tbuckley/cabot-search huggingface dataset:
Abstract 248: Prospective Study of Ventricular Function and Survival in Acute Phase of Chagas Disease: An Animal Experimental Model
Authors: Arthur L Vargas, Beatriz P Dias, Henrique T Moreira, Denise M Tanaka, Edgard C Oliveira Filho, Marcus V Simões, Benedito C Maciel, Andre Schmidt, José A Marin-Neto, Minna M Romano
Journal: Circulation Research (2020)

Background: Acute Cardiomyopathy secondary to Chagas disease is often subclinical when related to vector transmission. However, cases related to non-vector transmission as in patients submitted to cardiac transplant may have fatal outcomes. This study aimed to assess survival during the acute phase of Chagas disease and its relation to the ventricular function in an animal experimental model. Methods: Female Syrian hamsters (n=45) were separated in two groups: control group (CG):15 animals injected with saline solution; and infected group (IG): 30 animals inoculated with 3,5x10 4 trypomastigote forms of Trypanosoma cruzi,Y strain . Both groups were monitored daily and submitted to echocardiography with equipment dedicated to small animals (Vevo® 2100) in two different moments: baseline (before infection) and 15 days post infection. Left ventricular ejection fraction (LVEF) and global longitudinal myocardial strain (GLS) of left ventricle were measured. The IG was divided into animals with and without clinical sign (CS+) of disease: weight or fur loss, mucous wounds and lethargy. ANOVA for mixed models was used to compare the ventricular function parameters among groups over time. Survival analysis was studied using Kaplan-Meier curves and logrank test. Results: Total time follow up was 60 days. LVEF in IG was significantly reduced through time (53.80 ± 4.95 to 43.55 ± 12.10%) compared to CG (57.86 ± 7.52 to 59.73 ± 5.87%) (p=0.002). There was also a significant reduction of GLS (-18.97 ± 3.94 to -12.44 ± 4.79%) in the IG compared to CG (-19.58 ± 4.03 to -19.67 ± 4.04%) (p=0.012). Twelve animals from IG died (40.00%,12 out of 30) compared to one from CG (6.66%, 1 out of 15). Eleven out of the 12 dead animals from IG, presented, before, clinical signs (CS+). Survival was significant reduced in the IG compared to CG over time (p=0.02) (Figure 1). Conclusion: Reduced survival during the acute phase of experimental model of Chagas disease is related to the significant reduction of left ventricular function. The mortality rate in the IG is higher in the group which presents CS+.
Real-World Experience with a New Human Fibrinogen Concentrate (Fibryga®) in France for the Treatment of Bleeding Episodes and Surgical Prophylaxis
Authors: François Stephan, Laure Gutermann, Martine Pennetier, Stephanie Bourget, Sarah Djabarouti, Johanna Berdugo, Yann Fardini, Pierre Clerson, Bruce A. Schwartz
Journal: Blood (2020)
Results of a Phase I Trial of Lenalidomide, Rituximab (R2) and Ixazomib for Frontline Treatment of High Risk Follicular and Indolent Non-Hodgkin Lymphoma
Authors: Brian T. Hill, Deepa Jagadeesh, Alex V. Mejia Garcia, Robert M. Dean, Omer N. Koc, Matt Kalaycio, Kirsten M Boughan, Brenda W. Cooper, Allison M. Winter, Wesam B. Ahmed, Brad Pohlman, Christopher D'Andrea, Kelsey Holkovic, Ashley Morrison, Paolo Caimi, Mitchell Smith
Journal: Blood (2020)
Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia
Authors: Yi Xie, Xiaohao Zhang, Pengfei Xu, Nana Zhao, Ying Zhao, Yunzi Li, Ye Hong, Mengna Peng, Kang Yuan, Ting Wan, Rui Sun, Deyan Chen, Lili Xu, Jingjing Chen, Hongquan Guo, Wanying Shan, Juanji Li, Rongrong Li, Yunyun Xiong, Dezhi Liu, Yuhui Wang, George Liu, Ruidong Ye, Xinfeng Liu
Journal: Journal of Clinical Investigation (2020)

