tbuckley/cabot-search huggingface dataset:
Abstract 515: Non-invasive Method of Generating Human Induced-mesenchymal Stem Cells Derived From Urinary Epithelial Cells for Regenerative Therapy
Authors: Narasimman Gurusamy, SHEEJA RAJASINGH, Vijay Selvam, Vinoth Sigamani, Jayavardini Vasanthan, Shivaani Kirankumar, Rajasingh Johnson
Journal: Circulation Research (2020)

Introduction: Mesenchymal stem cells (MSCs) are multipotent adult stem cells having an extensive proliferation capacity in vitro and in vivo. These MSCs can differentiate into various mesoderm-type cells such as osteoblasts, cardiomyocytes, etc. A subpopulation of urinary epithelial cells (UECs) have been identified in urine samples, is considered a promising cell resource for generating autologous induced-pluripotent stem cells (iPSCs). Hypothesis: We hypothesize that the production of high quality, autologous, induced-MSCs (iMSCs) with high replicative potential suitable for the regenerative therapy, using an easy, and the most non-invasive method of isolation, from human UECs. Methods and Results: Human urine was collected and centrifuged to obtain the UECs, which were characterized by the expression of CK19 and ZO1. These UECs were reprogrammed to iPSCs using a cocktail of mRNAs (OCT4, KLF4, SOX2, c-MYC, Nanog and Lin28) along with Lipofectamine for 11 days in culture. These iPSCs were characterized by the expression of the pluripotent markers such as OCT4, SOX2 and SSEA4. The iPSCs were subsequently differentiated into iMSCs using the mesenchymal specific medium for 21 days. iMSCs were harvested at the end of 21 days, and they were characterized by the high levels of mRNA and protein expressions of mesenchymal specific markers such as CD73, CD90 and CD105 (Fig. 1A). FACS analysis showed that more than 93% of the cells were positive for the markers of MSCs (Fig. 1B) . Moreover, the obtained iMSCs have high proliferation capacity compared with the adult stem cells. Conclusions: We have developed an easy, non-invasive method for obtaining autologous, non-immunogenic and highly-proliferating iMSCs suitable for various regenerative therapies including cardiac diseases, from urinary epithelial cells.
Benefits and Safety of Long-Term Use of IMR-687 As Monotherapy or in Combination with a Stable Dose of Hydroxyurea (HU) in 2 Adult Sickle Cell Patients
Authors: Lanetta Bronte-Hall, Biree Andemariam, Blyden Gershwin, Sanne Lugthart, Timothy Mant, Jo Howard, Henry Fok, Perla Eleftheriou, Robert Ward Hagar, James Mason, Rahul Ballal, Joelle Lufkin, Eleanor Lisbon
Journal: Blood (2020)
Safety and Efficacy of Adding Venetoclax to Reduced Intensity Conditioning Chemotherapy Prior to Allogeneic Hematopoietic Cell Transplantation in Patients with High Risk Myeloid Malignancies
Authors: Jacqueline S. Garcia, Haesook Kim, Corey Cutler, Eric S. Winer, Richard M. Stone, Vincent T. Ho, Rizwan Romee, John Koreth, Mahasweta Gooptu, Sarah Nikiforow, Roman M Shapiro, David P. Steensma, Marlise R. Luskin, Martha Wadleigh, Fiona Loschi, Jeremy Ryan, Anthony Letai, R. Coleman Lindsley, Jennifer Brock, Robert J. Soiffer, Daniel J. DeAngelo, Joseph H. Antin
Journal: Blood (2020)
Abstract 333: Cardiomyocyte Death and Fibrotic Scarring in the Infarcted Neonatal Mouse Heart
Authors: Mary Mohr, Ge Tao, Shuang Li, Patrick Roddy
Journal: Circulation Research (2020)

As one the leading causes of death in the United States, myocardial infarction (MI) occurs every 40 seconds, causing severe public health burden. Following MI, the loss of healthy cardiomyocytes leads to decreased contractility and eventually heart failure. Mature mammalian cardiomyocytes have a low turnover rate at only 0.5-2% per year, insufficient for repopulating damaged myocardium after MI. However, a contradictory discovery was made showing that the neonatal mammalian heart is regenerative, although this reparative ability is lost within days after birth. A great amount of effort is needed to understand the mechanisms underlying neonatal cardiomyocyte regeneration. In the current project, we attempt to profile different types of cell death in regenerating and non-regenerating mouse models following MI, in order to gain insights into a favorable type of cardiomyocyte death during regeneration. We induced MI in postnatal day 1 (P1, regenerative), and postnatal day 7 (P7, non-regenerative) mouse hearts by left anterior descending artery occlusion (LAD-O). The progressive scar formation was assessed using Masson’s Trichrome staining at multiple timepoints up to 14 days after MI. At each time point, we profile three major types of regulated cell death, apoptosis, necroptosis, and ferroptosis, using immunofluorescence staining. We also used AC16, a human cardiomyocyte cell line, to investigate the role of cell density in the regulation of ferroptosis. We found that the scar formation was most dynamic between 2 and 3 days after MI and that the course of scar formation varied greatly between P1 and P7 hearts. Immunofluorescence of different cell death markers reveal differentially progressed cell death between P1 and P7 hearts after MI. Our results indicate a different pattern of cardiomyocyte death in the regenerative P1 heart compared to the non-regenerative P7 heart, that could be more favorable for myocardial regeneration.
