tbuckley/cabot-search huggingface dataset:
A Phase II Study of Brentuximab Vedotin Plus Adriamycin and Dacarbazine without Radiation in Non-Bulky Limited Stage Classical Hodgkin Lymphoma
Authors: Jeremy S. Abramson, Robert A. Redd, Jeffrey A. Barnes, Elizabeth Bengtson, Ronald W. Takvorian, Lubomir Sokol, Frederick Lansigan, Philippe Armand, Bijal D. Shah, Eric D Jacobsen, Donna S Neuberg, Ann S. LaCasce, Celeste M. Bello
Journal: Blood (2018)
Lymphopenia and an Elevated Monocyte Count At Diagnosis Do Not Predict a Poor Outcome After Autologous Transplants for Diffuse Large B-Cell Lymphoma in the First Remission
Authors: Mitsufumi Nishio, Satoshi Yamamoto, Tomoyuki Endo, Katsuya Fujimoto, Toshiya Sakai, Takeshi Kondo, Akio Shigematsu, Junichi Sugita, Satoshi Hashino, Junji Tanaka, Masahiro Imamura, Takanori Teshima
Journal: Blood (2012)
Women at risk for hip fracture following decline in bisphosphonate use.
Authors: Marcelo Coca Perraillon, Cathy J Bradley
Journal: Journal of Clinical Oncology (2019)

239 Background: Hip fractures in older adults are associated with increases in morbidity, mortality, and costs of care. Breast cancer treatment, including chemotherapy and endocrine treatment, interfere with bone health, increasing the risk of hip fracture for breast cancer survivors. Multiple studies report large and steady declines in hip fracture incidence coinciding with the availability of bisphosphonates to prevent osteoporosis, although black label warnings about side effects in 2011 steered physicians away from their widespread use. This study estimates trends in hip fracture incidence in a cohort of women with breast cancer before and after 2011. Methods: Retrospective observational study using 2007-2015 SEER-Medicare data for women aged 66 years or older continuously enrolled in fee-for-service Medicare with a first primary diagnosis of breast cancer. Primary outcome was an inpatient admission for a hip fracture within two years of cancer diagnosis. Monthly discrete time survival models were used to estimate the probability of hip fracture after diagnosis conditional on observable factors including demographic characteristics, comorbidities, and the concurrent use of bisphosphonates and cancer treatment. Results: A total of 67,577 patients met the inclusion criteria. The age adjusted incidence of hip fracture declined by 25.1% from 2007 to 2011; from 1093.662 (95% CI, 1027.9-1159.4) to 819.224 (95% CI, 762.1-876.4) per 100,000. However, the incidence of hip fractures stabilized after 2011, with a decline of only 4% from 2011 to 2014, when the incidence was 785.4 (95% CI, 728.6-842.1). The risk of hip fracture increases with age and the number of comorbid conditions. Although more women are prescribed bisphosphonates after a cancer diagnosis, prescription rates declined after 2011. Conclusions: The incidence of hip fractures in breast cancer survivors stabilized after years of steady declines. This significant change in incidence coincided with a large reduction in the use of bisphosphonates after warnings of rare but serious side effects were issued. More research is needed to prevent hip fracture in women with breast cancer and further consideration of available treatments is required for women at high risk for hip fracture.
Whole Genome Sequencing and RNA Sequencing of 27 Patients with Persistent Polyclonal B-Cell Lymphocytosis Reveals a High Mutation Frequency/Overexpression of Lymphoma Associated Genes: Really a Benign Disorder?