Oligodendrocytes express low-density lipoprotein receptor (LDLR) to endocytose cholesterol for the maintenance of adulthood myelination. However, the potential role of LDLR in chronic cerebral ischemia-related demyelination remains unclear. We used bilateral carotid artery stenosis (BCAS) to induce sustained cerebral ischemia in mice. This hypoxic-ischemic injury caused a remarkable decrease in oligodendroglial LDLR, with impaired oligodendroglial differentiation and survival. Oligodendroglial cholesterol levels, however, remained unchanged. Mouse miR-344e-3p and the human homolog miR-410-3p, 2 miRNAs directly targeting Ldlr, were identified in experimental and clinical leukoaraiosis and were thus implicated in the LDLR reduction. Lentiviral delivery of LDLR ameliorated demyelination following chronic cerebral ischemia. By contrast, Ldlr-/- mice displayed inadequate myelination in the corpus callosum. Ldlr-/- oligodendrocyte progenitor cells (OPCs) exhibited reduced ability to differentiate and myelinate axons in vitro. Transplantation with Ldlr-/- OPCs could not rescue the BCAS-induced demyelination. Such LDLR-dependent myelin restoration might involve a physical interaction of the Asn-Pro-Val-Tyr (NPVY) motif with the phosphotyrosine binding domain of Shc, which subsequently activated the MEK/ERK pathway. Together, our findings demonstrate that the aberrant oligodendroglial LDLR in chronic cerebral ischemia impairs myelination through intracellular signal transduction. Preservation of oligodendroglial LDLR may provide a promising approach to treat ischemic demyelination.
The Bone Marrow Microenvironment of Multiple Myeloma Long-Term Survivors at Single Cell Resolution
Authors: Raphael Lutz, Abdelrahman Mahmoud, Mohamed H.S. Awwad, Charles D. Imbusch, Tobias Boch, Brian G.M. Durie, Niels Weinhold, Marc S. Raab, Carsten Müller-Tidow, Simon Haas, Benedikt Brors, Hartmut Goldschmidt, Michael Hundemer
Journal: Blood (2020)
Tonic Signaling Leads to Off-Target Activation of T Cells Engineered with Chimeric Antigen Receptors That Is Not Seen in T Cells Engineered with T Cell Antigen Coupler (TAC) Receptors
Authors: Duane Moogk, Arya Afsahi, Vivian Lau, Anna Dvorkin-Gheva, Jonathan Bramson
Journal: Blood (2020)
Weekly Dosing Schedule of Brentuximab Vedotin in Mycosis Fungoides/Sezary Syndrome and Aggressive T Cell Lymphomas
Authors: Megan Lee, Molly Schiffer, Iris Isufi, Scott F. Huntington, Mina L. Xu, Stuart Seropian, Lohith Gowda, Shalin K. Kothari, Michael Girardi, Francine M. Foss
Journal: Blood (2020)
Myeloma Cell Associated Therapeutic Protein Discovery Using Single Cell RNA-Seq Data
Authors: Lijun Yao, Reyka G Jayasinghe, Tianjiao Wang, Julie O'Neal, Ruiyang Liu, Michael P. Rettig, Chia-Feng Tsai, Steven M. Foltz, Danny Kohnen, Smrithi Mani, Fernanda Martins Rodrigues, Michael C. Wendl, Matthew A. Wyczalkowski, Scott R. Goldsmith, Ying Zhu, Mark A Fiala, Liu Tao, Ravi Vij, Li Ding, John F. DiPersio
Journal: Blood (2020)
Preliminary Results of a Phase 1 Dose Escalation Study of the First-in-Class IgM Based Bispecific Antibody Igm-2323 (anti-CD20 x anti-CD3) in Patients with Advanced B-Cell Malignancies
Authors: Elizabeth Budde, Ajay K. Gopal, Ian W. Flinn, Loretta J. Nastoupil, Michael S. Gordon, Ching-Fai Pang, Bruce Keyt, Steve Carroll, Maya Leabman, Genevive Hernandez, Iris Sison, Daniel Chen, Wayne Godfrey, Philippe Armand
Journal: Blood (2020)
Effect of an Online Weight Management Program Integrated With Population Health Management on Weight Change
Authors: Heather J. Baer, Ronen Rozenblum, Barbara A. De La Cruz, E. John Orav, Matthew Wien, Nyryan V. Nolido, Kristina Metzler, Katherine D. McManus, Florencia Halperin, Louis J. Aronne, Guadalupe Minero, Jason P. Block, David W. Bates
Journal: JAMA (2020)

