tbuckley/cabot-search huggingface dataset:
Higher rates of bleeding and use of treatment products among young boys compared to girls with von Willebrand disease
Authors: Karon Abe, Brandi Dupervil, Sarah H. O'Brien, Meredith Oakley, Roshni Kulkarni, Joan Cox Gill, Vanessa Byams, Michael J. Soucie
Journal: American Journal of Hematology (2019)

Abstract There are limited observational studies among children diagnosed with von Willebrand Disease (VWD). We analyzed differences in bleeding characteristics by sex and type of VWD using the largest reported surveillance database of children with VWD (n = 2712), ages 2 to 12 years old. We found that the mean ages of first bleed and diagnosis were lowest among children with type 3 VWD. It was even lower among boys than girls among all VWD types, with statistically significant difference among children with type 1 or type 3 VWD. Children with type 3 VWD also reported higher proportions of ever having a bleed compared to other VWD types, with statistically higher proportions of boys compared to girls reporting ever having a bleed with type 1 and type 2 VWD. A similar pattern was observed with the use of treatment product, showing higher usage among type 3 VWD, and among boys than girls with type 1 and type 2 VWD. While there were no differences in life quality or in well‐being status by sex, children with type 3 VWD showed a greater need for mobility assistance compared to children with type 1 and type 2 VWD. In an adjusted analysis among children with type 1 VWD, boys showed a significant association of ever bleeding [hazard ratio 1.4; P ‐value &lt;.001)] compared to girls. Understanding phenotypic bleeding characteristics, well‐being status, treatment, and higher risk groups for bleeding among pre‐adolescent children with VWD will aid physicians in efforts to educate families about bleeding symptoms.
Implementation of a post discharge video visit telehealth initiative.
Authors: Samantha Burdette, Nathan Handley, Katlin Birchmeier, Atrayee Basu Mallick, Joanne Filicko, Adam Binder
Journal: Journal of Clinical Oncology (2019)

274 Background: Telehealth is increasingly used as a means to influence four domains of healthcare: access, cost, experience, and effectiveness. The medical oncology service at Thomas Jefferson University implemented a post-discharge video visit program for all patients discharged from the Advanced Practice Provider (APP) service following scheduled inpatient chemotherapy. Data were collected to assess clinical interventions that occurred. Barriers to participation in the visits were also assessed. Methods: All patients on the APP service were screened for eligibility for a post discharge video visit. Patients who were eligible (requirements: reliable internet connection, access to a smart device, active patient portal account, English language speaker) had video visits scheduled prior to discharge. Data regarding the visits (including patient demographics, eligibility, patient interest, and interventions performed) were recorded. Results: One hundred forty nine admissions were included in the analysis. Sixty (40.27%) resulted in the scheduling of a post discharge video visit; 37 (61.67%) of these visits were completed. Medication reconciliation/education occurred in 22 encounters (59.46%); symptom management occurred in 17 encounters (45.95%).The most common reason for not completing a visit was the patient not answering the video visit call (17 encounters (73.91%)). Of the 89 encounters in which patients were ineligible or declined, technological barriers were the most common reason for not participating (29.21%), followed by disinterest (17.10%) and non-English speaking (16.85%). Conclusions: While significant barriers to implementation of post-discharge video visits exist, when visits did occur, frequent interventions occurred. Further research to understand and alleviate barriers to telehealth implementation are merited. Care must be taken to avoid creating disparities among patient populations.
