tbuckley/cabot-search huggingface dataset:
Association Between High School Personality Phenotype and Dementia 54 Years Later in Results From a National US Sample
Authors: Benjamin P. Chapman, Alison Huang, Kelly Peters, Elizabeth Horner, Jennifer Manly, David A. Bennett, Susan Lapham
Journal: JAMA Psychiatry (2019)

Personality phenotype has been associated with subsequent dementia in studies of older adults. However, neuropathologic changes often precede cognitive symptoms by many years and may affect personality itself. Therefore, it is unclear whether supposed dementia-prone personality profiles (high neuroticism and low conscientiousness) are true risk factors or merely reflections of preexisting disease.To examine whether personality during adolescence-a time when preclinical dementia pathology is unlikely to be present-confers risk of dementia in later life and to test whether associations could be accounted for by health factors in adolescence or differed across socioeconomic status (SES).Cohort study in the United States. Participants were members of Project Talent, a national sample of high school students in 1960. Individuals were identified who received a dementia-associated International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code during any year between 2011 and 2013. The dates of our analysis were March 2018 to May 2019.Ten personality traits were measured by the 150-item Project Talent Personality Inventory. Socioeconomic status was measured by a composite based on parental educational level, income, occupation, and property ownership. Participants were also surveyed on demographic factors and height and weight.Medicare records were collected, with dementia diagnoses in the period of 2011 to 2013 classified according to the US Centers for Medicare & Medicaid Services ICD-9-based algorithm. Cox proportional hazards regression models estimated the relative risk of dementia based on the 10 personality traits, testing interactions with SES and adjusting for demographic confounders.The sample of 82 232 participants was 50.1% female, with a mean (SD) age of 15.8 (1.7) years at baseline and 69.5 (1.2) years at follow-up. Lower risk of dementia was associated with higher levels of vigor (hazard ratio for 1 SD, 0.93; 95% CI, 0.90-0.97; P < .001). Calm and maturity showed protective associations with later dementia that increased with SES. At 1 SD of SES, calm showed a hazard ratio of 0.89 (95% CI, 0.84-0.95; P < .001 for the interaction) and maturity showed a hazard ratio of 0.90 (95% CI, 0.85-0.96; P = .001 for the interaction).This study's findings suggest that the adolescent personality traits associated with later-life dementia are similar to those observed in studies of older persons. Moreover, the reduction in dementia risk associated with a calm and mature adolescent phenotype may be greater at higher levels of SES. Personality phenotype may be a true independent risk factor for dementia by age 70 years, preceding it by almost 5 decades and interacting with adolescent socioeconomic conditions.
Chromosome Banding Analysis, FISH and RT-PCR Performed in Parallel in Hypereosinophilic Syndrome Establishes the Diagnosis of Chronic Eosinophilic Leukemia in 22% of Cases: A Study on 40 Patients.
Authors: Claudia Schoch, Andreas Reiter, Sabina Bursch, Susanne Schnittger, Wolfgang Hiddemann, Wolfgang Kern, Torsten Haferlach
Journal: Blood (2004)
Barriers to fertility preservation (FP) in a prospective pan-Canadian study of young women with breast cancer (YWBC).