Online programs may help with weight loss but have not been widely implemented in routine primary care.To compare the effectiveness of a combined intervention, including an online weight management program plus population health management, with the online program only and with usual care.Cluster randomized trial with enrollment from July 19, 2016, through August 10, 2017, at 15 primary care practices in the US. Eligible participants had a scheduled primary care visit and were aged 20 to 70 years, had a body mass index between 27 and less than 40, and had a diagnosis of hypertension or type 2 diabetes. Follow-up ended on May 8, 2019.Participants in the usual care group (n = 326) were mailed general information about weight management. Participants in the online program only group (n = 216) and the combined intervention group (n = 298) were registered for the online program. The participants in the combined intervention group also received weight-related population health management, which included additional support from nonclinical staff who monitored their progress in the online program and conducted periodic outreach.The primary outcome was weight change at 12 months based on measured weights recorded in the electronic health record. Weight change at 18 months was a secondary outcome.Among the 840 participants who enrolled (mean age, 59.3 years [SD, 8.6 years]; 60% female; 76.8% White), 732 (87.1%) had a recorded weight at 12 months and the missing weights for the remaining participants were imputed. There was a significant difference in weight change at 12 months by group with a mean weight change of -1.2 kg (95% CI, -2.1 to -0.3 kg) in the usual care group, -1.9 kg (95% CI, -2.6 to -1.1 kg) in the online program only group, and -3.1 kg (95% CI, -3.7 to -2.5 kg) in the combined intervention group (P < .001). The difference in weight change between the combined intervention group and the usual care group was -1.9 kg (97.5% CI, -2.9 to -0.9 kg; P < .001) and the difference between the combined intervention group and the online program only group was -1.2 kg (95% CI, -2.2 to -0.3 kg; P = .01). At 18 months, the mean weight change was -1.9 kg (95% CI, -2.8 to -1.0 kg) in the usual care group, -1.1 kg (95% CI, -2.0 to -0.3 kg) in the online program only group, and -2.8 kg (95% CI, -3.5 to -2.0 kg) in the combined intervention group (P < .001).Among primary care patients with overweight or obesity and hypertension or type 2 diabetes, combining population health management with an online program resulted in a small but statistically significant greater weight loss at 12 months compared with usual care or the online program only. Further research is needed to understand the generalizability, scalability, and durability of these findings.ClinicalTrials.gov Identifier: NCT02656693.
Integrative genomic analysis of pediatric T-cell lymphoblastic lymphoma reveals candidates of clinical significance
Authors: Tasneem Khanam, Sarah Sandmann, Jochen Seggewiss, Charlotte Ruether, Martin Zimmermann, Allison B. Norvil, Christoph Bartenhagen, Gerrit Randau, Stephanie Mueller, Heidi Herbrueggen, Per Hoffmann, Stefan Herms, Lanying Wei, Marius Woeste, Christian Wuensch, Humaira Gowher, Ilske Oschlies, Wolfram Klapper, Wilhelm Woessmann, Martin Dugas, Birgit Burkhardt
Journal: Blood (2020)
The Role of 18f-FDG-PET/CT in Characterizing Depth of Response in High Risk Smoldering Multiple Myeloma Patients Treated with Carfilzomib, Lenalidomide, and Dexamethasone (KRd)
Authors: Elizabeth Hill, Neha Korde, Candis Morrison, Alexander Dew, Ashley Carpenter, Monica Epstein, Crystal Lu, Peter Choyke, Esther Mena, Liza Lindenberg, Ola Landgren, Dickran Kazandjian
Journal: Blood (2020)
THU0222 Transient bone marrow oedema and/or transient osteoporosis of the hip are associated with generalised diminution in bone mineral density: role of pre-existing bone fragility ?
