tbuckley/cabot-search huggingface dataset:
Abstract 211: Long Noncoding RNA Myocardial Infarction Associated Transcript, MIAT Exacerbates Maladaptive Cardiac Remodeling by Functioning as a Competing Endogenous RNA of MicroRNA-150 During Myocardial Infarction
Authors: Tatsuya Aonuma, Bruno Moukette, Il-man Kim
Journal: Circulation Research (2020)

Cardiac injury is accompanied by dynamic changes in the expression of noncoding RNAs such as microRNAs (miRs) and long noncoding RNAs (lncRNAs) that regulate target genes. We previously reported that β 1 -adrenergic receptor/β-arrestin1-responsive miR-150 plays a vital cardioprotective role in myocardial infarction (MI) via decreasing cardiac cell apoptosis (Fig. A). MiR-150 is regulated by MI-Associated Transcript (MIAT), a lncRNA that directly interacts with miR-150 and functions as its competing endogenous RNA in vitro . Gain-of-function single nucleotide polymorphisms in MIAT are associated with increased risk of MI in humans, and MIAT is upregulated in post-MI hearts, concurrent with downregulation of miR-150. Despite the increasing data from both human and rodent studies, the conserved functional MIAT/miR-150 axis in cardiac pathology has never been investigated in genetically modified mice. Here, we hypothesize that MIAT competitively sequesters miR-150 and blocks the inhibitory effect of miR-150 on proapoptotic genes, thereby increasing maladaptive post-MI remodeling. Using novel mouse models, we demonstrate that global genetic deletion of MIAT in mice protects hearts against MI, while genetic overexpression of MIAT worsens maladaptive cardiac remodeling. Moreover, MIAT downregulates miR-150 in the heart, while miR-150 does not repress MIAT. Importantly, we show that miR-150 overexpression prevents the detrimental post-MI effects caused by overexpression of MIAT (Fig. B). In conclusion, these findings reveal a pivotal functional interaction between MIAT and miR-150 as a novel epigenetic regulatory mechanism pertinent to ischemic cardiac injury.
Incidence of Pulmonary Embolus after Catheter Removal in Children with Central Venous Catheter Related Venous Thromboembolism: A Report from the CHAT Consortium
Authors: Julie Jaffray, Lisa Baumann Kreuziger, Brian Branchford, Arash Mahajerin, Choo Phei A Wee, E Vince S Faustino, Zakai A Neil, Stacy E. Croteau, Michael Silvey, John Fargo, James D. Cooper, Nihal Bakeer, Amy Stillings, Emily Krava, Guy Young, Neil A Goldenberg
Journal: Blood (2020)
The Prevalence and Clinical Impact of Neutropenia Among Arab Population with Iron Deficiency Anemia an Experience from Qatar
Authors: Hussam A Almasri, Ashraf Tawfiq Soliman, Vincenzo Desanctis, Arwa E Alsaud, Mona M Babikir, Mohammad N Kloub, Rita Wafik Ahmad, Mustafa A Al-Tikrity, Majd M Aldwairi, Ruoa Alhashimy, Mahmoud S Eisa, Shaima Ahmed, Mohamed A Yassin
Journal: Blood (2020)
Genome-Wide Association Study Identifies Variation in <i>ABO</i> As Risk Factor for Platelet Reactivity in Heparin-Induced Thrombocytopenia
Authors: Jason B Giles, Jérôme Rollin, Christian M Shaffer, Heidi E Steiner, Yukihide Momozawa, Ian Stanaway, Taisei Mushiroda, Claire Pouplard, Nancy Heddle, Michiaki Kubo, Elizabeth Phillips, Theodore E. Warkentin, Yves Gruel, Andreas Greinacher, Dan Roden, Jason Karnes
Journal: Blood (2020)
