tbuckley/cabot-search huggingface dataset:
Improving quality of cancer care: Lessons learned from the journey towards QOPI Certification.
Authors: Nafisa Abdelhafiez, Mona Mohamed Alshami, Mohammad Omar Al-Kaiyat, Tabrez Pasha, Nashmia Mutairi, Terry Gilmore, Mohammad Jahanzeb, Abdul Rahman Jazieh
Journal: Journal of Clinical Oncology (2019)

263 Background: To assess the quality of cancer care provided at our institution, we participated in Quality Oncology Practice Initiative (QOPI) of American Society of Clinical Oncology (ASCO). However, our initial two rounds revealed lower score than required for QOPI Certification. Our goal was to implement interventions based on lessons learned from the initial rounds. Methods: Prior to the third round and using plan-do-study-act (PDSA) cycles, we identified and worked on three processes: clarifying and enhancing the function of the team, optimizing communication and improving documentation. We created QOPI multi-disciplinary team to include more members from different disciplines. We enhanced the knowledge of the team regarding our electronic health records system (EHRS) by conducting educational sessions and nominating super users who are very competent in EHRS and peer-to-peer support was created. Members were entering data in group sessions with the help of super users. We established double check system for records to be reviewed by two team members before submission. communication was assured among team members through weekly in person meetings and with ASCO QOPI team via virtual meetings to address queries. Documentation was improved by creating newer templates that conform with QOPI requirements including chemotherapy treatment plan, end of treatment summary and documentation of treatment consent. Results: The implementation of these interventions over three PDSA cycles made noticeable improvement in the previously unmet standards resulting in a score that exceeded the benchmark in fall of 2017 (score of 93%). This made our practice eligible for on-site certification visit by ASCO QOPI surveyors on May 2018 to assess practice compliance with QOPI standards. After addressing the unmet standards from the visit, our center became the first QOPI Certified Center in the Middle East and Asia in October/2018. Conclusions: Our journey towards QOPI Certification highlights the importance of fundamental principles in health care: coordinated multidisciplinary team, effective communication and proper documentation that captures essential and critical items reflecting better quality of care.
JAK2 ex13InDel drives oncogenic transformation and is associated with chronic eosinophilic leukemia and polycythemia vera
Authors: Ami B. Patel, Anca Franzini, Emilie Leroy, Soo Jin Kim, Anthony D. Pomicter, Lidvine Genet, Michael Xiao, Dongqing Yan, Jonathan M. Ahmann, Archana M. Agarwal, Phillip Clair, Juanah Addada, Jonathan Lambert, Matthew Salmon, Gerald J. Gleich, Nicholas C. P. Cross, Stefan N. Constantinescu, Thomas O’Hare, Josef T. Prchal, Michael W. Deininger
Journal: Blood (2019)
Rac1 and Rac2 Rho GTPases Distinctly Regulate Stem Cell Engraftment and Mobilization and Are Novel Targets for Pharmacologically-Induced Progenitor Mobilization.
Authors: Jose A. Cancelas, Andrew W. Lee, Rethinasamy Prabhakar, Michael Jansen, YI Zheng, David A. Williams
Journal: Blood (2004)
Abstract 579: Involvement of the Alpha 1A-Adrenergic Receptor in the Cardiac Adaptation to Physiological Stress
Authors: Xenia Kaidonis, Wenxing Niu, Andrea Y Chan, Scott Kesteven, Jianxin Wu, Siiri E Iismaa, Michael Feneley, Robert M Graham
Journal: Circulation Research (2019)