Authors: T Pham, V Legré, P Champsaur, C Chagnaud, P Lafforgue
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Transient osteoporosis of the hip (TOH) and transient bone marrow oedema of the hip (TBMEH) are uncommon, closely associated and/or similar conditions, whose pathophysiology remains obscure. Several facts suggest that occult microfractures of the femoral head could be the cause of such entities. <h3>Objectives</h3> We conducted a prospective assessment of bone status in skeletal sites other than the affected hips to test the hypothesis of pre-existing underlying generalised bone fragility. <h3>Methods</h3> 13 consecutive patients with typical signs of TBMEH at MRI were enrolled, with careful exclusion of cases presenting with any sign consistent with either osteonecrosis or stress fractures of the femoral head. Five patients also had radiological signs of TOH. All had prospective bone status assessment including search for risk factors of bone fragility or history of fracture, laboratory tests, spine radiographs and lumbar and femoral neck (of the unaffected hip) by DEXA. <h3>Results</h3> There were 8 women (6 pregnant) and 5 men, aged 40 ± 11 years. Four had possible risk factors for osteoporosis, and only 1 had previous insufficiency fracture (rib). Lumbar BMD measurements by DEXA found 1 patient with normal BMD (T-score between 0 and 1SD), 9 patients had a T-score between 1 and 2.5 SD and 2 had T-score less than 2.5 SD. The BMD values were about 15% less than the age/sex matched reference population (mean Z-score 1.4 ± 0.64 SD). BMD values obtained in the unaffected hip in 6 cases confirmed these results. Separate &nbsp;analysis of males/females and pregnant/other patients yielded the same results. <h3>Conclusion</h3> Most patients with TBMEH and/or TOH have a generalised decrease in BMD. These results put together with data from the literature suggest that a pre-existing bone fragility is a predisposing factor to TBMEH and/or TOH.
Real-World Prognostic Biomarker Testing, Treatment Patterns and Dosing Among 1461 Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) from the informCLL Prospective Observational Registry
Authors: Anthony R. Mato, Jacqueline C. Barrientos, Jeff P Sharman, Danielle M. Brander, Meghan Gutierrez, Karen Kadish, Israel Arango-Hisijara, Sandhya Upasani, Jennifer Han, Qing Huang, Reethi Iyengar, Nilanjan Ghosh
Journal: Blood (2020)
Abstract 393: S-nitrosylation of Atg7 by Thioredoxin-1 (trx1) Protects the Heart Against Myocardial Ischemia via Autophagy Regulation
Authors: Narayani Nagarajan, Shinichi Oka, Gihoon NAH, Peiyong Zhai, Wataru Mizushima, Risa Mukai, Xiaoyong Xu, Chun-yang Huang, Changgong Wu, Tong Liu, Hong Li, Junichi Sadoshima
Journal: Circulation Research (2020)

Thioredoxin 1 (Trx1) is an oxidoreductase that reduces proteins with disulfide bonds. Trx1 also functions as a transnitrosylase, but this occurs only when Trx1 is oxidized at Cys32 and Cys35. In cultured cardiomyocytes (CMs), glucose deprivation (GD) induces oxidation of Trx1 and Trx1 is transnitrosylated. Thus, we hypothesized that Trx1 promotes GD-induced autophagy through its function as a transnitrosylase rather than as an oxidoreductase. GD-induced autophagy, evaluated by counting GFP-LC3 puncta, was inhibited in the presence of the transnitrosylation-defective Trx1C73S mutant (GFP-LC3 puncta per cell under GD; control: 38; Trx1 knockdown: 2*; Trx1C73S: 17*; p&lt;0.05 vs. control), suggesting that Cys73 in Trx1 plays an important role in mediating GD-induced autophagy. Mass spectrometric analyses and biochemical assays showed that Atg7, an essential autophagy regulator, is a Trx1 target and that Trx1 binds to Atg7 via Cys454 and Cys458 in Atg7, thereby transnitrosylating Atg7 at Cys294 and Cys402. Trx1C73S knock-in (Trx1C73S-KI) promoted coronary ligation (CL)-induced myocardial infarction (MI) (MI size/area at risk (AAR) (%); Wild type (WT): 21; Trx1C73S-KI: 42*; p&lt;0.05 vs. WT), in association with reduced S-nitrosylation of Atg7. To test the role of S-nitrosylation of Atg7 in mediating autophagy, we transduced an S-nitrosylation defective Atg7 mutant (Atg7CC294/402SS) into adult cardiomyocytes isolated from cardiac-specific Atg7 knockout mice. Compared to intact Atg7, Atg7CC294/402SS was less able to induce autophagy, as evidenced by reduced LC-3II formation (relative LC3-II; intact Atg7: 1.0; Atg7CC294/402SS: 0.81*; p&lt;0.05). Atg7C402S, but not Atg7C294S, knock-in exacerbated CL-induced MI (MI size/AAR (%); WT: 32; Atg7C402-KI: 42*; p&lt;0.05 vs. WT). These results suggest that Trx1 protects the heart against MI by mediating autophagy via S-nitrosylation of Atg7 at Cys402.