Abstract 170: Exosomal AAV-mediated SERCA2a Gene Transfer Improves Cardiac Function in a Mouse Model of Heart Failure
Authors: Marta Adamiak, Divya Jha, Yaxuan Liang, Prabhu Mathiyalagan, Neha Agarwal, Erik Kohlbrenner, Elena Chepurko, Dongtak Jeong, Delaine Ceholski, Nicole Dubois, Roger Hajjar, Susmita Sahoo
Journal: Circulation Research (2019)

Adeno-associated viruses (AAVs) are promising therapeutic tools for gene delivery to the heart. However, pre-existing antibodies (NAbs) to many cardiotropic AAV serotypes naturally present in humans pose a critical challenge for the translation of gene therapies to clinical applications. Here, we describe the use of exosomal AAVs (eAAV) as a robust heart gene delivery system that improves transduction efficiency while protecting from pre-existing immunity to the viral capsid. To obtain eAAV specimens from conditioned medium from AAV-producing HEK-293T cells, we have developed a state-of-the-art multi-step ultracentrifugation strategy. We demonstrated through electron microscopy-based visualization, size distribution measurements and distribution of AAV genomes in post-centrifugation iodixanol gradients, that our purification process enables isolation of eAAVs with high purity and minimal contamination with standard AAVs. Efficiency of heart targeting was then evaluated for eAAV9 or eAAV6 and standard AAV9 or AAV6 in human cardiomyocytes (hCMs) in vitro and in passive immunity nude mouse model in vivo . Regardless of the presence or absence of NAbs, we demonstrated that eAAVs are more efficient in transduction of cells in the same titer ranges as standard AAVs. To test the therapeutic efficacy, eAAV9-SERCA2a or AAV9-SERCA2a were injected intramyocardially in post-myocardial infarction (MI) mice preinjected with NAbs. Remarkably, eAAV9-SERCA2a outperformed standard AAVs 6 weeks post-MI, significantly improving cardiac function in the presence of NAbs (%EF 55.14 ± 3.50 vs. 27.31 ± 1.63, respectively). Additionally, we demonstrated in vivo that eAAV9-mediated gene delivery is more specific to CMs than to other cell types present in the heart, which suggests that eAAVs preserve cardiotropic properties of AAV9 serotype. With examination of colocalization of eAAVs and markers specific for endosomes (Rab5 and Rab7) in hCMs in vitro , our preliminary data indicated that eAAV infectious entry potentially involves trafficking via endocytic compartments. In conclusion, these results underline the therapeutic potential of eAAVs to evade NAbs, and to facilitate the clinical translation of AAV-based gene therapies to a larger human population.
Stearoyl CoA Desaturase Regulates Ferroptosis in Ovarian Cancer Offering New Therapeutic Perspectives
Authors: Michele Carbone, Gerry Melino
Journal: Cancer Research (2019)

Abstract Better therapies are urgently needed for ovarian cancer, which is associated with an overall median survival of less than 5 years from diagnosis. In this issue of Cancer Research, Tesfay and colleagues show that stearoyl CoA desaturase (SCD1) is expressed at high levels in different isotypes of ovarian cancer and that SCD1 protects ovarian cancer cells from cell death. Pharmaceutical inhibition of SCD1 induces apoptosis and ferroptosis in vitro and in vivo. Combination therapies of SCD1 inhibitors and ferroptosis inducers significantly decrease ovarian tumor masses in mice. This novel therapy may prove useful to treat women with ovarian cancer. See related article by Tesfay et al., p. 5355
Description of the First Cases with ADAMTS13 Mutations in Hungary
Authors: Marienn Réti, György Sinkovits, Orsolya Cseprekál, Dorottya Csuka, Ágnes Szilágyi, Zita Farkas, Zsolt Klucsik, Attila Szederjesi, László Wágner, György Reusz, Johanna A. Kremer Hovinga, János Rigó, Tamas Masszi, Zoltan Prohászka
Journal: Blood (2018)
National, Retrospective, Multi-Centre Comparison of Alemtuzumab- Versus ATG-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation for Aplastic Anemia: A Study From the British Society for Blood and Marrow Transplantation (BSBMT) (CTCR 09-03)
Authors: Judith C. W. Marsh, Rachel M Pearce, Mickey B Koh, Daniel Tang, ZiYi Lim, Antonio Pagliuca, Ghulam J. Mufti, John Snowden, Ajay J Vora, Brenda Gibson, Maria H Gilleece, Julia Lee, Keiren Kirkland, Gordon Cook
