tbuckley/cabot-search huggingface dataset:
Initial Results of a Phase I Study of TNB-383B, a BCMA x CD3 Bispecific T-Cell Redirecting Antibody, in Relapsed/Refractory Multiple Myeloma
Authors: Cesar Rodriguez, Anita D'Souza, Nina Shah, Peter M. Voorhees, Ben Buelow, Ravi Vij, Shaji K. Kumar
Journal: Blood (2020)
Scientists on the Spot: Phosphodiesterases and heart failure
Authors: Albano C Meli, Rodolphe Fischmeister
Journal: Cardiovascular Research (2020)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Variation in the Treatment of Multiple Myeloma in the Real World
Authors: Joshua Richter, Leena Chhun, Cheng Zheng, Jayne Piboonvaranggoon, Elora Mallick, Jennifer Wren, Grace Nam, Ricardo Lopez Barquilla, Alexandra Dardac, Sibel Blau, Francis M. Senecal, Swathi Namburi, Andrew J. Cowan, William I Bensinger, Shaji K. Kumar, Paul G. Richardson, Kenneth Anderson, C. Anthony Blau
Journal: Blood (2020)
Safety Analysis of Ruxolitinib (RUX) Vs Best Available Therapy (BAT) in Patients (pts) with Steroid-Refractory (SR) Acute Graft-Vs-Host Disease (aGVHD) in the Randomized Phase 3 REACH2 Study
Authors: Nikolas Von Bubnoff, Jason P Butler, Eva Maria Wagner, Edouard Forcade, Jaime Sanz Caballer, Domenico Russo, Giovanni Grillo, Tsila Zuckerman, Sinem Civriz Bozdag, Francis A. Ayuk, Friedrich Stoelzel, Sung-Soo Yoon, Jose Valentín García Gutiérrez, David Ritchie, Claude-Eric Bulabois, Marie Thérèse Rubio, Judith Xu, Juliane Morando, Bruyère Mahuzier, Satish Mahadevaiah Chandraiah, Gérard Socié
Journal: Blood (2020)
Fitusiran Treatment Impacts on Health-Related Quality of Life in Subjects with Hemophilia A and B with Inhibitors Assessed with the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL)
Authors: Sylvia Von Mackensen, Pratima Chowdary, Sarah Mangles, Qifeng Yu, Baisong Mei, Shauna R. Andersson, Pronabesh Dasmahapatra
Journal: Blood (2020)
Universal: An Allogeneic First-in-Human Study of the Anti-Bcma ALLO-715 and the Anti-CD52 ALLO-647 in Relapsed/Refractory Multiple Myeloma
Authors: Sham Mailankody, Jeffrey V. Matous, Michaela Liedtke, Surbhi Sidana, Shahbaz Malik, Rajneesh Nath, Olalekan O. Oluwole, Erin E. Karski, Wade Lovelace, Xiangdong Zhou, Srinand Nandakumar, Arun Balakumaran, Parameswaran Hari
Journal: Blood (2020)
Prospective Randomized Comparative Study of Myeloablative Fludarabine/Busulfan (Flu/Bu4) and Fludarabine/Busulfan/Total Body Irradiation (Flu/Bu4/TBI) Conditioning Regimen for Patients with Myeloid Diseases
Authors: Hyung C. Suh, Scott D. Rowley, Sukhdeep Kaur, Brittany Lukasik, Phyllis McKiernan, Michele Boonstra, Milissa Baker, Mary E Dilorenzo, Alan Skarbnik, Themba Nyirenda, David H. Vesole, Michele L. Donato
Journal: Blood (2020)
ABO blood type: a window into the genetics of acute respiratory distress syndrome susceptibility
Authors: Alicia N. Rizzo, Eric P. Schmidt
Journal: Journal of Clinical Investigation (2020)

The genetic factors that determine a patient's risk for developing the acute respiratory distress syndrome (ARDS) remain understudied. In this issue of the JCI, Reilly and colleagues analyzed data from three cohorts of critically ill patients and observed an association between the ABO allele A1 and the onset of moderate-severe ARDS. This association was most notable in patients with non-pulmonary sepsis (an indirect, vasculature-targeted mechanism of lung injury) and persisted in patients who lacked epithelial expression of the A antigen, suggesting an endothelial mechanism of A1-associated ARDS susceptibility. Critically ill patients with blood type A had increased circulating concentrations of endothelium-derived glycoproteins such as von Willebrand factor and soluble thrombomodulin, and marginal lungs from blood type A donors were less likely to recover function during ex vivo perfusion. These findings implicate A antigen glycosylation of endothelial cells as a critical, genetically determined risk factor for indirect lung injury that may contribute to the mechanistic heterogeneity of ARDS.