Authors: Anna Stengel, Alexander Höllein, Wolfgang Kern, Manja Meggendorfer, Claudia Haferlach, Wencke Walter, Stephan Hutter, Torsten Haferlach
Journal: Blood (2018)
Abstract 656: Construction and Application of an Epigenetic Atlas of the Human Heart
Authors: Dimple Prasher, Hao Zhang, Patrick M McCarthy, Gavin Oudit, Paul W Fedak, Steven C Greenway
Journal: Circulation Research (2019)

Epigenetic modifications, including DNA methylation, regulate gene expression and contribute to the differentiation of cells. Tissues are characterized by methylation patterns that reflect their specific functions and origin. Currently, there is limited knowledge of the epigenetic patterns of the heart. To address this gap, we generated methylation profiles for all anatomical regions of the human heart. We hypothesize that unique differentially methylated regions (DMRs) of DNA exist for each cardiac region and that these patterns are disrupted in heart failure. Using non-diseased cardiac tissue and reduced representation bisulfite sequencing on a Illumina platform, we generated genome-wide methylomes for the human right atrium (n=4), left atrium (n=4), right ventricle (n=4), left ventricle (n=4), aorta (n=3), pulmonary artery (n=2), mitral valve (n=3), tricuspid valve (n=3), aortic valve (n=3) and pulmonary valve (n=3). DMRs, defined as regions with significantly different mean methylation differences, were identified using Metilene. For each tissue we identified between 10-20 million reads covering 8-10 million CpG methylation sites and 4-228 tissue-specific DMRs. There were relatively few (4) different DMRs between the left and right ventricles but 228 unique DMRs were found in the vessels (aorta and pulmonary artery) compared to the ventricles including regions upstream of BMP3 and FOXC1 , genes implicated in cardiogenesis. We then applied this approach and normal data to the analysis of disease. We generated additional left ventricular methylomes from adult (n=3) and pediatric (n=3) patients with heart failure. We identified 19 unique DMRs in the adult group and 107 in the pediatric group. Genes associated with pediatric HF DMRs included ROCK1 and FBLN2 that have been previously implicated in contraction and remodelling. We have created an atlas of the human heart based upon differences in DNA methylation between the anatomical regions of the human heart. This data will help increase our understanding of cardiac development, identify new disease biomarkers and have application to a wide range of cardiac diseases
Applying quality improvement methodologies to decrease the time-to-activation of new clinical trials at an NCI-designated comprehensive cancer center.
Authors: Timothy J Brown, Erin Fenske Williams, Patrice Griffith, Asal Shoushtari Rahimi, Rhonda Oilepo, Hans J. Hammers, Theodore Willis Laetsch, Pamela Kurian, Penny Currykosky, Susan Partridge, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2019)

296 Background: Initiating a new clinical trial is burdensome and complex. The time to activate a clinical trial can directly affect the ability to provide innovative, state-of-the-art care to patients. We sought to understand the process of activating an oncology clinical trial at a matrix National Cancer Institute-designated, comprehensive cancer center. Methods: A multidisciplinary team of stakeholders within the cancer center, university, and affiliate hospitals held a retreat to map out the process of activating a clinical trial from packet receipt to enrollment of the first patient. We applied classical QI and Six Sigma methodology to determine bottlenecks and redundancies in activating a clinical trial. During this process, particular attention was paid to time to pass through each step and perceived barriers and bottlenecks were identified through group discussions. The time to activation was measured from the day the trial packet was received until the time when the trial was open for enrollment. Results: The process map identified 66 steps with 12 decision points to activate a new clinical trial. The following two steps were instituted first: 1) allow parallel scientific committee and institutional review board (IRB) review and 2) allow the clinical research coordination committee to review protocols for feasibility and university interest separate from the IRB approval process. These changes resulted in a mean time-to-activation change from 194 days at baseline to 135 days after these changes were implemented. The committee continues to track the activation time and this frame work is used to identify additional improvement steps. Conclusions: By applying quality improvement methodologies and Six Sigma principles, we were able to redesign redundant aspects of the process of activating a clinical trial at a matrix comprehensive cancer center. This was associated with a reduction of time to activation of trials. More importantly, the process map provides a framework to maintain these gains and implement further changes.
