tbuckley/cabot-search huggingface dataset:
Changes in Quality-of-Life Parameters in Patients Receiving Therapeutic Interventions for Cancer-Associated Anemia: A Systematic Review
Authors: Snigdha Marivada, Sandhya R. Panch, Kamyab Pirouz, Chhaya Kamwal, Alexandra Dreyzin, Alicia Livinski, David F. Stroncek, Xiaobai Li, Barbara Bryant
Journal: Blood (2021)
Antigen Glycosylation Is a Central Regulator of CAR T Cell Efficacy
Authors: Amanda Heard, Mehmet Emrah Selli, John Lattin, Jack Landmann, Jufang Chang, Helen Ha, Balraj Doray, Marco Ruella, Saar Gill, Katharina E. Hayer, Matthew D. Weitzman, Abby M. Green, Regina Fluhrer, Nathan Singh
Journal: Blood (2021)
Clonal Hematopoiesis of Indeterminate Potential Is Associated with Increased Age-Independent Morbidity and Mortality in Patients with COVID-19- the Beyond DNA COVID-19 Project
Authors: Marissa Li, Terra Lasho, Moritz Binder, Wazim Mohammed Ismail, Susan M. Geyer, Jenna Fernandez, Yael Kusne, Abhishek A. Mangaonkar, Minsuk Kim, Alexandre Gaspar Maia, Nicholas Chia, Mrinal M. Patnaik
Journal: Blood (2021)
Cell-penetrating peptides in protein mimicry and cancer therapeutics
Authors: Matjaž Zorko, Sarah Jones, Ülo Langel
Journal: Advanced Drug Delivery Reviews (2021)

Extensive research has been undertaken in the pursuit of anticancer therapeutics. Many anticancer drugs require specificity of delivery to cancer cells, whilst sparing healthy tissue. Cell-penetrating peptides (CPPs), now well established as facilitators of intracellular delivery, have in recent years advanced to incorporate target specificity and thus possess great potential for the targeted delivery of anticancer cargoes. Though none have yet been approved for clinical use, this novel technology has already entered clinical trials. In this review we present CPPs, discuss their classification, mechanisms of cargo internalization and highlight strategies for conjugation to anticancer moieties including their incorporation into therapeutic proteins. As the mainstay of this review, strategies to build specificity into tumor targeting CPP constructs through exploitation of the tumor microenvironment and the use of tumor homing peptides are discussed, whilst acknowledging the extensive contribution made by CPP constructs to target specific protein–protein interactions integral to intracellular signaling pathways associated with tumor cell survival and progression. Finally, antibody/antigen CPP conjugates and their potential roles in cancer immunotherapy and diagnostics are considered. In summary, this review aims to harness the potential of CPP-aided drug delivery for future cancer therapies and diagnostics whilst highlighting some of the most recent achievements in selective delivery of anticancer drugs, including cytostatic drugs, to a range of tumor cells both in vitro and in vivo.
Heme-Regulated eIF2α Kinase (HRI) Inhibition Decreases PKR Activation in HUDEP2 Cells
Authors: Yannis Hara, Dipti Gupta, Courtney Mercadante, Kim Alving, Yukio Nakamura, Sriram Krishnamoorthy, Alexandra Hicks, Melanie Demers
Journal: Blood (2021)
Predictive Model and Factors of Relapse after Allogeneic Stem Cell Transplantation in Adults with Ph-Positive Acute Lymphoblastic Leukemia
Authors: Kseniia S. Afanaseva, Evgeny A. Bakin, Olga V. Pirogova, Elena V. Morozova, Ildar M. Barkhatov, Anna G. Smirnova, Sergey N. Bondarenko, Ivan S. Moiseev, Alexander D. Kulagin
Journal: Blood (2021)
ERN-EuroBloodNet European Registry of Patients Affected by Red Blood Cell Disorders and COVID-19
Authors: Pablo Velasco, Filomena Longo, Andrea Piolatto, Eduardo J. Bardón-Cancho, Beatriz Ponce-Salas, Pagona Flevari, Ersi Voskaridou, Bart J. Biemond, Erfan Nur, Polyxeni Delaporta, Tatiana Besse-Hammer, Anna Ruiz-Llobet, Simona Raso, Anna Spasiano, Maria Elena Guerzoni, David Beneitez-Pastor, Laurence Dedeken, Alessia Pepe, Rosamaria Rosso, Joachim B. Kunz, Mariane de Montalembert, Saveria Campisi, Andreas Glenthøj, Paula Gonzalez Urdiales, Fleur Samantha Benghiat, Marie-Agnès Azerad, Christopher J. Saunders, Teresa Ferreira Faria, Tommaso Casini, Sabrina Bagnato, Ann Van de Velde, Veerle Labarque, Elisa Bertoni, An Van Damme, Michael D. Diamantidis, Roberta Russo, Eftichia Stiakaki, Alessandra Quota, Soteroula Christou, Maria Jose Teles, Ioannis Lafiatis, Jean-Louis Kerkhoffs, María Argüello Marina, Mikael Lorite, Alexis Rodriguez, Achille Iolascon, Ali T. Taher, Raffaella Colombatti, Noemi Roy, Maria Del Mar Mañú Pereira
Journal: Blood (2021)
Abstract 2432: Increase of Regional Metabolism in the Infarcted Zone and Cardiac Function After Intracoronary Transplantation of Autologous Bone Marrow Cells in Patients with Chronic Myocardial Infarction
Authors: Matthias Kostering, Tobias Zeus, Michael Brehm, Thomas Bartsch, Goeckmann Turan, Hag Mohammadi, Michael Dreher, Tillmann Fleissner, Mira Schannwell, Bodo E Strauer
Journal: Circulation (2006)

Background: After myocardial infarction (MI) necrotic cardiomyocytes are irrecoverable and represents a major cause of infarct-related heart failure and death. In experimental infarction in animal ...
Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
Authors: Yu-Cheng Chang, Yi-Hao Chiang, Kate Hsu, Chih-Kuang Chuang, Chen-Wei Kao, Yi-Fang Chang, Ming-Chih Chang, Ken-Hong Lim, Hung-I Cheng, Yen-Ning Hsu, Caleb G. Chen
Journal: Blood Cancer Journal (2021)

Abstract Tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the frontline treatments in chronic myeloid leukemia (CML). Growing evidence has shown that TKIs also enhance immunity. Since gamma-delta T (γδT) cells possess the potent anticancer capability, here we investigated the potential involvement of γδT cells in TKI treatments for CML. We characterized γδT cells isolated from chronic-phase CML patients before and during TKI treatments. γδT expression increased significantly in CML patients who achieved major molecular response (MMR) and deep molecular response (DMR). Their Vδ2 subset of γδT also expanded, and increased expression of activating molecules, namely IFN-γ, perforin, and CD107a, as well as γδT cytotoxicity. Mechanistically, TKIs augmented the efflux of isopentenyl pyrophosphate (IPP) from CML cells, which stimulated IFN-γ production and γδT expansion. Notably, the size of the IFN-γ + naïve γδT population in TKI-treated CML patients was strongly correlated with their rates to reach DMR and with the duration on DMR. Statistical analysis suggests that a cutoff of 7.5% IFN-γ + naïve subpopulation of γδT in CML patients could serve as a determinant for MR 4.0 sustainability. Our results highlight γδT cells as a positive regulator for TKI responses in CML patients.
A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300) in Patients with Polycythemia Vera
Authors: Srdan Verstovsek, Andrew T. Kuykendall, Ronald Hoffman, Yelena Ginzburg, Naveen Pemmaraju, Frank Valone, Nishit B Modi, Sarita Khanna, Paula G. O'Connor, Suneel K Gupta, Jean-Jacques Kiladjian
Journal: Blood (2021)
Small Molecule Kinase Inhibitor Sunitinib Specifically Targets Juvenile Myelomonocytic Leukemia Cells with SHP2(PTPN11) Mutation
Authors: Chunxiao He, Yuming Zhao, Junbin Huang, Yao Guo, Hongman Xue, Chun Chen, Yun Chen, Zhizhuang Joe Zhao
Journal: Blood (2021)
Understanding the Association between Red Blood Cell Transfusion Dependency and Humanistic, Psychosocial, and Psychological Burden in Patients with β-Thalassemia from the Patients' Perspective
Authors: Kwanza Price, Shaloo Gupta, Kacper Perkowski, Halley Costantino, Bryan Inyart, Lauren Ashka, Kelly Clapp, Russell L. Knoth
Journal: Blood (2021)
Diverse Drug Combinations with an Eed Inhibitor Confer Context-Specific Benefit across Multiple Tumor Types
Authors: Jessie Hao-Ru Hsu, Sasha Borodovsky, Yanjun Wang, Maryann San Martin, Minhui Shen, Haley Woods, Alan Rosen, Sharan Bagal, Philip Rawlins, James Robinson, Erin Code, Laura Prickett, Andrew Bloecher
Journal: Blood (2021)
Clinical Predictors of Outcome in Adult Patients with Acute Leukemias and Myelodysplastic Syndrome and COVID-19 Infection: Report from the American Society of Hematology Research Collaborative (ASH RC) Data Hub
Authors: Pinkal Desai, Aaron D Goldberg, Kenneth C. Anderson, Varun Narendra, Donna S. Neuberg, Vivek Radhakrishnan, Robert A. Redd, Gail J. Roboz, Laurie H. Sehn, Mikkael A. Sekeres, Maximilian Stahl, Martin S. Tallman, John Colton Thompson, Emily Tucker, William A. Wood, Lisa K. Hicks
Journal: Blood (2021)
Subcutaneous Marzeptacog Alfa (Activated) <i>Versus</i> Intravenous rFVIIa for Treatment of Episodic Bleeding in FVIII Deficient Hemophilia a Rats
Authors: Tom Knudsen, Peter Johansen, Jill Reckless, Shraddha Desai, Grant E. Blouse
Journal: Blood (2021)
Dysregulation of prostaglandins, leukotrienes and lipoxin A<sub>4</sub>in bronchiectasis
Authors: Pallavi Bedi, Kerstin Ziegler, Phil D Whitfield, Donald Davidson, Adriano Giorgio Rossi, Adam T Hill
Journal: Thorax (2021)

Introduction Bronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay of anti-inflammatory and proinflammatory lipid mediators could lead to the development of novel anti-inflammatory therapies for bronchiectasis. Aim The aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state. Methods Six healthy volunteers, 10 patients with mild bronchiectasis, 15 with moderate bronchiectasis and 9 with severe bronchiectasis were recruited. All participants had 60 mL of blood taken and underwent a bronchoscopy while in the stable state. Lipidomics was done on serum and bronchoalveolar lavage fluid (BALF). Results In the stable state, in serum there were significantly higher levels of prostaglandin E 2 (PGE 2 ), 15-hydroxyeicosatetranoic acid (15-HETE) and leukotriene B 4 (LTB 4 ) in patients with moderate–severe disease compared with healthy volunteers. There was a significantly lower level of lipoxin A 4 (LXA 4 ) in severe bronchiectasis. In BALF, there were significantly higher levels of PGE 2 , 5-HETE, 15-HETE, 9-hydroxyoctadecadienoic acid and LTB 4 in moderate–severe patients compared with healthy volunteers. In the stable state, there was a negative correlation of PGE 2 and LTB 4 with % predicted forced expiratory volume in 1 s and a positive correlation with antibiotic courses. LXA 4 improved blood and airway neutrophil phagocytosis and bacterial killing in patients with bronchiectasis. Additionally LXA 4 reduced neutrophil activation and degranulation. Conclusion There is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA 4 improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA 4 in bronchiectasis warrants further studies.
Efficacy of Inhaled Treprostinil on Multiple Disease Progression Events in Patients with Pulmonary Hypertension due to Parenchymal Lung Disease in the INCREASE Trial
Authors: Steven D. Nathan, Victor F. Tapson, Jean Elwing, Franz Rischard, Jinesh Mehta, Shelley Shapiro, Eric Shen, Chunqin Deng, Peter Smith, Aaron Waxman
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: The INCREASE study of inhaled treprostinil met its primary endpoint of change in 6-minute-walk distance at Week 16. In addition, there were significantly fewer clinical worsening events in patients receiving inhaled treprostinil. However, the incidence of multiple events in the same patient is unknown. Objectives: This post hoc analysis evaluated the effect of continued treatment with inhaled treprostinil on the frequency and impact of multiple disease progression events. Methods: Patients enrolled in INCREASE were analyzed for disease progression events, defined as at least 15% decline in 6-minute-walk distance, exacerbation of underlying lung disease, cardiopulmonary hospitalization, lung transplantation, at least 10% decline in forced vital capacity, or death during the duration of the 16-week study. Measurements and Main Results: In total, 147 disease progression events occurred in the inhaled treprostinil group (89/163 patients, 55%) compared with 215 events (109/163 patients, 67%) in the placebo group (P = 0.018). There was a lower incidence of each disease progression component in the inhaled treprostinil group: 6-minute-walk distance decline (45 vs. 64 events), lung disease exacerbation (48 vs. 72 events), FVC decline (19 vs. 33), cardiopulmonary hospitalization (23 vs. 33 events), and death (10 vs. 12). Fewer patients receiving inhaled treprostinil had multiple progression events compared with those receiving the placebo (35 vs. 58, 22% vs. 36%; P = 0.005). Conclusions: Patients who received inhaled treprostinil were significantly less likely to experience further disease progression events after an initial event compared with patients receiving placebo. These results support the continuation of inhaled treprostinil despite the occurrence of disease progression in clinical practice.
First-in-Human Dose-Finding Study of AAVhu37 Vector-Based Gene Therapy: BAY 2599023 Has Stable and Sustained Expression of FVIII over 2 Years
Authors: Steven W Pipe, John P Sheehan, Michiel Coppens, Hermann Eichler, Camila Linardi, Sara Wiegmann, Charles RM Hay, Toshko Lissitchkov
Journal: Blood (2021)
Heterogeneous Definitions of Secondary Acute Myeloid Leukemia (AML) Yield Distinct Outcomes in Response to First-Line Treatment with Hypomethylating Agents (HMA) and Venetoclax (Ven)
Authors: Irena Tan, Matthew Schwede, Paul Phan, Raymond Yin, Tian Y Zhang, Gabriel N. Mannis
Journal: Blood (2021)
ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1
Authors: Wenbin Zhong, Xiuye Cao, Guoping Pan, Qun Niu, Xiaoqin Feng, Mengyang Xu, Mingchuan Li, Yu Huang, Qing Yi, Daoguang Yan
Journal: Blood (2021)

Human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL), but the mechanism underlying its initiation remains elusive. In this study, ORP4L was expressed in ATL cells but not in normal T-cells. ORP4L ablation completely blocked T-cell leukemogenesis induced by the HTLV-1 oncoprotein Tax in mice, whereas engineering ORP4L expression in T-cells resulted in T-cell leukemia in mice, suggesting the oncogenic properties and prerequisite of ORP4L promote the initiation of T-cell leukemogenesis. For molecular insight, we found that loss of miR-31 caused by HTLV-1 induced ORP4L expression in T-cells. ORP4L interacts with PI3Kδ to promote PI(3,4,5)P3 generation, contributing to AKT hyperactivation; NF-κB-dependent, p53 inactivation-induced pro-oncogene expression; and T-cell leukemogenesis. Consistently, ORP4L ablation eliminates human ATL cells in patient-derived xenograft ATL models. These results reveal a plausible mechanism of T-cell deterioration by HTLV-1 that can be therapeutically targeted.
Obinutuzumab Short Duration Infusion Is Preferred By Healthcare Providers and Has Minimal Impact on Patient-Reported Symptoms Among Patients with Untreated, Advanced Follicular Lymphoma
Authors: Peter Trask, Jaisson Bortolini, Shinya Rai, Antonio Salar, Miguel Canales, Dirk Klingbiel, Joana Parreira, Maud Deraet, Ekaterina Vorozheikina, Kai Hübel, Thomas Buchholz
Journal: Blood (2021)
Regulation of Fetal Hemoglobin Expression By the VHL-HIF1α Oxygen Sensing System
Authors: Ruopeng Feng, Thiyagaraj Mayuranathan, Peng Huang, Phillip A Doerfler, Yichao Li, Yu Yao, Jingjing Zhang, Lance E. Palmer, Peng Xu, Kalin Mayberry, Shaela Wright, Chunliang Li, Yong Cheng, Gerd A. Blobel, M. Celeste Simon, Mitchell J. Weiss
Journal: Blood (2021)
Patient-Reported Outcomes in a Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard of Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma (ZUMA-7)
Authors: Mahmoud Elsawy, Julio C. Chavez, Irit Avivi, Jean-François Larouche, Luciano Wannesson, Kate Cwynarski, Keren Osman, Kelly Davison, Jakob D. Rudzki, Saurabh Dahiya, Kathleen Dorritie, Samantha Jaglowski, John Radford, Franck Morschhauser, David Cunningham, Alejandro Martin Garcia-Sancho, Dimitrios Tzachanis, Matthew L. Ulrickson, Reem Karmali, Natasha Kekre, Catherine Thieblemont, Gunilla Enblad, Peter Dreger, Ram Malladi, Namita Joshi, Wei-Jhih Wang, Caitlyn T. Solem, Julia Thornton Snider, Christina To, Marie José Kersten
Journal: Blood (2021)
Abstract 11304: Association Between Somatic and Mental Health Chronic Conditions with Major Adverse Cardiac Events in Patients Enrolled in Cardiac Rehabilitation
Authors: Audry Chacin Suarez, Jose Medina-inojosa, Alanna M Chamberlain, Amanda R Bonikowske, Thomas P Olson
Journal: Circulation (2021)

Introduction: The presence of chronic somatic and mental health conditions is complex and challenging for patients and the health care system due to the health deficit accumulation, worsening outcomes, and increased health care utilization. While previous studies on multimorbidity have focused on somatic chronic conditions, we aim to assess the relation between somatic, mental, and combined somatic-mental multimorbidity (SMM) and impact on Major Adverse Cardiac Events (MACE) in patients enrolled in phase II outpatient cardiac rehabilitation (CR). Methods: Using the Rochester Epidemiology Project records-linkage system, we