tbuckley/cabot-search huggingface dataset:
Evaluating end-of-life (EOL) care at the University of Rochester Medical Center (URMC) using quality oncology practice initiative (QOPI) metrics.
Authors: Titas Banerjee, Jason Harold Mendler, Nabeel Badri, Dwight Hettler, Julie Ann Berkhof, Karen J. Abbas, Manidhar Reddy Lekkala, Bahar Moftakhar, Karim Welaya, Carissa Treptow, Dilip Sankar Babu, Megan Baumgart
Journal: Journal of Clinical Oncology (2019)

12 Background: Inpatient mortality, defined as death within 30 days of an acute hospital admission, is often used as a quality benchmark for healthcare institutions and is an important metric for evaluating quality of care of patients with advanced malignancies. In this study we aimed to utilize QOPI performance data to identify areas of weakness in our practice that may contribute to inpatient mortality. Methods: We analyzed 11 EOL measures within the QOPI database which we collected between 2015 and 2018. These included all EOL measures related to hospice enrollment (measure IDs 42-47), chemotherapy administered within the last 2 weeks of life (ID 48), percentage of patients who died from cancer with at least one emergency department (ED) visit in the last 30 days of life (ID 49ed), and the percentage of patients who died from cancer admitted to the Intensive Care Unit (ICU) in the last 30 days of life (ID 49icu). Our rate was calculated for each measure and compared against QOPI aggregate data. We used a fisher’s exact test to determine statistical significance for each metric. Results: The number of patients from our institution included in each analysis ranged from 27 to 46. Compared to our peers, patients treated at our institution were more likely to visit an ED in the last 30 days of life (68% vs. 32%; P &lt; 0.0001), more likely to be admitted to the ICU in the last 30 days of life (29% vs. 9%; P = 0.0003), and more likely to be enrolled on hospice within the last 7 days of death (63% vs. 32%; P = 0.001). Conclusions: Analysis of QOPI EOL performance scores identified several metrics that may contribute to inpatient mortality at URMC. Ongoing participation in QOPI with a focus on EOL metrics will strengthen this analysis. We plan to use this data to guide quality improvement initiatives aimed at reducing impatient mortality and improving end of life care at our institution.
Abstract 155: Lin28 Enhances Cardiac Progenitor Cell Ability to Repair the Heart by Reprogramming Cellular Metabolism
Authors: Antonia Yuko, Justin Kurian, Nicole Kasatkin, Kelsey Busch, Fares AlHawaj, Lena Ma, Mohsin Khan, Sadia Mohsin, Steven Houser, Hong Wang
Journal: Circulation Research (2019)

Rationale: The adult Heart is largely a dormant organ supporting limited cellular turnover. In contrast, neonatal cardiac tissue proliferates and is capable of regeneration while operating under a specialized metabolic state. During transition to adulthood, cardiac metabolism undergoes a rapid shift that coincides with termination of regenerative processes. Whether altering cardiac metabolism recapitulates regenerative potential remains untested. Recently, introduction of Lin28, a metabolic regulator of pluripotency, enhances tissue repair after injury. Nevertheless, there are no studies characterizing the effect of Lin28 on cardiac repair. Objective: Determine the effect of Lin28 on cardiac progenitor cell function and cardiac repair after injury. Methods and Results: Lin28 expression coincides during heart development with c-kit and declines postnatal with complete abrogation in 3-week-old adult heart as measured by qRT-PCR and immunohistochemistry. CPCs were engineered with Lin28-GFP (CPCLin) lentivirus GFP expressing CPCs were used as controls (CPC-G). CPCLin demonstrated increased proliferation measured by CyQuant compared to CPC-G, concurrent with decreased apoptosis. Interestingly, CPCLin demonstrated a significant increase in lactate production, pyruvate kinase activity, glucose uptake together with enhancement of glycolysis and expression of glycolytic enzymes compared to CPC-G. Oxidative metabolism was also upregulated together with increased intracellular ATP in CPCLin compared to controls. Additionally, CPCLin demonstrated significantly reduced ROS generation as measured by CM-H 2 TMROS based FACS analysis compared to CPC-G. To determine in vivo efficacy, CPCLin and CPC-G were transplanted in the heart after myocardial infarction. CPC-Lin hearts showed significant increase in cardiac structure and function 8 weeks after MI. Increased persistence and proliferation of transplanted CPC-Lin cells together with reduced apoptosis were observed in CPCLin hearts compared to control CPC-G hearts 2 days after transplantation. Conclusions: Lin28 modification of CPCs reprograms cellular metabolism in CPCs enhancing proliferation and survival including ability to repair the heart after myocardial injury.
