tbuckley/cabot-search huggingface dataset:
Data Driven Computational Modeling of Hematopoiesis in Myelodysplastic Syndromes Unveils Differences in Hematopoietic Stem Cell Kinetics Compared to Age-Matched Healthy Controls
Authors: Michèle Kyncl, Lisa Bast, Lynette Henkel, Fabian Theis, Robert A.J. Oostendorp, Carsten Marr, Katharina S. Götze
Journal: Blood (2018)
Goals of care discussion and hospice enrollment.
Authors: Annika Gustafson, Mallika Sharma, Tracy Wong, Keith D. Eaton
Journal: Journal of Clinical Oncology (2019)

229 Background: When asked, many people wish to die at home. Yet, more than one third of cancer patients with poor prognosis die in hospital. Enrollment in hospice care is associated with reduced receipt of high-intensity care toward the end of life. Hospice is palliative care tailored to patients in the last 6 months of life. The ability to collect, organize, analyze and report documented Goals of Care (GOC) conversation data and the relationship to hospice enrollment is challenging. Seattle Cancer Care Alliance (SCCA) created a process to establish a sample baseline of documented GOC discussions, the healthcare setting in which they took place, and how this relates to hospice enrollment. Methods: We selected a sample of 50 decedent charts. Patients were verified as period of 6 months from date of death, documenting provider type, care setting that documented discussion took place and chart search terms. Results: Our sample consisted of 50 adult solid tumor cancer patients who died between March-May 2018. Using an SCCA created GOC discussion definition adapted from Ariadne Labs Serious Illness Care program, we found that 52% of patients had a GOC discussion in the last 6 months of life and of these, 92% discussed hospice with a provider, 77% received a hospice referral and 62% enrolled in hospice. 48% of our decedent sample did not have a GOC discussion. 46% had a hospice discussion of whom 100% enrolled in hospice. 46% received a hospice referral. 54% of patients did not discuss hospice of whom 30% enrolled in hospice. In looking at which providers talked with patients about hospice and in what care setting, we found that 44% discussed hospice with outpatient medical oncologist, 10% discussed hospice with an outpatient provider, 16% had a discussion while inpatient, and 30% had no hospice discussion at all. Conclusions: The majority of GOC discussions happened in the outpatient setting with medical oncologists. Many patients never had a discussion about hospice with their provider. Patients were most likely to enroll in hospice when it was specifically discussed, regardless of whether a GOC discussion took place.
Impact of cardiac function, refractory ascites and beta blockers on the outcome of patients with cirrhosis listed for liver transplantation
Authors: Valerio Giannelli, Olivier Roux, Cédric Laouénan, Pauline Manchon, Floriane Ausloos, Delphine Bachelet, Pierre-Emmanuel Rautou, Emmanuel Weiss, Richard Moreau, Alexandre Mebazaa, Alain Cohen-Solal, François Durand, Claire Francoz
Journal: Journal of Hepatology (2019)
Low-Dose Humanized Anti-CD20 Monoclonal Antibody (MAb), Veltuzumab, in Adult Immune Thrombocytopenic Purpura (ITP): Initial Results of a Phase I/II Study.
Authors: Howard A. Liebman, Mansoor N. Saleh, Rashid Abassi, Thomas M. Cosgriff, Nick Teoh, Matthew J Leoni, William Wegener, David M Goldenberg
Journal: Blood (2008)
Abstract 453: Phenotyping by ECG Dynamics During Sleep Predicts Cardiovascular Disease Risk Factors in a Multicenter Study of Asymptomatic Middle-aged Community Adults
Authors: Tracie K Lin, Daniel Wendelken, Brian O'Rourke, Steven R Jones, Naresh M Punjabi, Deeptankar DeMazumder
Journal: Circulation Research (2019)