identified patients from Olmsted County, Minnesota who were 18 years old and attended (≥1) CR sessions at Mayo Clinic Rochester. The prevalence of 18 (somatic=13; mental=5) chronic conditions defined by the US Department of Health and Human Services was ascertained electronically. Results: We included 618 patients; 24.4% were female. Patients were 61.5±11.0 years old with 38.0% ≥65 years old. Overall median number of chronic conditions was 6 (Range 0-13) with 98.8% of patients having ≥2 conditions. The prevalence of combined SMM was 44.6%. Mean follow-up was 7.3± 4.5 years, 147 (23.7%) patients had MACE (number): acute coronary syndrome (46), percutaneous coronary intervention (33), heart failure (16), stroke (8), coronary artery bypass grafting (4), ventricular arrhythmias (4), or death (65). Risk of MACE in patients with SMM was significantly higher compared to patients with only somatic conditions (HR: 1.62, 95% CI: 1.14-2.30, p=0.01 ), Figure 1. The association remained significant after adjustment for age and sex ( p=0.006 ). Conclusions: Our results show that somatic-mental multimorbidity (SMM) in CR patients is highly prevalent and imposes a higher risk of MACE compared with patients who have only somatic conditions highlighting the importance of individualized assessment and care plans to reduce adverse events and mortality.
Enrollment Characteristics and Outcomes of Hispanic and Black AYA ALL Patients Enrolled on a U.S. Intergroup Clinical Trial: A Comparison of the CALGB 10403 (Alliance) Cohort with U.S. Population-Level Data
Authors: Lori Muffly, Jun Yin, Sawyer Jacobson, Anjali Advani, Selina M. Luger, Martin S. Tallman, Mark R. Litzow, Matthew C. Foster, Frederick R. Appelbaum, Richard A. Larson, Theresa Keegan, Wendy Stock
Journal: Blood (2021)
Molecular Detection of Airborne <i>Mycobacterium tuberculosis</i> in South African High Schools
Authors: Erick W. Bunyasi, Keren Middelkoop, Anastasia Koch, Zeenat Hoosen, Humphrey Mulenga, Angelique K. K. Luabeya, Justin Shenje, Simon C. Mendelsohn, Michele Tameris, Thomas J. Scriba, Digby F. Warner, Robin Wood, Jason R. Andrews, Mark Hatherill
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: South African adolescents carry a high tuberculosis disease burden. It is not known if schools are high-risk settings for Mycobacterium tuberculosis (MTB) transmission. Objectives: To detect airborne MTB genomic DNA in classrooms. Methods: We studied 72 classrooms occupied by 2,262 students in two South African schools. High-volume air filtration was performed for median 40 (interquartile range [IQR], 35-54) minutes and assayed by droplet digital PCR (ddPCR)-targeting MTB region of difference 9 (RD9), with concurrent CO2 concentration measurement. Classroom data were benchmarked against public health clinics. Students who consented to individual tuberculosis screening completed a questionnaire and sputum collection (Xpert MTB/RIF Ultra) if symptom positive. Poisson statistics were used for MTB RD9 copy quantification. Measurements and Main Results: ddPCR assays were positive in 13/72 (18.1%) classrooms and 4/39 (10.3%) clinic measurements (P = 0.276). Median ambient CO2 concentration was 886 (IQR, 747-1223) ppm in classrooms versus 490 (IQR, 405-587) ppm in clinics (P < 0.001). Average airborne concentration of MTB RD9 was 3.61 copies per 180,000 liters in classrooms versus 1.74 copies per 180,000 liters in clinics (P = 0.280). Across all classrooms, the average risk of an occupant inhaling one MTB RD9 copy was estimated as 0.71% during one standard lesson of 35 minutes. Among 1,836/2,262 (81.2%) students who consented to screening, 21/90 (23.3%) symptomatic students produced a sputum sample, of which one was Xpert MTB/RIF Ultra positive. Conclusions: Airborne MTB genomic DNA was detected frequently in high school classrooms. Instantaneous risk of classroom exposure was similar to the risk in public health clinics.
Radical Improvement in Prognosis of CNS Ptlds Using Methotrexate Dose Alorithm Regardless of Renal Function
Authors: Sylvain Choquet, Anne Lavaud, Inès Boussen, Damien Roos-Weil, Veronique Morel, Silvia Solorzano, Madalina Uzunov, Veronique Leblond
Journal: Blood (2021)