tbuckley/cabot-search huggingface dataset:
"Building a More Inclusive Blood System in Canada": A Mixed-Methods Evaluation of a Workshop to Guide Medical Students to Develop as Health Advocates Through Advancing Health Equity in Blood Product Donation for Gay, Bisexual, and Queer Men
Authors: Aaron Rosenfeld, Owen Baribeau, Kasey Berscheid, Sze Wah Samuel Chan, Kaveh Farrokhi, David Herman, Anna Lee, Romy Segall, Navjit Singh, Hayley Wroot, Warren Fingrut
Journal: Blood (2021)
Cardiac Amyloid Reaching for Extended Survival (CARES): Study Design of Two Placebo-Controlled, Double-Blind, Randomized, International Phase 3 Trials Assessing Cael-101 in Patients with Mayo Stage Iiia or Stage IIIb AL Amyloidosis
Authors: Ashutosh D. Wechalekar, John Silowsky, Eileen Daniel, Mark Harnett, Michael Spector, Susan B. Sobolov, Candida Cristina Quarta, Michael R. Kurman, Mark Tulchinskiy, Amit Bhattacharyya, Michaela Liedtke
Journal: Blood (2021)
Ethnic Disparities in Waldenström's Macroglobulinaemia in the United Kingdom - Analysis from the Wmuk Rory Morrison Registry
Authors: Aisha S Patel, Jahanzaib Khwaja, Helen McCarthy, Guy Pratt, Jaimal Kothari, Jindriska Lindsay, Roger G Owen, Josephine Crowe, Dima El-Sharkawi, Nilima Parry-Jones, Kirsty Cuthill, Maria Atta, Kim Linton, Agapi Parcharidou, Charalampia Kyriakou, Deborah Turner, Jeffery Smith, Simona Gatto, Nicola Crosbie, Suzanne O Arulogun, Shirley D'Sa
Journal: Blood (2021)
Etavopivat, an Allosteric Activator of Pyruvate Kinase-R, Improves Sickle RBC Functional Health and Survival and Reduces Systemic Markers of Inflammation and Hypercoagulability in Patients with Sickle Cell Disease: An Analysis of Exploratory Studies in a Phase 1 Study
Authors: Theodosia A. Kalfa, Marilyn J. Telen, Santosh L. Saraf, R. Clark Clark Brown, Katie Giger Seu, Sandra K. Larkin, Maria D. Ribadeneira, Patricia Schroeder, Eric Wu, Patrick Kelly, Frans A. Kuypers
Journal: Blood (2021)
Evaluating the Role of Baseline Geriatric Assessment in Predicting Quality of Life in Older Adults with Non-Hodgkin Lymphoma on Oral Targeted Therapies
Authors: Othman Salim Akhtar, Chong Wang, Kristopher Attwood, Desi Carozza, Elizabeth R. Gage-Bouchard, Tunazzina Kaijar, Paola Ghione, Francisco J. Hernandez-Ilizaliturri, Tanya M. Wildes, Pallawi Torka
Journal: Blood (2021)
Reversing A <i>β</i> Fibrillation and Inhibiting A <i>β</i> Primary Neuronal Cell Toxicity Using Amphiphilic Polyphenylene Dendrons
Authors: Siyuan Xiang, Jessica Wagner, Thorsten Lückerath, Klaus Müllen, David Y. W. Ng, Jana Hedrich, Tanja Weil
Journal: Advanced Healthcare Materials (2021)

Uncontrolled amyloid-beta (Aβ) fibrillation leads to the deposition of neurotoxic amyloid plaques and is associated with Alzheimer's disease. Inhibiting Aβ monomer fibrillation and dissociation of the formed fibers is regarded as a promising therapeutic strategy. Here, amphiphilic polyphenylene dendrons (APDs) are demonstrated to interrupt Aβ assembly and reduce Aβ-cell interactions. Containing alternating negatively charged sulfonic acid and hydrophobic n-propyl peripheral groups, APDs bind to the secondary structure of the Aβ aggregates, inhibiting fibrillation and disassemble the already formed Aβ fibrils. APDs reveal vesicular cellular uptake in endosomes as well as cell compatibility for endothelial and neuronal cells, and significantly reduce Aβ-induced neuron cytotoxicity in vitro. Moreover, they are transported into the brain and successfully cross the blood-brain barrier after systemic application in mice, indicating their high potential to inhibit Aβ fibrillation in vivo, which can be beneficial for developing therapeutic strategy for Alzheimer's disease.
Health impacts of the new WHO air quality guidelines in European cities
Authors: Sasha Khomenko, Marta Cirach, Evelise Pereira-Barboza, Natalie Mueller, Jose Barrera-Gómez, David Rojas-Rueda, Kees de Hoogh, Gerard Hoek, Mark Nieuwenhuijsen
Journal: The Lancet Planetary Health (2021)
A Retrospective Head-to-Head Comparison between Pacritinib and Ruxolitinib in Patients with Myelofibrosis and Moderate to Severe Thrombocytopenia
Authors: John Mascarenhas, Prithviraj Bose, Jean-Jacques Kiladjian, Ruben A. Mesa, Aaron T. Gerds, Vikas Gupta, Claire N. Harrison, Abdulraheem Yacoub, Valentín Garcia Gutierrez, Alessandro M. Vannucchi, Christof Scheid, Patricia Velez Tenza, Sarah A Buckley, Karisse Roman-Torres, Stephen T. Oh, Marta Sobas, David Lavie, Srdan Verstovsek
Journal: Blood (2021)
Early Transfusion with Mesenchymal Stem Cell Derived Extracellular Vesicles: A New Transfusion Strategy for Life-Threatening Hemorrhage and Traumatic Brain Injury
Authors: Simone E Dekker, Ted Bambakidis, Aaron M Williams, Ben Biesterveld, Umar Bhatti, Yongqing Li, Zachary Pickell, Benjamin Buller, Hasan B Alam
Journal: Blood (2021)
Coughs and sneezes spread diseases: but do ‘aerosol generating’ procedures?
Authors: David T Arnold, Fergus W Hamilton, Ed Moran
Journal: Thorax (2021)

The COVID-19 pandemic has led to the widespread use of continuous positive airway pressure (CPAP) and high flow nasal oxygen systems (HFNO) for respiratory support, with the former recently shown to reduce the requirement for intubation and mechanical ventilation, easing pressure on intensive care and improving outcomes.1

One major concern remains the theoretical risk for aerosolisation of SARS-CoV-2, with both CPAP and HFNO currently considered ‘aerosol generating procedures’ (AGPs). This classification, endorsed by Public Health England, the WHO and US CDC, dichotomises medical procedures into those that potentially generate infectious aerosol (smaller particles, generally <5 µm with the potential to remain suspended for extended periods) and those that do not.2 Enhanced infection control precautions (eg, airborne mask protection, increased ventilation, cohorting) are thus advised when patients undergo AGPs but are not mandated outside these settings.

The evidence supporting this concept of AGPs is largely based on epidemiological observation, particularly from the SARS pandemic, with limited physical data supporting the role of aerosol generation in most AGPs.3 Studies conducted over the course of the pandemic are undermining the AGP paradigm, with convincing evidence that …
Celecoxib (Celebrex®) induces apoptosis in MCF-7, BT-20, (breast carcinomas) A-375 (melanoma) and HT-29 (colorectal carcinoma) but does not activate Caspases 3, 8, or 9 in cells grown in monolayer
Authors: David H. Kinder, Ryan Schneider, Amy Aulthouse
Journal: Cancer Research (2005)

2687  Celecoxib (Celebrex®, Pfizer) is a COX-2 selective anti-inflammatory agent used to treat arthritis and other inflammatory processes. It has recently been shown that Celecoxib will decrease the numbers of polyps in patients with Familial Adenomatous Polyposis (FAP) for which it now has FDA approval. Evidence is mounting that Celecoxib will decrease the incidence of breast cancer, and may have usefulness in the treatment of several different tumor types as a chemotherapeutic agent. Several studies have been conducted examining activation of caspase 3 in response to Celecoxib, with no clear results. Thus, we undertook the study of Celecoxib and its affects on 4 tumor cell lines in monolayer, as well as in an agarose suspension method we recently developed. We found that Celecoxib inhibits growth of the BT-20 and MCF-7 breast tumor cell lines as well as A375 melanoma and HT-29 colon carcinoma in monolayer. IC50 values of 60, 55, 45 and 50 μM, respectively, were obtained. We examined caspase expression, and found that Caspases 3, 8, and 9 were not activated in response to treatment at any time point. Staining with Hoechst Stain showed nuclear coalescence, but no DNA fragmentation was found to occur. In the agarose culture methods, where cells grow unattached to plastic, we did not observe cell death but did observe inhibition of mitosis as the treated cells did not form colonies when compared to control. Single cells were seen to be viable as indicated by lack of Trypan blue staining. This suggests that cell death caused by Celecoxib in monolayer does not involve the caspase pathways despite apoptotic appearance, but involves a different pathway altogether and may be unique to the monolayer growth.
223 Potent inhibition of PI3Kδ promotes enhanced T cell stemness and mitochondrial fitness
Authors: Guillermo Rangel RIvera, Connor Dwyer, Hannah Knochelmann, Aubrey Smith, Anna Cole, Megan Wyatt, Brandon Ware, Chrystal Paulos
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Durable responses have been observed with adoptive T cell therapy (ACT) in chemotherapy and immunotherapy refractory patients. However, current T cell products do not always lead to therapeutic responses. Therapy failure has been attributed to terminally-differentiated T cell profiles, diminished host engraftment and poor mitochondrial metabolism. T cell activation and a switch towards glycolysis is regulated by signals downstream of the PI3K signaling pathway. We hypothesized that by inhibiting the T cell specific PI3Kδ subunit, that we would prevent overt T cell differentiation, enhance mitochondrial metabolism and improve anti-tumor immunity of adoptively transferred T cells. Methods To test this, we primed melanoma-specific CD8+ pmel-1 T cells in the presence of increasing concentrations of CAL-101, a PI3Kδ specific inhibitor, and infused them into B16F10 tumor-bearing mice, following non-myeloablative total body irradiation. In vitro we tested how PI3Kδ inhibition altered T cell stemness features by flow cytometry and RNA sequencing. Further, we tested the ability of PI3Kδ inhibited T cells to survive against antigen rechallenge, and assessed how mitochondrial phenotypes changed using dyes indicating mass, membrane potential and reactive oxygen species. Moreover, we tested how real time mitochondrial respiration was changed with PI3Kδ inhibition via seahorse. Results Potent inhibition of PI3Kδ in vitro enhanced tumor immunity and survival in a dose dependent manner. High doses of CAL-101 enriched T cells with phenotypic and transcriptional signatures of stemness. We found that CAL-101 decreased glucose uptake and increased mitochondrial mass and membrane potential while reducing mitochondrial reactive oxygen species. Potent inhibition of PI3Kδ enhanced mitochondrial respiration, however gene expression of fatty acid oxidation was not enriched, suggesting an alternative pathway involved in the enhanced spare respiratory capacity of CAL-101 treated T cells. Conclusions These findings indicate that blocking PI3Kδ is sufficient to mediate lasting tumor immunity of adoptively transferred T cells by preserving stemness features and improving mitochondrial fitness. Our data suggest that addition of CAL-101 to ACT expansion protocols could greatly improve responses to solid tumors by rewiring T cell stemness and promoting mitochondrial fitness. Acknowledgements We would like to thank all the researchers and clinicians leading the way in translating immunological principles into effective therapies, as well as the patients whose support is integral for the furthering of medicine. Ethics Approval All animal procedures performed at the Medical University of South Carolina or Emory University were approved by each university’s Institutional Animal Care &amp; Use Committee, protocol number 0488 or 201900225, respectively
Bispecific LV20.19 CAR T-Cells Expanded in IL-7 and IL-15 Have Greater Polyfunctionality and Polyfunctional Strength Than CAR T-Cells Expanded in IL-2
Authors: Joanna C. Zurko, Huiqing Xu, Katherine Chaney, Timothy S. Fenske, Mehdi Hamadani, Dina Schneider, Parameswaran Hari, Bryon Johnson, Nirav N. Shah
Journal: Blood (2021)
Establishment of Patient-Derived Organoid Culture Platform of Mantle Cell Lymphoma
Authors: Lei Nie, Yang Liu, Yuxuan Che, Yijing Li, Wei Wang, Jingling Jin, Qingsong Cai, Jovanny Vargas, Joseph McIntosh, Alexa A Jordan, Vivian Changying Jiang, Yixin Yao, Michael Wang
Journal: Blood (2021)
Abstract 9524: The Challenge of Treating a Previously Surgical Revascularized Patient With Acute ST-Elevation Myocardial Infarction (STEMI) and Coronary-Subclavian Steal Syndrome
Authors: Henrique Trombini Pinesi, Pedro H Marins, Hadrien F Balzan, Fabio Cetinic Habrum, Bruna R Matuck, Marina A de Medeiros, Fabio G Pitta, Eduardo G Lima, Cibele L Garzillo, Carlos V Serrano
Journal: Circulation (2021)