Impact of Age on Treatment and Outcome in Newly Diagnosed DLBCL (Diffuse Large B-cell Lymphoma) Patients in the United States Veteran Population (2011-2017)
Authors: Snegha Ananth, Madison H. Williams, Ryan A. Williams, Jean Pierre Blaize, David Gregorio, Michael M. Song, Gerardo Manuel Rosas, Lakene Raissa Djoufack Djoumessi, Brian Warnecke, Abhishek Pandya, Vivian Dee, Michael Mader, Juan J. Toro, Kathleen Franklin, Phillip Nazarewicz, Zohra Nooruddin
Journal: Blood (2020)
Mesenchymal Stromal Cell (MSC) Compassionate Use in France in Treatment of Steroid-Refractory Graft-Versus-Host-Disease (GVHD) after Approval By the Expert Committee of Société Française De Greffe De Moelle Et Thérapie Cellulaire (SFGM-TC)
Authors: Lea Bosdure, Laurence Blanc, Nimrod Buchbinder, Valerie Coiteux, Gaelle Fossard, Sylvie Francois, Marie Ouachee, Catherine Paillard, Cecile Pochon, Arthur Sterin, Nadine Petitpain, Jacques-Olivier Bay, Marie Thérèse Rubio, Danièle Bensoussan, Jean-Hugues Dalle
Journal: Blood (2020)
Preliminary Results of a Phase II Study to Determine the Safety of Defibrotide in Children and Adolescents with Sickle Cell Disease-Associated Acute Chest Syndrome (IND 127812)
Authors: Jordan Milner, Deborah Friedman, Marise D'Souza, Krishnan Sankaran, Liana Klejmont, Erin Morris, Harshini Mahanti, Neida Otero, Jessica C. Hochberg, Adele Brudnicki, Ken R. Cooke, Mitchell S Cairo
Journal: Blood (2020)
Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes
Authors: Meng Wang, Huzi Xu, Yinzheng Li, Chujin Cao, Han Zhu, Yuxi Wang, Zhi Zhao, Guangchang Pei, Fan Zhu, Qian Yang, Xuan Deng, Cheng Zhou, Yi Guo, Jianliang Wu, Wenhui Liao, Juan Yang, Ying Yao, Rui Zeng
Journal: Theranostics (2020)

Rationale: Capillaries are composed of endothelial cells and the surrounding mural cells, pericytes. Microvascular repair after injury involves not only the proliferation of endothelial cells but also pericyte-based vessel stabilization. Exogenous bone marrow derived-putative endothelial progenitor cells (b-pEPCs) have the potential for vascular repair; however, their effect on vascular structure stabilization and pericyte-related pathobiological outcomes in the injured kidney has not been fully examined. Methods: We applied ischemia-reperfusion (IR) to induce renal vascular injury and renal fibrosis in mice. Platelet-derived growth factor receptor β (PDGFR-β)-DTR-positive mice were generated to deplete pericytes, and exogenous b-pEPCs and the PDGFR-β ligand, PDGF chain B (PDGF-BB), were employed to explore the relationship among b-pEPCs, pericytes, vascular repair, and early renal fibrosis. Results: Administration of b-pEPCs reduced IR-induced pericyte-endothelial detachment, pericyte proliferation, and myofibroblast transition via a paracrine mode, which preserved not only vascular stabilization but also ameliorated IR-initiated renal fibrosis. PDGF-BB upregulated the expression of PDGFR-β, exacerbated vascular abnormality, and pericyte-myofibroblast transition, which were ameliorated by b-pEPCs administration. The exogenous b-pEPCs and their culture medium (CM) induced vascular injury protection, and renal fibrosis was blocked by selective deletion of pericytes. Conclusion: Exogenous b-pEPCs directly protect against IR-induced vascular injury and prevent renal fibrosis by inhibiting the activation of PDGFR-β-positive pericytes.