Introduction: ECG-based predictive analytics have typically focused on static assessment of beat-to-beat heart rate variability (HRV) during wakefulness. However, there is increasing evidence that quantification of time-related changes as well as non-beat-to-beat complexity indices, such as entropy, can provide important untapped insight. Methods: Analysis of HRV, QT variability (QTV), QT entropy (QTen), QT entropy rate (QTa) and RR entropy (RRen) in 5-min bins were performed on home polysomnographs of 6,300 asymptomatic community adults (Sleep Heart Health Study). Rate of change of ECG variables was quantified by linear regression in one- to four-hour epochs. Stepwise regression was used to identify age-, sex-, race-, comorbidity-, and sleep state-associated influences on ECG values. Results: Predictive multivariate models were generated for congestive heart failure, diabetes, obstructive sleep apnea, and history of myocardial infarction, each with sleep state-specific and ECG variable rate of change being of the highest predictive value in ECG-based models (Table 1). Conclusion: Although aggregate beat-to-beat HRV is associated with cardiovascular risk factors, unique time-varying and sleep stage-specific findings provide additional predictive power. By way of demonstrating that distinct classes of dynamic ECG features were predictive of each risk factor studied, our study suggests a potential role for patient-specific ECG phenotyping using a comprehensive analytical platform. Dynamic ECG assessment during sleep with attention to entropy-derived measures, in particular, may enhance precise risk stratification in otherwise low-risk individuals.
Adjusting Hospital Reimbursement to Account for Social Influences on Health
Authors: Matthew M. Davis, Kristin Kan
Journal: JAMA Network Open (2019)

The strength of the social safety net matters most when the risk to individuals is highest.Acute illnesses and injuries requiring hospital-level care are some of the greatest health risks that children and adults face.In the United States, 2 of the oldest social safety net programs are Medicare and Medicaid, which together now constitute 37% of national health expenditures compared with 34% for private health insurance. 1Medicare and Medicaid have endured for more than 50 years, despite political efforts to constrain growth in government spending, in large part because they cover the costs of hospital care that can be economically catastrophic for individuals and families.Medicare and Medicaid also function as a safety net for hospitals by reimbursing institutions for the expenses of hospitalizations not paid by patients themselves.In the case of children's hospitals that provide care to large numbers of patients with Medicaid coverage, such reimbursement often falls short of covering the hospitals' care-delivery costs. 2 This shortfall is the rationale for the Medicaid Disproportionate Share Hospital (DSH) payment policy, which enables states to work with the federal government to provide payments to hospitals to offset the costs of uncompensated and undercompensated inpatient care.Even accounting for DSH payments, the costs of providing inpatient care for children on Medicaid often exceed reimbursement, creating a chronic strain for hospitals with a mission to care for the underserved.
Abstract 139: Systemic Analysis and Discovery of Embryonic Stem Cell-derived Exosomal Long Non-coding RNAs as Potential Therapeutic Modulators of Myocardial Repair
Authors: Grace Huang
Journal: Circulation Research (2019)