Effects of Tamoxifen on the Mutant Allele Burden and Disease Course in Patients with Myeloproliferative Neoplasms - Results of the Tamarin Study
Authors: Claire Harrison, Joanna Baxter, Rebecca H. Boucher, Thomas McKerrell, Aimee Jackson, Rachel S Fletcher, Adam J. Mead, Steve Knapper, Joanne Ewing, Nauman M Butt, Manish Jain, Sebastian Francis, Fiona J Clark, Jason Coppell, Mary Frances McMullin, Frances Wadelin, Srinivasan Narayanan, Dragana Milojkovic, Mark W. Drummond, Mallika Sekhar, Maike Paramor, James Roberts, Rachel Glover, Erica Harris, Luigi Grassi, Alba Rodriguez-Meira, Jason Carroll, José-Ezequiel Martín, Giuditta Corbizi Fattori, Zijian Fang, Anna L Godfrey, Simón Méndez-Ferrer
Journal: Blood (2020)
Daratumumab, Ixazomib, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma
Authors: Shaji K. Kumar, Prashant Kapoor, Betsy Laplant, Liang Phuong-Dung, Eli Muchtar, Francis K. Buadi, Wilson I Gonsalves, Gabriella C Malave, Alanna M. Vossen, David Dingli, Ronald S. Go, Rahma M Warsame, Taxiarchis Kourelis, Yi L. Hwa, Amie Fonder, Miriam A. Hobbs, John A. Lust, Martha Q. Lacy, Angela Dispenzieri, Suzanne R. Hayman, Nelson Leung, S. Vincent Rajkumar, Morie A. Gertz
Journal: Blood (2020)
Effects of primary care C-reactive protein point-of-care testing on antibiotic prescribing by general practice staff: pragmatic randomised controlled trial, England, 2016 and 2017
Authors: Charlotte Victoria Eley, Anita Sharma, Hazel Lee, Andre Charlett, Rebecca Owens, Cliodna Ann Miriam McNulty
Journal: Eurosurveillance (2020)

Background C-reactive protein (CRP) testing can be used as a point-of-care test (POCT) to guide antibiotic use for acute cough. Aim We wanted to determine feasibility and effect of introducing CRP POCT in general practices in an area with high antibiotic prescribing for patients with acute cough and to evaluate patients’ views of the test. Methods We used a McNulty–Zelen cluster pragmatic randomised controlled trial design in general practices in Northern England. Eight intervention practices accepted CRP testing and eight control practices maintained usual practice. Data collection included process evaluation, patient questionnaires, practice audit and antibiotic prescribing data. Results Eight practices with over 47,000 patient population undertook 268 CRP tests over 6 months: 78% of patients had a CRP &lt; 20 mg/L, 20% CRP 20–100 mg/L and 2% CRP &gt; 100 mg/L, where 90%, 22% and 100%, respectively, followed National Institute for Health and Care Excellence (NICE) antibiotic prescribing guidance. Patients reported that CRP testing was comfortable (88%), convenient (84%), useful (92%) and explained well (85%). Patients believed CRP POCT aided clinical diagnosis, provided quick results and reduced unnecessary antibiotic use. Intervention practices had an estimated 21% reduction (95% confidence interval: 0.46–1.35) in the odds of prescribing for cough compared with the controls, a non-significant but clinically relevant reduction. Conclusions In routine general practice, CRP POCT use was variable. Non-significant reductions in antibiotic prescribing may reflect small sample size due to non-use of tests. While CRP POCT may be useful, primary care staff need clearer CRP guidance and action planning according to NICE guidance.
Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels
Authors: Samantha Ferrari, Chiara Pagani, Mariella D'Adda, Nicola Bianchetti, Annamaria Pelizzari, Doriana Gramegna, Chiara Bottelli, Luisa Lorenzi, Gabriella Vona, Alessandra Tucci, Giuseppe Rossi
Journal: Blood (2020)
Prevention of Complications in the Cardiac Intensive Care Unit: A Scientific Statement From the American Heart Association
Authors: Christopher B. Fordyce, Jason N. Katz, Carlos L. Alviar, Cynthia Arslanian-Engoren, Erin A. Bohula, Bram J. Geller, Steven M. Hollenberg, Jacob C. Jentzer, Daniel B. Sims, Jeffrey B. Washam, Sean van Diepen
Journal: Circulation (2020)

Contemporary cardiac intensive care units (CICUs) have an increasing prevalence of noncardiovascular comorbidities and multisystem organ dysfunction. However, little guidance exists to support the development of best-practice principles specific to the CICU. This scientific statement evaluates strategies to avoid the potentially preventable complications encountered within contemporary CICUs, focusing on those that are most applicable to the CICU environment. This scientific statement reviews evidence-based practices derived in non–CICU populations, assesses their relevance to CICU practice, and highlights key knowledge gaps warranting further investigation to attenuate patient risk.
Overcome radiation resistance in hypoxic cancer cells by inhibition of glycolysis
Authors: Rui-Hua Xu, Geetha Achanta, Yan Zhou, Michael J. Keating, Peng Huang
Journal: Cancer Research (2005)

1229  Malignant solid tumors with insufficient blood supply contain a large portion of hypoxic cells that exhibit a high degree of resistance to radiation and chemotherapy partly due to increase of hypoxia inducible factor-1 (HIF-1) and expression of other cellular survival molecules. The residual hypoxic cancer cells surviving radiotherapy/chemotherapy eventually proliferate and lead to cancer relapse. Because cancer cells in hypoxic environment largely depend on glycolysis to generate ATP due to lack of oxygen for the mitochondrial ATP synthesis through oxidative phosphorylation, we tested the hypothesis that inhibition of glycolysis may severely deplete energy supply in hypoxic cancer cells, rendering them unable to repair DNA damage caused by radiation. Using human colon cancer HCT116 cells, we demonstrated that under hypoxic conditions the cancer cells were significantly less sensitive to ionizing radiation (IR) that under normoxic conditions. Inhibition of glycolysis effectively depleted cellular ATP, and preferentially killed cancer cells under hypoxic conditions. Importantly, combination of IR with glycolytic inhibition exhibited synergistic activity against the hypoxic cancer cells, as demonstrated by colony formation assay. Fluorescent microscopic analysis demonstrated that inhibition of glycolysis suppressed the foci formation of the H2AX protein complex, suggesting that ATP depletion disabled the cellular ability to repair IR-induced DNA strand breaks. Furthermore, glycolytic inhibition led to a decrease in protein synthesis and significantly suppressed HIF-1α accumulation under hypoxia, likely further compromising the cell survival pathway. Our findings suggest that inhibition of glycolysis is an effective strategy to effectively kill hypoxic cancer cells, and its combination with radiotherapy is synergistic and may have significant clinical applications in cancer treatment.
