tbuckley/cabot-search huggingface dataset:
EPCO-03. GLIOMA ONCOGENESIS IN THE CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY (CMMRD) SYNDROME
Authors: Léa Guerrini-Rousseau, Jane Merlevede, Philippe Denizeau, Felipe Andreiuolo, Pascale Varlet, Stéphanie Puget, Kevin Beccaria, Thomas Blauwblomme, Odile Cabaret, Nadim Hamzaoui, Franck Bourdeaut, Cécile Faure-Conter, Martine Muleris, Chrystelle Colas, Tiphaine Adam de Beaumais, David Castel, Etienne Rouleau, Laurence Brugières, Jacques Grill, Marie-Anne Debily
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Constitutional Mismatch Repair Deficiency (CMMRD) is a cancer predisposition due to bi-allelic mutations in one of the four main mismatch repair (MMR) genes (PMS2, MSH2, MSH6 or MLH1) associated with early onset of cancers, especially glioblastomas (GBM). Our aim was to decipher the molecular specificities of gliomas occurring in this context. METHODS A comprehensive analysis of clinical, histopathological and genomic data (whole exome sequencing) was performed for 12 children with a CMMRD for which we had available frozen brain tumor material (10 GBM and 2 anaplastic astrocytomas). RESULTS Eight patients harbored an ultra-mutated phenotype with more than 100 somatic non synonymous (NS) SNV/Mb. No correlation was observed between the number of mutation and sex, age, overall survival or mutated MMR gene. POLE and POLD1 exonuclease domain driver somatic mutations were described for eight and one patients respectively. The 4/12 tumors without POLE somatic mutation did not show the classical ultra-hypermutation pattern. All patients with POLE mutation had already more than 20 NS SNV/Mb (median 40NS SNV/Mb, [range 23-114]) suggesting that the hypermutation phenomenon started before the appearance of the somatic POLE mutation. The mutational signatures of the tumors, dominated by the MMR signatures, were not modified after the onset of the POLE mutation when analyzing the different mutation bursts. Specific recurrent somatic mutations were observed in SETD2 (9/12), TP53 (9/12), NF1 (9/12), EPHB2 (8/12), and DICER1 (7/12). Only half of the tumors overexpressed PDL1 by immunohistochemistry and this overexpression was not associated with a higher tumor mutation burden. CONCLUSION CMMRD-associated gliomas have a specific oncogenesis that does not trigger usual pathways and mutations seen in sporadic pediatric or adult GBM. Frequent alterations in other pathways (e.g. MAPK or DNA-PK pathway) may suggests the use of other targeted therapies aside from PD1 inhibitors.
The Role of ETO and CtBP1 in CBFA2T3-GLIS2 Mediated Transcriptional Regulation and Leukemogenesis
Authors: Elizabeth A. R. Garfinkle, Anitria Cotton, Pratima Nallagatla, Jing Ma, Guangchun Song, Sharnise Mitchell, Taylor Wilson, Jinjun Dang, Tanja Andrea Gruber
Journal: Blood (2021)
STEM-10. UPSTREAM REGULATORS OF THE GLIOMA STEM CELL PHENOTYPE
Authors: Alexandra Calinescu, Zain Sultan, McKenzie Kauss, Wajd Al-Holou, Jason Heth
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Recurrence of the disease is attributed in part to the presence of Glioma Stem Cells (GSC), which are resistant to chemo- and radiotherapy and can initiate tumor formation. Molecularly, GSCs resemble the mesenchymal subtype that is associated with worse prognosis. GSCs share many characteristics with Neural Stem Cells (NSCs) including proliferative potential, migratory capacity, telomerase activity, diverse progeny and similar gene signature, however differ fundamentally from NSCs in their tumor forming ability. RNA-Seq analysis of GSCs and NSCs illustrates significant enrichment in GSCs of transcription factors (TFs) known to be dysregulated in cancer, chief among them being SIX1, a developmental TF with documented roles in progression of multiple cancers. Overexpression of SIX1 in A172 GBM cells enhances proliferation, promotes resistance to radiotherapy and alters expression of a core set of 4 developmental TFs (POU3F2, SALL2, OLIG2 and SOX2) capable to reprogram differentiated GBM cells into GSCs (Suva et al., 2014). Analysis of SIX1 in surgical samples from glioma patients illustrates that high expression of SIX1 correlates with tumor grade, finding corroborated in the TCGA and CGGA data sets. Surprisingly, primary NSCs, after extended time in culture, increase their proliferation rate, acquire a mesenchymal transcriptional signature akin to GSCs, including high expression of SIX1, and form deadly tumors when implanted into the brains of mice. Comparing the epigenetic landscape of transformed and normal NSCs we identify a significant enrichment of accessible chromatin at promoter and enhancer loci in transformed NSCs, including at regulatory regions of SIX1 and of genes that define mesenchymal GBM. These data suggest that SIX1 may represent an upstream regulator of the GSC phenotype and may drive malignant transformation of NSCs. Genetic and epigenetic loss of function analyses are ongoing to test this hypothesis.