Expression of <i>Vav1-Myo1F</i> Fusion Affects T-Cell Differentiation and Induces T-Cell Lymphoma
Authors: Jose Rodriguez Cortes, Robert Albero Gallego, Ioan Filip, Juan Angel Patino, Anisha Cooke, Wen-Hsuan Lin, Anouchka P Laurent, Bobby B Shih, Aidan Quinn, Raul Rabadan, Adolfo A. Ferrando, Teresa Palomero
Journal: Blood (2020)
In Vitro Validation of Micro-RNAs (miRNAs) Associated to Treatment Failure in Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Adriana Sas, Leyre Bento, Josep Muncunill, Jordi Martínez-Serra, Teresa Ros, Víctor Asensio, Oliver Vögler, Antonio Salar, Antonia Sampol, Regina Alemany, Antonio Gutierrez
Journal: Blood (2020)
Homologous Recombination DNA Repair Gene Aberrations—Are We More Alike Than Different?
Authors: Mili Arora, Frederick J. Meyers
Journal: JAMA Network Open (2020)

Sabine Schmid, MD; Aurelius Omlin, MD; Celestia Higano, MD; Christopher Sweeney, MD; Nieves Martinez Chanza, MD; Niven Mehra, MD; Malou C. P. Kuppen, MD; Himisha Beltran, MD; Vincenza Conteduca, MD; Daniel Vargas Pivato de Almeida, MD; Fernando Cotait Maluf, MD; William K. Oh, MD; Che-Kai Tsao, MD; Oliver Sartor, MD; Elisa Ledet, MD; Giuseppe Di Lorenzo, MD; Steven M. Yip, MD; Kim N. Chi, MD; Diletta Bianchini, MD; Ugo De Giorgi, MD; Aaron R. Hansen, MD; Tomasz M. Beer, MD; Pernelle Lavaud, MD; Rafael Morales-Barrera, MD; Marcello Tucci, MD; Elena Castro, MD; Kostas Karalis, MD; Andries M. Bergman, MD; Mo Linh Le, MD; Ursina Zürrer-Härdi, MD; Carmel Pezaro, MD; Hiroyoshi Suzuki, MD; Andrea Zivi, MD; Dirk Klingbiel, PhD; Sämi Schär, PhD; Silke Gillessen, MD
MHC Class II on Ccl19+ Reticular Cells Mitigates Graft-Versus-Host Disease Via Maintenance of Regulatory T Cells
Authors: Muhammad Haroon Shaikh, Juan Gamboa Vargas, Josefina Peña Mosca, Duc Dung Le, Hermann Einsele, Burkhard Ludewig, Andreas Beilhack
Journal: Blood (2020)
Outcome of Children with Different Non-Malignant Disorders Given Alphabeta T and B-Cell Depleted HLA-Haploidentical Hematopoietic Stem Cell Transplantation (TBdepl-haploHSCT)
Authors: Pietro Merli, Daria Pagliara, Federica Galaverna, Giuseppina Li Pira, Valentina Bertaina, Stefania Gaspari, Emilia Boccieri, Marco Becilli, Giovanna Del Principe, Olivia Marini, Francesca Del Bufalo, Francesco Quagliarella, Antonio Giacomo Grasso, Tiziana Corsetti, Matteo Di Nardo, Luisa Strocchio, Mattia Algeri, Franco Locatelli
Journal: Blood (2020)
Abstract 507: Activation of the Classically Pro-Apoptotic Death Receptor 5 Promotes Physiological Hypertrophy and Cardiomyocyte Survival
Authors: Toby Thomas, Miles Tanner, Laurel Grisanti
Journal: Circulation Research (2020)