<i>SF3B1</i> mutations in the Driver Clone Increase the Risk of Evolution to Myelofibrosis in Patients with Myeloproliferative Neoplasms (MPN)
Authors: Lin-Pierre Zhao, Rafael Daltro De Oliveira, Clemence Marcault, Juliette Soret, Nicolas Gauthier, Emmanuelle Verger, Nabih Maslah, Blandine Roux, Nathalie Parquet, Christine Dosquet, Delphine Rea, Jean-Marc Zini, William Vainchenker, Emmanuel Raffoux, Stephane Giraudier, Bruno Cassinat, Jean-Jacques Kiladjian, Lina Benajiba
Journal: Blood (2020)
TAK-169, a Novel Recombinant Immunotoxin Specific for CD38, Induces Powerful Preclinical Activity Against Patient-Derived Multiple Myeloma Cells
Authors: Wassilis S.C. Bruins, Wenrou Zheng, Jack P. Higgins, Erin K. Willert, John Newcomb, Ajeeta B Dash, Niels W.C.J. Van De Donk, Sonja Zweegman, Tuna Mutis
Journal: Blood (2020)
Abstract PO-011: Role of tumor heterogeneity, tumor microenvironment and tumor initiating cell in gastric carcinogenesis from the perspective of development of hypothesis for its clinical application
Authors: Kalyan Kusum Mukherjee, Dattatreya Mukherjee
Journal: Cancer Research (2020)

Abstract Gastric Cancer (GC) is one of the most malignant type of cancer due to its rapid progression, distant metastasis and resistant to conventional chemotherapy. This study is to search the development towards specific therapy to overcome conventional chemotherapy resistance and probable hypothesis to develop it. It is known that tumor heterogeneity plays a fundamental essential role in cancer development and chemo resistance. Gastric Carcinoma Tumor initiating cell (GATIC) controls high tumerogenicity, maintenance of self renewal potential, formation of cancer and non cancer cells and chemotherapy resistance. Identifying the putative specific cell marker for purification and functional validation of GATIC, tracing the origin of GATIC, decoding the regulatory mechanism of GATIC, pave the way for the development of GATIC targeted therapy which is in phase of preclinical study and clinical trial. Alteration of tumor microenvironment is deeply implicated in tumor progression and metastasis in gastric cancer patient. Interaction between tumor cell and their microenvironment with cytokines and miRNA in extracellular vesicles such as exosome can have a substantial impact on tumor characteristics. Interaction and its clinical impact of alteration of GC microenvironment will be discussed. In the possible treatment hypothesis the level IL6, M1, CXCl12/CXCR may be blocked and the level of M2, C8+T cell and CCK2R may be amplified to develop TEM directed targeted therapy. After uncovering the mechanism of chemo resistance the differentiation therapy and elimination therapy of gastric carcinoma may be a sustainable targeted therapy. In this context over expression of ATOH1 in GATICS and Lentiviral vector based knockdown of PGK1 may be a treatment method to overcome Chemo resistance of GC. In the way of elimination therapy Cyclopamine and Vismodegib may be a feasible targeted therapy in GC. molecules which is specific suppressor of Wnt/B catenin may be used as a selective therapy for GATIC. Citation Format: Kalyan Kusum Mukherjee, Dattatreya Mukherjee. Role of tumor heterogeneity, tumor microenvironment and tumor initiating cell in gastric carcinogenesis from the perspective of development of hypothesis for its clinical application [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-011.
Ixazomib-Based Induction Followed By Single-Agent Ixazomib Maintenance in Transplant Ineligible, Newly Diagnosed Multiple Myeloma Patients: Updated Results of the EMN10-Unito Trial
Authors: Roberto Mina, Alessandra Larocca, Paolo Corradini, Nicola Cascavilla, Anna Marina Liberati, Norbert Pescosta, Francesca Fazio, Giovannino Ciccone, Andrea Capra, Francesca Patriarca, Annalisa Bernardini, Delia Rota Scalabrini, Michele Cea, Renato Zambello, Anna Baraldi, Angelo Belotti, Mario Boccadoro, Sara Bringhen
Journal: Blood (2020)
NHS offers lung volume reduction procedures for severe emphysema
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Lung volume reduction is being made available for adults in England who have severe emphysema, after NHS England approved the treatment. An estimated 660 people in England are currently suitable for the treatment, and this number could increase to around 1200 over the next five years.

Emphysema is one of the presentations of chronic obstructive pulmonary disease (COPD). It is caused by inhaling noxious materials, such as tobacco smoke, leading to the breakdown of elastic tissue in the lung. Around 1.1 million people in England have a COPD diagnosis.