TEM-GBM: An Open-Label, Phase I/IIa Dose-Escalation Study Evaluating the Safety and Efficacy of Genetically Modified Tie-2 Expressing Monocytes to Deliver IFN-α within Glioblastoma Tumor Microenvironment
Authors: Bernhard Gentner, Gaetano Finocchiaro, Francesca Farina, Marica Eoli, Capotondo Alessia, Elena Anghileri, Gabriele Antonarelli, Matteo Barcella, Maria Grazia Bruzzone, Matteo Giovanni Carrabba, Valeria Cuccarini, Giorgio D'Alessandris, Francesco Di Meco, Valeria Ferla, Paolo Ferroli, Filippo Gagliardi, Mariagrazia Garramone, Federico Legnani, Pietro Mortini, Matteo Maria Naldini, Alessandro Olivi, Roberto Pallini, Monica Patanè, Rosina Paterra, Bianca Pollo, Marco Saini, Silvia Snider, Valentina Brambilla, Tiziana Magnani, Stefania Mazzoleni, Zahid Bashir, Carlo Russo, Luigi Naldini, Fabio Ciceri
Journal: Blood (2021)
A transvalvular polypectomy of a giant ileal inflammatory fibroid polyp by retrograde single-balloon enteroscopy
Authors: Felice Rizzi, Marco Sacco, Wilma Debernardi Venon, Do An Andrea Trinh, Marco Pennazio
Journal: Endoscopy (2021)

Small-bowel tumors, both malignant and benign, are rare lesions accounting for no more than 2 % of gastrointestinal malignancies [1]. We report the case of an asymptomatic 61-year-old man who underwent a screening colonoscopy in an out-patient hospital conducted up to the ascending colon owing to a dolichocolon. A cecal mass was observed that could not be correctly defined. A subsequent computed tomography (CT)-based virtual colonoscopy showed a 6-cm finger-like-shaped polyp with its base in the terminal ileum approximately 5 cm proximal to ileocecal valve ([Fig. 1]). A repeat colonoscopy was again unsuccessful. Apart from a left nephrectomy for a renal clear cell carcinoma in 2006, the patient’s past medical history was otherwise unremarkable.