Cardiovascular disease is the leading cause of death in the U.S. Exogenous stem cell therapy has emerged as a novel therapeutic approach and various stem cell types, including embryonic stem cells (ESCs), bone marrow stem cells and mesenchymal stem cells, have been studied for cardiac regenerative cell therapy. Even though there was great enthusiasm with promising initial results in pre-clinical disease models, stem cell-based therapy demonstrated modest benefits in clinical trials. Emerging evidence suggests that stem cells can secrete a large number of soluble factors to evoke a resident cell response for tissue regeneration. In this perspective, stem cells-derived exosome therapy has been recently put forward as an alternative cell-free modality for cardiac repair after myocardial infarction (MI). Our previous study indicated that ESC-derived exosomes (ESC-exo) promote endogenous cardiac repair and enhanced cardiac function following MI. However, the mechanisms underlying ESC-exo mediated cardiac repair and regeneration still need to be fully elucidated. RNA-sequencing data on ESC-exo revealed that non-coding RNAs, including long non-coding RNAs (lncRNA), are selectively sorted into exosomes and highly enriched compared to control fibroblasts. Unlike exosomal miRNA, exosomal lncRNAs have not been well-studied in the context of tissue repair. To investigate the reparative role of lncRNA in protecting against MI, we first systemically analyzed and discovered ESC-derived exosomal lncRNAs in silico. We analyzed novel lncRNAs from ESC- and MEF-exo based on differential expression by microarray analysis, lncRNA classification, human homology and non-coding potential prediction. For lncRNAs enriched in the ESC-exo population, we selected 2 potential lncRNAs of interest for further study: Gm4890 and XLOC 01990, which are confirmed for expression by qRT-PCR results. Gm4890 and XLOC are mainly located in nucleus rather than cytoplasm implicating their function on transcriptional regulation. Ongoing studies are evaluating the functional roles for these ESC-exo enriched lncRNAs.
Re: Daniel A. Leongamornlert, Edward J. Saunders, Sarah Wakerell, et al., Germline DNA Repair Gene Mutations in Young-onset Prostate Cancer Cases in the UK: Evidence for a More Extensive Genetic Panel. Eur Urol 2019;76:329–37
Authors: Xiaoling Lin, Brian T. Helfand, Jianfeng Xu
Journal: European Urology (2019)
Straightforward Transition to Bay 81-8973 Prophylaxis in Patients with Hemophilia A: Prospective Real-World Data from the Taurus Non-Interventional Study Show That Number of Infusions per Week Is Maintained or Reduced
Authors: Michael Wang, Beng Fuh, Philip Maes, Maria Eva Mingot-Castellano, Rubén Berrueco, Phu-Quoc Le, Stephan Rauchensteiner, Cristina Santoro
Journal: Blood (2018)
A modulator of wild-type glucocerebrosidase improves pathogenic phenotypes in dopaminergic neuronal models of Parkinson’s disease
Authors: Lena F. Burbulla, Sohee Jeon, Jianbin Zheng, Pingping Song, Richard B. Silverman, Dimitri Krainc
Journal: Science Translational Medicine (2019)

New small-molecule modulators of wild-type glucocerebrosidase improve pathogenic phenotypes in different cellular models of Parkinson’s disease.
Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice
Authors: Samuel Vorbach, Albert Gründer, Fengbiao Zhou, Christoph Koellerer, Jonas S. Jutzi, Manuela Simoni, Laura Riccetti, Peter J. Valk, Mathijs A. Sanders, Carsten Müller-Tidow, Jerzy-Roch Nofer, Heike L. Pahl, Francesco Potì
Journal: Leukemia (2019)
Abstract 419: Beneficial Effects of scaRNA Modulated Human iPSC-derived Cardiomyocytes Exposed Under Hypoxic Conditions
Authors: Sheeja Rajasingh, Vinoth Sigamani, Andras Czirok, Dona G Isai, Vijay Selvam, Johnson Rajasingh
Journal: Circulation Research (2019)

Introduction: Studies have shown that mRNA splicing is regulated by small cajal-body associated RNAs (scaRNAs) and plays a significant role in mammalian cardiac development and differentiation, but the potential contribution to human in vitro differentiation of iPSCs into CMCs remains unknown. In this study, the comparison of scaRNA20 modified and unmodified iPSCs derived-CMCs (iCMCs) will allow us to understand the role of scaRNAs in cardiac differentiation. Hypothesis: We hypothesize that the scaRNA20 modulated iCMCs are capable of withstanding better at low-oxygen environment than the normal iCMCs which will facilitate for cardiac therapy. Methods and Results: To show how ischemic cardiomyopathy effects on CMC contractility, skin fibroblast derived normal iCMCs (SF-N-iCMCs) and scaRNA20-OE-iCMCs were subjected to hypoxic condition (1% O 2 ). Our particle image velocimetry (PIV) analysis shows that the contractility is reduced in normal iCMCs whereas the scaRNA20-OE-iCMCs maintained the contractility under hypoxic condition (Fig. A-C) . Moreover, the qRT-PCR data show that the SF-N-iCMCs exposed to hypoxic condition decreased the expression of scaRNA20 (Fig. D). These data suggest that the scaRNA20-OE-iCMCs are capable of withstanding the low-oxygen environment at the infarcted heart. Conclusions: We report for the first time the beneficial effects of scaRNA20 modulated CMCs prior to transplantation will be an effective therapy for cardiac regeneration. &lt;!--EndFragment--&gt;
Abstract 642: Single-Cell RNA-seq Unveils Unique Transcriptomic Signatures of Organ-Specific Endothelial Cells
Authors: David T Paik, Lei Tian, Ian M Williams, Chun Liu, Hao Zhang, Damon Williams, Ridhima Mishra, Sean M Wu, Joseph C Wu
Journal: Circulation Research (2019)