Journal: Blood (2011)
Abstract 119: Multi-Omics Investigation of Cardiomyocyte-to-Fibroblast Crosstalk in Human iPSC Models
Authors: Edward Lau, Mark J Chandy, Damon R Williams, Rajani Shrestha, June-Wha Rhee, Joseph C Wu
Journal: Circulation Research (2019)

Introduction: Cardiac cells communicate with each other in part through secreted proteins known as cardiokines. The total repertoire of proteins secreted by cardiac cells is unknown. We aim to apply human iPSC models and large-scale multi-omics to identify secreted proteins and the crosstalk signals they mediate. Method: We optimized an experimental protocol to recover and identify cell-specific secreted proteins from human iPSC-cardiac cells. Human iPSCs were differentiated into cardiomyocyte (CM) and endothelial cells (EC) using established protocols, after which secreted proteins were extracted from the conditioned medium for analysis. We combined multiplexed aptamer-based large-scale protein quantification platform and high-resolution mass spectrometry to identify secreted proteins from iPSC-CM, iPSC-ECs, and primary ventricular fibroblasts. An in-silico filter was implemented to prioritize bona fide cardiokines over proteins externalized by passive lysis. Result: We identified 146 candidate cardiokines at 1% false discovery rate, including cell-specific cardiokines as well as a common core secretome of three cardiac cells. We analyzed the data to identify potential signals secreted by cardiomyocytes to mediate fibroblast function, using a ligand-receptor model based on proteomics and single-cell transcriptomics data to prioritize cardiokines secreted by iPSC-CMs and which bind to fibroblast-expressed receptors. To examine their roles in fibrosis regulation, we selected three candidate cardiokines (PLAU, FGF7, and CXCL12) for verification using immunodetection, and exposed their recombinant proteins at multiple concentrations to human ventricular fibroblasts. The results nominated cardiokine-specific effects on recipient cell gene expression including evidence of modulation of fibroblast transcription and translation pathways. Conclusion: We demonstrate a multi-omics approach in iPSC models to explore the large-scale human secretome of multiple cardiac cell types. The approach holds promise for identifying disease markers and understanding intercellular communication in cardiac development and diseases.
Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index
Authors: Alexandra Legge, Susan Kirkland, Kenneth Rockwood, Pantelis Andreou, Sang‐Cheol Bae, Caroline Gordon, Juanita Romero‐Diaz, Jorge Sanchez‐Guerrero, Daniel J. Wallace, Sasha Bernatsky, Ann E. Clarke, Joan T. Merrill, Ellen M. Ginzler, Paul R. Fortin, Dafna D. Gladman, Murray B. Urowitz, Ian N. Bruce, David A. Isenberg, Anisur Rahman, Graciela S. Alarcón, Michelle Petri, Munther A. Khamashta, M. A. Dooley, Rosalind Ramsey‐Goldman, Susan Manzi, Asad A. Zoma, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz‐Irastorza, S. Sam Lim, Murat Inanc, Ronald F. van Vollenhoven, Andreas Jonsen, Ola Nived, Manuel Ramos‐Casals, Diane L. Kamen, Kenneth C. Kalunian, Soren Jacobsen, Christine A. Peschken, Anca Askanase, John G. Hanly
Journal: Arthritis & Rheumatology (2019)

Objective The Systemic Lupus International Collaborating Clinics ( SLICC ) frailty index ( FI ) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. Methods The baseline visit was defined as the first visit at which both organ damage ( SLICC /American College of Rheumatology Damage Index [ SDI ]) and health‐related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow‐up, adjusting for relevant demographic and clinical characteristics. Results The 1,549 systemic lupus erythematosus ( SLE ) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow‐up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI . Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow‐up (incidence rate ratio [ IRR ] 1.19 [95% confidence interval 1.13–1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI , and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. Conclusion Our findings indicate that the SLICC FI predicts damage accrual in incident SLE , which further supports the SLICC FI as a valid health measure in SLE .