Angiotensin Signaling Is Essential for Stress Erythropoiesis but Results in Retention of Dysfunctional Mitochondria in Erythrocytes That Generate Excessive Reactive Oxygen Species
Authors: Parul Rai, Swarnava Roy, Diamantis G. Konstantinidis, Sithara Raju Ponny, Marthe-sandrine Eiymo Mwa Mpollo, Archana Shrestha, Theodosia A. Kalfa, Punam Malik
Journal: Blood (2020)
Tax food according to its carbon footprint, health alliance urges
Authors: Jacqui Wise
Journal: BMJ (2020)

The UK Health Alliance on Climate Change has called for a food carbon tax to be levied on all food producers according to the carbon footprint of their products unless the food industry takes voluntary action to reduce the climate impact of food by 2025.

The alliance, which includes 10 royal colleges, the BMA, The BMJ , and the Lancet , gave recommendations to reduce the UK’s food related greenhouse gas emissions.1 The range of measures includes reducing food waste, improving food labelling, amending public procurement rules around …
Trial-in-Progress: Brentuximab Vedotin in Combination with Lenalidomide and Rituximab in Subjects with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Nancy L. Bartlett, Christopher A. Yasenchak, Robert B. Sims, Grzegorz S. Nowakowski
Journal: Blood (2020)
Advantage of 68Ga-PSMA PET/CT on Postradiotherapy Response Assessment of Juvenile Nasal Angiofibroma
Authors: Pirabu Sakthivel, Alok Thakar, Sreedharan Thankarajan Arunraj, Ashu Seith Bhalla, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2020)

Abstract Prostate-specific membrane antigen (PSMA) is universally expressed in the endothelial cells of tumor-associated neovasculature of juvenile nasopharyngeal angiofibroma. Functional 68 Ga-PSMA PET/CT also enables easier differentiation of the residual tumor from postoperative changes. An 18-year-old man with the residual intracranial disease received radiotherapy after surgery. In PSMA PET/CT imaging, uptake was noted initially only in the residual disease, and the same was absent after successful response to radiotherapy, unlike contrast MRI, which showed persistent enhancement. Functional 68 Ga-PSMA PET/CT may be a very useful tool clinically for identifying early responses to radiotherapy compared with conventional structural imaging.
Gamma knife radiosurgery for uveal melanomas and metastases: a systematic review and meta-analysis
Authors: Tariq Parker, Grant Rigney, Justiss Kallos, S Tonya Stefko, Hideyuki Kano, Ajay Niranjan, Alexander L Green, Tipu Aziz, Pamela Rath, L Dade Lunsford
Journal: The Lancet Oncology (2020)
von Willebrand factor to protein C ratio-related thrombogenicity with systemic inflammation is predictive of graft dysfunction after liver transplantation: Retrospective cohort study
Authors: Hye-Mee Kwon, Kyoung-Sun Kim, Jihoon Park, Junhyeop Jeong, Young-Jin Moon, Jun-Gol Song, Gyu-Sam Hwang, Ki-Hun Kim, In-Gu Jun
Journal: International Journal of Surgery (2020)
Abstract 420: Mrs2 is the Authentic Mammalian Mitochondrial Mg <sup>2+</sup> Channel
Authors: Prema Velusamy, Shanmughapriya Santhanam
Journal: Circulation Research (2020)

Magnesium (Mg 2+ ) is an important cation critical for cellular functions and tissue integrity. Mitochondria have been demonstrated to be capable of both accumulate and release Mg 2+ . However, the exact molecular machinery associated with mitochondrial Mg 2+ (mMg 2+ ) influx has not yet been delineated. In the present study we characterized the mammalian mMg 2+ channel, Mrs2 and comprehensively studied its role in energy metabolism. Protein flux, membrane fractionation and STED microscopy studies revealed Mrs2 to localize on the inner mitochondrial membrane with its N and C-terminus in the matrix. Western blot and qPCR analysis confirmed the