The ‘fight or flight’ response, involving sympathetic nervous system activation and catecholamine release, is central to survival. Resulting activation of adrenergic receptors (ARs) drives physiological responses, such as positive inotropy, which to date has been attributed solely to β 1 -AR/Gs/adenylyl cyclase/protein kinase A pathway-activation. We previously demonstrated that overexpression of the α 1A -AR is cardioprotective in rodents in the setting of pathological cardiac stress; a finding in agreement with studies of α 1A -AR inactivation. However, it remains unknown if α 1A -ARs also protect the heart from physiological stress. Using a tamoxifen-inducible, cardiomyocyte-specific α 1A -AR knockdown mouse model, we evaluated cardiac responses to swim exercise. Treatment of adult (8-12 week) mice with 4-OH tamoxifen (Tam) resulted in a 7.4 fold decrease (p&lt;0.001) in cardiac α 1A -AR mRNA levels, with no compensatory changes in expression of β 1 -, β 2 - or α 2 -AR subtypes. A 90 minute, twice daily, four-week swim challenge induced eccentric cardiac hypertrophy, with Tam- and vehicle-treated mice displaying similar increases in heart weight/tibia length (mean increase: 1.4 and 1.6mg/mm, respectively; p&lt;0.001 vs sedentary mice) and left ventricular chamber radius (mean increase: 0.16 and 0.17mm, respectively; p&lt;0.001 vs sedentary mice) with no change in wall thickness. Consistent with physiological hypertrophy, Igf-1 mRNA increased 1.7 and 0.7 fold (p=0.004 vs sedentary mice), respectively, with no increase in Nppb , Myh7 or Acta1 mRNA. Cardiac function, assessed by micromanometry and echocardiography, showed increases in dP/dt min/EDV (mean: -117 vs -150 mmHg/s/μL; p=0.011), end-diastolic volume (mean: 76.9 vs 68.0μL; p=0.038) and end-systolic volume (mean: 29.4 vs 21.9μL; p=0.018), as well as a decrease in ejection fraction (mean: 63 vs 68%; p=0.046) in Tam- compared with vehicle-treated mice, respectively. Thus, despite a similar hypertrophic response, mice with cardiomyocyte-specific α 1A -AR inactivation showed an impaired contractile response to a sustained swim challenge. These findings are consistent with cardiomyocyte α 1A -ARs playing an important role in maintaining cardiac contractility in response to physiological stress.
Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function
Authors: Mathilda Bedin, Olivia Boyer, Aude Servais, Yong Li, Laure Villoing-Gaudé, Marie-Josephe Tête, Alexandra Cambier, Julien Hogan, Veronique Baudouin, Saoussen Krid, Albert Bensman, Florie Lammens, Ferielle Louillet, Bruno Ranchin, Cecile Vigneau, Iseline Bouteau, Corinne Isnard-Bagnis, Christoph J. Mache, Tobias Schäfer, Lars Pape, Markus Gödel, Tobias B. Huber, Marcus Benz, Günter Klaus, Matthias Hansen, Kay Latta, Olivier Gribouval, Vincent Morinière, Carole Tournant, Maik Grohmann, Elisa Kuhn, Timo Wagner, Christine Bole-Feysot, Fabienne Jabot-Hanin, Patrick Nitschké, Tarunveer S. Ahluwalia, Anna Köttgen, Christian Brix Folsted Andersen, Carsten Bergmann, Corinne Antignac, Matias Simons
Journal: Journal of Clinical Investigation (2019)

BACKGROUND. Proteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.
Compliance of protocol-driven hepatitis B serological screening in patients receiving anti-CD20 monoclonal antibody therapy.
Authors: Lauren Schluenz, Kate Jeffers, Joseph Kalis
Journal: Journal of Clinical Oncology (2019)

261 Background: The US Food and Drug Administration has issued a boxed warning for anti-CD20 monoclonal anti-bodies for the reactivation of Hepatitis B virus (HBV) infection. The National Comprehensive Cancer Network (NCCN) Non-Hodgkin Lymphoma and Infectious Diseases Society of America guidelines recommend routine serologic testing for all patients receiving anti-CD20 antibody therapy. NCCN specifies serologic screening of HBV surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) should be completed prior to initiation of anti-CD20 therapy. In March 2018, UCHealth included HBV screening into the EHR oncology templates which include an anti-CD20 monoclonal antibody. The purpose of this study was to assess the impact of this template modification on compliance to guideline recommended screening for patients receiving anti-CD20 monoclonal antibody therapy. Methods: This was a retrospective chart review of patients who received an anti-CD20 monoclonal antibody for an oncologic indication between April 1, 2017 to November 30, 2017 (pre-template change) and April 1, 2018 to November 30, 2018 (post-template change) at any of the UCHealth Cancer Care and Hematology Centers. The primary objective was the composite compliance rate of HBsAg and HBcAb screening completed prior to receipt of treatment. Secondary objectives included compliance rate of each screening test, days between screening and treatment, screening for initial compared to relapse therapy, and rate of hepatitis C virus screening. Results: The addition HBV serologic screening to the EHR oncology templates containing an anti-CD20 agent improved screening compliance of HBsAg and HBcAb by 6.7% as a system (2017: 89.7% vs 2018: 96.4% [p = 0.133]). Secondary endpoints saw an increase in testing of each individual screening, testing for patients in the relapse setting, and HCV screening. Additionally, a reduction was seen in median days between screening and start of therapy (2017: 11 (4.5-30.3 IQR) vs 2018: 7 (2-14 IQR) [p = 0.008]). Conclusions: The addition of HBV serologic screening to EHR oncology templates increased compliance to guideline recommended screening for patients receiving anti-CD20 antibody therapy.
Abstract 182: Left Ventricular Diastolic Dysfunction in HIV-infected ART-naive and HIV-negative Tanzanian Adults: A Cross-sectional Study
Authors: Justin Kingery, Edmund Damas, Samuel Kalluvya, Altaf Pirmohamed, Parag Goyal, Myung Hee Lee, Fredrick Kalokola, Bernard Desdarius, Robert Peck
Journal: Circulation Research (2019)