Authors: Ellen Warner, Samantha Yee, Maureen Seminsky, David Lipson, Karen Glass, Shu Foong, Erin Diane Kennedy, Steven Narod, May Lynn Quan
Journal: Journal of Clinical Oncology (2019)

136 Background: Despite ASCO recommendations that oncologists routinely offer FP to young cancer patients prior to treatment, studies show that only a minority of YWBC are given this option. We sought to determine whether an intervention, including educational materials and regular reminders to breast surgeons, would improve FP referral. The current report examines the rates of FP discussion, referral, uptake and reasons for declining, according to participants’ self-reported pre-diagnosis fertility plans. Methods: Consecutive women ≤ age 40 newly diagnosed with breast cancer at 30 Canadian sites were offered enrolment in a national study of YWBC. At 3 months each participant was surveyed regarding her pre-diagnosis (dx) fertility plans and post-dx oncofertility management. Results: Of the 712 recruits (09/15 to 08/18) with invasive disease (mean age 36), 46%, 15% and 29% had 0, 1 or 2 children respectively and 77% were in a stable relationship. Among the 480 women who completed the fertility survey, 392 (82%) indicated they had a pre-treatment fertility discussion initiated by a health care provider (HCP) - in 232 cases (48%) the surgeon/nurse and in 130 cases (27%) the medical oncologist/ nurse. Only 14 (16%) of the 88 women not approached by a HCP initiated such a discussion. Rates of FP discussion, referral and uptake are shown below. Among the 38 women who definitely wanted (more) children prior to dx and were offered FP but declined the consult or procedure, the commonest reasons were cost (n = 9) and fear that treatment delay (n = 8) or FP (n = 4) could cause recurrence. Conclusions: Post-intervention FP discussion rates were higher than previously reported. Yet 26% of patients who had definitely/probably not completed their family were not referred for a FP consult. Cost remains a significant FP barrier. Studies are needed to confirm the long-term safety of FP for ER+ patients. [Table: see text]
Allogeneic Transplantation for Minimal Residual Disease Negative Acute Lymphoblastic Leukemia According to 2016 Who Classification: A Single Center Retrospective Analysis
Authors: Xingyu Cao, Deyan Liu, Jianping Zhang, Zhijie Wei, Min Xiong, Yue Lu, Yanli Zhao, Jiarui Zhou, Ruijuan Sun, Hongxing Liu
Journal: Blood (2018)
A Descriptive Analysis of Obinutuzumab Usage in a Single Canadian Centre
Authors: Nicole Bourrier, Ivan Landego, Mandy Squires, Oliver Bucher, Zeb Aurangzeb, Erin Streu, Theresa Whiteside, Irena Hibbert, Marc Geirnaert, David Dawe, Spencer Bruce Gibson, James B. Johnston, Versha Banerji
Journal: Blood (2018)
Genome-Scale Crispr-Cas9 Knockout Studies Reveal Mutifactorial and Functionally Overlapping Mechanisms of Myeloma Cell Resistance to Proteasome Inhibition
Authors: Michal Sheffer, Yiguo Hu, Ophir Shalem, Neville Sanjana, Eugen Dhimolea, Subhashis Sarkar, Megan A. Bariteau, Blake T. Aftab, Richard W.J. Groen, Feng Zhang, Constantine S. Mitsiades
Journal: Blood (2014)
Association between the Risk of Low/High-Count Monoclonal B-Cell Lymphocytosis (MBL) and the Chronic Lymphocytic Leukemia (CLL) Polygenic Risk Score (PRS)
Authors: Geffen Kleinstern, Sara J. Achenbach, Dennis P. Robinson, Aaron D. Norman, Kari G. Chaffee, Connie E. Lesnick, Sameer A. Parikh, Timothy G. Call, Janet E. Olson, James R. Cerhan, Neil E. Kay, Curtis A. Hanson, Tait D. Shanafelt, Susan L. Slager
Journal: Blood (2018)
Clustering of Bleeding Symptoms in Patients Previously Diagnosed As Type 3 Von Willebrand Disease: Results from a Large Cohort of Type 3 Von Willebrand Disease (the 3Winters-Ips Project)
Authors: Alberto Tosetto, Zahra Badiee, Mohammad-Reza Baghaipour, Luciano Baronciani, Javier Battle, Erik Berntorp, Imre Bodó, Ulrich Budde, Giancarlo Castaman, Jeroen C.J. Eikenboom, Peyman Eshghi, Cosimo Ettorre, Anne Goodeve, Jenny Goudemand, Charles Richard Morris Hay, Hamid Hoorfar, Mehran Karimi, Bijan Keikhaei, Riitta Lassila, Frank W.G. Leebeek, Maria Fernanda Lopez Fernandez, Pier Mannuccio Mannucci, Maria Gabriella Mazzucconi, Massimo Morfini, Johannes Oldenburg, Ian Peake, Rafael Parra Lòpez, Flora Peyvandi, Reinhard Schneppenheim, Andreas Tiede, Gholamreza Toogeh, Marc Trossaert, Omidreza Zekavat, Eva M.K. Zetterberg, Augusto B Federici
Journal: Blood (2018)
The Timing of Acute Renal Failure Strongly Affects Survival of Immunoglobulin Light Chain (AL) Amyloidosis Patients Undergoing Autologous Stem Cell Transplantation,