Endothelial cells (ECs) display considerable functional heterogeneity depending on the vessel and tissue in which they are located. While these functional differences are presumably imprinted in the transcriptome, the pathways and networks which sustain EC heterogeneity have not been fully delineated. To investigate the transcriptional control of EC specification, we analyzed single-cell RNA-sequencing (scRNA-Seq) data from tissue-specific mouse ECs generated by the Tabula Muris consortium. We found a strong correlation between tissue-specific EC transcriptomic measurements generated by either scRNA-Seq or bulk RNA-Seq, thus validating the approach. Using a graph-based clustering algorithm, we found that certain tissue-specific ECs cluster strongly by tissue (e.g. liver, brain) whereas others (i.e. adipose, heart) have considerable transcriptional overlap with ECs from other tissue. Using gene set enrichment analysis, we identified novel markers of tissue-specific ECs and signaling pathways that may be involved in maintaining their identity. By performing pseudotime trajectory analysis, we found that ECs from endoderm-derived tissues appear to be more developmentally immature when compared with the highly specialized ECs of ectoderm-derived tissues such as brain. In addition, we compared these data from mouse with human fetal heart scRNA-seq data for interspecies correlation in organ-specific EC gene expression. Finally, we identified potential angiocrine interactions between tissue-specific ECs and other cell types by analyzing ligand and receptor expression patterns. In summary, we have utilized scRNA-Seq to uncover transcriptional networks which maintain EC identity and identify novel developmental and angiocrine relationships between tissue-specific ECs.
Importance of Transcription Factor Nrf2 for Cereblon Expression and Clinical Response to Combination of Lenalidomide and Erythropoietin in Lower-Risk Myelodysplastic Syndromes
Authors: Radka Bokorová, Jaroslav Polak, Anna Jonasova, Radana Neuwirtova, Marie Lauermannova, Jaroslav Cermak, Marketa Stastna, Cyril Salek, Dana Mikulenkova, Zuzana Zemanova, Jana Brezinova, Kyra Michalova, Denisa Myslivcova, Ota Fuchs
Journal: Blood (2018)
Abstract 708: Platelet Derived Growth Factor-Beta Communication Axis is Critical for Mediating Pericyte-Endothelial Cell Interactions and Angiogenic Support in Combination Therapy of Human Umbilical Cord Perivascular Cells and Endothelial Progenitor Cells
Authors: Farwah Iqbal, Peter Szaraz, Clifford Librach
Journal: Circulation Research (2019)