Objective: To compare the prevalence and associated factors of left ventricular diastolic dysfunction in HIV-infected, ART naïve and HIV-negative Tanzanian adults. Methods: A cross-sectional analysis of a longitudinal study including: 257 HIV-infected, ART naïve adults and 265 HIV-negative controls. Echocardiography and traditional risk factors were performed and determined by standard investigations. The primary outcome was prevalence of left ventricular diastolic dysfunction. Secondary outcomes were factors associated with and grade of dysfunction. Results: Compared to HIV-negative controls, HIV-infected, ART naïve adults had a 2-fold higher prevalence of diastolic dysfunction (OR=2.06 [1.16-3.66], p=0.01). Additionally, age, female sex, obesity and hypertension were significantly associated with dysfunction in HIV-negative adults; whereas, only age and hypertension were associated with dysfunction in HIV-infected adults. As compared to HIV-negative controls, significantly more HIV-infected, ART naïve adults had higher grade dysfunction (p=0.02) and more ventricular hypertrophy. HIV-infected adults with diastolic dysfunction also expressed higher levels of inflammatory cytokines including TNFa, IL6, IL8, IL33 and sST2 as compared to both HIV-negative and HIV-infected adults without dysfunction. Conclusions: HIV-infected Tanzanian adults have a 2-fold higher prevalence of left ventricular diastolic dysfunction in the period immediately following diagnosis and before ART initiation as compared to HIV-negative adults, and this dysfunction is of higher grade and is associated with myocardial hypertrophy. These data identify diastolic dysfunction in an international cohort in the immediate post-diagnosis, pre-ART period similar to that previously reported in the post-ART period in high-income countries. Additionally, traditional cardiovascular risk factors are not significantly associated with dysfunction in HIV-infected adults; however, cytokine patterns are present and may be important for risk stratification in this group. Therefore, studies delineating appropriate screening for this population are needed.
TREK-1 and TRAAK Are Principal K+ Channels at the Nodes of Ranvier for Rapid Action Potential Conduction on Mammalian Myelinated Afferent Nerves
Authors: Hirosato Kanda, Jennifer Ling, Sotatsu Tonomura, Koichi Noguchi, Sadis Matalon, Jianguo G. Gu
Journal: Neuron (2019)

Rapid conduction of nerve impulses is critical in life and relies on action potential (AP) leaps through the nodes of Ranvier (NRs) along myelinated nerves. While NRs are the only sites where APs can be regenerated during nerve conduction on myelinated nerves, ion channel mechanisms underlying the regeneration and conduction of APs at mammalian NRs remain incompletely understood. Here, we show that TREK-1 and TRAAK, the thermosensitive and mechanosensitive two-pore-domain potassium (K2P) channels, are clustered at NRs of rat trigeminal Aβ-afferent nerves with a density over 3,000-fold higher than that on their somas. These K2P channels, but not voltage-gated K+ channels as in other parts of nerves, are required for rapid AP repolarization at the NRs. Furthermore, these channels permit high-speed and high-frequency AP conduction along the myelinated afferent nerves, and loss of function of these channels at NRs retards nerve conduction and impairs sensory behavioral responses in animals.
A Synthetic Lethality Druggable Genome RNAi Screen Identifies Genes Mediating Sensitivity To Lenalidomide In Multiple Myeloma Including RSK2
Authors: Yuan Xiao Zhu, Laura Bruins, Chang-Xin Shi, Jessica Schmidt, Chris Sereduk, Mia Champion, Esteban Braggio, Holly Yin, A. Keith Stewart
Journal: Blood (2013)
Efficacy of Yttrium-90 Iburitumomab Tiuxetan for Early Relapsed/Refractory Indolent B-Cell Lymphoma: A Single Institute Retrospective Analysis in the Rituximab Era
Authors: Keiichi Nakata, Shigeo Fuji, Ryo Nakata, Kazuhito Tsutsumi, Shuhei Kida, Midori Koike, Yuma Tada, Hiroaki Masaie, Hitoshi Yoshida, Jun Ishikawa
Journal: Blood (2018)
Acupuncture for dysphagia after chemoradiation therapy in head and neck cancer: A randomized sham-controlled study.
Authors: Weidong Lu, Jochen H. Lorch, Peter M Wayne, Roger B Davis, Roy B. Tishler, Marshall R. Posner, Laura A Goguen, Hailun Li, Eric Macklin, Elaine Burke, Zachary Jaffa, Nicholas J Dreyer, Tyler C Haddad, Julie E Buring, David S. Rosenthal, Robert I. Haddad
Journal: Journal of Clinical Oncology (2013)