Hierarchical micro/nanofibrous membranes of sustained releasing VEGF for periosteal regeneration
Authors: Liang Wu, Yong Gu, Lili Liu, Jincheng Tang, Jiannan Mao, Kun Xi, Zhirong Jiang, Yidi Zhou, Yun Xu, Lianfu Deng, Liang Chen, Wenguo Cui
Journal: Biomaterials (2019)
Abstract 17720: Perinatal Outcomes and Current Status after Prenatal Diagnosis of Heterotaxy Syndrome
Authors: Maria C Escobar, Yishay Salem, Brian Kalish, Rahul Rathod, Tal Geva, Sitaram Emani, David W Brown, Wayne Tworetzky
Journal: Circulation (2012)

Heterotaxy syndrome (HS) has a wide spectrum of cardiac defects and outcomes. Prenatal diagnosis (Dx) impacts perinatal outcome and management. The aim of this study was to describe the current sta...
Impact of Age on Outcomes Following Initial Therapy with Various Chemotherapy and Chemoimmunotherapy Regimens in Patients with Chronic Lymphocytic Leukemia (CLL): Results of CALGB Studies
Authors: Jennifer A. Woyach, Amy S. Ruppert, Bercedis Peterson, Kanti R. Rai, Thomas S. Lin, Frederick R. Appelbaum, Martin S. Tallman, Andrew R Belch, Richard A. Larson, John C. Byrd
Journal: Blood (2011)
Abstract 712: mRNA Stability in Pluripotency and Differentiation of Induced Pluripotent Stem Cells
Authors: Hien T Luong, Sahana S Babu, John Henderson, Phuong T Quach, Prasanna Krishnamurthy
Journal: Circulation Research (2019)

Background: Induced- pluripotent stem cells (iPSC) have distinct transcriptional machinery for the maintenance of pluripotency and achievement of differentiation with the regulation of pluripotency markers, growth factors, and differentiation factors. The Hu family of RNA-binding proteins, HuR (also known as ELAVL1 or human embryonic lethal abnormal vision-like protein), binds to the 3'-untranslated region of mRNAs and regulates transcript stability and translation. However, the role of HuR in pluripotency or differentiation of iPSC to cardiomyocytes (iCM) remains unclear. Methods: HuR knockdown in human dermal fibroblast-derived iPSCs was achieved by CRISPR/Cas9 or lentiviral shRNA transduction and subsequently differentiated into cardiomyocytes (iCM). Then, the expression of HuR, pluripotency and cardiomyocyte markers were evaluated following the initiation of differentiation. Results: At basal level, HuR expression was higher in the iPSCs compared to dermal fibroblasts. Upon differentiation of iPSCs into iCM, HuR mRNA expression gradually reduced with significantly lower levels on day 17. As expected, pluripotency markers gradually reduced upon differentiation with significantly lower levels from day 6 onwards. We observed a corresponding increase in ISL1, MESP1 (mesoderm/cardiac progenitor markers) from day 3 through day 8 with a steep fall from day 8 to day 17. This was associated with Myosin light chain-2V and GATA4 expression increases from day 8 through day 17. Interestingly, knockdown of HuR resulted in clumps of colonies with differentiated cells and a corresponding increase in cardiac-troponin positive cells. However, as a general observation, HuR knockdown reduced beating intensity compared to wild type cells. Conclusions: Based on these data, we could speculate that HuR might be necessary for maintenance of pluripotency and loss of which renders cells to differentiate in culture. HuR knockdown yields higher number of c-troponin positive cells but its effect on functional maturity of iCM needs to be further evaluated.
