cheryl A. Keller, Belinda Giardine, Simone Sidoli, Ben Garcia, Stella T Chou, Ross C Hardison, Chris Vakoc, Junwei Shi, Gerd A. Blobel
Journal: Blood (2017)
Sequence Impact Of Pomalidomide and Carfilzomib On Treatment Response In Relapsed Multiple Myeloma
Authors: Tomer M Mark, John N. Allan, Angelique Boyer, Adriana C Rossi, Roger N Pearse, Faiza Zafar, Karen Pekle, Linda Tegnestam, David Jayabalan, Morton Coleman, Ruben Niesvizky
Journal: Blood (2013)
Editor's Note: Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism
Authors: Min Jia, Trygve Andreassen, Lasse Jensen, Tone Frost Bathen, Indranil Sinha, Hui Gao, Chunyan Zhao, Lars-Arne Haldosen, Yihai Cao, Leonard Girnita, Siver Andreas Moestue, Karin Dahlman-Wright
Journal: Cancer Research (2019)

The editors are publishing this note to alert readers to concerns about [this article][1] ([1][2]). The editors were made aware of duplicated Western blot bands in Fig. 4A. Specifically, two sets of Western blot bands are duplicates: (i) T47D CCTα in the top right panel and T47D cadherin in the
A novel hamstring strain injury prevention system: post-match strength testing for secondary prevention in football
Authors: Martin Wollin, Kristian Thorborg, Michael Drew, Tania Pizzari
Journal: British Journal of Sports Medicine (2019)

Despite the resources applied to the prevention of hamstring injuries in sport, between 2001 and 2014 the hamstring injury incidence and burden did not decline in male professional football.1 2 Consideration of alternative and complementary prevention strategies are needed.3 One-time only preseason screening for hamstring injury risk factors has limited value for preventing hamstring injuries.4 In-season monitoring of hamstring function has been advocated as a secondary prevention strategy.3 Since a player’s isometric knee flexion strength may decrease before suffering a hamstring strain (HS) injury,5 regular hamstring strength monitoring may be valuable. In-season monitoring can ensure players have restored hamstring muscle strength after the demands of a match and prior to undertaking high workloads in training or playing another match. Identifying a post-match impairment (‘subclinical stage of injury’),6 7 allows for early intervention and may be a practical way to lower susceptibility of hamstring injury (online supplementary material figure 1).

### Supplementary data

[bjsports-2019-100707supp001.pdf]

In this letter, we report our proof-of-concept hamstring injury prevention system that incorporated secondary prevention for hamstring injury in football. We also compared …
Does Delayed Childbearing Increase Risk?
Authors: Judith G. Baggs
Journal: JAMA (1993)

<h3>To the Editor.</h3> —In their study of delayed childbearing and risk of poor perinatal outcomes, Cnattingius et al<sup>1</sup>find an association between risks for the fetus and increasing maternal age. One variable they did not mention or control for is paternal age. I suspect a strong positive relationship exists between maternal and paternal age. Without at least including that variable, we have no way of knowing which is the stronger influence. I realize that such data, like cohabitation with the infant's father, smoking, or education, may be more difficult to obtain, but the issues warrant consideration.
A standardized workflow to improve the consent process among patients initiating an oral anticancer drug.
Authors: Jessica S. Brown, Dawn L. Hershman, Daniel O'Neil, Lois Brafman, Deborah A. Fuentes, Laura Graafland, Cynthia Law, Meghna S. Trivedi, Kevin Kalinsky, Katherine D. Crew, Melissa Kate Accordino
Journal: Journal of Clinical Oncology (2019)