Introduction: Coronary-subclavian steal syndrome (CSSS) is a rare cause of myocardial ischemia after coronary artery bypass grafting (CABG), due to significant stenosis of the proximal portion of the left subclavian artery. It is characterized by blood flow inversion in the left internal thoracic artery, diverting the blood flow from the coronary artery to the left medio-distal subclavian artery. We report a case of a patient who underwent complex surgery to correct the CSSS. Case report: A 70-year-old male patient, with history of both percutaneous coronary intervention (PCI) of the right coronary artery and CABG, was admitted to the emergency room with STEMI and complete atrioventricular block. He was initially managed to the cath lab where a transvenous pacemaker was implanted and coronary angiography showed occlusion of the left main, proximal right coronary and left subclavian arteries. Only saphenous vein - second marginal graft was patent and, despite severe stenosis in the proximal portion of the circumflex artery, this artery was responsible for irrigation of the entire left coronary system, as well as retrograde filling of the left internal thoracic artery - anterior descending artery graft. A conservative approach was proposed. For a better anatomically interpretation, coronary angiotomography was indicated and showed obstruction of the left subclavian artery after its origin, with 2.2cm length and refilling before the origin of the ipsilateral vertebral and internal mammary arteries. In addition, most visceral branches demonstrated severe atherosclerosis, and the right common iliac artery and left external iliac artery were occluded. After discussion with the Heart Team, it was decided to perform a left carotid-subclavian graft with a segment of the saphenous vein. The procedure was successful, with no complications and lasted 5 hours. The patient was discharged from hospital one week later. Discussion: CSSS is rare and difficult to treat. The most common treatment is angioplasty of the subclavian artery, which was not possible in this case due to the lack of femoral access and the extension of the occlusion. In this patient, with a high risk of death, the bypass surgical revascularization with saphenous graft became the only feasible treatment.
CD33 BiTE ® Construct Mediated Immunological Synapse Formation and Downstream Signaling in T Cells Is Dependent on Expression of Costimulatory Molecules on Target Cells
Authors: Anetta Marcinek, Bettina Brauchle, Gerulf Hänel, Sonja M Lacher, Nora Zieger, Roman Kischel, Michael von Bergwelt, Karsten Spiekermann, Sebastian Theurich, John R James, Veit L Buecklein, Marion Subklewe
Journal: Blood (2021)
Recommendations for future extensions to the HGNC gene fusion nomenclature
Authors: Alex H. Wagner, Yassmine Akkari, Marilyn Li, Angshumoy Roy, Karen Tsuchiya, Gordana Raca
Journal: Leukemia (2021)

CONCLUSIONWe appreciate the challenges of developing consensus recommendations, particularly in domains as complex and diverse as gene fusions and structural variation.The recommendations put forth by the HGNC are an advancement that, most importantly, is driving the community towards consistency in the representation of gene fusions.We look forward to future expansions of these recommendations which address the ongoing challenges in disambiguating this complex class of variation.
Single-Unit Transfusion Is Non Inferior to Double Unit Transfusion in Patients with Hematological Disorders Receiving Allogeneic or Autologous Bone Marrow Transplant or Induction Chemotherapy for Acute Leukemia: The 1versus2 Prospective Multicentric Randomized Clinical Trial
Authors: Sylvain Chantepie, Jean-Baptiste Mear, Anais R Briant, Jean-Pierre Vilque, Anne-Claire Gac, Stephane Cheze, Stephane Girault, Pascal Turlure, Jean-Pierre Marolleau, Delphine Lebon, Amandine Charbonnier, Fabrice Jardin, Pascal Lenain, Laure Peyro Saint Paul, Véronique Abonnet, Jean-Jacques Dutheil, Yannick Chene, Agnès Bazin, Oumedaly Reman, Jean-Jacques Parienti
Journal: Blood (2021)
Magnetic resonance-based eye tracking using deep neural networks
Authors: Markus Frey, Matthias Nau, Christian F. Doeller
Journal: Nature Neuroscience (2021)

