tbuckley/cabot-search huggingface dataset:
Patient-Reported Experiences during and Following Treatment with Belantamab Mafodotin (Belamaf) for Relapsed/Refractory Multiple Myeloma (RRMM) in the DREAMM-2 Study
Authors: Laurie Eliason, Julia Correll, Mona Martin, Anna Cardellino, Joanna Opalinska, Trisha Piontek, Boris Gorsh, Sandhya Sapra, Rakesh Popat
Journal: Blood (2020)
A current and future outlook on upcoming technologies in remote monitoring of patients with heart failure
Authors: Tarek Bekfani, Marat Fudim, John G.F. Cleland, Ana Jorbenadze, Stephan von Haehling, Avraham Lorber, Alexander M.K. Rothman, Kenneth Stein, William T. Abraham, Horst Sievert, Stefan D. Anker
Journal: European Journal of Heart Failure (2020)
An Adaptive, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)
Authors: Kenneth W. Wood, James Geib, Eric Wu, Jason Berlin, Irena Webster, Kenneth I. Ataga, Jo Howard, Jeremie H. Estepp, Marilyn J. Telen, Julie Brevard
Journal: Blood (2020)
Mortality due to cancer treatment delay: systematic review and meta-analysis
Authors: Timothy P Hanna, Will D King, Stephane Thibodeau, Matthew Jalink, Gregory A Paulin, Elizabeth Harvey-Jones, Dylan E O’Sullivan, Christopher M Booth, Richard Sullivan, Ajay Aggarwal
Journal: BMJ (2020)

Abstract Objective To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. Design Systematic review and meta-analysis. Data sources Published studies in Medline from 1 January 2000 to 10 April 2020. Eligibility criteria for selecting studies Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. Results The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P&lt;0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. Conclusions Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
Oscillating lncRNA <i>Platr4</i> regulates <i>NLRP3</i> inflammasome to ameliorate nonalcoholic steatohepatitis in mice
Authors: Yanke Lin, Shuai Wang, Lu Gao, Ziyue Zhou, Zemin Yang, Jingpan Lin, Shujing Ren, Huijie Xing, Baojian Wu
Journal: Theranostics (2020)

Background: Understanding the molecular events and mechanisms underlying development and progression of nonalcoholic steatohepatitis is essential in an attempt to formulating a specific treatment. Here, we uncover Platr4 as an oscillating and NF-κB driven lncRNA that is critical to the pathological conditions in experimental steatohepatitis Methods: RNA-sequencing of liver samples was used to identify differentially expressed lncRNAs. RNA levels were analyzed by qPCR and FISH assays. Proteins were detected by immunoblotting and ELISA. Luciferase reporter, ChIP-sequencing and ChIP assays were used to investigate transcriptional gene regulation. Protein interactions were evaluated by Co-IP experiments. The protein-RNA interactions were studied using FISH, RNA pull-down and RNA immunoprecipitation analyses Results: Cyclic expression of Platr4 is generated by the core clock component Rev-erbα via two RevRE elements (i.e., -1354/-1345 and -462/-453 bp). NF-κB transcriptionally drives Platr4 through direct binding to two κB sites (i.e., -1066/-1056 and -526/-516 bp), potentially accounting for up-regulation of Platr4 in experimental steatohepatitis. Intriguingly, Platr4 serves as a circadian repressor of Nlrp3 inflammasome pathway by inhibiting NF-κB-dependent transcription of the inflammasome components Nlrp3 and Asc. Loss of Platr4 down-regulates Nlrp3 inflammasome activity in the liver, blunts its diurnal rhythm, and sensitizes mice to experimental steatohepatitis, whereas overexpression of Platr4 ameliorates the pathological conditions in an Nlrp3-dependent manner. Mechanistically, Platr4 prevents binding of the NF-κB/Rxrα complex to the κB sites via a physical interaction, thereby inhibiting the transactivation of Nlrp3 and Asc by NF-κB. Conclusions:Platr4 functions to inactivate Nlrp3 inflammasome via intercepting NF-κB signaling. This lncRNA might be an attractive target that can be modulated to ameliorate the pathological conditions of steatohepatitis.
An Epidemiological, Retrospective Cross-Sectional Study to Capture the Real-World Complication Burden, and Disease Management Paradigms in Transfusion-Dependent Beta-Thalassemia Adults in Greece: Interim Results of the Ulysses Study
Authors: Antonis Kattamis, Ersi Voskaridou, Sophia Delicou, Evangelos Klironomos, Ioannis Lafiatis, Fotini Petropoulou, Michael D. Diamantidis, Stylianos Lafioniatis, Loukia Evliati, Eleni Kapsali, Kiki Karvounis-Marolachakis, Despoina Timotheatou, Alexandra Kourakli
Journal: Blood (2020)
Abstract 552: Bradykinin Receptor B1/ Matrix Metalloprotease 3 Pathway is a Novel Target in Preventing Cardiac Ischemia-reperfusion Injury
Authors: Qin Zhang, Lizhuo Ai, Lifeng Liu, Cristian Betancourt, Maura Knapp, Albert Sitikov, Willard W Sharp, James K Liao, Rongxue Wu
Journal: Circulation Research (2020)