6058 Background: Dysphagia is a common side effect following chemoradiation (CRT) in pts with head and neck cancer (HNC). The purpose of this pilot trial was to assess the feasibility of recruiting HNC pts and to collect preliminary data on the efficacy and safety of acupuncture on dysphagia-related QOL. Methods: Pts were eligible if diagnosed with stage III-IV HNC, without evidence of distance metastasis, receiving curative-intent CRT. Pts were randomized to 12 sessions of either active or sham acupuncture, once every two weeks, over 24 weeks from during CRT to 20-week post-CRT. All study personnel and the pts were blinded; the treating acupuncturists were not. MDADI and other questionnaires were measured at baseline (end of CRT), end of acupuncture, and at six months follow-up (12-month post-CRT). Data were analyzed by repeated-measures ANOVA adjusting for baseline. Results: Accrual was completed in December 2011. Among 42 pts enrolled, 35 (83%) received at least 8 sessions of acupuncture, and 28 (67%) received all 12. Six pts withdrew due to time constraints. No serious side effects were observed. The mean MDADI total scores improved from baseline in both treatment arms [64.5 (SE+2.4) vs. 71.4 (SE±3.1), p = 0.048; 64.5 (SE±2.4) vs. 77.8 (SE±3.0), p&lt; 0.001]; the difference in improvement was not significant (p = 0.12). The median feeding tube duration did not differ between active and sham treatments (n = 39, median 125 days vs. 147 days, p = 0.93). Conclusions: Acupuncture is a safe and feasible treatment for HNC pts. There were improvements in QOL parameters from end of CRT to the time points examined that did not differ between the two arms. Efficacy of acupuncture to improve swallowing-related QOL in HNC pts may require more frequent or longer duration of treatment. Clinical trial information: NCT00797732.
Enhanced Selective Inhibition of KRAS Mutant Hematopoietic Progenitor Cell Expansion By MEK and Bcl-2 Inhibition
Authors: Huan-Ting Lin, Kenji Kubara, Kazuto Yamazaki, Masatoshi Takagi, Takuya Naruto, Tomohiro Morio, Takashi Okumura, Makoto Otsu
Journal: Blood (2018)
A Combination of Fludarabine/Rituximab with Escalating Doses of Lenalidomide in Previously Untreated Chronic Lymphocytic Leukemia (CLL): The REVLIRIT CLL5 AGMT Phase I/II Study, Clinical and Exploratory Analyses of Induction Results
Authors: Alexander Egle, Michael Steurer, Franz Gassner, Roland Geisberger, Thomas Melchardt, Lukas Weiss, Michael A. Fridrik, Josef Thaler, Alois Lang, Richard Greil
Journal: Blood (2011)
Abstract 114: Myocardial B Cells Regulate the Composition of Leukocytes in the Heart as Well as Myocardial Growth
Authors: Luigi Adamo, Cibele Rocha-Resende, Sarah Evans, Jesse Williams, Hao Dun, Wenjun Li, Cedric Mpoy, Buck Rogers, Daniel Kreisel, Kory Lavine, Gwendalyn Randolph, Douglas L Mann
Journal: Circulation Research (2019)