Lung volume reduction is an approach …
Abstract PO-097: High resolution analysis of clonal dynamics using lineage tracing and single cell transcriptomics
Authors: Eric A. Brenner, Daylin Morgan, Aziz Al'Khafaji, Catherine Gutierrez, Catherine J. Wu, Amy Brock
Journal: Cancer Research (2020)

Abstract The immense evolutionary capacity of cancer poses major challenges to current therapeutic efforts, and results from the vast clonal heterogeneity and ability of individual cancer cells to adapt to diverse selective pressures. More complete mechanistic understanding of the basis of therapeutic resistance has been limited by difficulties in coupling genetic identity of cells to their respective transcriptomic and functional outputs. To this end, we developed a novel high-complexity expressed barcode system, ClonMapper, that integrates DNA barcoding with single-cell RNA-sequencing and clonal isolation to characterize thousands of clones within a mixed cancer cellpopulation. In applying this system to breast cancer and B cell cancer cell lines in the setting of resistance to doxorubicin and fludarabine-based chemotherapy, we discover pretreatment sub-populations with distinct expression profiles that not only confer distinct treatment survivorship trajectories, but also provide the basis for long-term clonal equilibrium between co-existing clones in the absence of treatment. These data reveal the diverse clonal characteristics and therapeutic responses of a heterogeneous cancer cell population and highlight the unprecedented resolution that can be achieved using ClonMapper. Citation Format: Eric A. Brenner, Daylin Morgan, Aziz Al'Khafaji, Catherine Gutierrez, Catherine J. Wu, Amy Brock. High resolution analysis of clonal dynamics using lineage tracing and single cell transcriptomics [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-097.
The biological role of metabolic reprogramming in pancreatic cancer
Authors: Tatsunori Suzuki, Motoyuki Otsuka, Takahiro Seimiya, Takuma Iwata, Takahiro Kishikawa, Kazuhiko Koike
Journal: MedComm (2020)

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease and highly resistant to all forms of therapy. PDAC cells reprogram their metabolism extensively to promote their survival and growth. Reflecting the vital role of altered metabolism, experimental and clinical trials targeting the rewired metabolism are currently underway. In this review, we summarize the vital role of metabolic reprogramming in the development of PDAC and the future of novel therapeutic applications.
Impact of Sars-Cov-2 Infection in Hematopoietic Transplant Patients: Experience from the Madrid Group
Authors: Rebeca Bailén, Mi Kwon, Beatriz Aguado, Rafael F. Duarte, Maria Calbacho, Anabelle Chinea, Pilar Llamas, Rosalía Riaza Grau, Jose Angel Hernandez-Rivas, Victor Jimenez Yuste, Carmen Martínez-Chamorro, F. Javier Penalver, Ataulfo González, Juan F del Campo, Keina Quiroz, Gillen Oarbeascoa, Julio Garcia Suarez, José Luis Díez-Martín
Journal: Blood (2020)
SAT0202 Short-term erosive progression on magnetic resonance images is highly correlated with long-term radiographic progression in rheumatoid arthritis wrists
Authors: M Østergaard, M Hansen, M Stoltenberg, KE Jensen, M Szkudlarek, M Klarlund, P Gideon, B Pedersen-Zbinden, I Lorenzen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> In patients with rheumatoid arthritis (RA) to compare the development of wrist joint bone erosions on conventional radiography (CR) performed annually for 5 years with erosions detected by magnetic resonance imaging (MRI) at baseline and 1-year follow-up. <h3>Methods</h3> Fifteen patients with RA (disease duration 0.5–20 years, median 1.5 years) were followed for 5 years. MRI of the dominant wrist was performed at year 0 and 1, and CR at years 0, 1, 2, 3, 4 and 5. In each image set, the number of wrist bones (metacarpal bases, carpal bones, radius and ulna) with erosions was determined. <h3>Results</h3> The number of bones with erosions detected by CR and MRI at the different time points are shown in the Table 1. The total number of CR-erosions at baseline and after 5 years, compared with the number of MRI-erosions at baseline, were 21% and 64%, respectively. The MRI-erosion score at 1 year was the parameter from the initial 1 year of follow-up, that showed the closest statistical correlation with the radiographic erosion score at 5 years (rho = 0.67, p = 0.006), while corresponding correlations for radiographic erosion scores at baseline and 1 year were rho = 0.41 (p = 0.12, NS) and rho = 0.60 (p = 0.02). The erosive progression rate on radiographs during the 5 years (CR 5 minus CR 0) was significantly correlated with the MRI erosive progression rate during the initial year (MRI 1 minus MRI 0) (rho = 0.64, p = 0.01), and, more weakly, with the corresponding 1-year radiographic progression rate (rho = 0.56, p = 0.03). <h3>Conclusion</h3> In the present study, short-term (1-year) MRI progression was highly significantly correlated with long-term (5 year) erosive progression. The study suggests that MRI is more useful than radiography itself for prediction of long term radiographic joint damage in rheumatoid arthritis.