Introduction: Impaired endothelial function leads to the progression of heart failure after Ischemia-reperfusion (IR). Kinin activation of bradykinin receptor 1 (B1R), a G protein-coupled receptor that has been found to induce capillary leakage, may serve as a critical mediator in cardiac microvascular barrier dysfunction. However, the underlying mechanisms are not clear. We found that B1R inhibition abolished IR-induced endothelial matrix metalloprotease (MMP3) expression and improved endothelial barrier formation. Thus, we hypothesized that B1R antagonist protects against cardiac IR injury through an MMP3 pathway. Methods and Results: MMP3-/- mice and their littermate controls (WT) were subjected to either cardiac IR or sham control. The baseline characteristics of these mice showed minimal phenotypes. Cardiac function was determined at 3, 7 and 24 days post-IR by echocardiography. The MMP3-/- mice displayed improved cardiac function compared to the control mice, as determined by fractional shortening (26% ± 1.1 MMP3-/- vs. 21% ± 0.9 WT, p&lt;0.05, n=5) and ejection fraction (48% ± 1.9 MMP3-/- vs. 42% ± 2.8.1 WT, p&lt;0.05, n=5), and treating with B1R antagonist (300 μg/Kg) significantly reduced serum MMP3 levels (p&lt;0.01). Compared to the control mice, MMP3-/- mice had significantly less infarction/area at risk 24 hours post-IR demonstrated through TTC staining. In vitro studies revealed that cellular hypoxia-reoxygenation (HR) injury significantly increased both B1R and MMP3 expression levels in primary isolated cardiac mice microvascular endothelial cells (mCMVEC). MMP3 levels were measured via ELISA. Moreover, B1R agonist treatment (1uM) increased MMP3 levels, while the use of the antagonist attenuated the increase of MMP3 in response to HR. Finally, the use of B1R antagonist improved MMP3 induced endothelial barrier dysfunction, which was measured by the electric cell-substrate impedance sensing (ECIS) system. Taken together, the results demonstrated that B1R antagonist abolished IR induced MMP3 induction and that the deletion of MMP3 is protective of cardiac function upon IR injury. Conclusions: MMP3 is a critical regulator of cardiac microvascular barrier function, and B1R/MMP3 could potentially serve as a novel therapeutic target for heart failure in response to IR injury.
Two-Year Follow-up of Investigator-Initiated Phase 1 Trials of the Safety and Efficacy of Fully Human Anti-Bcma CAR T Cells (CT053) in Relapsed/Refractory Multiple Myeloma
Authors: Siguo Hao, Jie Jin, Songfu Jiang, Zonghai Li, Wenhao Zhang, Min Yang, Kang Yu, Wei Wang, Linjun Chen, Haitao Meng, Mingxia He, Jun Xiao, Rong Tao, Xin Huang, Chongyun Xing, Daijing Yuan, Jianbo Wan, Shasha Wang, Lihui Dai, Hong Ma
Journal: Blood (2020)
The Elevation of LIVER Enzymes in Patients with Atrial Fibrillation and COVID-19 Is a Marker of Bad Evolution and Mortality
Authors: Juan Jose Cerezo Manchado, Pável E Olivera, María Dolores Lopez Abellan, Desiree Campoy Castaño, César A Velasquez, Carlos Rodriguez Rojas, Veronica Ramos Arenas, Katia Flores, Rubén Cárdenas Gámez, Luis García de Guadiana Romualdo, Teodoro Iturbe Hernandez, Jorge Sierra, Ramón Salinas
Journal: Blood (2020)
Efficacy and Safety of Phosphoinositide 3-Kinase (PI3K) Inhibitors in Non-Hodgkin's Lymphoma: A Systematic Review and Meta-Analysis
Authors: Sana Irfan Khan, Muhammad Yasir Anwar, Abdul Rafae, Anam Khan, Atif Irfan Khan, Sobia Aamir, Syeda Sabeeka Batool, Asim Tameez Ud Din, Israr Khan, Anum Javaid, Haifza Abeera Qadeer, Zahoor Ahmed, Rohail Gul, Zobia Aijaz, Faiz Anwer
Journal: Blood (2020)
Covid-19: Antibody prevalence in England fell from 6.0% to 4.4% over three months, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Antibody prevalence in England fell from 6.0% to 4.4% over three months, study finds Elisabeth MahaseThe number of people in England who tested positive for IgG antibodies against covid-19 fell by 26% from June to September, a large study of 365 000 adults has found.
Combination of Osimertinib and Bevacizumab as First-line Treatment for Patients With Metastatic <i>EGFR</i>-Mutant Lung Cancers
Authors: Chuang Qi, Huanxi Cui, Dongsheng Chen
Journal: JAMA Oncology (2020)