259 Background: The American Society of Clinical Oncology and The Oncology Nursing Society’s guidelines recommend that consent be obtained and patient education provided prior to oral anticancer drug (OACD) initiation. The aim of this quality improvement project was to improve documentation rates of consent and education prior to OACD initiation in an outpatient breast oncology clinic. Methods: Plan-Do-Study-Act (PDSA) methodology was used to identify the root causes of inadequate OACD documentation; and to evaluate a standardized OACD workflow that included a multidisciplinary (physician, nurse practitioner [NP], and administrative staff) checklist on the disposition sheet and standardized patient education material, used in the Columbia University Irving Medical Center Breast Oncology Clinic. New OACD prescriptions were identified in the electronic health record (EHR) from 2/1/18-4/1/18 (pre-intervention) and 6/5/18-8/17/18 (post-intervention). Documentation of consent and education were evaluated by EHR review. Consent (yes/no) was determined by physician documentation in either the corresponding clinic note or scanned consent form, and education (yes/no) was determined by NP documentation in the education section of the clinic note. Documentation rates were compared pre- and post-intervention. Results: Pre-intervention, 19 patients received a new OACD, and 0 (0%) had documentation of consent or patient education. Root cause analysis revealed the driver of inadequate documentation was the inability to identify patients with a new OACD prescription at the time of their clinic visit. After implementation of the OACD workflow, 23 patients initiated a new OACD, 15 (65.0%) had documentation of consent and 7 (30.0%) had OACD education documented in the EHR. Conclusions: After the first PDSA cycle, documentation of consent and education improved from baseline. However, improvement in both metrics are still needed. Patient volume, staff changes, and the format of the OACD checklist may have limited the efficacy of this intervention. In the next PDSA cycle, the consent process will be linked to the required OACD pre-approval process to further increase OACD documentation.
CD200 Checkpoint Reversal: A Novel Approach to Immunotherapy
Authors: Zhengming Xiong, Elisabet Ampudia Mesias, G. Elizabeth Pluhar, Susan K. Rathe, David A. Largaespada, Yuk Y. Sham, Christopher L. Moertel, Michael R. Olin
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Advances in immunotherapy have revolutionized care for some patients with cancer. However, current checkpoint inhibitors are associated with significant toxicity and yield poor responses for patients with central nervous system tumors, calling into question whether cancer immunotherapy can be applied to glioblastoma multiforme. We determined that targeting the CD200 activation receptors (CD200AR) of the CD200 checkpoint with a peptide inhibitor (CD200AR-L) overcomes tumor-induced immunosuppression. We have shown the clinical efficacy of the CD200AR-L in a trial in companion dogs with spontaneous high-grade glioma. Addition of the peptide to autologous tumor lysate vaccines significantly increased the median overall survival to 12.7 months relative to tumor lysate vaccines alone, 6.36 months. Experimental Design: This study was developed to elucidate the mechanism of the CD200ARs and develop a humanized peptide inhibitor. We developed macrophage cell lines with each of four CD200ARs knocked out to determine their binding specificity and functional response. Using proteomics, we developed humanized CD200AR-L to explore their effects on cytokine/chemokine response, dendritic cell maturation and CMV pp65 antigen response in human CD14+ cells. GMP-grade peptide was further validated for activity. Results: We demonstrated that the CD200AR-L specifically targets a CD200AR complex. Moreover, we developed and validated a humanized CD200AR-L for inducing chemokine response, stimulating immature dendritic cell differentiation and significantly enhanced an antigen-specific response, and determined that the use of the CD200AR-L downregulated the expression of CD200 inhibitory and PD-1 receptors. Conclusions: These results support consideration of a CD200AR-L as a novel platform for immunotherapy against multiple cancers including glioblastoma multiforme.
Abstract 191: Difference in Calcium Sensitivity Between Right and Left Ventricles With Lower Expression of Calcium Binding Proteins in Right Ventricular Myocytes
Authors: Young Keul Jeon, Ji Hyun Jang, Jae Boum Youm, Yin Hua Zhang, Sung Joon Kim
Journal: Circulation Research (2019)