A Phase I Study of FT538, a First-of-Kind, Off-the-Shelf, Multiplexed Engineered, iPSC-Derived NK Cell Therapy As Monotherapy in Relapsed/Refractory Acute Myelogenous Leukemia and in Combination with Daratumumab or Elotuzumab in Relapsed/Refractory Multiple Myeloma
Authors: Murali Janakiram, Ravi Vij, David S. Siegel, Ted Shih, Sara Weymer, Bahram Valamehr, Yu-Waye Chu, Jeffrey S. Miller
Journal: Blood (2020)
Post-Mortem Diagnostics in COVID-19 AKI, More Often but Timely
Authors: Jan G. Zijlstra, Matijs van Meurs, Jill Moser
Journal: Journal of the American Society of Nephrology (2020)

Coronavirus disease 2019 (COVID-19) is a new and devastating disease with renal involvement that deserves an intense and collaborative research effort. Golmai et al.1 make use of classic autopsy with the modern modification of postmortem, fine-needle kidney biopsy. Autopsy was originally developed to investigate macroscopic, light-microscopic, postmortem, anatomic and histologic changes associated with disease. Standard autopsy is mildly time sensitive, with autolysis developing several hours after death. However, new developments in pathophysiologic diagnostics—protein, RNA, and DNA analyses—require faster sample handling and careful sample storage to prevent postmortem effects. Golmai et al.1 do not describe how long after death biopsies were performed, but state the majority of samples show signs of autolysis. This precludes protein, RNA, and most DNA analyses because we would be observing mostly postmortem effects. Similar to sepsis, COVID-19 microscopic changes in the kidney are limited, with most studies showing some acute tubular necrosis, which cannot fully explain AKI. A large proportion of renal failure in patients with COVID-19 and those with sepsis seems to be attributed to functional defects without major histologic changes. Therefore, modern protein and nucleic-acid techniques might shed some light on the underlying mechanisms driving renal failure. We have shown that kidney biopsies can be performed at the bedside within 1 hour after death, and that gene expression analyses are feasible.2,3 Mortality of patients with COVID-19 was shown to be higher in patients with AKI.4 Yet, the mechanisms driving renal failure in patients with COVID-19 still remain largely unknown. Therefore, we plead for more studies to investigate postmortem renal biopsy specimens taken rapidly after death to enable the use of modern molecular diagnostics, together with classic autopsy, to investigate mechanisms of AKI induced by COVID-19. Disclosures All authors have nothing to disclose. Funding None.