Population-Based Analysis of Temporal Trends in the Prevalence of Depressed Mood Among Sexual Minority and Heterosexual Youths From 1999 Through 2017
Authors: Alexandra H. Bettis, Richard T. Liu
Journal: JAMA Pediatrics (2019)

AOR, 0.68; 95% CI, 0.59-0.79;P < .001),Asian American race (AOR, 0.46; 95% CI, 0.35-0.61;P < .001),Hispanic ethnicity (AOR, 0.56; 95% 0.48-0.65;P < .001),no insurance (AOR, 0.61; 95% CI, 0.47-0.80;P < .001),and no health care visit (AOR, 0.65; 95% CI, 0.53-0.81;P < .001).Variables associated with increased odds of surgery included maternal education beyond high school (AOR, 1.25; 95% CI, 1.04-1.50;P = .02),North Central/Midwest region (AOR, 1.34; 95% CI, 1.14-1.58;P < 001), Southern region (AOR, 1.33; 95% CI, 1.14-1.55;P < .001),low birth weight (AOR, 1.59; 95% CI, 1.35-1.88;P < .001),trisomy 21 (AOR, 3.02; 95% CI, 1.58-8.65;P = .003),and congenital heart disease (AOR, 4.37; 95% CI, 2.37-8.06;P < .001).Discussion | Using a large, nationally representative crosssectional survey, we observed a decline in odds of surgery from 1998 to 2017 that was most significant in children younger than 1 year.We controlled for demographic variables and clinical factors expected to impact surgical exposure.While surgical techniques have continually evolved, we are unaware of drastic changes in surgical management for infants during this period.Our findings support the hypothesis that alternative factors including parental and practitioner concerns about anesthetic exposure may have affected surgical decision-making in infants.Interestingly, while maternal education may improve awareness of anesthesia risk, this was associated with increased odds of surgery.This study was limited by lack of data on procedure type, anesthetic details, associated outcomes, and inability to control for all confounders.We therefore recommend further prospective studies assessing these trends and associated health outcomes. Conclusions |The period prevalence and adjusted odds of surgery declined significantly from 1997 through 2017 for children younger than 1 year.
Jumping Translocations 1q12 Contribute to Copy Number (CN) Alterations in Multiple Myeloma (MM): Unexpected Focal Amplifications of Receptor Chromosomes (RC)
Authors: Jeffrey Sawyer, Erming Tian, John D. Shaughnessy, Janet Lukacs, Regina Lichti Binz, Edward Thomas, Gael Sammartino, Charles Swanson, Christoph Heuck, Yazan Alsayed, Elias J. Anaissie, Bijay Nair, Sarah Waheed, Saad Usmani, Frits van Rhee, Bart Barlogie
Journal: Blood (2011)
TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge
Authors: Alicia A. Nugent, Karin Lin, Bettina van Lengerich, Steve Lianoglou, Laralynne Przybyla, Sonnet S. Davis, Ceyda Llapashtica, Junhua Wang, Do Jin Kim, Dan Xia, Anthony Lucas, Sulochanadevi Baskaran, Patrick C.G. Haddick, Melina Lenser, Timothy K. Earr, Ju Shi, Jason C. Dugas, Benjamin J. Andreone, Todd Logan, Hilda O. Solanoy, Hang Chen, Ankita Srivastava, Suresh B. Poda, Pascal E. Sanchez, Ryan J. Watts, Thomas Sandmann, Giuseppe Astarita, Joseph W. Lewcock, Kathryn M. Monroe, Gilbert Di Paolo
Journal: Neuron (2020)
Ethical Challenges of Risk, Informed Consent, and Posttrial Responsibilities in Human Research With Neural Devices
Authors: Saskia Hendriks, Christine Grady, Khara M. Ramos, Winston Chiong, Joseph J. Fins, Paul Ford, Sara Goering, Henry T. Greely, Katrina Hutchison, Michael L. Kelly, Scott Y. H. Kim, Eran Klein, Sarah H. Lisanby, Helen Mayberg, Hannah Maslen, Franklin G. Miller, Karen Rommelfanger, Sameer A. Sheth, Anna Wexler
Journal: JAMA Neurology (2019)

Developing more and better diagnostic and therapeutic tools for central nervous system disorders is an ethical imperative. Human research with neural devices is important to this effort and a critical focus of the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Despite regulations and standard practices for conducting ethical research, researchers and others seek more guidance on how to ethically conduct neural device studies. This article draws on, reviews, specifies, and interprets existing ethical frameworks, literature, and subject matter expertise to address 3 specific ethical challenges in neural devices research: analysis of risk, informed consent, and posttrial responsibilities to research participants.