Haplo-Identical Stem Cell Transpant Is a Feasible and Safe Treatment Option for Patients with Severe Thalassemia
Authors: Suradej Hongeng, Usanarat Anurathapan, Samart Pakakasama, Duantida Songdej, Nongnuch Sirachainan, Ampaiwan Chuansumrit, Borje S Andersson
Journal: Blood (2018)
Abstract 893: MicroRNA-448 Regulates the Cardiac Sodium Channel During Ischemia
Authors: Gyeoung-Jin Kang, An Xie, Samuel Dudley
Journal: Circulation Research (2019)

Background: The cardiac voltage-gated sodium channel ( SCN5A ; encoding Na v 1.5) plays a key role in cardiac conduction. The sodium channel is downregulated in cardiomyopathy, contributing to arrhythmic risk. In part, this downregulation is because of abnormal mRNA splicing and reduced mRNA stability. The reason for decreased mRNA stability is unclear, however. Objective: Here, we examined whether microRNA-448 (miR-448)can contribute to SCN5A mRNA instability. Methods: Datasets from the Gene Expression Omnibus database were utilized to screen miR-448 in human and mouse heart tissues. The relationship between SCN5A and miR-448 was predicted by three independent prediction tools. The expressions of SCN5A and miR-448 were determined by quantitative real time polymerase chain reaction. Protein levels of Na v 1.5 were determined by Western blot. The effect of miR-448 mimic on sodium current was determined in induced pluripotent stem cells-derived cardiomyocytes. Mouse myocardial infarction was created by left anterior descending coronary artery ligation. Results: The expression of miR-448 is increased in stressed heart after myocardial infarction. The binding sequence for miR-448 is well-conserved in 3’-UTR of SCN5A and miR-448 directly bound to a consensus cis element, suppressing SCN5A expression and sodium currents. miR-448 expression wass increased by hypoxia. Activated by hypoxia, HIF1α and NF-κB activated were major transcriptional regulator for MIR448 . Conclusion: These results indicated that miR-448 contributed to post-transcriptional modification of SCN5A . miR-448 is likely one cause of sodium channel downregulation during ischemia and may represent a target for antagomir therapy to reduce arrhythmic risk associated with cardiomyopathy.. Keywords: SCN5A, miR-448, Cardiomyocyte, Hypoxia, NF-κB, HIF1α
Validation of the Nccn-Ipi for Diffuse Large B-Cell Lymphoma in Latin American Patients: A Study from the Latin-American Group of Lymphomas (GELL)
Authors: Brady E. Beltrán, Victoria Otero, Marialejandra Torres Viera, Camila Peña, Myriam Lucía Rodriguez, Gabriel Borelli, Teodoro Chisesi, Fabiola Valvert Gamboa, Abel Berrios, Gregorio Ignacio, Carlos Sérgio Chiattone, Sally Paredes, Denisse A. Castro, Maria Elena Cabrera, Raul Gabus, Eduardo Sotomayor, Jorge J. Castillo
Journal: Blood (2018)
Stromal-targeting radioimmunotherapy mitigates the progression of therapy-resistant tumors
Authors: Evangelia Bolli, Matthias D’Huyvetter, Aleksandar Murgaski, Danielle Berus, Geert Stangé, Emile J. Clappaert, Sana Arnouk, Ana Rita Pombo Antunes, Ahmet Krasniqi, Tony Lahoutte, Amanda Gonçalves, Marnik Vuylsteke, Geert Raes, Nick Devoogdt, Kiavash Movahedi, Jo A. Van Ginderachter
Journal: Journal of Controlled Release (2019)
Socioeconomic deprivation and cancer outcomes in patients treated in clinical trials.