Heart failure is hallmarked by a combination of cardiomyocyte hypertrophy and death. Apoptosis, one of the primary mechanisms of cell death, occurs through finely tuned extrinsic or intrinsic pathways. Of the mediators involved in extrinsic apoptotic signaling, some have been extensively studied, such as tumor necrosis factor ((TNF)-α), while others have been relatively untouched. One such receptor is Death Receptor 5 (DR5) which, along with its ligand TNF-Related Apoptosis Inducing Ligand (TRAIL), have recently been implicated as a biomarker in determining the progression and outcome in patients following multiple heart failure etiologies, suggesting a novel role of DR5 signaling in the heart. These studies suggest a potentially protective role for DR5 in the heart; however, the function of TRAIL/DR5 in the heart has been virtually unstudied. Our goal was to explore the role of TRAIL/DR5 in cardiomyocyte hypertrophy and survival with the hypothesis that DR5 promotes cardiomyocyte survival and growth through non-canonical mechanisms. Mice treated with the DR5 agonist bioymifi or a DR5 agonist antibody, MD5-1, were absent of cell death, while an increase in hypertrophy was observed without a decline in cardiac function. In isolated cardiomyocytes, this pro-hypertrophic phenotype was determined to operate through MMP-dependent cleavage of HB-EGFR, leading to transactivation of EGFR and ERK1/2 signaling. To determine the role of DR5 in heart failure, a chronic catecholamine administration model was used and DR5 activation was found to decrease cardiomyocyte death and cardiac fibrosis. ERK1/2, a well characterized pro-survival, pro-hypertrophic kinase is activated in the heart with DR5 agonist administration and may represent the mechanistic link through which DR5 is imparting cardioprotection. In summary, DR5 activation promotes cardiomyocyte hypertrophy and survival and prevents cardiac fibrosis via a non-canonical MMP-EGFR-ERK1/2 pathway. Taken together, these studies identify a previously undetermined role for DR5 in the heart and identify novel therapeutic target for the treatment of heart failure.
Integrated Expression of Circulating miR375 and miR371 to Identify Teratoma and Active Germ Cell Malignancy Components in Malignant Germ Cell Tumors
Authors: Lucia Nappi, Marisa Thi, Nabil Adra, Robert J. Hamilton, Ricardo Leao, Jean-Michel Lavoie, Maryam Soleimani, Bernhard J. Eigl, Kim Chi, Martin Gleave, Alan So, Peter C. Black, Robert Bell, Siamak Daneshmand, Clint Cary, Timothy Masterson, Lawrence Einhorn, Craig Nichols, Christian Kollmannsberger
Journal: European Urology (2020)
Statin treatment renal MCP-1 expression and renal fibrosis in two distinct models of progressive renal disease
Authors: Eduardo Mantovani, Leonardo T Rodrigues, Humberto Delle, Luciana Carvalho, Clarice Kazue Fujihara, Denise M. A. C Malheiros, Irene de Lourdes Noronha, Roberto Zatz, Jose M Vieira Junior
Journal: Journal of the American Society of Nephrology (2003)
Quality-Adjusted Time without Symptoms of Disease and Toxicity (Q-TWiST) Analysis of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed High-Risk/Secondary Acute Myeloid Leukemia (AML)
Authors: Jorge E. Cortes, Tara Lin, Geoffrey L Uy, Robert J. Ryan, Stefan Faderl, Jeffrey E. Lancet
Journal: Blood (2020)