Authors: Nelson Leung, Shaji Kumar, Angela Dispenzieri, Martha Q Lacy, Francis K Buadi, Suzanne R Hayman, David Dingli, William J Hogan, Dennis A. Gastineau, Siobhan V Glavey, Morie A Gertz
Journal: Blood (2011)
Abstract 254: Kinase-dead Pi3kγ Expression in the Cardiac Myocytes Regulates Fibroblast Signaling and Myofibroblast Differentiation
Authors: Maradumane L Mohan, Lisa M Grove, Anita Sahu, Robert S Papay, Mitchell A Olman, Sathyamangla V Naga Prasad
Journal: Circulation Research (2019)

Phosphoinositide 3 Kinase γ (PI3Kγ) is an anti-apoptotic molecule acting through Akt pathway. Even though, role of PI3Kγ in cardiac fibrosis has been established, the mechanistic details by which PI3Kγ regulates cardiac myofibroblast differentiation are not clear. Myofibroblasts are hallmark of tissue fibrosis, characterized by smooth muscle α-actin (αSMA) over-expression. We have previously shown that αSMA abundance in cardiac lysates from PI3Kγ null mice (PI3Kγ -/- ) showed significant baseline and pressure overload [Transverse Aortic Constriction (TAC)] induced upregulation compared to wildtype (WT), indicating that loss of PI3Kγ predisposes the hearts towards fibrosis. Furthermore, isolated cardiac fibroblasts (CF) from PI3Kγ -/- exhibited a myofibroblast phenotype with αSMA in stress fibers. Moreover, cardiomyocyte-specific over-expression of kinase-dead PI3Kγ (PI3Kγ inact ) in the global PI3Kγ -/- (PI3Kγ inact /PI3Kγ -/- ) reduced αSMA abundance and myofibroblast differentiation suggesting unique kinase-independent function of PI3Kγ in myocyte-initiated pathway that drives CF to become myofibroblasts. Conditioned media experiments showed that PI3Kγ -/- myocytes release pro-fibrotic factors and PI3Kγ inact /PI3Kγ -/- myocytes release fibrosis protective factors. We have previously observed that PI3Kγ regulated MAPK signaling in fibroblasts in a kinase-independent manner by sequestering PP2A association and activity. Previous studies have shown that fibroblast growth factor mediated activation of the signaling pathway downregulates αSMA and that this inhibition of αSMA expression is through negative regulation by extracellular regulated kinase (ERK). Consistent with these previous observations, PI3Kγ possibly mediates αSMA and myofibroblast differentiation through regulation of ERK signaling in the fibroblasts. Intriguingly, we observed presence of PI3Kγ when lysates of isolated CF from PI3Kγ inact /PI3Kγ -/- were immunoblotted for PI3Kγ. These data indicate that a unique communication between myocytes and fibroblasts regulated by PI3Kγ, leads to a compensatory mechanism that results in expression of PI3Kγ in the fibroblasts, thereby regulating fibroblast signaling in myofibroblast differentiation.
Abstract 880: The Role of Sialidase Neu3 in the Cardiac Response to Ischemia and Reperfusion Injury
Authors: Marco Piccoli, Maria Elena Canali, Andrea Ghiroldi, Federica Cirillo, Luigi Anastasia
Journal: Circulation Research (2019)

Reperfusion strategies are life-saving approaches to restore the blood flow in the cardiac tissue after acute myocardial infarction (AMI). However, they come with the drawback that they inevitably induce ischemia/reperfusion injury (IRI), resulting in increased cardiomyocytes damage and heart failure. In this context, the physiological activation of several pro-survival kinases, such as Akt and Erk, as well as of the hypoxia inducible factor (HIF) has been recognized to be critical during IRI. Along with this line, we recently discovered a novel, PHDs independent, mechanism of HIF-1; activation mediated by sialidase Neu3. Interestingly, Neu3 is upregulated under chronic hypoxia in cyanotic congenital cardiac patients. Moreover, induced activation of Neu3 increased myoblast resistance to hypoxic stress. Thus, in this study, we further investigated the possible role of Neu3 in protecting cardiac myoblasts during IRI. In particular, we set-up an in-vitro model of IRI on H9C2 rat cardiomyoblasts. Results showed a modulation of Neu3 during IRI, with a progressive down-regulation during the ischemic phase, followed by a reactivation during the reperfusion phase. Remarkably, overexpression of Neu3 significantly increased cardiomyoblasts resistance to IRI, both in terms of cell proliferation and resistance to apoptosis. Treatment with Akt and Erk inhibitors, as well as with a Neu3 specific inhibitor completely reverted the beneficial effects mediated by Neu3 upregulation. In conclusion, our results show that Neu3 activation has a cardioprotective effect during IRI, calling for further studies to unveil its full potential as a therapeutic target to treat cardiac ischemia and reperfusion injury and to improve patients recover after AMI.