Authors: Joseph M. Unger, Anna Moseley, Scott David Ramsey, Raymond U. Osarogiagbon, Banu Symington, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2019)

162 Background: Studies using cancer registry data have shown that cancer patients living in socioeconomically disadvantaged areas have worse cancer outcomes. Socioeconomic deprivation (SD) has not been systematically examined in clinical trial patients, who are uniformly staged according to trial eligibility criteria and have access to protocol-directed care. Methods: We examined survival for patients enrolled in phase III clinical trials for all major cancers conducted by SWOG from 1985-2012. SD was measured using trial participant’s residence zip codes linked to the Area Deprivation Index (ADI) , a comprehensive index composed of 17 indicators reflecting a diverse set of socioeconomic variables, scored from 0-100, split into quintiles. Five-year overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) were examined using Cox regression, adjusting for age (in 5 year intervals), sex, race (black v. non-black), and, for a subset of patients, insurance status (Medicaid/no insurance v. other). Analyses were stratified by cancer histology and stage. Results: In total, n = 41,182 patients from 55 trials comprising 24 cancer histology and stage-specific strata were examined. Compared to trial participants in the most affluent areas (ADI 0%-20%), trial participants from areas with the highest SD (ADI 80%-100%) had worse OS (HR = 1.26, 95% CI, 1.18-1.35, p &lt; .001), PFS (HR = 1.19, 95% CI, 1.12-1.27, p &lt; .001) and CSS (HR = 1.25, 95% CI, 1.17-1.35, p &lt; .001). Results were similar after also adjusting for insurance status. For each outcome, there was a continuous increase in risk of an event as the ADI quintile increased. Conclusions: In cancer patients with access to protocol-directed care in clinical trials, area-level SD was associated with worse survival, even after adjusting for patient-level race and insurance. Future research should examine whether the etiology of this residual disparity is related to reduced access to supportive care or post-protocol therapy, and/or to differences in health status not reflected by protocol staging criteria. Policies to mitigate socioeconomic differences in cancer outcomes should emphasize access to cancer care services beyond initial therapy.
Developing a strategy for delivering educational information to patients with cancer.
Authors: Emily Elizabeth Monteleone, Meredith Rachek, Alison Ibsen, Cheryl M. Carrino, Edwin Wortham, Andre Hook, Scott Steele
Journal: Journal of Clinical Oncology (2019)

190 Background: Patients’ preferences and ability to receive information regarding their cancer diagnosis and treatment vary greatly. Large academic medical centers are skilled at diagnosing and treating cancer. The perceived patient experience can be influenced by the delivery of information provided to them by clinical teams, support staff, and online resources. This project identified nuances in how cancer patients absorb and reference information regarding their diagnosis and treatment; specifically, treatment modalities, side effects, and resources available. The objective was to develop a strategy to improve and standardize the delivery and availability of educational information in our large academic medical center. Methods: Development of a team that has influence and understanding in various communication functions throughout the enterprise. Primary focus was on cancer patients. Research was conducted in three phases. Phase one was a patient panel survey electronically administered. Phase two involved observations and interviews of current breast cancer patients. Phase three incorporated the feedback received and design concepts generated from research during phases one and two, and involved six cancer patient focus groups. Results: Panel survey results contained feedback from 777 participants previously diagnosed with or caring for someone with cancer. Observations and interviews encompassed over 40 hours of information gathering from all stages of the breast cancer treatment process, including survivorship. Focus groups involved 7-9 patients (50 total) each of varying ages and diagnoses, with 4 of the 6 groups treated at our cancer center. Conclusions: In getting to know patients, large academic medical centers can tailor their educational information to ensure everyone receives what is needed and wanted in the time and manner best suited for them. Core components of the strategy being developed are 1) formulating ways to personalize the delivery of information, 2) methods to allow patients’ caregivers to participate in educational discussions remotely, 3) enabling on demand access to content previously discussed in person, 4) setting expectations for the intent of appointments ahead of time.