Introduction: First Trimester Human Umbilical Cord Perivascular Cells (FTM HUCPVC) have higher cardiovascular regenerative potential compared to older sources of MSC. We designed a cell combination therapy with FTM HUCPVC and endothelial progenitor cells (EPC) to enhance angiogenesis after MI. However, the mechanism of PVC-EPC interaction is unclear. Hypothesis: Platelet derived growth factor beta receptor (PDGFB-R) expression of HUCPVC mediates homing and integration with endothelial networks and required for supporting neovasculature. Methods: Expression of pericyte markers PDGFB-R and CD146 of xeno-free expanded (HPL 2.5%) FTM and term HUCPVC was analyzed by flow cytometry. PDGFB-driven trans-ECM migration was assessed by Corning Biocoat Invasion assay with 1-100 ng/ml PDGFB. siRNA for PDGFB-R, CD146 and scrambled control was used with lipofectamine for 72 hours. Silencing was confirmed by qPCR and flow cytometry. 10% HPL was used for PDGFB-R desensitization. HUCPVC of all treatment groups were co-cultured with EPC and rat aortic rings on Matrigel TM . Cell migration, endothelial adhesion and network properties were quantified. Statistics: one-way ANOVA N=5 Results: PDGFB-R and CD146 expression and endothelial network augmenting function of FTM HUCPVC was significantly higher than of term HUCPVC. PDGFB dependent migration of FTM HUCPVC was disabled by both ligand (&lt;10%) and siRNA-based (&lt;5%) downregulation of PDGFB-R. Fluorescence microscopy (24 h) showed limited homing and endothelial interactions of PDGFB-R-reduced FTM HUCPVC. PDGFB-R-reduced FTM HUCPVC had significantly decreased network growth and nodes ( p &lt;0.0001) compared to control groups (day3). In EPC co-cultures, PDGFB-R-reduced FTM HUCPVC had limited endothelial interactions and coverage compared to control FTM HUCPVC. PDGFB-R-reduced FTM HUCPVC treated networks had significantly thinner ( p &lt;0.001) and shorter tubules ( p &lt;0.001) compared to control FTM HUCPVC groups. Down-regulation of C146 did not alter FTM HUCPVC pericyte properties. Conclusions: PDGFB-R is crucial for the homing and endothelial support of HUCPVC. This interaction is critical in vascular cell combination therapies and PDGFB-R expression can be a novel criterion for cardiovascular cell therapy.
Magnesium supplementation for the treatment of restless legs syndrome and periodic limb movement disorder: A systematic review
Authors: Nathaniel S. Marshall, Yasmina Serinel, Roo Killick, Julia M. Child, Isabelle Raisin, Callum M. Berry, Tea Lallukka, Rick Wassing, Richard WW. Lee, Rajeev Ratnavadivel, Hima Vedam, Ron Grunstein, Keith KH. Wong, Camilla M. Hoyos, Elizabeth A. Cayanan, Maria Comas, Julia L. Chapman, Brendon J. Yee
Journal: Sleep Medicine Reviews (2019)
Phosphatidylserine-Exposing, Tumor-Derived Microparticles Enhance Procoagulant Activity of Platelets and Endothelial Cells after Neo-Adjuvant Chemotherapy in Invasive Breast Cancer
Authors: Cong Zhang, Yan Kou, Lili Zou, Hui Liang, Li Hou, Tao Li, Yan Zhang, Baorong Li, Yingmiao Liu, Juan Zhang, Jialan Shi, Changjun WU
Journal: Blood (2018)
Association of Early Direct Bilirubin Levels and Biliary Atresia Among Neonates
Authors: Fatima Noorulla, Russell Dedon, M. Jeffrey Maisels
Journal: JAMA Network Open (2019)

Sanjiv Harpavat, MD, PhD; Joseph A. Garcia-Prats, MD; Carlos Anaya, MD; Mary L. Brandt, MD; Philip J. Lupo, PhD; Milton J. Finegold, MD; Alice Obuobi, MD; Adel A. ElHennawy, MD; William S. Jarriel, MD; Benjamin L. Shneider, MD
Abstract 202: The R21C Mutation in Troponin I Has a Founder Effect in South Lebanon and Causes Malignant Hypertrophic Cardiomyopathy
Authors: Akl Fahed, Georges Nemer, Fadi Bitar, Samir Arnaout, Antoine Abche, James Ware, Manal Batrawi, Athar Khalil, Steven DePalma, Barbara McDonough, Mariam Arabi, Jonathan Seidman, Christine Seidman
Journal: Circulation Research (2019)