Specificity and Heterogeneity of Trained Immunity in Hematopoietic Stem and Progenitor Cells
Authors: Bailee N. Kain, Pam Luna, Daniel Hormaechea Agulla, Laure Maneix, Daniel Enrique Morales-Mantilla, Duy Le, Brandon Tran, Marcus A Florez, Jack Toups, Hyojeong Han, Roman Jaksik, Andre Catic, Chad Shaw, Katherine Y. King
Journal: Blood (2021)
Abstract 10175: An Artificial Intelligence-Based Smartwatch Ecg Analysis Improves the Detection of Atrial Arrhythmia
Authors: Laurent Fiorina, Pascale Chemaly, Joffrey Cellier, Salem Younsi, Mina Ait Said, Fiorella Salerno, Jerome Horvilleur, Jerome Lacotte, Vladimir Manenti, Christine Henry, Christophe Gardella, Baptiste Lefebvre
Journal: Circulation (2021)

Introduction: Smartwatch ECGs (SW-ECG) have been identified as a noninvasive solution to assess abnormal heart rhythms, especially atrial arrhythmias (AA) which are related to stroke risk. This study assesses the detection of AA with the Apple Watch and compares the accuracy of two algorithms, the original companion application (ECG 1.0 App) and a novel deep neural network (DNN), in a population typical of an electrophysiology department. Hypothesis/Objective: To determine if a novel DNN can improve the detection of AA on SW-ECGs. Methods: 146 simultaneous pairs of 12-lead ECGs (GE Mac 2000 or Mindray BeneHeart R12) and SW-ECGs have been collected on 144 patients from the electrophysiology department of one tertiary center. 12-lead ECGs were adjudicated by an expert electrophysiologist as 40 AA and 106 not AA and considered as ground truth. The SW-ECGs were processed by the ECG 1.0 App and the DNN in parallel. The proportions of inconclusive diagnoses returned and the performances were assessed and compared. Results: Overall, the ECG 1.0 App yielded inconclusive diagnoses for 25% (37/146) of all SW-ECGs while the DNN reduced that number to 1% (2/146). After excluding SW-ECGs with an inconclusive diagnosis (37/146), the ECG 1.0 App and the DNN had a sensitivity of 62% (95% CI, 55%-70%) and 96% (95% CI, 93%-99%) respectively, and both had a specificity of 95% (95% CI, 92%-99%). Conclusions: A novel DNN improved the performance for the detection of AA. It reduced the burden of inconclusive diagnostics by 24% and improved the sensitivity by 34% with no change in specificity. Routine application of this SW-ECG analysis offers significant promise in arrhythmia diagnosis. Further investigations are needed to assess the classification of atrial arrhythmias more precisely.
Tasquinimod Targets Immunosuppressive Myeloid Cells, Increases Osteogenesis and Has Direct Anti-Myeloma Effects By Inhibiting c-Myc Expression in Vitro and In Vivo
Authors: Rong Fan, Hatice Satilmis, Niels Vandewalle, Elke De Bruyne, Eline Menu, Andrew D Chantry, Holly Evans, Marie Törngren, Helena Eriksson, Karine Breckpot, Ken Maes, Karin Vanderkerken, Kim De Veirman
Journal: Blood (2021)
Incidence and Predictors of Sars-Cov-2 Antibody Responses Following COVID-19 Vaccination in Allogeneic Stem Cell Transplant Recipients
Authors: Janna C. Minehart, Christopher Catania, Linda Perry, Mary Ellen Martin, Jacqueline Smith, Shannon R. McCurdy, Keith W. Pratz, Selina M. Luger, Colleen Timlin, Alexander E. Perl, Mindy Schuster, David L Porter, Alison W. Loren, Elizabeth O. Hexner, Noelle V Frey
Journal: Blood (2021)
Use of Monoclonal Antibody Therapy in Hematologic Patients with Mild-to-Moderate COVID-19: A Retrospective Single-Center Experience
Authors: Idoroenyi Amanam, Janny M. Yao, Alfredo Puing, Ni-Chun Tsai, Diana Samuels, Dat Ngo, Stephanie Ho, Haris Ali, Ahmed Aribi, Shukaib Arslan, Andrew S. Artz, Myo Htut, Paul Koller, Amandeep Salhotra, Karamjeet S. Sandhu, Liana Nikolaenko, Anna B Pawlowska, Geoffrey Shouse, Anthony S. Stein, Guido Marcucci, Stephen J Forman, Ryotaro Nakamura, Sanjeet S Dadwal, Monzr M. Al Malki
Journal: Blood (2021)
<i>Prompt CR Plus Consolidation Therapy Yields Improve Survival after Allogeneic Transplantation for AML Patients Receiving Myeloablative, but Not Reduced-Intensity Conditioning: A CIBMTR Analysis</i>
Authors: Michael M. Boyiadzis, Marcos J.G. de Lima, Mei-Jie Zhang, Karen Chen, Christopher S. Hourigan, Partow Kebriaei, Mark R. Litzow, Kristin M. Page, Wael Saber, Daniel J. Weisdorf
Journal: Blood (2021)
Targeting HLA-DR loss in hematologic malignancies with an inhibitory chimeric antigen receptor
Authors: Fan Fei, Liang Rong, Nan Jiang, Alan S. Wayne, Jianming Xie
Journal: Molecular Therapy (2021)