A physician engagement learning strategy to reduce care variation in breast cancer across a clinically integrated network.
Authors: Trever Bradley Burgon, Jon M. Richards, Carrie E. Nelson, David R. Paculdo, Diana Tamondong-Lachica, Wilfredo L. Liangco, John Williamson Peabody
Journal: Journal of Clinical Oncology (2019)

30 Background: Advocate Physician Partners (APP) is a 5,000+ physician CIN associated with Advocate Aurora Health. APP wanted to standardize care among their 100+ medical oncologists who work in 20+ independent and employed practices. We approached standardization as a learning opportunity that could be best done through active engagement. Methods: From January 2016 to November 2017, we utilized the Clinical Performance and Value (CPV Ò ) simulated patient platform to measure clinical practice and provide feedback across APP. Over six rounds, a total of 119 APP medical oncologists were scored against evidence-based work-up and treatment criteria. To determine if any of the learnings found on the CPVs translated into practice, we used registry and claims data on unnecessary imaging for early stage breast cancer. Results: In the simulated breast cancer patients, we found an overall improvement of 13.3% in primary diagnosis accuracy and 15.3% in treatment (p&lt;0.001 for both). Preferred guideline-based hormonal therapy and chemotherapy similarly improved by 15.1% (p=0.018). To compare the CPV improvements with patient-level improvements, we looked specifically at unnecessary imaging and testing which declined overall by 35.7% (p=0.006); the associated costs fell by 31.3%. In early stage breast cancer, the CPV-measured use rates for CT or PET/CT (p=0.026) and other scans (p=0.012) decreased, showing better alignment with guidelines (see Table). When we analyzed the patient claims data, we found these showed similar declines in potentially unneeded breast cancer testing. Conclusions: Active learning, using CPV simulations, increased adherence to evidence-based practices, which translated into practice as evidenced by registry/claims data showing fewer unnecessary imaging in early stage breast cancer. [Table: see text]
Abstract 720: Prenatal Exposure of Cigarette Smoke Impacts Cardiac Regeneration
Authors: Katharina Schimmel, Isabel Morgado, Cheng-Yu Tsai, Alessandro Evangelisti, Sudeshna Fisch, Soeun Ngoy, Dian-Jian Lee, Seema Dangwal, Kevin Alexander, Jennifer E Ward, Ronglih Liao
Journal: Circulation Research (2019)

Background: Neonatal mammalian hearts have the unique characteristic to fully repair and regenerate following injury. This discovery has led to visionary endeavors to understand and subsequently reawaken regeneration processes in the human adult heart that are lost after birth, contributing to heart failure and death after ischemic insults. In utero exposure to tobacco smoke has detrimental effects on fetal development and growth. However, the consequences of prenatal exposure to cigarette smoke on murine neonate’s cardiac regeneration have never been explored. Methods: To study the impact of cigarette smoke during the entire pregnancy on cardiac regeneration in the offspring, plugged female wild type C57LB/6J mice were exposed either to cigarette smoke (n=6) or filtered air (control, n=6). Two days after birth, 5 pups from each litter were assigned to the two experimental groups: Myocardial infarction (MI) and sham. Detrimental effects of in utero exposure to tobacco smoke on the recovery of cardiac function following MI surgery were followed using two-dimensional speckle tracking echocardiography and strain imaging. To investigate the underlying mechanism, cardiac tissue of the infarct and remote zone was collected for non-coding RNA analysis. Results: In utero exposure to cigarette smoke significantly compromised cardiac regeneration in neonates. At both early and late time points in the phase of cardiac repair, hearts of neonates exposed to cigarette smoke during pregnancy showed a marked impairment of cardiac regenerative potential. In particular, ejection fraction, fractional area change and shortening, as well as left ventricular internal diameter during systole remained pathologically changed following MI insult in the smoked group until the very endpoint. Conclusions: Collectively, we here provide evidence that in utero exposure to cigarette smoke strongly compromises cardiac regeneration in the newborn offspring. This result reinforces smoking cessation during pregnancy. Additionally, understanding the changes in non-coding RNA expression in a setting of preserved versus disrupted repair of the heart might be an important first step towards the identification of key cellular processes in cardiac regeneration after injury.