Virus-induced p38 MAPK activation facilitates viral infection
Authors: Yuting Cheng, Fang Sun, Luyao Wang, Minjun Gao, Youli Xie, Yu Sun, Huan Liu, Yufeng Yuan, Wei Yi, Zan Huang, Huan Yan, Ke Peng, Yingliang Wu, Zhijian Cao
Journal: Theranostics (2020)

Rationale: Many viral infections are known to activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway. However, the role of p38 activation in viral infection and the underlying mechanism remain unclear. The role of virus-hijacked p38 MAPK activation in viral infection was investigated in this study. Methods: The correlation of hepatitis C virus (HCV) infection and p38 activation was studied in patient tissues and primary human hepatocytes (PHHs) by immunohistochemistry and western blotting. Coimmunoprecipitation, GST pulldown and confocal microscopy were used to investigate the interaction of p38α and the HCV core protein. In vitro kinase assays and mass spectrometry were used to analyze the phosphorylation of the HCV core protein. Plaque assays, quantitative real time PCR (qRT-PCR), western blotting, siRNA and CRISPR/Cas9 were used to determine the effect of p38 activation on viral replication. Results: HCV infection was associated with p38 activation in clinical samples. HCV infection increased p38 phosphorylation by triggering the interaction of p38α and TGF-β activated kinase 1 (MAP3K7) binding protein 1 (TAB1). TAB1-mediated p38α activation facilitated HCV replication, and pharmaceutical inhibition of p38α activation by SB203580 suppressed HCV infection at the viral assembly step. Activated p38α interacted with the N-terminal region of the HCV core protein and subsequently phosphorylated the HCV core protein, which promoted HCV core protein oligomerization, an essential step for viral assembly. As expected, SB203580 or the HCV core protein N-terminal peptide (CN-peptide) disrupted the p38α-HCV core protein interaction, efficiently impaired HCV assembly and impeded normal HCV replication in both cultured cells and primary human hepatocytes. Similarly, severe fever with thrombocytopenia syndrome virus (SFTSV), herpes simplex virus type 1 (HSV-1) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection also activated p38 MAPK. Most importantly, pharmacological blockage of p38 activation by SB203580 effectively inhibited SFTSV, HSV-1 and SARS-CoV-2. Conclusion: Our study shows that virus-hijacked p38 activation is a key event for viral replication and that pharmacological blockage of p38 activation is an antiviral strategy.