Left ventricle (LV) and right ventricle (RV) have distinctive structural and functional characteristics as well as heterogeneous physiological properties. The RV is exposed to a relatively low pulmonary vasculature, which results in less mechanical afterload. Consistent with these physiological differences, the RV has a thinner free wall than the LV, and the movement of its contraction is geometrically different. Despite these definite differences, the studies of basic excitation-contraction coupling and calcium homeostasis of RV has been less studied than in LV. To establish the interventricular difference, we evaluated the basic electrophysiological and calcium-contractile properties of myocyte with or without β-adrenergic stimulation. Analyses of contraction and Ca 2+ signaling and action potential duration (APD) in isolated RV myocytes showed more prominent APD prolongation with less significant changes in sarcomere shortening and calcium transient, implying less efficient E-C coupling RV myocytes. To investigate the prolonged APD of RV, we measured transient outward potassium (Ito) current and L-type calcium channel (LTCC) current of two ventricles. Although the peak current of two ion channel was not different significantly in two ventricle, the half inactivation voltage of RV Ito was smaller than LV. Comparing with LV, RV myocytes showed round peak, slower early relaxation, and faster late relaxation, suggesting the difference of calcium sensitivity between two ventricles. To investigate the difference, we examined the expression level of calcium-binding proteins that regulate myofilament activities. Using immunoblotting from enriched protein of myofilament fraction, we found that the calcium binding proteins such as troponin I were lower in RV. Taken together, our results suggest that calcium binding proteins of RV was differ from that of LV, which induce the modified calcium sensitivity. We confirmed that reduced calcium binding proteins induced the decrease of calcium sensitivity and modified E-C coupling using Bers’ mathematical rat cardiomyocyte model. The calcium sensitivity of RV is a clue to explain the different physiological properties of the RV.
Molecular Signatures to Improve Diagnosis, Prognostication and Identification of Oncogenic Pathways in Peripheral T and NK Cell Lymphoma.
Authors: Javeed Iqbal, Dennis Weisenburger, Timothy C. Greiner, Shigeo Nakamura, Julie M. Vose, Masao Seto, Jan Delabie, Francoise Berger, Florence Loong, Wing-Yan Au, Young-Hyeh Ko, Ivy Sng, Lynette M Smith, Can Kucuk, Huimin Geng, James Armitage, Wing C. Chan
Journal: Blood (2008)
Validation of the Korean Version of the Minneapolis-Manchester Quality of Life Instrument for Childhood Cancer Survivors
Authors: Hyeon Jin Park, Yoon Yi Kim, Young Ae Kim, Young Ho Yun, Byung Ho Nam, Ha Kyoung Kim, Smita Bhatia, Young Joo Kwon, Soo Hyun Lee, Byung-Kiu Park, Thad. T Ghim, Hyoung Jin Kang, Hee Young Shin, Hyo Seop Ahn
Journal: Blood (2008)
Abstract 822: Enhanced Left Ventricle TGFβ2 Signaling in a Model of Dilated Cardiomyopathy
Authors: Andrew Antolic, Ahmed B Alsalem, Da Young Lee, Zhe Jiao, Michael A Burke
Journal: Circulation Research (2019)

Pathological gene transcription and induction of proinflammatory signaling is a hallmark of dilated cardiomyopathy (DCM) and HF. Previous studies from our lab identified TGFβ2 as a putative driver of inflammation during DCM progression. To study the role of TFGβ2 in DCM hearts, we analyzed TFGβ signaling networks, as well as TFGβ2-induced gene expression changes from mice carrying a human DCM mutation in phospholamban (PLN R9C ). ELISA was used to confirm TGFβ isoform levels in PLN and wild type (WT) hearts: only TGFβ2 was significantly increased in PLN R9C mice (TGFβ1: 1.6-fold, p=0.15; TGFβ2: 9.6-fold, p=0.01; TGFβ3: 1.0-fold, p=0.88) (Figure). Levels of total SMAD2 (1.5-fold, p=0.002), phosphorylated SMAD2 (P-SMAD2; 3.9-fold, p=0.0003), and the P-SMAD2/SMAD2 ratio (2.6-fold, p=0.0004) were greater in PLN R9C mice. Treatment with exogenous TGFβ2 results in activation of cultured cardiac fibroblasts from WT hearts ( Col1a1 (3.3-fold), Col4a1 (2.7-fold), Ctgf (6.4-fold), Eng (2.6-fold), Fn1 (2.8-fold), Lox (2.6-fold), Mmp2 (2.8-fold), Postn (4.1-fold), Rhob (3.6-fold), Tgfb1 (3.6-fold), Tgfb2 (2.9-fold), Tgfb3 (3.0-fold), Tie1 (2.4-fold), Thsb1 (4.3-fold)). Our results demonstrate that TGFβ2 levels are increased and that TGFβ signaling is activated in PLN R9C hearts with DCM. These data suggest that TGFβ2 is a specific and potent inflammatory mediator in the heart and mark this isoform as a potential therapeutic target in DCM.