Abstract 565: Response of the Ischemic Myocardium to Adrenergic Stimulation as Detected by Hyperpolarized [1- <sup>13</sup> C]pyruvate
Authors: Gaurav Sharma, Wei Chen, Weina Jiang, Aaron L Anderson, Craig R Malloy, A. Dean Sherry, Chalermchai Khemtong
Journal: Circulation Research (2019)

Metabolic imaging by nuclear methods is widely used to access ischemic myocardium but provide limited information about individual enzyme-catalyzed reactions. 13 C hyperpolarization methods are sensitive to flux in specific key enzymes such as lactate dehydrogenase and pyruvate dehydrogenase. We tested the hypothesis that LDH flux is increased while PDH flux is abolished in low-flow ischemia. Metabolism of HP [1- 13 C]pyruvate was studied in four groups: (1) normal perfusion pressure (NPP), 100 cm H 2 O; (2) NPP with epinephrine; (3) low-perfusion pressure (LPP), 25 cm H 2 O; (4) LPP with epinephrine. Hearts excised from male Sprague-Dawley rats were perfused (37°C) at an initial pressure of 100 cm H 2 O using standard Langendorff method with Krebs-Henseleit buffer containing 0.75% bovine serum albumin, 0.4 mM non-labeled free fatty acid, 5.5 mM [U- 13 C]glucose, 1 mM [3- 13 C]pyruvate, 0.1 mM [3- 13 C]lactate. Perfusion pressure was reduced to 25 cm H 2 O after 30 min of perfusion for ischemia group and epinephrine added at 50 th min of perfusion. HP [1- 13 C]pyruvate was injected to heart and subsequently, 13 C NMR spectra were acquired. The freeze clamped heart tissues were extracted with perchloric acid and analyzed by high-resolution 1 H and 13 C NMR (14.1 T). The 31 P NMR spectroscopy confirmed significant myocardial ischemia under LPP conditions, demonstrated by a marked increase in the [Pi]/[ATP] ratio. Surprisingly, increased LDH flux was observed in the ischemic hearts (+18.4%) while the metabolism of HP [1- 13 C]pyruvate by PDH remained unchanged as indicated by bicarbonate production. To investigate the oxidative capacity of mitochondria, epinephrine was used to stimulate hearts. As anticipated, epinephrine increased heart rate (+23%) and coronary flow (+11%) under NPP. Epinephrine increased heart rate (-60%) but did not alter coronary flow under LPP. We found that epinephrine had no effect on the rate of bicarbonate production under LPP. The study demonstrated that the conversion of pyruvate to lactate increased in ischemic hearts but the degree of pyruvate oxidation was not affected by the low-flow ischemia. Adrenergic stimulation did not increase PDH flux in these ischemic hearts. Translation to human is likely to provide new data from low-flow myocardium.
A Leukemic Progression Model of Severe Congenital Neutropenia Uncovers a Novel Mechanism of AML Development Involving Elevated Inflammatory Responses, Mutation of CXXC4 and Decreased TET2 Levels
Authors: Patricia Olofsen, Szabolcs Fatrai, Paulette van Strien, Julia Obenauer, Remco Hoogenboezem, Claudia Erpelinck-Verschueren, Onno Roovers, Torsten Haferlach, Peter Valk, Rebekka Schneider, Emma De Pater, Ivo Touw
Journal: Blood (2018)