Hypertrophic Cardiomyopathy (HCM) occurs in 1 of every 500 people and has a wide phenotypic variability. In the majority of cases, HCM is caused by known mutations in genes that code for sarcomere proteins. Although gene testing is widely available for HCM, knowing the phenotype caused by different gene mutations remains a challenging task. We recruited 28 families with HCM, of which 19 (67.8%) have at least one patient with pediatric onset. Index patients from 20 families received targeted sequencing for a panel of genes including TNNI3 , and 7 families received Sanger sequencing for the TNNI3 . We identified a missense mutation p.R21C in TNNI3 segregating with HCM in four families from South Lebanon. Through cascade screening, we identified 30 patients from the four families; twenty of them (67%) had a clinical diagnosis of HCM with a median age of 37 years, while 9 (30%), with a median age 21 years, had no evidence of HCM on echocardiography. An additional 27 members of the families had evidence of HCM, including 22 with SCD in the setting of no past medical history, and their carrier status for p.R21C was implied from the pedigrees. Survival analysis for 57 HCM patients with the mutation revealed a markedly decreased age at first adverse event as compared to 47 HCM patients with the MYBPC3 p.R502W mutation. Founder mutations in HCM that cause a severe phenotype are uncommon. The p.R21C mutation in TNNI3 is the first HCM mutation described in the Lebanese population and has a founder effect in South Lebanon. Early and more frequent screening with different imaging modalities as well as tailored management might be warranted for carriers of this mutation.
Incidence of Transformation to Large Cell Lymphoma and to Second Malignancies in Symptomatic Patients with Waldenstrom’s Macroglobulinemia (WM) Treated with Cladribine (2-CdA) Combination Induction Therapy
Authors: Ronjay Rakkhit, Kay B Delasalle, Maria B. Gavino, Sheeba K. Thomas, Meletios A Dimopoulos, Fredrick B. Hagemeister, Maria Alma Rodriguez, Peter McLaughlin, Raymond Alexanian, Donna M. Weber
Journal: Blood (2008)
Monitoring of Minimal Residual Disease After Allogeneic Stem Cell Transplantation In Relapsed Childhood ALL Allows The Identification Of Impending Relapse - Results Of The ALL BFM SCT 2003 Trial
Authors: Peter Bader, Hermann Kreyenberg, Arend von Stackelberg, Cornelia Eckert, Meisel Roland, Pötschger Ulrike, Daniel Stachel, Martin Schrappe, Andre Schrauder, Ansgar Schulz, Peter Lang, Ingo Mueller, Michael H. Albert, Thomas Klingebiel, Christina Peters
Journal: Blood (2013)
Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods
Authors: Brian J. Haas, Alexander Dobin, Bo Li, Nicolas Stransky, Nathalie Pochet, Aviv Regev
Journal: Genome biology (2019)

Accurate fusion transcript detection is essential for comprehensive characterization of cancer transcriptomes. Over the last decade, multiple bioinformatic tools have been developed to predict fusions from RNA-seq, based on either read mapping or de novo fusion transcript assembly.
Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn
Authors: Stuart J. Spechler, John G. Hunter, Karen M. Jones, Robert Lee, Brian R. Smith, Hiroshi Mashimo, Vivian M. Sanchez, Kerry B. Dunbar, Thai H. Pham, Uma K. Murthy, Taewan Kim, Christian S. Jackson, Jason M. Wallen, Erik C. von Rosenvinge, Jonathan P. Pearl, Loren Laine, Anthony W. Kim, Andrew M. Kaz, Roger P. Tatum, Ziad F. Gellad, Sandhya Lagoo-Deenadayalan, Joel H. Rubenstein, Amir A. Ghaferi, Wai-Kit Lo, Ronald S. Fernando, Bobby S. Chan, Shirley C. Paski, Dawn Provenzale, Donald O. Castell, David Lieberman, Rhonda F. Souza, William D. Chey, Stuart R. Warren, Anne Davis-Karim, Shelby D. Melton, Robert M. Genta, Tracey Serpi, Kousick Biswas, Grant D. Huang
Journal: New England Journal of Medicine (2019)

Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine).