tbuckley/cabot-search huggingface dataset:
Abstract MP144: Identification of Epigenetic Regulators of Cardiac Hypertrophy by an Epigenome-wide Association Study in Mice
Authors: Christoph D Rau, Milagros Romay, Eleanor Wong, Wilson Tan, Aldons J Lusis, Roger Foo, Yibin Wang
Journal: Circulation Research (2020)

We previously reported a study of heart failure in a large cohort of inbred mouse strains, the Hybrid Mouse Diversity Panel (HMDP), treated with the beta-adrenergic agonist isoproterenol, which identified over 30 genome-wide significant loci for heart failure-related traits. Our approach combined systems-level tools with the benefits of a curated model organism population to identify genetic variations that drive heart failure. We now expand this study into the epigenome. Recent research has demonstrated that DNA methylation affects the progression of cardiovascular phenotypes. This research suggests that DNA methylation may serve as an additional marker of genes involved in heart failure-associated phenotypes. Using Reduced Representational Bisulfite Sequencing, we profiled left ventricular tissue samples from 88 strains of the HMDP both before and after isoproterenol challenge (30 mg/kg/day for 21 days). We identified approximately 168,000 CpGs that vary across the panel and associated them with a set of phenotypes in both control and treated animals using the epigenome-wide association study (EWAS) algorithm MACAU. 179 significant associations were recovered at an FDR of 5%, including loci that associated pre-treatment CpG methylation with 19 different post-treatment phenotypes. By combining these EWAS loci with information from the Wellcome Trust Mouse Genomes Resource and prior work done in the heart failure HMDP, we identify several high-confidence candidate genes, including Coro1a , a gene whose pre-treatment promoter methylation status predicts post-treatment wall thickening and Eprs , which predicts right ventricular weight post-treatment. Mospd3 , a gene that was associated with right ventricular weight post-treatment in both EWAS and GWAS analyses was studied further using neonatal rat ventricular myocytes. This in vitro work demonstrates that Mospd3 knockdown results in reduced cellular hypertrophy and changes to hypertrophy-related gene expression. Further analysis of the EWAS loci using in vitro and in vivo techniques will likely validate additional genes and elucidate how DNA methylation acts to regulate pathways underlying heart failure.
Establishment of an In Vivo Mouse Model to Study and Overcome Infusion Related Reactions Associated with Fcgriib Antibody Administration
Authors: Ingrid Karlsson, Linda Mårtensson, Marie Borggren, Mathilda Kovacek, Carl Roos, Therese Blidberg, Robert Oldham, Mats Jerkeman, Martin J.S. Dyer, Andrew Davies, Raul Córdoba, Pau Abrisqueta, Stephen Beers, Ingrid Teige, Andres McAllister, Sean H Lim, Mark S Cragg, Björn Frendéus
Journal: Blood (2020)
Validating a Patient-Reported Outcomes–Derived Algorithm for Classifying Symptom Complexity Levels Among Patients With Cancer
Authors: Linda Watson, Siwei Qi, Andrea DeIure, Eclair Photitai, Lindsi Chmielewski, Louise Smith
Journal: Journal of the National Comprehensive Cancer Network (2020)

The patient-reported outcomes (PROs) symptom complexity algorithm, derived from self-reported symptom scores using the Edmonton Symptom Assessment System and concerns indicated on the Canadian Problem Checklist, has not been validated extensively.This is a retrospective chart review study using data from the Alberta Cancer Registry and electronic medical records from Alberta Health Services. The sample includes patients with cancer who visited a cancer facility in Alberta, Canada, from February 2016 through November 2017 (n=1,466).The effect size (d=1.2) indicates that the magnitude of difference in health status between the severe- and low-complexity groups is large. The symptom complexity algorithm effectively classified subgroups of patients with cancer with distinct health status. Using Karnofsky performance status, the algorithm shows a sensitivity of 70.3%, specificity of 84.1%, positive predictive value of 79.1%, negative predictive value of 76.7%, and accuracy of 77.7%. An area under the receiver operating characteristic of 0.824 was found for the complexity algorithm, which is generally regarded as good, This same finding was also regarded as superior to the alternative algorithm generated by 2-step cluster analysis (area under the curve, 0.721).The validity of the PRO-derived symptom complexity algorithm is established in this study. The algorithm demonstrated satisfactory accuracy against a clinician-driven complexity assessment and a strong correlation with the known group analysis. Furthermore, the algorithm showed a higher screening capacity compared with the algorithm generated from 2-step cluster analysis, reinforcing the importance of contextualization when classifying patients' symptoms, rather than purely relying on statistical outcomes. The algorithm carries importance in clinical settings, acting as a symptom complexity flag, helping healthcare teams identify which patients may need more timely, targeted, and individualized patient symptom management.
Tfeb Links MYC Signaling to Epigenetic Control of Acute Myeloid Leukemia Cell Death and Differentiation
Authors: Seongseok Yun, Nicole D. Vincelette, Mario Fernandez, Xiaoqing Yu, Chunying Yang, Taro Hitosugi, Chia-Ho Cheng, Audrey Freischel, Ling Zhang, Gregory Watson, Weimin Li, Hsin-An Hou, Franz Xaver Schaub, Alexis Vedder, Ling Cen, Kathy McGraw, Daniel Murphy, Andrea Ballabio, Scott H. Kaufmann, Anders Berglund, John L. Cleveland
Journal: Blood (2020)
Patient Expectations and Perceptions of Treatment in CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma
Authors: Adam D. Cohen, Parameswaran Hari, Myo Htut, Jesus G. Berdeja, Deepu Madduri, Saad Z. Usmani, Alicia J. Allred, Yunsi Olyslager, Arnob Banerjee, Jenna D. Goldberg, Jordan M. Schecter, Carolyn C. Jackson, Katharine S. Gries, John Fastenau, William Deraedt, Marlene J. Carrasco, Muhammad Akram, Farah Hossain, Sigrid Crawford, Ross Morrison, Lynda Doward, Andrzej Jakubowiak, Sundar Jagannath
Journal: Blood (2020)
Prognostic Impact of Prior Heart Failure in Patients Hospitalized With COVID-19
Authors: Jesus Alvarez-Garcia, Samuel Lee, Arjun Gupta, Matthew Cagliostro, Aditya A. Joshi, Mercedes Rivas-Lasarte, Johanna Contreras, Sumeet S. Mitter, Gina LaRocca, Pilar Tlachi, Danielle Brunjes, Benjamin S. Glicksberg, Matthew A. Levin, Girish Nadkarni, Zahi Fayad, Valentin Fuster, Donna Mancini, Anuradha Lala
Journal: Journal of the American College of Cardiology (2020)
Anti-Thymocyte Globulin (ATG) for Prophylaxis of Severe Graft Vs. Host Disease after Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis
Authors: Muhammad Ashar Ali, Muhammad Yasir Anwar, Sobia Aamir, Saad Ur Rahman, Richi Kashyap, Sana Irfan Khan, Usman Ali Akbar, Anum Waqar, Anam Khan, Wajeeha Aiman, Faiz Anwer
Journal: Blood (2020)
SARS-CoV-2 membrane glycoprotein M antagonizes the MAVS-mediated innate antiviral response
Authors: Yu-Zhi Fu, Su-Yun Wang, Zhou-Qin Zheng, None Yi Huang, Wei-Wei Li, Zhi-Sheng Xu, Yan-Yi Wang
Journal: Cellular and Molecular Immunology (2020)

A novel SARS-related coronavirus (SARS-CoV-2) has recently emerged as a serious pathogen that causes high morbidity and substantial mortality. However, the mechanisms by which SARS-CoV-2 evades host immunity remain poorly understood. Here, we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response. We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways. This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3, leading to attenuation of the innate antiviral response. Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARS-CoV-2 is a potential target for the development of SARS-CoV-2 interventions.
Analysis of tumor-infiltrating NK and T cells highlights IL-15 stimulation and TIGIT blockade as a combination immunotherapy strategy for soft tissue sarcomas
Authors: Sean J Judge, Morgan A Darrow, Steve W Thorpe, Alicia A Gingrich, Edmond F O'Donnell, Alyssa R Bellini, Ian R Sturgill, Logan V Vick, Cordelia Dunai, Kevin M Stoffel, Yue Lyu, Shuai Chen, May Cho, Robert B Rebhun, Arta M Monjazeb, William J Murphy, Robert J Canter
Journal: Journal for ImmunoTherapy of Cancer (2020)

Purpose Given the unmet need for novel immunotherapy in soft tissue sarcoma (STS), we sought to characterize the phenotype and function of intratumoral natural killer (NK) and T cells to identify novel strategies to augment tumor-infiltrating lymphocyte (TIL) function. Experimental design Using prospectively collected specimens from dogs and humans with sarcomas, archived specimens, and The Cancer Genome Atlas (TCGA) data, we evaluated blood and tumor NK and T cell phenotype and function and correlated those with outcome. We then assessed the effects of interleukin 15 (IL-15) stimulation on both NK and T cell activation and TIGIT upregulation. Finally, we evaluated cytotoxic effects of IL-15 combined with TIGIT blockade using a novel anti-TIGIT antibody. Results TILs were strongly associated with survival outcome in both archived tissue and TCGA, but higher TIL content was also associated with higher TIGIT expression. Compared with blood, intratumoral NK and T cells showed significantly higher expression of both activation and exhaustion markers, in particular TIGIT. Ex vivo stimulation of blood and tumor NK and T cells from patients with STS with IL-15 further increased both activation and exhaustion markers, including TIGIT. Dogs with metastatic osteosarcoma receiving inhaled IL-15 also exhibited upregulation of activation markers and TIGIT. Ex vivo, combined IL-15 and TIGIT blockade using STS blood and tumor specimens significantly increased cytotoxicity against STS targets. Conclusion Intratumoral NK and T cells are prognostic in STS, but their activation is marked by significant upregulation of TIGIT. Our data suggest that combined IL-15 and TIGIT blockade may be a promising clinical strategy in STS.
Abstract 447: Myristoylation of Protein Kinase C Beta II Peptide Inhibitor Facilitates Rapid Attenuation of Phorbol 12-myristate 13-acetate in Activated Superoxide Release in Isolated Rat Polymorphonuclear Leukocytes
Authors: Sunit G Singh, Tameka Dean, Michael Lloyd, Rourke Decker, Jeremy Castro, Ian T Madison, Michael Suarez, Rose Martorana, Melinda Beale, Redona Gjoka, Daphne Metellus, Annam Humayun, Jennifer Dang, Qian Chen, Robert Barsotti, Lindon Young
Journal: Circulation Research (2020)

Protein kinase C beta II (PKCβII) activates polymorphonuclear leukocyte (PMN) superoxide (SO) production via NADPH oxidase (NOX-2) phosphorylation to exacerbate myocardial ischemia/reperfusion (I/R) injury. In prior studies, myristoylation (myr) of PKCβII peptide inhibitor (N-myr-SLNPEWNET; myr-PKCβII-), which disrupts PKCβII translocation/phosphorylation of NOX-2, was shown to dose-dependently attenuate PMN SO release induced by phorbol 12-myristate 13-acetate (PMA), a broad-spectrum PKC agonist. However, the role of myr on the inhibitory effects of myr-PKCβII- has yet to be elucidated. We hypothesized that myr-PKCβII peptide activator (N-myr-SVEIWD; myr-PKCβII+) would augment, myr-PKCβII- would attenuate, and scrambled myr-PKCβII- (N-myr-WNPESLNTE; myr-PKCβII-scram), a control for myr, would not affect PMA-induced PMN SO release compared to unconjugated peptides and nontreated controls. Rat PMNs (5х10 6 ) were incubated for 15 min at 37 o C in the presence/absence of SO dismutase (SOD; 10 μg/mL), unconjugated PKCβII+/-, myr-PKCβII+/-, or myr-PKCβII-scram (all 20 μM). SO release was measured by the change in absorbance at 550 nm via ferricytochrome c reduction after PMA (100 nM) stimulation for 390 sec. Data were analyzed by ANOVA using Student-Newman-Keuls post hoc analysis. Myr-PKCβII- significantly attenuated SO release (0.30±0.02; n=27; p&lt;0.05) compared to nontreated controls (0.46±0.01; n=73), myr-PKCβII+ (0.46±0.03; n=25), unconjugated PKCβII+ (0.43±0.04; n=15), PKCβII- (0.43±0.02; n=22) and myr-PKCβII-scram (0.65±0.04; n=22). SOD (n=8), which rapidly converts SO to H 2 O 2 , significantly reduced absorbance by 94±7%, indicating that absorbance increased mainly due to PMA stimulation. Cell viability (trypan blue exclusion) was similar in all groups (94±2%). Unexpectedly, myr-PKCβII-scram significantly stimulated the highest increase in absorbance compared to all groups (p&lt;0.01). Future studies will determine whether myr-PKCβII-scram augments absorbance by a different mechanism. Results suggest that myr improves myr-PKCβII- delivery compared to unconjugated PKCβII- but does not affect inhibition of PMA-induced PMN SO release. Myr-PKCβII- may thus effectively limit inflammation-induced I/R injury.
Violence against female health workers is tip of iceberg of gender power imbalances
Authors: Asha S George, Frances E McConville, Shaheem de Vries, Gustavo Nigenda, Shabnum Sarfraz, Michelle McIsaac
Journal: BMJ (2020)

WoMen's HealtH and Gender InequalItIesViolence against female health workers is tip of iceberg of gender power imbalances Tackling gender power relations is key to ensuring the safety and wellbeing of health workers and the ability to deliver quality care, say Asha George and colleagues Key Messages• Violence against female health work- ers is an extreme form of abuse of power within the health workforce • Tackling underlying gendered power dynamics is key to stopping violence against female health workers• Achieving good quality healthcare worldwide requires the rights of the women responsible for delivering care to be acknowledged, protected, respected, supported, and promoted on 2 August
Ruxolitinib, a JAK1/2 Inhibitor, Is Efficacious in a Novel Humanized GvHD Model Characterized By Enhanced NK, NK-T and T-Cell Engraftment
Authors: Eduardo Huarte, Michael Peel, Philip Dube, Lynn Stephens, Becky Stewart, Brian Long, Philip Czerniak, Julian Oliver, Paul Smith
Journal: Blood (2020)
Abstract 414: A Canine Myocardial Slice Model of Doxorubicin Induced Cardiotoxicity to Study Autophagy Modulation and Its Effect on Extracellular Vesicle Associated Mirna
Authors: Sally R Robinson, Nicholas A Robinson, Asma Boukhalfa, Dawn M Meola, Howard H Chen, Vicky K Yang
Journal: Circulation Research (2020)

Dogs with cancer treated with chemotherapy agents such as doxorubicin (DOX) develop cardiovascular toxicity, providing an opportunity to evaluate cardioprotective strategies in the setting of cancer treatment translatable to human disease. However, due to the lack of a suitable approach to culture primary adult canine cardiomyocytes, mechanistic interrogation of cardiotoxicity after cancer therapy remains a challenge. Our study thus aims to validate a canine myocardial slice culture model to study autophagy modulation and the role of extracellular vesicle (EV) associated miRNA in the setting of DOX induced cardiotoxicity. We hypothesize that induction of autophagy in canine myocardial tissue will reduce apoptosis, exert early changes to EVs, and ameliorate DOX cardiotoxicity. Left ventricular tissue from client-owned donated adult dog hearts was sectioned with a vibratome and viability of the cultured myocardial slices was evaluated by histology and MTT assay. Apoptosis was quantified by TUNEL, and autophagy by fluorescent LC3 protein puncta. Secreted EVs were isolated from cultured tissue by size exclusion chromatography and characterized by nanoparticle tracking analysis, transmission electron microscopy and immunoblot. Canine myocardial slices are consistently viable for 7 days in culture - cardiomyocyte morphology is maintained with low levels of apoptosis, and baseline autophagy is observed. Induction of autophagy with rapamycin treatment results in reduced apoptosis. Cardiac tissue derived extracellular vesicles showed typical size, morphology and enrichment of proteins including tetraspanin CD9 and will be evaluated for changes to EV miRNA profile with autophagy modulation. The canine myocardial slice model allows, for the first-time, the elucidation of complex cross-talk among apoptosis, autophagy, and EVs with molecular and cellular resolutions. Detecting early changes in canine cardiomyocyte autophagy to halt cardiac damage rather than managing its consequences is a paradigm shift translatable towards preventing chemotherapy associated cardiotoxicity.