Abstract 144: Ultrasound Mediated Transfection of SERCA2a and Cx43 Genes Assisted Bone Marrow Stem Cells Transplantation to Improve Heart Failure and Ventricular Arrhythmia After Myocardial Infarction
Authors: Yuming Mu, Wei Wang, Baihetiya Tayier, Lina Guan
Journal: Circulation Research (2019)

Objective: We aimed to investigate the possibility of combining BMSCs transplantation (BMSCs T) with sarcoplasmic reticulum Ca2+ATase (SERCA2a) and connexins 43 (Cx43) genes transfection mediated by ultrasound-targeted microbubble destruction (UTMD) to treat heart failure (HF) and ventricular arrhythmia (VA) after MI. Methods: HF rats received BMSCs T 4 weeks after AMI. Two days later, microbubbles carried SERCA2a and Cx43 genes were injected via tail vein, then ruptured by irradiation. 63 rats were divided into 7 groups : 1)SHAM; 2)HF; 3)UTMD; 4)BMSCs + UTMD; 5)BMSCs + UTMD-SERCA2a; 6)BMSCs + UTMD-Cx43; 7)BMSCs+ UTMD-SERCA2a/Cx43-1:1. Left ventricular ejection fraction (LVEF), cardiac tolerance to electrical stimulation were examined 28 days after BMSCs T. Results: The LVEF of gene transfection groups were improved than before: BMSCs + UTMD-SERCA2a (39.6±3.6% vs. 34.3±4.3%); BMSCs + UTMD-Cx43 (40.1±5.6% vs. 35.1±5.2%); BMSCs + UTMD-SERCA2a/Cx43-1:1 (41.7±6.8% vs. 35.1±5.2%) (P &lt; 0.05). Stimulating with 7V voltage, the frequencies of inducing VA in BMSCs + UTMD-SERCA2a, BMSCs + UTMD-Cx43 and BMSCs + UTMD-SERCA2a/Cx43-1:1 were 13.07±4.77Hz, 13.94±1.29Hz and 13.97±1.91Hz, which were higher than HF and non-gene groups (P &lt; 0.05). With 8V, the frequencies in BMSCs + UTMD-Cx43 and BMSCs+ UTMD-SERCA2a/Cx43-1:1 were also higher than other groups but SHAM (P &lt; 0.05). The frequency of double-gene group was higher than single-gene groups with 8V (P &lt; 0.05). Conclusion: Our results suggest that BMSCs T assisted by UTMD-mediated SERCA2a and Cx43 genes transfection can improve HF and VA after MI, and especially for the stability of cardiac electrical activity with double-gene.
Flt3 Mutations in Proximity to an Ubiquitin Dependent Endocytosis Motif Suspend Its Hdm2 Modulation.