Background: B cells are the second most prevalent leukocyte in the murine naïve heart. However, since current models state that B cells continually recirculate between primary and secondary lymphoid organs without accumulating in peripheral tissues, the origin and function of this sizeable myocardial leukocyte pool remains unknown. Goal: To investigate the origin and function of myocardial B cells in the naïve heart. Results: Bone marrow transplant experiments showed that the murine myocardium harbors a large population of bone marrow derived B cells and a small population of embryo derived B cells. Parabiosis, heart transplant, and adoptive transfer experiments showed that all myocardial B cells recirculate between the heart, the spleen, and likely other organs. Immunohistochemistry showed that the vast majority of myocardial B cells resides in the myocardial microcapillaries and make intimate contact with the endothelium. 10X single cell RNA sequencing showed that myocardial B cells are heterogeneous and have a specific gene expression pattern different from that of peripheral blood B cells. Ex vivo perfusion of hearts from B cell deficient mice with wild type peripheral blood suggested that myocardial B cells “adhere” to the microvascular endothelium. In vivo microscopy confirmed that a subgroup of circulating B cells pauses on microvascular endothelial cells. Finally, analysis of B cell deficient and B cell depleted mice showed that B cells modulate the composition of the myocardial leukocyte pool and myocardial growth. Conclusions: Myocardial B cells are an accumulation of a heterogeneous subgroup of circulating B lymphocytes that, upon arrival in the heart, makes intimate contact with the microvascular endothelium. Myocardial B cells regulate the composition of the myocardial leukocyte pool and myocardial mass. These findings highlight a novel unexpected relationship between B cells and myocardial physiology and suggest a paradigm shift in our current understanding of B cell biology in the naïve state.
Cost of Care at NCI-Designated Comprehensive Cancer Centers Vs. Other Treatment Sites for Young Adults with Newly-Diagnosed Acute Lymphoblastic Leukemia (ALL)
Authors: Julie A. Wolfson, Smita Bhatia, Jill Ginsberg, Laura Becker, David Bernstein, Henry (Joe) Henk, Gary H. Lyman, Paul Nathan, Diane Puccetti, Jennifer J. Wilkes, Lena E. Winestone, Kelly Kenzik
Journal: Blood (2018)
Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment
Authors: Cameron H. Flayer, Erik D. Larson, Anjali Joseph, Sean Kao, Wenxiu Qu, Austin Van Haren, Christopher M. Royer, Lisa A. Miller, John P. Capitanio, Thais Sielecki, Melpo Christofidou-Solomidou, Angela Haczku
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 816: Surgical Bilateral Stellate Ganglionectomy Reduces Mitochondrial Reactive Oxygen Species (mROS) and Prevents Sudden Cardiac Death (SCD) in Non-ischemic Heart Failure (HF)
Authors: Swati Dey, Brian O'Rourke, Deeptankar DeMazumder
Journal: Circulation Research (2019)

Introduction: Current therapies for SCD are limited. Bilateral sympathetic stellate ganglionectomy ( BSG ) is a promising new adjunctive therapy in patients with ischemic HF who have incessant ventricular tachyarrhythmias ( VT/VF ) despite optimal medical management. The underlying mechanisms are unknown. The effect of BSG in non-ischemic HF is unclear. Hypothesis: BSG prevents VT/VF and SCD in non-ischemic HF by restoring sympathovagal balance and reducing mROS. Methods: We used a unique pressure-overload guinea pig model that closely mimics human non-ischemic HF, including a high incidence of spontaneous VT/VF/SCD. We randomized the animals to non-failing controls, HF+Sham, or HF+BSG surgery. We used intention to treat analysis to evaluate VT/VF-free survival. We analyzed continuous ECG (VT/VF burden, heart rate variability, QT variability) and echo (cardiac function). In isolated left ventricular (LV) myocytes, we measured Ca 2+ transients and mitochondrial reactive oxygen species (mROS) using targeted ratiometric probes. Results: Half of the HF+Sham animals experienced SCD in 4 weeks. In contrast, BSG abolished SCD, reduced VT/VF, and increased parasympathetic tone (beyond corresponding reductions in sympathetic tone). Fractional shortening of the LV was markedly reduced in HF+Sham (0.28±0.02) vs. control (0.50±0.01), but preserved by BSG (0.45±0.02). Whereas HF+Sham increased mROS levels in LV myocytes (fractional oxidation, F ox : 0.53±0.015) compared to control (0.29±0.020), BSG reduced mROS (0.38±0.035). Mitochondrial antioxidant capacity, as indexed by H 2 O 2 challenge of LV myocytes, was compromised in HF+Sham (F ox : 0.81±0.040) compared to control (0.44±0.061), but preserved by BSG (0.48±0.023). Conclusions: Surgical BSG prevents SCD in non-ischemic HF by reducing mROS, decreasing sympathetic tone, and by increasing parasympathetic tone (possibly by facilitating cholinergic transdifferentiation). This promising new minimally-invasive surgical therapy may be particularly useful in patients with non-ischemic HF on optimal medical therapy who require recurrent ICD shocks to prevent SCD. Patients in the early stages of HF who are not eligible for ICDs but remain at higher SCD risk may also benefit from BSG surgery.