Reducing Time to Chemotherapy Administration in the Outpatient Setting of a Tertiary Cancer Centre Using a Design Thinking Approach
Authors: Wei-Ying Jen, Zhi Yao Chan, Mary Chong, Mariana Ibrahim, Melinda Khoo, Judith Lee, Meng Tuck Lee, Yee Mei Lee, Siew Woon Lim, Noel Ng, Ednajoy Ngo, Belinda Tan, Rui Xian Tay, Constance Teo, Yuet Peng Wong, Cheng Ean Chee, Yen-Lin Chee
Journal: Blood (2020)
Novel Target Genes and Epigenetic Pathways Involved in High Risk Acute Lymphoblastic Leukemia
Authors: Sara Deola, Dhanya Kizhakayil, Sheanna M Herrera, Muhammad Elnaggar, Che-Ann Lachica, Giusy Gentilcore, Ayman Saleh, Anila Ejaz, Zehra Fadoo, Kulsoom Ghias, Irene Pusceddu, Irene M Cavattoni, Ramzi Temanni, Najeeb A Syed, Fazulur R Vempalli, Patrizia Comoli, Tommaso Mina, Chiara Cugno
Journal: Blood (2020)
COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
Authors: Per Ljungman, Rafael De La Camara, Malgorzata Mikulska, Gloria Tridello, Beatriz Aguado, Yves Beguin, Rodrigo Martino Bufarull, Fabio Ciceri, Lucía López Corral, Claudia Crippa, Dries Deeren, Rafael F. Duarte, María Laura Fox, Anna Grassi, María-José Jimenez, Safiye Koculu, Mi Kwon, Juan Carlos Vallejo Llamas, Jose Luiz Lopez Lorenzo, Stephan Mielke, Javier López Jiménez, Zoraida Mesa Morales, Kim H. Orchard, Rocio Parody Porras, Victoria Potter, María Suárez-Lledó, Nicolaas Schaap, Celestine Simand, Luisa Sisinni, John A Snowden, Daniele Vallisa, Ipek Yonalhindilerden, Alienor Xhaard, Nina Simone Knelange, Angel Cedillo, Nicolaus Kröger, Jose Luis Piñana Sanchez, Jan Styczynski
Journal: Blood (2020)
Genome-wide mutational signatures revealed distinct developmental paths for human B cell lymphomas
Authors: Xiaofei Ye, Weicheng Ren, Dongbing Liu, Xiaobo Li, Wei Li, Xianhuo Wang, Fei-Long Meng, Leng-Siew Yeap, Yong Hou, Shida Zhu, Rafael Casellas, Huilai Zhang, Kui Wu, Qiang Pan-Hammarström
Journal: The Journal of Experimental Medicine (2020)

Both somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase (AID). Dysregulation of these processes has been linked to B cell lymphomagenesis. Here we performed an in-depth analysis of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) genomes. We characterized seven genomic mutational signatures, including two B cell tumor-specific signatures, one of which is novel and associated with aberrant SHM. We further identified two major mutational signatures (K1 and K2) of clustered mutations (kataegis) resulting from the activities of AID or error-prone DNA polymerase η, respectively. K1 was associated with the immunoglobulin (Ig) switch region mutations/translocations and the ABC subtype of DLBCL, whereas K2 was related to the Ig variable region mutations and the GCB subtype of DLBCL and FL. Similar patterns were also observed in chronic lymphocytic leukemia subtypes. Thus, alterations associated with aberrant CSR and SHM activities can be linked to distinct developmental paths for different subtypes of B cell lymphomas.