Recurrent Mutations of the <i>C-C Motif Chemokine Ligand 22</i> (<i>CCL22</i>) Define a Distinct Subgroup of Chronic Lymphoproliferative Disorder of NK Cells (CLPD-NK)
Authors: Constance Baer, Shunsuke Kimura, Ilaria Iacobucci, David J Feith, Wencke Walter, Manja Meggendorfer, Thomas L. Olson, Aakrosh Ratan, Martha-Lena Müller, Mitra Rana, Chunxu Qu, Ravi Kalathur, Claudia Haferlach, Wolfgang Kern, Thomas P. Loughran, Charles G Mullighan, Torsten Haferlach
Journal: Blood (2020)
Abstract 401: Head to Heart: Mental Health as a Precursor for Heart Disease in San Joaquin Muslim Population
Authors: Maha Siddiqui
Journal: Circulation Research (2020)

Introduction: Islamophobia affects the mental health of the large San Joaquin (SJ) Muslim population leading to psychological distress and mental health concerns which can further lead to High Blood Pressure (HBP) and cardiovascular disease (CVD). SJ has a growing rate of Muslim immigrants who may be at risk for psychological distress and CVD. Objectives: Trainees conducted Kessler psychological distress tests, HBP and CVD screenings at mosques to reduce the risk of CVD and spread awareness about mental health, CVD and its implications in the Muslim population due to environmental racism in the most underserved county for health care, SJ. Methods: I trained medically ambitious low-income minority female high school students to conduct weekly Kessler psychological distress tests, blood pressure screenings and serve as a health technology coach. Each student monitored 2 hypertensive and psychological distressed patients of 40 hypertensive, psychological distressed, at risk for CVD and low-income Muslim residents. Kessler psychological distress tests and CVD screenings were conducted at all SJ mosques to spread awareness about mental health and heart health and track psychological distress and HBP in the Muslim community. Findings: -About 58% (304 of 527) of SJ Muslim population are at risk for CVD -About 42% (221 of 527) of SJ Muslim population are Stage 1 hypertensive -About 19% (98 of 527) of SJ Muslim population are Stage 2 hypertensive -About 61% (319 of 527) of SJ Muslim population are hypertensive and psycologically distressed Direct Outcomes: -Youth learned the value of empathy, multiculturalism and service to disadvantaged communities through the program and volunteering -Female empowerment and program students are determined to pursue medicine and address community concerns -Improved patient provider trust -Development of self advocacy for health in the Muslim communityIncreased awareness on CVD, HBP, and mental health among the Muslim communityIncreased participation of youth and females in an otherwise adult and male dominant environments (i.e. mosques) -Awareness, education among Muslim community for better heart and mental health -Better understanding in how to manage and seek referral for mental health concerns
Abstract 319: Tnf-α and Il-1β Decrease Myofibroblast Differentiation in 3d-cultured Mitral Valve Interstitial Cells
Authors: Amadeus Zhu, Jane Grande-Allen
Journal: Circulation Research (2020)

Background: Fibrosis contributes to many heart valve diseases such as calcific aortic valve disease, rheumatic heart disease, and secondary mitral regurgitation. Heart valve leaflets are populated by quiescent, fibroblast-like valve interstitial cells (VICs). During fibrosis, VICs differentiate into activated, myofibroblast-like cells that adversely remodel the extracellular matrix. Activated VICs overexpress α-smooth muscle actin (ACTA2/αSMA) and smooth muscle 22-α (TAGLN/SM22α) and display increased contractility. Tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) have been reported to either promote or inhibit fibrosis, depending on tissue type. Understanding how TNF-α and IL-1β affect VIC activation in the mitral valve of the heart could enable development of pharmaceutical treatments for heart valve diseases, which are currently managed surgically. Methods: To avoid artifactual activation on tissue culture plastic, VICs were encapsulated in biomimetic scaffolds consisting of polyethylene glycol (4% w/v) functionalized with protease-degradable (GGGPQGIWGQGK) and integrin-binding (RGDS) peptides. These 3D cultures were treated with 10 ng/ml TNF-α, 10 ng/ml IL-1β, or vehicle for 2 days in low-serum (1%) media. RNA and protein were measured via qRT-PCR, western blotting, and immunostaining. To measure contractility, VICs were encapsulated in collagen I (2.5 mg/ml) gels and allowed to contract freely for 2 days. Results: TNF-α and IL-1β significantly decreased RNA expression of ACTA2 (TNF-α: -91±6%, IL-1β: -99±1% change vs. vehicle) and TAGLN (TNF-α: -77±9%, IL-1β: -93±1% change). TNF-α and IL-1β also significantly decreased αSMA protein expression (TNF-α: -76±11%, IL-1β: -91±5% change) and the percentage of αSMA-positive cells (vehicle: 21±3%, TNF-α: 13±2%, IL-1β: 13±5% positive). Finally, TNF-α and IL-1β attenuated VIC-mediated collagen gel contraction (vehicle: 81±7%, TNF-α: 71±3%, IL-1β: 61±4% contraction). Conclusions: TNF-α and IL-1β decrease VIC activation in a 3D culture model of the mitral valve. These results reveal novel pathway targets for reducing fibrosis during mitral valve disease. Future work will use this model to study the downstream signaling events that drive VIC de-activation.
Lenalidomide Enhance CAR T-Cells Response in Patients with Refractory/Relapsed Large B Cell Lymphoma Experiencing Progression after Infusion
Authors: Catherine Thieblemont, Sylvie Chevret, Vincent Allain, Roberta Di Blasi, Florence Morin, Laetitia Vercellino, Sandrine Roulland, Karin Tarte, Veronique Meignin, Sophie Caillat-Zucman
Journal: Blood (2020)
Covid-19: England’s daily deaths are still “likely to exceed” first wave peak despite projection changes
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: England's daily deaths are still "likely to exceed" first wave peak despite projection changes Elisabeth MahaseThe UK government has admitted to errors in slides showing forecasts of daily covid-19 hospital admissions and deaths that were used to support a second lockdown in England, 1 leading to concerns over transparency and whether the restrictions were justified.