Targeted Degradation of IRAK4 Protein Via Heterobifunctional Small Molecules for Treatment of MYD88 Mutant Lymphoma
Authors: Joseph Kelleher, Laurent Audoly, Veronica Campbell, Jesse Chen, Nan Ji, Hari Kamadurai, Henry Li, Christine Loh, Haojing Rong, Dominico Vigil, Matt Weiss, Karen Yuan, Yi Zhang, Nello Mainolfi
Journal: Blood (2018)
Abstract 906: Age-Dependent Modifications in Cardiac Myofilament Proteins are Graded by Overall Health, Measured as Frailty, in Aging Male and Female C57BL/6 Mice
Authors: Alice Kane, Elise S Bisset, Kaitlyn Keller, W G Pyle, Susan E Howlett
Journal: Circulation Research (2019)

Previously, we showed that the age-dependent decline in ventricular function in male mice is proportional to overall health, as quantified with a frailty index (FI) tool. This tool is based on the accumulation of deficits in health across many systems, but not the cardiovascular system per se . Here we investigated whether frailty grades age-dependent modifications in myofilaments in young and aged mice of both sexes. Myofilaments were isolated from ventricles of adult (12-13 mos; n=5 males, 5 females) and aged (22-23 mos; n=6 males, 5 females) mice. FI scores were obtained from all mice. Actomyosin Mg-ATPase activity as a function of increasing calcium concentration and phosphorylation of major myofilament proteins were quantified and compared between groups. Results showed that myofilament calcium sensitivity (EC 50 values) was similar regardless of age or sex and was not affected by FI score. Maximal actomyosin Mg-ATPase activity increased with age in females, but this was not linked to frailty. Hill coefficients declined with age in males only and were lower than females in the older group (p&lt;0.05). However when all mice were examined, Hill coefficients declined as frailty increased (r=0.68, p=0.001). Total phosphorylation levels of myosin-binding protein C (MyBP-C), desmin, tropomyosin and essential myosin light chain (ELC) increased with age, but only in males. Interestingly, phosphorylation of MyBP-C (r=0.49; p=0.03), desmin (r=0.65; p=0.003), tropomyosin (r=0.62; p=0.004) and ELC (r=0.71; p=0.001) were highly correlated with overall health (FI scores). By contrast there was no link between frailty and phosphorylation of actin, troponin T and troponin I. These findings suggest that poor overall health, quantified in an FI, predicts changes in the myofilaments across the life course in both sexes. This may contribute to changes in cardiac contractile function in frail older adults.
Mcl-1 Is Overexpressed in Multiple Myeloma and Correlates with Disease Severity.
Authors: Soraya Wuilleme-Toumi, Nelly Robillard, Patricia Gomez-Bougie, Philippe Moreau, Steven Le Gouill, Herve Avet-Loiseau, Jean-Luc Harousseau, Martine Amiot, Regis Bataille
Journal: Blood (2004)
Abstract 200: Targeting the Highly Abundant Circular RNA, circHeart, in Cardiomyocytes Attenuates Pressure Overload Induced Hypertrophy
Authors: Tingsen B Lim
Journal: Circulation Research (2019)

Objectives: Circular RNAs (circRNAs) are single-stranded non-coding RNAs that form a covalent closed looped structure and are generated during gene transcription. In our genome-wide analysis of cardiac circRNA expression in both human and mouse hearts we identified a highly abundant circRNA, named here as circHeart and hypothesize an important role for circHeart in cardiomyocyte physiology and homeostasis. Materials and method: We undertook FISH to visualize the localization of circHeart . Online tools have predicted multiple potential miRNA binding sites on circHeart , including the cardiac-enriched microRNA-133a (miR-133a). We assessed the interactions of circHeart with these miRNAs by luciferase and pull-down assays and performed AAV9-mediated RNAi knockdown and overexpression of circHeart in mice in vivo . In vivo phenotype was tracked by echocardiography, electrocardiogram and histological studies. Transverse aortic constriction (TAC) was also performed. Results: FISH imaging showed circHeart localized largely to the cardiomyocyte cytosol. Luciferase and reciprocal pull-down assays suggest circHeart can interact with miR-133a. MiR-133a is a well-known regulator of cardiac hypertrophy and antagomir-133a treatment has been shown to induce cardiac hypertrophy in vivo . In our studies, while AAV9 RNAi-mediated knockdown of circHeart has no apparent baseline effect in the heart it suppresses pathological cardiac hypertrophy post-TAC. More strikingly, AAV9-mediated overexpression of circHeart in vivo resulted in mouse mortality between 3-4 days post-transduction and surviving mice showed evidence of dilated cardiomyopathy. Known targets of miR-133a were concordantly modulated in the knockdown and overexpression mouse model. Conclusion: CircRNAs have huge potential role as therapeutic targets and/or disease biomarkers and represent a new avenue for cardiovascular research. Taken together, our data are consistent with a mechanistic model of circHeart sequestering miR-133a. Inhibiting circHeart abundance presents a potential target for treating cardiac hypertrophy.