Abstract Viewing behavior provides a window into many central aspects of human cognition and health, and it is an important variable of interest or confound in many functional magnetic resonance imaging (fMRI) studies. To make eye tracking freely and widely available for MRI research, we developed DeepMReye, a convolutional neural network (CNN) that decodes gaze position from the magnetic resonance signal of the eyeballs. It performs cameraless eye tracking at subimaging temporal resolution in held-out participants with little training data and across a broad range of scanning protocols. Critically, it works even in existing datasets and when the eyes are closed. Decoded eye movements explain network-wide brain activity also in regions not associated with oculomotor function. This work emphasizes the importance of eye tracking for the interpretation of fMRI results and provides an open source software solution that is widely applicable in research and clinical settings.
Trial in Progress: The Randomized, Double-Blind, Placebo-Controlled Phase Ib CROSSWALK-a Trial Evaluating the Safety of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOEs) in Patients with Sickle Cell Disease (SCD)
Authors: Pablo Bartolucci, Kenneth I. Ataga, Michael U. Callaghan, Lucia De Franceschi, Caterina Minniti, Ari Alexandrou, Diane-Charlotte Imbs, Richard Fox, Himika Patel, Alexandre Sostelly, Jonathan Schimmel
Journal: Blood (2021)
Two-Year Evaluation of the German Clinical Amyloidosis Registry
Authors: Ute Hegenbart, Niklas Fuhr, Laura Huber, Christoph Kimmich, Kaya Veelken, Tobias Dittrich, Rita Ziehl, Fabian aus dem Siepen, Alexander Carpinteiro, Timon Hansen, Carsten Müller-Tidow, Axel Benner, Stefan Schönland
Journal: Blood (2021)
Outcomes of Patients with Diffuse Large B Cell and High-Grade B Cell Lymphomas with Synchronous CNS and Systemic Involvement at Diagnosis Treated with High-Dose Methotrexate and R-CHOP: A Single-Center Retrospective Study
Authors: Megan Fleming, Ying Huang, Emily Dotson, David A. Bond, John C. Reneau, Narendranath Epperla, Jonathan E. Brammer, Beth Christian, Lapo Alinari, Robert Baiocchi, Kami J. Maddocks, Yazeed Sawalha
Journal: Blood (2021)
Long-Term Follow-up of the Italian Flexible Sigmoidoscopy Screening Trial
Authors: Carlo Senore, Emilia Riggi, Paola Armaroli, Luigina Bonelli, Stefania Sciallero, Marco Zappa, Arrigo Arrigoni, Claudia Casella, Cristiano Crosta, Fabio Falcini, Franco Ferrero, Mario Fracchia, Orietta Giuliani, Mauro Risio, Antonio G. Russo, Carmen Beatriz Visioli, Stefano Rosso, Nereo Segnan, A. Carnevali, A. Agnolucci, P. Ceccatelli, F. Mirri, A. Penna, G. Genta, A. Marutti, A. Guelfi, B. Gatteschi, G. Fiori, G. Fabbretti, S. Gasperoni, A. Bertone, M. Pennazio, M. Spandre, Marco Silvani, M. Demaria
Journal: Annals of Internal Medicine (2021)

Recent reports showed that the protective effect of flexible sigmoidoscopy (FS) screening was maintained up to17 years, although differences were reported by sex.To assess long-term reduction of colorectal cancer (CRC) incidence and mortality after a single FS screening.Parallel randomized controlled trial. (ISRCTN registry number: 27814061).6 centers in Italy.Persons aged 55 to 64 years expressing interest in having FS screening if invited, recruited from 1995 to 1999 and followed until 2012 (incidence) and 2014 to 2016 (mortality).Eligible persons were randomly assigned (1:1 ratio) to either the once-only FS screening group or control (usual care) group.Incidence and mortality rate ratios (RRs) and rate differences.A total of 34 272 persons (17 136 in each group) were included in the analysis; 9911 participants had screening in the intervention group. Median follow-up was 15.4 years for incidence and 18.8 years for mortality. Incidence of CRC was reduced by 19% (RR, 0.81 [95% CI, 0.71 to 0.93]) in the intention-to-treat (ITT) analysis, comparing the intervention with the control group, and by 33% (RR, 0.67 [CI, 0.56 to 0.81]) in the per protocol (PP) analysis, comparing participants screened in the intervention group with the control persons. Colorectal cancer mortality was reduced by 22% (RR, 0.78 [CI, 0.61 to 0.98]) in the ITT analysis and by 39% (RR, 0.61 [CI, 0.44 to 0.84]) in the PP analysis. Incidence of CRC was statistically significantly reduced among both men and women. Colorectal cancer mortality was statistically significantly reduced among men (ITT RR, 0.73 [CI, 0.54 to 0.97]) but not among women (ITT RR, 0.90 [CI, 0.59 to 1.37]).Self-selection of volunteers from the general population sample targeted for recruitment may limit generalizability.The strong protective effect of a single FS screening for CRC incidence and mortality was maintained up to 15 and 19 years, respectively.Italian Association for Cancer Research, Italian National Research Council, Istituto Oncologico Romagnolo, Fondo "E. Tempia," University of Milan, and Local Health Unit ASL-Torino.