Spatial Genomic Heterogeneity in Multiple Myeloma: Surrogate Markers and Its Significance for Understanding the Evolutionary Processes Leading to Relapse
Authors: Leo Rasche, Tobias Meissner, Grant Gershner, Cody Cody Ashby, Ruslana G. Tytarenko, Owen W. Stephens, Michael Bauer, Sharmilan Thanendrarajan, Carolina D. Schinke, Joshua Epstein, Frits van Rhee, Maurizio Zangari, Bart Barlogie, Brian A Walker, Faith E Davies, Gareth J. Morgan, Niels Weinhold
Journal: Blood (2017)
Impact of Two Different Types of Rabbit ATG on Immune Reconstitution and Overall Results after Allogeneic Hematopoetic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in Children
Authors: Camille Feltesse, Karima Yakouben, Mony Fahd, Marie Ouachee, Lou le Mouel, Jérôme Le Goff, Guislaine Carcelain, Valérie Guérin, André Baruchel, Sylvie Chevret, Jean-Hugues Dalle
Journal: Blood (2020)
Abstract 4738: Plaque Regression in Patients With Diabetes Mellitus After Rosuvastatin Treatment: A Serial Intravascular Ultrasound Analysis From the COSMOS Study
Authors: Tadateru Takayama, Takafumi Hiro, Hiroyuki Daida, Masakazu Yamagishi, Atsushi Hirayama, Satoshi Saito, Tetsu Yamaguchi, Masunori Matsuzaki
Journal: Circulation (2009)

Background and Purpose: It has been documented that patients with DM have a higher cardiac event rate than those without DM even after lipid-lowering therapy. However, its exact mechanism from the ...
Prolonged Lymphopenia and Infection Risk Is Mitigated By Antimicrobial Prophylaxis in Patients with Indolent Non-Hodgkin Lymphoma (iNHL) Treated with Bendamustine +/- Anti-CD20 Antibody: The Australasian Lymphoma Alliance Experience
Authors: Kate Manos, Masa Lasica, Andrew Grigg, Pietro R Di Ciaccio, Jonathan Wong, Usha Chandra Sekaran, Joel Wight, Zhong Goh, Hayden Jina, Llewyn Butler, Costas K. Yannakou, Nada Hamad, Gareth P. Gregory, Shane A Gangatharan, Tara Cochrane, Kristen Piper, Leonid Churilov, Eliza A Hawkes
Journal: Blood (2020)
Evaluating the evidence for a neuroimaging subtype of posttraumatic stress disorder
Authors: Michael Esterman, Anna Stumps, Audreyana Jagger-Rickels, David Rothlein, Joseph DeGutis, Francesca Fortenbaugh, Adrienne Romer, William Milberg, Brian P. Marx, Regina McGlinchey
Journal: Science Translational Medicine (2020)

A recent study used functional neuroimaging and cognitive tasks to identify posttraumatic stress disorder (PTSD) subtypes. Specifically, this study found that a subgroup of patients with verbal memory impairment had a unique neural signature, namely, decreased ventral attention network (VAN) resting-state functional connectivity, and these same individuals responded poorly to psychotherapy. Although this represents one of the first studies to propose a neurocognitive subtype of PTSD and has far-reaching translational potential, the generalizability and specificity of the observed neural network and cognitive domain remain unclear. We attempted to conceptually replicate and extend these findings in a similar cohort of combat-exposed veterans (n = 229) tested using a standardized battery of neuropsychological tests and a priori criteria for cognitive impairments. First, we conducted identical and complementary analyses to determine whether subjects with PTSD and neuropsychologically defined verbal memory deficits exhibited the VAN connectivity biomarker. Second, we examined whether cognitive deficits in other domains implicated in PTSD (executive functioning and attention) exhibited the VAN signature. Across multiple measures of verbal memory, we did not find that the subgroup of individuals with PTSD and memory impairments had lower VAN connectivity. However, a subgroup of individuals with PTSD and attentional impairments did have lower VAN connectivity, suggesting that the original subtype could have been related to attention and not memory impairments. Overall, our findings suggest that the previously identified memory-impaired PTSD subtype may not generalize. Further consideration of neuropsychological methods will be important for neurocognitive markers to be implemented clinically.