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Cytomegalovirus Promotes Aberrant Memory CD4 T Cell Differentiation and Immune Function after Allogeneic Stem Cell Transplantation
Authors: Albert Yeh, Madan Jagasia, Kimberly Dahlman, Jonathan Michael Irish, Anupama Reddy, Sierra Barone, Kate Chilson, Lynn E. Onstad, Ping Zhang, Tae Kon Kim, Stephanie J. Lee, Geoff R Hill
Journal: Blood (2020)
Abstract 541: A Hedgehog-signaling Dependent Gene Regulatory Network Directly Delays Second Heart Field Differentiation to Prevent Congenital Heart Disease
Authors: Megan Rowton, Ariel Rydeen, Perez-Cervantes Carlos, Nikita Deng, Emery Lu, Jessica Jacobs-Li, Andrew Hoffmann, Jeffrey Steimle, Xinan Holly Yang, Alexander Guzzetta, Sonja Lazarevic, Chul Kim, Shuhan Yu, Mervenaz Koska, Erika Hanson, Sunny Sun-Kin Chan, Daniel J Garry, Kohta Ikegami, Michael Kyba, Ivan P Moskowitz
Journal: Circulation Research (2020)

The first heart field (FHF) and the second heart field (SHF) comprise the major progenitor pools for the developing vertebrate heart. We investigated the delayed differentiation of the SHF relative to the FHF, a major distinguishing feature of these fields. Single-cell transcriptional profiling of the SHF revealed a differentiation trajectory of SHF progenitors to cardiomyocytes. Hedgehog (Hh) signaling was highly enriched in the progenitor state in signaling pathway analysis, suggesting a possible role in cardiomyocyte differentiation control. Transcriptional profiling of the SHF following removal of active Hh signaling in vivo revealed inappropriate cardiomyocyte gene expression. We observed precocious cardiomyocyte differentiation in the SHF in vivo in Hh mutants, which led to Congenital Heart Disease (CHD). Modeling active Hh signaling in a novel mouse embryonic stem cell (mESC) line through transient expression of the activating Hh transcription factor (TF), GLI1, in cardiac progenitors delayed the onset of cardiomyocyte differentiation. GLI1 directly activated a progenitor-specific gene regulatory network, dominated by repressive TFs, that prevented the acquisition of the cardiomyocyte gene regulatory network. Maintained expression of one GLI1 target TF, FOXF1, repressed the cardiomyocyte differentiation program. FOXF1 binding sites were identified at putative regulatory elements near repressed cardiac genes involved in contraction, electrical impulse propagation and transcriptional regulation. Finally, FOXF1 repressed the activity of these elements in vitro , indicating that FOXF1 can directly repress the activation of genes essential for cardiomyocyte differentiation. Together, these results indicate that a Hh-dependent gene regulatory network including transcriptional repressors directly delays the onset of cardiomyocyte gene expression to delay SHF differentiation. Abrogation of Hh signaling and the resultant premature differentiation of cardiac progenitors provides a molecular mechanism for the ontogeny of some CHD.
Functional analysis of low-grade glioma genetic variants predicts key target genes and transcription factors
Authors: Mohith Manjunath, Jialu Yan, Yeoan Youn, Kristen L Drucker, Thomas M Kollmeyer, Andrew M McKinney, Valter Zazubovich, Yi Zhang, Joseph F Costello, Jeanette Eckel-Passow, Paul R Selvin, Robert B Jenkins, Jun S Song
Journal: Neuro-Oncology (2020)