Authors: Line Wergeland, Eystein Oveland, Gry Sjoholt, Siv Lise Bedringaas, Randi T. Hovland, Oystein Bruserud, Bjorn T. Gjertsen
Journal: Blood (2007)
Abstract 714: Mapping the Transcriptional Dynamics of Pluripotent Stem Cell-derived Endothelial Cell Differentiation by Single Cell RNA Sequencing
Authors: Ian R McCracken, Richard S Taylor, Fernando De La Cuesta, Ross Dobie, Beth E Henderson, Joanne C Mountford, Axelle Caudrillier, Neil C Henderson, Chris P Ponting, Andrew H Baker
Journal: Circulation Research (2019)

Objectives: Human embryonic stem cell derived endothelial cell (hESC-EC) differentiation offers a model to study the process of endothelial development, commitment and maturation, thus potentially informing future regeneration strategies. We used high throughput single cell RNA sequencing (scRNA-seq) to characterise the cellular heterogeneity and associated transcriptional signatures throughout hESC-EC differentiation. Methods and Results: Using an established eight-day hESC-EC (H9) differentiation protocol yielding 66% CD31 + /CD144 + cells, we sampled cells for scRNA-seq (10X Chromium) at pluripotent (day 0), mesodermal (day 4), early (day 6) and late (day 8) endothelial stages (total 21,369 cells). The pluripotent and mesodermal population were largely homogeneous prior to the emergence of distinct endothelial and mesenchymal populations. Pseudotime analysis characterised the transcriptional signatures throughout differentiation, revealing a bifurcation point giving rise to both populations. Repeating the study with a second hESC line (RC11) produced equivalent populations and transcriptional signatures. In addition, scRNA-seq analysis of an alternative hESC-EC differentiation protocol revealed substantially more heterogeneity, including nephrogenic and haemogenic populations. However, pseudotime analysis revealed common expression of known and uncharacterised endothelial transcription factors across both protocols. Comparison of hESC-EC to foetal and mature EC revealed their transcriptional distinction, suggesting their non-specified nature. Conclusions: We sequenced over 105,000 cells allowing characterisation of hESC-EC differentiation across different hESC lines and protocols. We identified a common bifurcation point and remarkable concordance between the transcriptional signatures across different hESC lines and differentiation protocols. This included identifying novel transcription factors that may drive endothelial commitment and maturation.
Prognostic Value of Serum Beta-2 Microglobulin during and after Completing Chemotherapy in Marginal Zone Lymphoma
Authors: Byung Woo Yoon, Jung Yong Hong, Dok Hyun Yoon, Kyoung Min Lee, Shin Kim, Jung Sun Park, Chan-Sik Park, Jooryung Huh, Chan-jeoung Park, Seongsoo Jang, Jin-Sook Ryu, Sang Wook Lee, Cheolwon Suh
Journal: Blood (2018)
Radiofrequency Ablation of Liver Metastases from Colorectal Cancer Induces a Cancer-Specific T Cell Repertoire in Humans
Authors: Markus W. Loeffler, Bianca Nussbaum, Philipp S. Jurmeister, Jan Budczies, Daniel Johannes Kowalewski, Stephan Clasen, Ingmar Koenigsrainer, Stefan Beckert, Silvia Wagner, Bence Sipos, Florian Bullinger, Olaf H. Riess, Philippe Pereira, Alfred Koenigsrainer, Lothar Kanz, Stefan Stevanovic, Carsten Denkert, Hans-Georg Rammensee, Cecile Gouttefangeas, Sebastian Haen
Journal: Blood (2018)
Abstract 417: A 3D iPSC-derived Scaffold-Assisted Microfluidic Model of Ventricular Ejection
Authors: Christos Michas, Pranjal Nautiyal, Arvind Agarwal, Alice E White, Christopher S Chen
Journal: Circulation Research (2019)

Organ-on-a-chip technology fosters the potential of in vitro models of cardiac function. Nevertheless, modeling the ventricular ejection has been challenging due to the lack of 3D scaffolds of ventricular-like geometry that can accommodate the tissue while providing structural stability and contractile directionality. Using two-photon direct laser writing, we fabricate a concave, 1mm 3 scaffold that is then embedded in a microfluidic, organ-on-a-chip system. We seed the system with iPSC-derived cardiac tissue and demonstrate the ability of the scaffold to preserve the 3D concave tissue structure, promote cardiomyocyte alignment and generate significant ejection fractions. The presented system sets the foundation for novel in vitro studies on ventricular function and remodeling.
Classical Hodgkin Lymphoma Patients Have an Increased Incidence of Idiopathic Acquired Aplastic Anemia
Authors: Taylor Linaburg, Adam R. Davis, Noelle V. Frey, Daniel J. Landsburg, Stephen J. Schuster, Jakub Svoboda, Yimei Li, Yuliya Borovskiy, Timothy S. Olson, Adam Bagg, Elizabeth O. Hexner, Daria V. Babushok
Journal: Blood (2018)
A Retrospective Study to Evaluate the Survival Rates in R-CHOP Chemotherapy Followed by Autologous Stem Cell Transplantation for the Treatment of Diffuse Large B Cell Lymphoma
Authors: Mark H. Lee, Sung-Yong Kim, Inho Kim, Seonyang Park, Yeo-Kyeoung Kim, Yang Soo Kim, Ho Sup Lee, Jeong-A Kim, Jinny Park, Seok Jin Kim, Sung Kyu Park, Byeong-Bae Park, Hyeok Shim, Hyeon Seok Eom, Junglim Lee
Journal: Blood (2012)
Myelodysplasia-Associated Immunophenotypic Abnormalities of Bone Marrow (BM) Cells in Multiple Myeloma (MM): Are They Present At Diagnosis or Can Be Induced by Lenalidomide?