Chimeric antigen receptor natural killer (CAR-NK) cells have remarkable cytotoxicity against hematologic malignancies; however, they may also attack normal cells sharing the target antigen. Since human leukocyte antigen DR (HLA-DR) is reportedly lost or downregulated in a substantial proportion of hematologic malignancies, presumably a mechanism to escape immune surveillance, we hypothesize that the anti-cancer specificity of CAR-NK cells can be enhanced by activating them against cancer antigens while inhibiting them against HLA-DR. Here, we report the development of an anti-HLA-DR inhibitory CAR (iCAR) that can effectively suppress NK cell activation against HLA-DR-expressing cells. We show that dual CAR-NK cells, which co-express the anti-CD19 or CD33 activating CAR and the anti-HLA-DR iCAR, can preferentially target HLA-DR-negative cells over HLA-DR-positive cells in vitro. We find that the HLA-DR-mediated inhibition is positively correlated with both iCAR and HLA-DR densities. We also find that HLA-DR-expressing surrounding cells do not affect the target selectivity of dual CAR-NK cells. Finally, we confirm that HLA-DR-positive cells are resistant to dual CAR-NK cell-mediated killing in a xenograft mouse model. Our approach holds great promise for enhancing CAR-NK and CAR-T cell specificity against malignancies with HLA-DR loss.
Overview of DaxibotulinumtoxinA for Injection: A Novel Formulation of Botulinum Toxin Type A
Authors: Nowell Solish, Jean Carruthers, Joely Kaufman, Roman G. Rubio, Todd M. Gross, Conor J. Gallagher
Journal: Drugs (2021)

Botulinum toxin type A (BoNTA) products are widely used for therapeutic and aesthetic indications, but there is a need for longer-lasting treatments that maintain symptom relief between injections and reduce the frequency of re-treatment. DaxibotulinumtoxinA for Injection (DAXI) is a novel BoNTA product containing highly purified 150-kDa core neurotoxin and is the first to be formulated with a proprietary stabilizing excipient peptide (RTP004) instead of human serum albumin. The positively charged RTP004 has been shown to enhance binding of the neurotoxin to neuronal surfaces, which may enhance the likelihood of neurotoxin internalization. DAXI produces robust, extended efficacy across both aesthetic and therapeutic indications. In an extensive glabellar lines clinical program, DAXI showed a high degree of efficacy, a consistent median time to loss of none or mild glabellar line severity of 24 weeks, and median time until return to baseline of up to 28 weeks. In adults with cervical dystonia, DAXI at 125 U and 250 U significantly improved Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores, with a median duration of efficacy of 24 and 20 weeks, respectively, which compares favorably with the 12-14 weeks' duration reported for approved BoNTA products. Overall, DAXI was well tolerated, and the consistent extended duration of effect suggests that DAXI has the potential to improve the management of both aesthetic and therapeutic conditions.Botulinum toxin is used to block the nerve signals that cause muscles to contract. Products containing botulinum toxin are commonly given by injection to treat muscle spasms (such as cervical dystonia, a painful condition where the neck muscles contract involuntarily) and for cosmetic treatment of frown lines. However, the effects of the currently approved botulinum toxin products typically wear off about 3–4 months after injection and so the injections must be repeated regularly. A new product called DAXI (DaxibotulinumtoxinA for Injection) has been developed. In this product, the botulinum toxin is formulated with a unique protein (called RTP004) that has been designed to help deliver the botulinum toxin to the nerve cells. Research suggests that the RTP004 protein in DAXI adheres the botulinum toxin to the nerves close to the injection site, potentially making its effect last longer. To date, DAXI has been studied in over 3800 patients. The studies have shown that DAXI is effective for treating neck spasms (cervical dystonia) and for reducing the appearance of frown lines. Importantly, the effects of DAXI lasted up to 6 months, which is longer than seen with other botulinum toxin products. The side effects seen with DAXI are consistent in nature and frequency with those seen with other botulinum toxin products. These findings suggest that DAXI can improve both medical and cosmetic treatments due to its longer-lasting effect.