The mRNA m6A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function
Authors: Christopher Mapperley, Louie N. van de Lagemaat, Hannah Lawson, Andrea Tavosanis, Jasmin Paris, Joana Campos, David Wotherspoon, Jozef Durko, Annika Sarapuu, Junho Choe, Ivayla Ivanova, Daniela S. Krause, Alex von Kriegsheim, Christian Much, Marcos Morgan, Richard I. Gregory, Adam J. Mead, Dónal O’Carroll, Kamil R. Kranc
Journal: The Journal of Experimental Medicine (2020)

The mRNA N6-methyladenosine (m6A) modification has emerged as an essential regulator of normal and malignant hematopoiesis. Inactivation of the m6A mRNA reader YTHDF2, which recognizes m6A-modified transcripts to promote m6A-mRNA degradation, results in hematopoietic stem cell (HSC) expansion and compromises acute myeloid leukemia. Here we investigate the long-term impact of YTHDF2 deletion on HSC maintenance and multilineage hematopoiesis. We demonstrate that Ythdf2-deficient HSCs from young mice fail upon serial transplantation, display increased abundance of multiple m6A-modified inflammation-related transcripts, and chronically activate proinflammatory pathways. Consistent with the detrimental consequences of chronic activation of inflammatory pathways in HSCs, hematopoiesis-specific Ythdf2 deficiency results in a progressive myeloid bias, loss of lymphoid potential, HSC expansion, and failure of aged Ythdf2-deficient HSCs to reconstitute multilineage hematopoiesis. Experimentally induced inflammation increases YTHDF2 expression, and YTHDF2 is required to protect HSCs from this insult. Thus, our study positions YTHDF2 as a repressor of inflammatory pathways in HSCs and highlights the significance of m6A in long-term HSC maintenance.
Abstract 396: 3d-Engineered Aligned Co-axial Nanofibrous Cardiac Patch for Drug Screening and Cardiac Repair Applications
Authors: Mahmood Khan, Divya Sridharan, Naresh Kumar, Arunumar Palaniappan, Julie A Dougherty, Dona G Isai, Andras Czirok, Heather Powell
Journal: Circulation Research (2020)

Introduction: Recent studies have demonstrated the great potential of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for testing the efficacy of various cardiac drugs. Additionally, studies have shown that the hiPSC-CMs grown in a 3D environment express better physiological characteristics than 2D cultures. The convergence of polymeric cardiac patch technology with hiPSC-CMs has opened up innovative ways for generating biomimetic 3D cardiac tissues. Hypothesis: The central hypothesis of this study was to develop a 3D cardiac tissue model for pharmacological testing of various cardiac drugs on a 3D nanofibrous aligned co-axial cardiac patch. Methods: A co-axial (Co-A) PCL-gelatin aligned nanofibrous patch was fabricated using the electrospinning technique and its mechanical properties were assessed using Universal Test Machine. Then, the hiPSC-CMs were cultured on this Co-A patch for 2 weeks and the LDH assay was performed to determine the cell viability. The functionality of the cardiac patch was determined by an assessment of calcium cycling in hiPSC-CMs. Further, particle image velocimetry (PIV) and microelectrode array (MEA) was used to evaluate the physiological functionality of the cardiac patch in response to various cardiac drugs. Results: Our studies showed that the mean diameter and thickness of aligned Co-A nanofibrous patch was 578±184 nm and 115±11 μm respectively, while its tensile strength was 0.780 ± 0.098 MPa. Further, confocal imaging confirmed the core-shell structure of the Co-A patches with a core diameter of 2.21 ± 0.50 μm. Additionally, The hiPSC-CMs cultured on these aligned Co-A patches showed an aligned morphology and expressed Troponin-T, GATA4, α-sarcomeric actinin, and connexin-43. The hiPSC-CMs seeded on a 3D scaffold showed efficient calcium cycling properties, which were similar to the hiPSC-CMs cultured in 2D scaffold. Furthermore, PIV and MEA analysis showed that hiPSC-CMs cultured in 2D and 3D showed a similar response to various cardiac drugs, isoproterenol, verapamil and E4031. Conclusions: Overall, this study demonstrated a successful fabrication of aligned Co-A nanofibrous cardiac patch and its evaluation as a 3D cardiac tissue model in-vitro, which could be applied towards drug screening, toxicity studies and cardiac repair applications for ischemic heart disease.