High-Dose Melphalan Significantly Increases Mutational Burden in Multiple Myeloma Cells at Relapse: Results from a Randomized Study in Multiple Myeloma
Authors: Mehmet K. Samur, Marco Roncador, Anil Aktas-Samur, Mariateresa Fulciniti, Abdul Hamid Bazarbachi, Raphael Szalat, Masood A. Shammas, Adam S Sperling, Paul G. Richardson, Florence Magrangeas, Stephane Minvielle, Anjan Thakurta, Aurore Perrot, Jill Corre, Philippe Moreau, Kenneth Anderson, Giovanni Parmigiani, Herve Avet-Loiseau, Nikhil C. Munshi
Journal: Blood (2020)
PD-L1 Pathway Markers and Chromosome 9p24.1 Alterations in Patients with Classic Hodgkin Lymphoma Treated with Frontline Single Agent Pembrolizumab (PEM) Followed By AVD Chemotherapy
Authors: Pamela B. Allen, Xinyan Lu, Qing C Chen, Liron Barnea Slonim, Madina Sukhanova, Hatice Savas, Joan Chmiel, Kaitlyn O'Shea, Andrew M. Evens, Ranjana Advani, Barbara Pro, Reem Karmali, Brett Alan Palmer, Jeffrey Bearden, Eric Mou, Gary Dillehay, Leo I. Gordon, Jane N. Winter
Journal: Blood (2020)
Abstract 400: Tip60 Depletion in Neonatal Cardiomyocytes Reduces the DNA Damage Response and Increases Cell-cycle Activation
Authors: Xinrui Wang, Carri Lupton, Amelia Lauth, Tina C Wan, Michaela Patterson, John A Auchampach, John W Lough
Journal: Circulation Research (2020)

Tip60 ( T at i nteractive p rotein, 60 kD) is a tumor suppressor encoded by the Kat5 gene that functions as a pan-acetylase. Among its targets, Atm ( a taxia- t elangiectasia m utated) undergoes auto-phosphorylation (pATM) when acetylated by Tip60 to induce the DNA damage response (DDR). Because pAtm-induced activation of the DDR is known to cause proliferative senescence in neonatal cardiomyocytes (CMs), we hypothesize that Tip60 is one of the upstream components in this pathway. Using mice containing floxed Kat5 alleles and a tamoxifen-inducible Cre-recombinase transgene driven by Myh6 (Kat5 flox/flox;Myh6-merCremer ), we assessed the effect of depleting Tip60 from neonatal CMs via a single injection of tamoxifen on postnatal day 0 (P0). Immunofluorescent microscopy revealed reduced pAtm-positive CMs at three postnatal stages (P7, P12, P39), accompanied by activation of the cell-cycle as indicated by significantly increased percentages of 5’-bromodeoxyuridine (BrdU)-, phosphohistone H3 (pH3)- and Ki67-positive CMs. In addition to cell-cycle activation, Tip60 depletion promoted nuclear division followed by cytokinesis, as indicated by increased percentage of mononuclear diploid CMs at P12. Accordingly, qPCR revealed that Tip60 depletion increased expression of mRNAs encoding the fetal markers Nppa, Nppb, Myh7 , and Acta1 at P39, which in the absence of CM hypertrophy (assessed by WGA staining) suggested maintenance of a proliferation-competent state. These effects occurred concomitant with depressed levels of mRNAs encoding cell-cycle inhibitors ( Meis1, p27 ) and a trend toward increased levels of G 2 -phase cell-cycle activators ( cyclins A2, B1 ; Cdk1 ) in Tip60-depleted hearts. These findings suggest that depletion of Tip60 at birth inhibits the DDR and delays replicative senescence in neonatal CMs.
Functional impact of cancer patient‐associated Bcl‐xL mutations
Authors: Tiantian Zhang, Joseph HyungJoon Na, Samantha Li, Zhengming Chen, George Zhang, Sharon Pang, Anthony F. Daniyan, Yi Li, Lei Shi, Yi‐Chieh Nancy Du
Journal: MedComm (2020)

Bcl-xL, an antiapoptotic protein, is frequently overexpressed in cancer to promote survival of tumor cells. However, we have previously shown that Bcl-xL promotes migration, invasion, and metastasis independent of its antiapoptotic function in mitochondria. The pro-metastatic function of Bcl-xL may require its translocation into the nucleus. Besides overexpression, patient-associated mutations of Bcl-xL have been identified in large-scale cancer genomics projects. Understanding the functions of these mutations will guide the development of precision medicine. Here, we selected four patient-associated Bcl-xL mutations, R132W, N136K, R165W, and A201T, to investigate their impacts on antiapoptosis, migration, and nuclear translocation. We found that all four mutation proteins could be detected in both the nucleus and cytosol. Although all four mutations disrupted the antiapoptosis function, one of these mutants, N136K, significantly improved the ability to promote cell migration. These data suggest the importance of developing novel Bcl-xL inhibitors to ablate both antiapoptotic and pro-metastatic functions of Bcl-xL in cancer.