The Hundred-Person Platelet Releasate Project (100PREPs): A Barcode for Human Health and Disease
Authors: Patricia Maguire, Paulina Szklanna, Martin Parsons, Kieran Wynne, Hugh O'Connor, Karen O'Connell, Karl Egan, Christopher McGuigan, Scott Rickard, Fionnuala Ni Ainle
Journal: Blood (2018)
Association of ambient fine particulate matter with increased emergency ambulance dispatches for psychiatric emergencies: a time-series analysis
Authors: Jia Jia Liu, Feng Wang, Hui Liu, Ya Bin Wei, Hui Li, Jingli Yue, Jianyu Que, Louisa Degenhardt, Julia Lappin, Lin Lu, Yanping Bao, Jing Wang
Journal: The Lancet (2019)
Disulfiram May Contribute to Apoptosis of Myeloma Cells By Reactivating of Cell Cycle Regulating Gene CDKN2A
Authors: Denisa Hrckova Drozdkova, Jan Gursky, Petra Luzna, Sabina Sevcikova, Jiri Minarik, Katerina Smesny Trtkova
Journal: Blood (2018)
Abstract 160: Atg7-Dependent Activation of Mitochondrial Autophagy in Cardiomyocytes
Authors: Chowdhury S Abdullah, Richa Aishwarya, Shafiul Alam, Mahboob Morshed, Sumitra Miriyala, Manikandan Panchatcharam, Md. Shenuarin Bhuiyan
Journal: Circulation Research (2019)

Introduction: Autophagy-related protein 7 (Atg7) has been studied for its role in cellular macroautophagy induction and regulation in different cell systems. We have previously reported that Atg7 regulates cardiac macroautophagy. However, whether Atg7 plays any role in the initiation and regulation of mitochondrial autophagy (mitophagy) in cardiomyocytes remains elusive. Objective: We investigated subcellular localization and molecular function of Atg7 in the regulation of mitophagy through a series of in vitro and in vivo experiments. Methods and Results: We isolated mitochondria from mouse hearts by subcellular fractionation and conducted biochemical experiments which revealed localization of Atg7 on the mitochondrial membrane. Next, we co-stained for Atg7 in isolated heart mitochondria stained with Mitotracker dye and found Atg7 localizes to mitochondrial membrane. To elucidate molecular function of Atg7 on mitophagy, adenovirus-mediated Atg7 overexpressed cultured neonatal rat cardiomyocytes (NRCs) were treated with mitophagy inducer carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in vitro and stained with organelle-specific mitochondria and lysosome dyes to count mitophagy fluorescent dots by confocal microscopy. Atg7 overexpressed NRCs exhibited an increase in mitophagy dots than β-gal treated NRCs following CCCP induction. Further, we have treated cardiac specific Atg7 overexpressed (Atg7 Tg) mice and littermate non-transgenic (Ntg) mice with CCCP to assess mitophagy induction in vivo . Immunoblotting confirmed enhanced accumulation of mature autophagolysosomal marker LC3-II protein in mitochondrial fraction from Atg7 Tg hearts. Conclusions: Our in vitro and in vivo findings indicate that Atg7 localizes to the mitochondrial membrane, regulates recruitment and initiation of mitophagy machinery, and facilitates mitophagy in cardiomyocytes.
Factors Associated With Achalasia Treatment Outcomes: Systematic Review and Meta-Analysis
Authors: Renske A.B. Oude Nijhuis, Leah I. Prins, Nahid Mostafavi, Faridi S. van Etten-Jamaludin, Andreas J.P. M. Smout, Albert J. Bredenoord
Journal: Clinical Gastroenterology and Hepatology (2019)
Endothelial Cells Express No Detectable Erythropoietin Receptor Protein and Erythropoietin Does Not Induce Angiogenesis In Vivo.
Authors: Angela Coxon, Angus Sinclair, Ivonne Archibeque, Juan Estrada, Stephen Kaufman, Norma Rogers, Susan Swift, Lynn Tran, Steve Elliott
Journal: Blood (2007)
Histone Deacetylase 11 (HDAC11) Is a Regulatory Checkpoint of T-Cell Function: Implications for T-Cell Adoptive Immunotherapy
Authors: Karrune V. Woan, Dapeng Wang, Zi Wang, Fengdong Cheng, Lianet Vazquez, David Woods, Yu Yu, Eva Sahakian, Hongwei Wang, Elphine Telles, Lirong Peng, Liqing Wang, Wayne W. Hancock, Bruce R. Blazar, Noreen Luetteke, Edward Seto, Javier Pinilla, Alejandro Villagra, Xue-Zhong Yu, Eduardo M. Sotomayor
Journal: Blood (2011)
12 Months Report from a Phase 3 Study of Plerixafor+G-CSF Vs. Placebo+G-CSF for Mobilization of Hematopoietic Stem Cell for Autologous Transplant in Patients with Multiple Myeloma
Authors: John F. DiPersio, Edward A. Stadtmauer, Auayporn P. Nademanee, Ivana NM Micallef, Patrick J. Stiff, Gary Bridger, Gary Calandra
Journal: Blood (2008)
Competing Risk Survival Analysis In Patients With Symptomatic Waldenström’s Macroglobulinemia (WM): Disease Unrelated Mortality Accounts For Differences In Survival In Patients &gt;75 Years
Authors: Efstathios Kastritis, Marie-Christine Kyrtsonis, Evdoxia Hatjiharissi, Argiris S. Symeonidis, Amalia Vassou, Panagiotis Repousis, Sosana Delimpasi, Anastasia Sioni, Eurydiki Michalis, Michalis Michael, Elina Vervessou, Ekaterini Stefanoudaki, Michael Voulgarelis, Costas Tsatalas, Evangelos Terpos, Meletios A. Dimopoulos
Journal: Blood (2013)
Extracellular Matrix-Related Genes Are Deregulated in Peripheral Blood from Patients with Myelofibrosis and Related Neoplasms
Authors: Vibe Skov, Mads Thomassen, Lasse Kjær, Caroline Riley, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Journal: Blood (2018)
Evaluation of AMG 531 Efficacy in Splenectomized Patients with Chronic Immune Thrombocytopenic Purpura (ITP) in a Randomized Placebo-Controlled Phase 3 Study.
Authors: Terry B. Gernsheimer, Vinod Pullarkat, Francis M. Senecal, Louis M. Aledort, Craig M. Kessler, Miguel A. Sanz, Howard A. Liebman, Frank T. Slovick, Reggie Kelly, Matthew Guo, Janet Nichol
Journal: Blood (2007)
Keratinocyte Growth Factor Factor (Palifermin) in Combination with Tacrolimus and Methotrexate for the Prevention of Acute Graft-Vs-Host Disease (aGVHD) in Patients at High Risk of Agvhd.
Authors: Christopher M. Reynolds, John E. Levine, Joseph P. Uberti, Voravit Ratanatharathorn, Lois J. Ayash, Samuel M. Silver, Gregory A. Yanik, Pavan R. Reddy, Cooke R. Kenneth, Becker W. Michael, Hutchinson J. Raymond, L. J Ferrara
Journal: Blood (2004)
Targeted Ablation of Ventricular Tachycardia Guided by Wavefront Discontinuities During Sinus Rhythm
Authors: Zaid Aziz, Dalise Shatz, Michael Raiman, Gaurav A Upadhyay, Andrew D. Beaser, Stephanie A. Besser, Nathaniel A. Shatz, Zihuan Fu, Ruhong Jiang, Takuro Nishimura, Hongtao Liao, Hemal M. Nayak, Roderick Tung
Journal: Circulation (2019)

Accurate and expedited identification of scar regions most prone to reentry is needed to guide ventricular tachycardia (VT) ablation. We aimed to prospectively assess outcomes of VT ablation guided primarily by the targeting of deceleration zones (DZ) identified by propagational analysis of ventricular activation during sinus rhythm.Patients with scar-related VT were prospectively enrolled in the University of Chicago VT Ablation Registry between 2016 and 2018. Isochronal late activation maps annotated to the latest local electrogram deflection were created with high-density multielectrode mapping catheters. Targeted ablation of DZ (>3 isochrones within 1cm radius) was performed, prioritizing later activated regions with maximal isochronal crowding. When possible, activation mapping of VT was performed, and successful ablation sites were compared with DZ locations for mechanistic correlation. Patients were prospectively followed for VT recurrence and mortality.One hundred twenty patients (median age 65 years [59-71], 15% female, 50% nonischemic, median ejection fraction 31%) underwent 144 ablation procedures for scar-related VT. 57% of patients had previous ablation and epicardial access was employed in 59% of cases. High-density mapping during baseline rhythm was performed (2518 points [1615-3752] endocardial, 5049±2580 points epicardial) and identified an average of 2±1 DZ, which colocalized to successful termination sites in 95% of cases. The median total radiofrequency application duration was 29 min (21-38 min) to target DZ, representing ablation of 18% of the low-voltage area. At 12±10 months, 70% freedom from VT recurrence (80% in ischemic cardiomyopathy and 63% in nonischemic cardiomyopathy) was achieved. The overall survival rate was 87%.A novel voltage-independent high-density mapping display can identify the functional substrate for VT during sinus rhythm and guide targeted ablation, obviating the need for extensive radiofrequency delivery. Regions with isochronal crowding during the baseline rhythm were predictive of VT termination sites, providing mechanistic evidence that deceleration zones are highly arrhythmogenic, functioning as niduses for reentry.
The Importance of Patients and Caregivers Education to Prevent Central Line Associated Bloodstream Infections in Children with Malignancies: A Single Center Experience
Authors: Alessandro Di Gangi, Cecilia Maria Pini, Francesco Baccelli, Maria Vittoria Micheletti, Giorgio Costagliola, Sayla Bernasconi, Mariacristina Menconi, Gabriella Casazza
Journal: Blood (2018)
Response to the Letter to the Editor Concerning the Publication “Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma”
Authors: Bernhard Scheiner, Matthias Pinter
Journal: Liver Cancer (2019)

We agree that several factors may have influenced the mean platelet volume (MPV), but even if they did, our results show that larger MPV -no matter what caused it -was associated with longer survival in two large, independent cohorts.It is also possible that the assessment of MPV may be subject to variability to some degree.However, the large sample size of our cohort, the validation of our results in an independent cohort, and the fact that MPV was associated with survival in other cancer types [3][4][5] as well supports the validity of our findings.Given the retrospective nature of our study, it is impossible to control for potential confounders.Thus, our results can only be seen as associations, and we agree with the author that a prospective study would help to better understand the role of MPV in patients with hepatocellular carcinoma.
A New Multiparametric Flow Cytometry Technique Based on Combined Side Population (SP) and Aldehyde Deshydrogenase (ALDH) Functionalities Identifies a Hierarchy within the Human Hematopoietic Stem/Progenitor Compartment.
Authors: Olivier Pierre-Louis, Denis Clay, Bernadette Guerton, Christophe Desterke, Aurelie Chabanon, Jean-Valer Malfuson, Jean-Jacques Lataillade, Marie-Caroline Le Bousse-Kerdiles
Journal: Blood (2007)