Authors: Sergio Matarraz, Bruno Paiva, Maria Victoria Mateos, María Diez-Campelo, Estefania Perez, María-Belén Vidriales, Lucía López-Corral, Pilar Giraldo, Miguel T. Hernandez, Felipe de Arriba, Javier De La Rubia, Joan Bargay, Fernando Leal da Costa, Graça Esteves, Juan José Lahuerta, Laura Rosiñol, Joan Blade, Jesus F. San Miguel, Alberto Orfao
Journal: Blood (2011)
Clonal Trajectories in Persons with Acute Myeloid Leukemia and Normal Cytogenetics Relapsing after Intensive Chemotherapy and after Allotransplants. Does Pretransplant Conditioning Contribute to Mutation Topography?
Authors: Ya-Lan Zhou, Li-Xin Wu, Robert Peter Gale, Run-Qing Lu, Jin-Lan Li, Hao Jiang, Qian Jiang, Bin Jiang, Zi-Long Wang, Ting-Ting He, Yue Wang, Xiao-Xiao Zhang, Xiaohui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Guorui Ruan
Journal: Blood (2018)
Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity
Authors: Eunyoung Chun, Sydney Lavoie, Diogo Fonseca-Pereira, Sena Bae, Monia Michaud, Hamid R. Hoveyda, Graeme L. Fraser, Carey Ann Gallini Comeau, Jonathan N. Glickman, Miles H. Fuller, Brian T. Layden, Wendy S. Garrett
Journal: Immunity (2019)
Incidence and Predictors of 30-Day Readmissions Following Autologous Hematopoietic Cell Transplantation (auto-HCT) in the US
Authors: Binod Dhakal, Smith Giri, Adam Levin, Rein Lisa, Timothy S. Fenske, Saurabh Chhabra, Nirav N Shah, Aniko Szabo, Anita D'Souza, Marcelo C. Pasquini, Parameswaran Hari, Mehdi Hamadani
Journal: Blood (2018)
Abstract 907: Understanding Cardiomyocyte Mechanosensing Utilizing CRISPR-Cas9 Based Screening Methods
Authors: Feria Ladha, Anthony Pettinato, Ketan Thakar, J. T Hinson
Journal: Circulation Research (2019)

Heart failure (HF) is a leading cause of premature death that affects approximately 6.5 million patients in the United States and costs over $30 billion annually. HF is a complex disease that involves genetic and environmental factors, and is characterized by gradual deterioration of cardiac pump function. A key process implicated in the development of HF is mechanotransduction—the ability of cardiomyocytes to sense and respond to mechanical forces. While mechanotransduction signaling may play an adaptive role in response to changes in mechanical load, this process can become maladaptive, and ultimately lead to pathological hypertrophy and eventual HF. Gaining insight into cardiac mechanotransduction would solidify our understanding of how cardiomyocytes sense mechanical perturbations and will provide novel targets for the prevention and management of cardiomyopathy and HF. To study perturbations in cardiomyocyte mechanosensing, we have developed a B-type natriuretic peptide (BNP) reporter assay in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), which uses bright red fluorescent protein (tdTomato) to parallel endogenous BNP expression. Our reporter has been validated as a robust, scalable, and quantitative molecular marker of sarcomere function (inside-out) and substrate stiffness (outside-in). We have also generated a custom CRISPR guide RNA (gRNA) library targeting 75 extrinsic and intrinsic components of the cardiomyocyte mechanotransduction apparatus, enabling efficient analysis of single gene knockouts in our BNP reporter and providing a novel high-throughput model for interrogating the mechanical regulation of BNP expression. These gene candidates will be further tested in an in vitro HF model to assess functional response and the potential for phenotypic correction.