Luspatercept Improves Quality of Life and Reduces Red Blood Cell Transfusion Burden in Patients with Non-Transfusion-Dependent β-Thalassemia in the BEYOND Trial
Authors: Antonis Kattamis, Vip Viprakasit, Maria Domenica Cappellini, Ersi Voskaridou, Antonio Piga, John B. Porter, Thomas D. Coates, Gian Luca Forni, Jeevan K. Shetty, Dimana Miteva, Oriana Esposito, Wen-Ling Kuo, Shien Guo, Christopher Pelligra, Jennifer Lord-Bessen, Aylin Yucel, Ali T. Taher
Journal: Blood (2021)
Natural Course of Isolated Pulmonary Valve Stenosis in Pediatric Patients
Authors: Güven Serçin, Öztarhan Kazım
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Aim: The aim of our study is to be able to predict the prognosis of patients with isolated pulmonary valvular stenosis on the basis of age and degree of stenosis. Identification of the course of pulmonary stenosis of different age groups will significantly contribute both to the physicians and the relatives of the patient. Material and Methods: 105 pediatric patients diagnosed with isolated pulmonary valvular stenosis were included in our study. We investigated the impact of the gradient of stenosis and the age at the time of diagnosis on the natural course of pulmonary stenosis. Mean follow-up time of the children was 19 months, 25.45±22.48 months. The patients were divided into four groups over their trans-valvular gradient degrees and&lt;20 mmHg was defined as transient, 20-39 mmHg mild, 40-59 mmHg moderate, 60 mmHg and over as severe pulmonary stenosis. Results: Between two to five months, none of the moderate stenosis cases progressed unlike other patient groups. The decline in the final gradient versus initial gradient was significant in children between two to five months and six months to two years in our study, and yet there was no significant change of initial and final gradients in patients under one month, and at two years and over. Conclusion: It would be reasonable to conclude that the progression of pulmonary valvular stenosis is benign in patients with pulmonary valvular stenosis under 40 mmHg of systolic gradient diagnosed after 6th month of life.