ubiquitous distribution of Mrs2 in all metabolically active tissues. We adopted lentiviral based strategy to stably knock down (KD) Mrs2 in vitro . Primarily, the use of FRET-based mMg 2+ sensor, MitoMario showed a decreased influx of Mg 2+ into mitochondria in Mrs2 KD cells. This was further confirmed by patch clamping the mitoplasts of the control and Mrs2 KD cells. Because Mg 2+ is an important co-factor in the machineries that replicate, we next assessed the mitochondrial copy number. The decreased influx of mMg 2+ impacted the mitochondrial copy number and electron transport chain (ETC) complex assembly. The defective ETC assembly was marked by increased generation of mitochondrial reactive oxygen species, increased proton leak, decreased ATP levels, and also prompted a metabolic switch from mitochondrial oxidative phosphorylation to glucose oxidation in Mrs2 KD cells. Additionally, Mrs2 KD cells had an increased sensitivity to mROS-induced mitochondrial permeability transition pore opening. To further study the role of Mrs2 in cardiac mitochondrial metabolism and cellular energetics, we have successfully adopted the CRISPR/Cas9 mediated gene targeting strategy to generate the cardiac-specific Mrs2 knock out mouse model. Our study is the first of its kind to characterize the mitochondrial Mg 2+ channel and its impact on mitochondrial copy number and cell viability. Our findings not only identify Mrs2 as an authentic mitochondrial Mg 2+ channel, but also validates the critical role of mMg 2+ in maintaining the bioenergetic state of the cell.
Maintaining confidentiality of emerging results in COVID-19 vaccine trials is essential
Authors: Philip R Krause, Thomas R Fleming, Susan S Ellenberg, Ana Maria Henao-Restrepo, PR Krause, T Fleming, MM Alejandria, B Bhargava, S Ellenberg, PJ Garcia, E Halloran, AM Henao-Restrepo, I Longini, MC Miranda Montoya, M Roses, H Sommerfelt
Journal: The Lancet (2020)
An Autochthonous Mouse Model of<i>Myd88</i>- and<i>BCL2</i>-Driven Diffuse Large B-cell Lymphoma Reveals Actionable Molecular Vulnerabilities
Authors: Ruth Flümann, Tim Rehkämper, Pascal Nieper, Pauline Pfeiffer, Alessandra Holzem, Sebastian Klein, Sanil Bhatia, Moritz Kochanek, Ilmars Kisis, Benedikt W. Pelzer, Heinz Ahlert, Julia Hauer, Alexandra da Palma Guerreiro, Jeremy A. Ryan, Maurice Reimann, Arina Riabinska, Janica Wiederstein, Marcus Krüger, Martina Deckert, Janine Altmüller, Andreas R. Klatt, Lukas P. Frenzel, Laura Pasqualucci, Wendy Béguelin, Ari M. Melnick, Sandrine Sander, Manuel Montesinos-Rongen, Anna Brunn, Philipp Lohneis, Reinhard Büttner, Hamid Kashkar, Arndt Borkhardt, Anthony Letai, Thorsten Persigehl, Martin Peifer, Clemens A. Schmitt, Hans Christian Reinhardt, Gero Knittel
Journal: Blood Cancer Discovery (2020)

Based on gene expression profiles, diffuse large B cell lymphoma (DLBCL) is sub-divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL. Two of the most common genomic aberrations in ABC-DLBCL are mutations in MYD88, as well as BCL2 copy number gains. Here, we employ immune phenotyping, RNA-Seq and whole exome sequencing to characterize a Myd88 and Bcl2-driven mouse model of ABC-DLBCL. We show that this model resembles features of human ABC-DLBCL. We further demonstrate an actionable dependence of our murine ABC-DLBCL model on BCL2. This BCL2 dependence was also detectable in human ABC-DLBCL cell lines. Moreover, human ABC-DLBCLs displayed increased PD-L1 expression, compared to GCB-DLBCL. In vivo experiments in our ABC-DLBCL model showed that combined venetoclax and RMP1-14 significantly increased the overall survival of lymphoma bearing animals, indicating that this combination may be a viable option for selected human ABC-DLBCL cases harboring MYD88 and BCL2 aberrations.
Estimation of the Impact on Treatment Costs of a Switch to Nonacog Beta Pegol (N9-GP) for the Treatment of Adults with Hemophilia B in Canada Based on Real-World Factor IX (FIX) Consumption and Clinical Outcomes Pre- and Post-Switch
Authors: Vance MacDonald, Xin Ying Lee, Alexandre Caillaud, Maria Luckevich, Anthony Bentley
Journal: Blood (2020)
Treatment Patterns and Outcomes of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Hypomethylating Agents (HMA) in the United States (US)
Authors: Timothy S. Pardee, Jessica Oschwald, Esprit Ma, Tao Xu, Melissa Montez, Giridharan Ramsingh, Wan-Jen Hong, Michelle Choi, Evelyn M. Flahavan
Journal: Blood (2020)
Continued Long Term Responses to Ibrutinib + Venetoclax Treatment for Relapsed/Refractory CLL in the Blood Cancer UK TAP Clarity Trial
Authors: Peter Hillmen, Rebecca H. Boucher, Nichola Webster, Surita Dalal, Kristian Brock, Francesca Yates, Chhaya Sankhalpara, Donald Macdonald, Christopher Fegan, Alison McCaig, Anna Schuh, Andrew Pettitt, John G. Gribben, Piers Patten, Stephen Devereux, Adrian Bloor, Christopher P Fox, Francesco Forconi, Andrew Rawstron, Peter Hillmen
Journal: Blood (2020)
Abstract PO-051: Tumor stem cells arising from a non-stem origin maintain a differentiated phenotype and modulate T cell activity
Authors: Cherie’ R. Scurrah, Bob Chen, Nick Markham, Alan Simmons, Austin Southard-Smith, Mary Macedonia, Eunyoung Choi, Qi Liu, Kay Washington, Bob Coffey, Jeremy Goettel, Ken Lau
Journal: Cancer Research (2020)

Abstract Tumor stem cells (TSCs) contribute to cancer mortality via therapeutic resistance, tumor recurrence, and metastatic mechanisms. However, the origins of the stem capacity to TSCs remains in question, but all TSCs descend from the original tumor cell-of-origin where the first oncogenic event occurred. Tumors arising from different cells-of-origin are histologically identical, but it is unknown whether TSCs that arose from different origins are molecularly and functionally distinct. Using mouse models driving identical Apc mutations from Lrig1-expressing and Mist1-expressing cells, we characterized TSCs of tumors driven from stem and non-stem cells-of-origin using single cell RNA sequencing (scRNA-seq), organoids, and multiplexed imaging. We revealed reduced stem capacity but increased class II antigen presentation ability for non-stem cell (Mist1) driven TSCs compared with stem cell (Lrig1) driven TSCs, which resulted in a favorable immune microenvironment skewed towards active cytotoxic response in Mist1-driven tumors. These results suggest that the cell-of-origin of tumorigenesis provides a specific context by which TSCs are generated, dictating their interactions with the tumor microenvironment. Citation Format: Cherie’ R. Scurrah, Bob Chen, Nick Markham, Alan Simmons, Austin Southard-Smith, Mary Macedonia, Eunyoung Choi, Qi Liu, Kay Washington, Bob Coffey, Jeremy Goettel, Ken Lau. Tumor stem cells arising from a non-stem origin maintain a differentiated phenotype and modulate T cell activity [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-051.
Impact of Different T Cell Depletion Protocols on Immune Reconstitution Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Amandine Pradier, Adrien Petitpas, Anne-Claire Mamez, Federica Giannotti, Sarah Morin, Elif Mahne, Yan Beauverd, Mitja Nabergoj, Carmen De Ramon Ortiz, Maria Anastasiou, Maria Mappoura, Thien-An Tran, Christian Ayer, Anna Petropoulou, Benjamin Bruno, Paraskevi Stakia, Laura Bounaix, Stavroula Masouridi-Levrat, Federico Simonetta, Yves Chalandon
Journal: Blood (2020)