Virus-Specific T Lymphocytes Maintain Their In Vivo Phenotype and Functional Competence After Automated Processing To Generate a Cellular Product For Immunotherapy
Authors: Anne Richter, Liane Preussner, Verena Traska, Michaela Peters, Ayse Oysal, Katharina Ruhnke, Olaf Brauns, Sven Kramer, Juergen Schmitz, Mario Assenmacher
Journal: Blood (2013)
Abstract 410: A Novel Combination Therapy Using First Trimester Human Umbilical Cord-Derived Mesenchymal Stromal Cells and Endothelial Progenitor Cells Significantly Improves Angiogenesis and Cardiac Recovery Following Myocardial Infarction
Authors: Farwah Iqbal, Alexander Johnston, Poonam Mander, Brandon Wyse, Jun Wu, Ren-Ke Li, Peter Szaraz, Clifford Librach
Journal: Circulation Research (2019)

Introduction: Umbilical cord-derived MSC show pericyte-like characteristics and demonstrate significant angiogenic potential via paracrine and direct support to the vasculature. Endothelial progenitor cells (EPC) have the potential to initiate vascular structures while maintaining paracrine properties following ischemic injury. Hypothesis: A combination therapy of first trimester umbilical cord MSC (FTM HUCPVC) with rat EPC will promote significant angiogenesis, cardiomyocyte survival and lead to functional cardiac recovery in a rat model of MI. Methods: MI was induced by LAD ligation on 8-week-old Fox rnu rats. 1 week later, rats with notable decrease (&lt;30%) in ejection fraction (EF) were randomly separated into 4 treatment groups (n=9) and received intramyocardial injection of: G1: Media; G2: FTM HUPVC (3х10 6 cells/rat); G3: EPC (2.2х10 6 cells/rat); G4: FTM HUCPVC - EPC combination (1:2, total cells 3х10 6 cells/rat). Endpoint analysis was at 5-days and 4-weeks after injection. Results: 5-days after injection, exclusively G4 animals showed significant cardiac recovery, improved EF and FS compared to G1 - G2 - G3 ( p &lt;0.01). IHC analysis showed significantly less apoptosis (caspase-3), more protease activity and sarcomeric actin in combination groups G4 compared to G1-G2-G3 ( p &lt;0.001). More FTM HUCPVC and EPC colocalized adjunct to small capillaries in G4 . Significant increase of human Angpt-2 was detected in G4 compared to G1-G2-G3 (p&lt;0.0001). Analysis at 4-weeks post-injection showed significant improvements in end-systolic volume (128μl) and EF (43%) in G4 compared to G2 (160μl) (35%) G3 (180μl) (30%) respectively (B) . LV contractility (dpdt, tau) significantly improved in G4 compared to G1 , G2 , G3 (p&lt;0.001). Significant reduction in scar tissue and increased LV myocardial mass was found in G4 and G2. IHC analysis showed significantly more and larger (9um) capillaries localized in LAD injured myocardium in G4 compared to G1-G2-G3 ( p &lt;0.001). Significantly more sarcomeric actinin and connexin-43 was identified in G4 compared to G1-G2-G3 . Conclusions: Our results show the superior potential of FTM HUCPVC - EPC combination cell therapy for faster and greater cardiovascular repair and recovery compared to single-cell-type treatments for MI.
Resolution of Intractable Leg Ulcers Associated with Antiphospholipid Syndrome (APS) with Prophylactic Dose of Aspirin (ASA) and Enoxaparin: A Case Report
Authors: Carlos Dobler, Larissa A Szeyko, Mark M Landeros, Carmen P Arango, Luis S Noble, Sheeba Varughese Tano, Juan Herrada
Journal: Blood (2018)
Genome-Wide Association Study (GWAS) Of Venous Thromboembolism (VTE) In African-Americans From The Electronic Medical Records &amp; Genomics (eMERGE) Networkm
Authors: John A. Heit, Mariza de Andrade, Sebastian M Armasu, Iftikhar J Kullo, Jyotishman Pathak, Christopher G Chute, Omri Gottesman, Erwin P Bottinger, Joshua C Denny, Dan M Roden, Rongling Li, Marylyn D Ritchie
Journal: Blood (2013)
A Chemokine Receptor CXCR4 Plays a Crucial Role for Repairing Ischemic Tissue through Regulation of HIF-2a
Authors: Masumi Nagano, Ken-ichi Kimura, Toshiharu Yamashita, Hiromi Hamada, Kinuko Ohneda, Hiroyuki Yoshikawa, Osamu Ohneda
Journal: Blood (2008)