Efficacy of Treatments for Patients with Triple-Class Refractory (TCR) Multiple Myeloma (MM): Benchmark for New Agents Utilizing Real-World Data (RWD)
Authors: Luciano J. Costa, Robert Frank Cornell, Natalie S. Callander, Saurabh Chhabra, Michaela Liedtke, Ankit Kansagra, Kelly N. Godby, Susan Bal, Smith Giri, Ehsan Malek, Yubin Kang, Ravi Vij, Saad Z. Usmani, Parameswaran Hari, Shaji Kumar
Journal: Blood (2021)
Knock out of CD123 or CLL-1 By CRISPR-Cas9 Editing from Human Hematopoietic Stem Cell Transplants Provide New Possibilities for Increasing Therapeutic Index and Safety for AML Treatment
Authors: Chong Luo, Gabriella Angelini, Sushma Krishnamurthy, Jessica Lisle, Meltem Isik, Azita Ghdossi, Christopher Cummins, Michael Pettiglio, Dane Hazelbaker, Gary Ge, Patrick Tavares, Mugdha Nikam, Elizabeth Paik, John Lydeard, Michelle Lin, Tirtha Chakraborty
Journal: Blood (2021)
Clinician-Based Performance Status and Its Correlation with Patient-Reported Outcomes: Findings from a Prospective Observational Study in Patients with Mantle Cell Lymphoma
Authors: Jakub Svoboda, Jonathon B. Cohen, Chaitra S. Ujjani, David Andorsky, Andre H. Goy, Anita Kumar, Scott D Ramsey, Mike Wallington, James M Eudicone, Rick Hermann, Victor Gonzalez, Michael Wang, John M. Pagel
Journal: Blood (2021)
Efficacy and Safety of Pegcetacoplan Treatment in Complement-Inhibitor Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria: Results from the Phase 3 Prince Study
Authors: Raymond S Wong, Juan Ramon Navarro, Narcisa Sonia Comia, Yeow Tee Goh, Henry Idrobo, Daolada Kongkabpan, David Gomez-Almaguer, Mohammed Al-Adhami, Temitayo Ajayi, Paulo Alvarenga, Pascal Deschatelets, Cedric Francois, Federico Grossi, Teresita Dumagay
Journal: Blood (2021)
Abstract 9419: Quantification and Novel Algorithm of Echocardiography Against Magnetic Resonance Imaging for Isolated Tricuspid Regurgitation
Authors: Tom Wang, Kevser Akyuz, Reza Reyaldeen, Zoran B Popovic, Gosta B Pettersson, A Gillinov, Scott D Flamm, Brian P Griffin, Bo Xu, Milind Y Desai
Journal: Circulation (2021)

Background: Transthoracic echocardiography (TTE) is the first-line imaging modality to evaluate isolated tricuspid regurgitation (TR), however comparisons with magnetic resonance imaging (MRI) measurements have seldomly been studied. We assessed the correlation, discriminative ability and derived a novel TTE-based algorithm using TR and right heart parameters to identify isolated severe TR by MRI. Methods: Isolated TR patients graded at least moderate-to-severe by TTE and undergoing MRI between January 2007-June 2019 were studied. TR and right heart parameters were analyzed by correlation, receiver-operative characteristics analysis and classification and regression tree algorithm for detection of severe TR by MRI (regurgitant volume &gt; 45mL and/or fraction &gt; 50%). Results: In 262 isolated TR patients, 108 (41.2%) had severe TR by MRI. There were moderate correlations and discrimination for most TTE-derived TR parameters and indexed right atrial volume (Pearson r=0.428-0.645) for TR quantification by MRI. This included a mean absolute and percentage difference of +10mL and +19% for regurgitant volume by TTE higher than MRI. However, there were none to modest correlations between TTE-derived right ventricle parameters with MRI-derived TR or right ventricle quantification. Key TTE parameters to identify severe TR by MRI in the decision tree regression algorithm were right atrial volume indexed &gt;47cm 2 /m 2 , then effective regurgitant orifice area &gt;0.45 cm 2 , and finally those with right ventricle free wall strain &gt;-9.5% had the highest risk. Conclusion: TTE-derived TR and right atrial quantification had moderate correlation and discrimination of severe TR by CMR, from which a novel TTE-based decision tree algorithm was derived, while RV correlation was relatively poor between TTE and CMR.
Evaluation of the Incidence and Risk Factors Associated with Bleeding Events in Patients Receiving Acalabrutinib Therapy
Authors: Pooja S. Kumar, Tracy Wiczer, Lindsay Rosen, Arthur J. Pollauf, Amy Zheng, Marilly Palettas, Leylah Azali, Seema A Bhat, John C. Byrd, Kerry Rogers, Jennifer A. Woyach, Adam S Kittai
Journal: Blood (2021)