Large-scale genome-wide association studies (GWAS) have implicated thousands of germline genetic variants in modulating individuals' risk to various diseases, including cancer. At least 25 risk loci have been identified for low-grade gliomas (LGGs), but their molecular functions remain largely unknown.We hypothesized that GWAS loci contain causal single nucleotide polymorphisms (SNPs) that reside in accessible open chromatin regions and modulate the expression of target genes by perturbing the binding affinity of transcription factors (TFs). We performed an integrative analysis of genomic and epigenomic data from The Cancer Genome Atlas and other public repositories to identify candidate causal SNPs within linkage disequilibrium blocks of LGG GWAS loci. We assessed their potential regulatory role via in silico TF binding sequence perturbations, convolutional neural network trained on TF binding data, and simulated annealing-based interpretation methods.We built an interactive website (http://education.knoweng.org/alg3/) summarizing the functional footprinting of 280 variants in 25 LGG GWAS regions, providing rich information for further computational and experimental scrutiny. We identified as case studies PHLDB1 and SLC25A26 as candidate target genes of rs12803321 and rs11706832, respectively, and predicted the GWAS variant rs648044 to be the causal SNP modulating ZBTB16, a known tumor suppressor in multiple cancers. We showed that rs648044 likely perturbed the binding affinity of the TF MAFF, as supported by RNA interference and in vitro MAFF binding experiments.The identified candidate (causal SNP, target gene, TF) triplets and the accompanying resource will help accelerate our understanding of the molecular mechanisms underlying genetic risk factors for gliomas.
Abstract 202: In Vitro Effect of Trisulfate Disaccharide on ICa (L-type), INa, IK, and the Na/Ca Exchange Current Recorded From Rat Ventricular Myocytes by Patch Clamp
Authors: Enio R Vasques, Helena Nader, Ivarne Tersariol, Godoy Carlos
Journal: Circulation Research (2020)

Background: Ion channels are pharmacological targets for antiarrhythmic action, and drugs currently used for this purpose are generally not specific to a site of action and may act on several channels and even trigger proarrhythmic phenomena. Trisulfate disaccharide (TD) is an heparin fragment known to act on the sodium calcium exchanger (NCX), reducing intracellular calcium in overload situations and reversing arrhytmias, but its action on other ionic currents is unknown. Objective: To evaluate by patch clamp the action of TD at different concentrations in NCX and ionic currents in situations of intracellular calcium overload. Materials and Methods: Adult rat myocytes were obtained from a sample from ventricles. Currents were measured using the whole-cell variant of the patch clamp method. Creation of voltage clamp pulses and data acquisition was controlled by a computer with pClamp software. Peak inward current amplitude was measured for ion currents. For Na/Ca exchange current a ramp voltage protocol was employed. Three different concentrations of Cai (300nM, 400nM and 600nM) were used in separate experiments. One drug concentration was applied per cell (10, 30 and 100 micromolar each). The current sensitive to 5mM nickel was taken as the Na/Ca exchange current. The effects of TD on the INa, L-type Ca, and the potassium currents, transiente outward current (Ito), inwardly rectifying potassium current (IK1), and sustained current (Isus) recorded from adult rat ventricular myocytes were also examined in the same conditions. Results: TD concentration-dependently increased the inward Na/Ca exchange current in all intracellular calcium concentration. The effects of TD on the INa, L-type Ca, and the potassium currents, Ito, IK1 and Isus was associated with less than 30% mean reduction on any current at the highest concentration of TD tested (100 micromolar) and still below the positive block controls for different channels that is above 40% block. Conclusion: TD acts on NCX under different concentrations used, without affecting other ionic currents, suggesting specificity in the mechanism of action and possibly not exerting a pro-arrhythmic activity, this effect being desirable for its possible use in reversal of cardiac arrhythmias.
Increased Hydroxyurea Prescribing Practices over Ten Years with Improved Clinical Outcomes in Children with Sickle Cell Anemia: A Single Center's Experience
Authors: Kristine Anne Karkoska, Kevin E Todd, Kelly Clapp, Lynette Fenchel, Theodosia A. Kalfa, Punam Malik, Omar Niss, Charles T. Quinn, Russell E. Ware, Patrick T. McGann
Journal: Blood (2020)
Prognostic Value of Refined Disease Risk Index (rDRI) and Conditioning Regimen in Adult Patients Receiving Unrelated Cord Blood Transplantation (UCBT) for Haematological Malignancies - 15-Year Follow-up of Multicenter Study in Singapore
Authors: Qianhuang Ian Q Wu, Yeh Ching Linn, William YK Hwang, Michelle Poon, Lip Kun Tan, Yang Liang Boo, Yeow Tee Goh, Aloysius YL Ho, Liang Piu Koh
Journal: Blood (2020)
Response to: ‘Correspondence on ‘Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases’’ by Aydin<i>et al</i>
Authors: Dalifer Dayanira Freites Nuñez, Leticia Leon, Arkaitz Mucientes, Luis Rodriguez-Rodriguez, Judit Font Urgelles, Alfredo Madrid García, Jose Ignacio Colomer, Juan A Jover, Benjamín Fernandez-Gutierrez, Lydia Abasolo
Journal: Annals of the Rheumatic Diseases (2020)

We appreciate the interest of Aydin et al 1 in our study about risk factors for hospital admissions related to COVID-19 in patients with inflammatory rheumatic diseases (IRD).2 COVID-19 pandemic is a matter in constant update and certainly an enormous challenge for researchers, clinicians, healthcare workers and epidemiologists. In this sense, all together are making enormous efforts in their fields to overcome this global crisis. In relation to research advances, there has been an explosion in the publication of articles related to COVID-19. In this pandemic situation, it is true that it has been a challenge and a race against the clock for researchers and some publications could be less rigorous than expected.3 For this reason, and according to Aydin et al ,1 the critical reading it is important to interpret the results, paying special attention to the limitations of each study.

The role of IRD, their therapies and other potential factors in the risk of SARS-CoV-2 infection and …
High Prevalence of Pericardial Involvement in College Student Athletes Recovering From COVID-19
Authors: Daniel Brito, Scott Meester, Naveena Yanamala, Heenaben B. Patel, Brenden J. Balcik, Grace Casaclang-Verzosa, Karthik Seetharam, Diego Riveros, Robert James Beto, Sudarshan Balla, Aaron J. Monseau, Partho P. Sengupta
Journal: JACC. Cardiovascular imaging (2020)
Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes
Authors: Amulya Yellala, Elizabeth R. Lyden, Heather Nutsch, Avyakta Kallam, Kai Fu, Timothy C. Greiner, Philip Bierman, Matthew A. Lunning, R. Gregory Bociek, James O. Armitage, Julie M. Vose
Journal: Blood (2020)
Venetoclax Inhibition of Pyrimidine Synthesis Guides Methods for Integration with Decitabine or 5-Azacytidine That Are Non-Myelosuppressive
Authors: Xiaorong Gu, Rita Tohme, Mendel Goldfinger, Benjamin K. Tomlinson, Nneha Sakre, Shannon Hanmer, Babal K. Jha, Jaroslaw P. Maciejewski, Amit Verma, Yogenthiran Saunthararajah
Journal: Blood (2020)
Polatuzumab Vedotin Plus Bendamustine and Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Updated Results of a Phase Ib/II Randomized Study and Preliminary Results of a Single-Arm Extension
Authors: Laurie H. Sehn, Mark Hertzberg, Stephen Opat, Alex F. Herrera, Sarit E Assouline, Christopher Flowers, Tae Min Kim, Andrew McMillan, Muhit Ozcan, Violaine Safar, Gilles Salles, Lisa Musick, Jamie Hirata, YiMeng Chang, Grace Ku, Matthew J Matasar
Journal: Blood (2020)