A Multi-Center Analysis of the Impact of Dose Level of R-EPOCH on Outcomes of Patients with Double/Triple-Hit B-Cell Lymphoma
Authors: Matthew J Cortese, Wei Wei, Sebastian Cerdena, Marcus Watkins, Marissa Olson, Gray Jodon, Jeff Kaiser, Bradley Haverkos, Mitchell E. Hughes, Natalie S Grover, Anson Snow, Victor M. Orellana-Noia, Magdalena A Rainey, Mohammad Ahsan Sohail, Joslyn Rudoni, Craig A. Portell, Timothy J Voorhees, Daniel J. Landsburg, Manali Kamdar, Brad S. Kahl, Brian T. Hill
Journal: Blood (2020)
Involvement of both intrinsic and extrinsic cell death pathways by 8-amino-adenosine in multiple myeloma
Authors: Jennifer A. Frey, Irene M. Pedersen, John C. Reed, Mary Ayres, Nancy L. Krett, Steven T. Rosen, Varsha Gandhi
Journal: Cancer Research (2005)

3264  Multiple Myeloma (MM) is an indolent B-cell malignancy, which readily becomes resistant to traditional chemotherapeutic agents. The novel adenosine analog, 8-amino-adenosine (8-NH2-Ado), has been evaluated as a potential therapeutic molecule (Mol Cancer Ther 3:1411, 2004). Studies of 8-NH2-Ado in the MM cell line, MM.1S demonstrated cytotoxicity with an IC50 of 300 nM to 3 μM. The analog accumulated as its triphosphate, 8-NH2-ATP, with a simultaneous decrease in the intracellular ATP pool. Additionally, incubation with 8-NH2-Ado predominantly inhibited RNA synthesis, which is a unique characteristic because analogs such as cladribine and fludarabine primarily inhibit DNA synthesis. The DNA-directed nucleoside analogs initiate cell death primarily through the intrinsic pathway of cell death. Because the mechanism of action of 8-NH2-Ado is RNA directed with an effect on cellular bioenergy, it is likely that cell death may be induced through multiple pathways. To test this postulate, caspase activation was quantified by fluorometric assays. Upon treatment of MM.1S cells with 10 μM 8-NH2-Ado for 12 hrs, caspases-8 and -10 were activated 26- and 46-fold, respectively, suggesting that the extrinsic cell death pathway is involved. In addition, caspases that participate in the intrinsic cell death pathway such as caspases-9, -6, and -3 were activated 28-, 22-, and 9-fold under these conditions. In contrast to these caspases, the endoplasmic reticulum stress related caspase-12 was not activated. To determine the temporal relationship between extrinsic and intrinsic cell death pathways and to identify the initiating caspases, activation of caspases-8 and -9 was evaluated at early time points. Both caspases-8 and -9 were activated at 2 hrs indicating involvement of both these routes for 8-NH2-Ado induced cell death. Previous studies have demonstrated that proapoptotic proteins Bax and Bak induce cell death through the mitochondrial (intrinsic cell death) pathway. To investigate if 8-NH2-Ado could induce cell death in cells lacking Bax and Bak, apoptosis of wild-type and Bax/Bak double knock-out (DKO) MEFs was analyzed by Annexin V binding after incubations with 8-NH2-Ado. Following 6 hrs of treatment with 5 μM 8-NH2-Ado, 65% of the wild type MEFs were Annexin positive, whereas only 31% of the DKO cells were positive, but this value increased to 67% by 18 hrs in DKO cells. Hence, while 8-NH2-Ado was able to induce apoptosis in the DKO cells, the effect was delayed by 12 hrs compared to the WT cells suggesting that both the intrinsic and extrinsic pathways are required for efficient 8-NH2-Ado induced cytotoxicity. Ongoing investigations focus on the upstream signaling of these pathways by 8-NH2-Ado in order to understand the mechanism of cell death by this RNA-directed nucleoside analog.
Immunophenotypes and Clinical Outcomes in Adult Patients with Sickle Cell Disease: Lymphopenia Correlates with End Organ Damage
Authors: Stephen Zachary Peeke, Qi Gao, Jaeun Choi, Khadijah Abdallah, Ashley Buscetta, Andrew Crouch, Shuo You, Vence L. Bonham, Caterina P Minniti
Journal: Blood (2020)
Expanded Comorbidity Definitions Improve Application of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) for Children and Young Adults with Non-Malignant Diseases Receiving Allogeneic Hematopoietic Cell Transplantation
Authors: Larisa Broglie, Brian D Friend, Brent Logan, Caitrin Fretham, Gary J. Schiller, Bipin N. Savani, Edward A. Stadtmauer, Saurabh Chhabra, Marcelo C. Pasquini, Monica Thakar, Mohamed Sorror
Journal: Blood (2020)