tbuckley/cabot-search huggingface dataset:
Advances in Human Lung Transplantation
Authors: Aparna C. Swaminathan, Jamie L. Todd, Scott M. Palmer
Journal: Annual Review of Medicine (2020)

Lung transplantation improves survival and quality of life in patients with advanced pulmonary disease. Over the past several decades, the volume of lung transplants has grown substantially, with increasing transplantation of older and acutely ill individuals facilitated by improved utilization and preservation of available donor organs. Other advances include improvements in the diagnosis and mechanistic understanding of frequent post-transplant complications, such as primary graft dysfunction, acute rejection, and chronic lung allograft dysfunction (CLAD). CLAD occurs as a result of the host immune response to the allograft and is the principal factor limiting long-term survival after lung transplantation. Two distinct clinical phenotypes of CLAD have emerged, bronchiolitis obliterans syndrome and restrictive allograft syndrome, and this distinction has enabled further understanding of underlying immune mechanisms. Building on these advances, ongoing studies are exploring novel approaches to diagnose, prevent, and treat CLAD. Such studies are necessary to improve long-term outcomes for lung transplant recipients.
Empagliflozin Ameliorates Diastolic Dysfunction and Left Ventricular Fibrosis/Stiffness in Nondiabetic Heart Failure
Authors: Carlos G. Santos-Gallego, Juan Antonio Requena-Ibanez, Rodolfo San Antonio, Alvaro Garcia-Ropero, Kiyotake Ishikawa, Shin Watanabe, Belen Picatoste, Ariana P. Vargas-Delgado, Eduardo J. Flores-Umanzor, Javier Sanz, Valentin Fuster, Juan J. Badimon
Journal: JACC. Cardiovascular imaging (2020)
Clinical Characteristics and Outcomes of COVID-19–Infected Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Hua Zhang, Han Han, Tianhui He, Kristen E Labbe, Adrian V Hernandez, Haiquan Chen, Vamsidhar Velcheti, Justin Stebbing, Kwok-Kin Wong
Journal: JNCI Journal of the National Cancer Institute (2020)

Previous studies have indicated coronavirus disease 2019 (COVID-19) patients with cancer have a high fatality rate.We conducted a systematic review of studies that reported fatalities in COVID-19 patients with cancer. A comprehensive meta-analysis that assessed the overall case fatality rate and associated risk factors was performed. Using individual patient data, univariate and multivariable logistic regression analyses were used to estimate odds ratios (OR) for each variable with outcomes.We included 15 studies with 3019 patients, of which 1628 were men; 41.0% were from the United Kingdom and Europe, followed by the United States and Canada (35.7%), and Asia (China, 23.3%). The overall case fatality rate of COVID-19 patients with cancer measured 22.4% (95% confidence interval [CI] = 17.3% to 28.0%). Univariate analysis revealed age (OR = 3.57, 95% CI = 1.80 to 7.06), male sex (OR = 2.10, 95% CI = 1.07 to 4.13), and comorbidity (OR = 2.00, 95% CI = 1.04 to 3.85) were associated with increased risk of severe events (defined as the individuals being admitted to the intensive care unit, or requiring invasive ventilation, or death). In multivariable analysis, only age greater than 65 years (OR = 3.16, 95% CI = 1.45 to 6.88) and being male (OR = 2.29, 95% CI = 1.07 to 4.87) were associated with increased risk of severe events.Our analysis demonstrated that COVID-19 patients with cancer have a higher fatality rate compared with that of COVID-19 patients without cancer. Age and sex appear to be risk factors associated with a poorer prognosis.
Daratumumab (DARA) Plus Carfilzomib, Pomalidomide, Dexamethasone (KPd) in Lenalidomide Refractory Multiple Myeloma (MM): A Multi-Center MMRC Study
Authors: Jagoda Jasielec, Jeff Zonder, Benjamin A Derman, Donna E. Reece, Craig E. Cole, Jesus G. Berdeja, Brittany Wolfe, Sarah Major, Kathryn M. Tinari, Andrew Stefka, Fabrizio Fazzi, Megan Whelan, Christine Gleason, Amanda McIver, Evangelia Andreatos, Bernadette M. Libao, Daniel Juergens, Kent Griffith, Andrzej Jakubowiak
Journal: Blood (2020)
Transcriptional Heterogeneity Governs Cell Fate Diversification during Pre-Leukemia to Leukemia Progression
Authors: Shikha Gupta, Ana Filipa Domingues, Oliwia Cyran, George Giotopoulos, Sudhakaran Prabakaran, Brian J. P. Huntly, Oliver M. Dovey, George S. Vassiliou, Cristina Pina
Journal: Blood (2020)
Covid-19: Doctors question ethics of treating adults in paediatric ICUs
Authors: Clare Dyer
Journal: BMJ (2020)

<h3>Abstract</h3> Basigin is an essential host receptor for invasion of <i>Plasmodium falciparum</i> into human erythrocytes, interacting with parasite surface protein PfRH5. PfRH5 is a leading blood-stage malaria vaccine candidate and a target of growth-inhibitory antibodies. However, basigin is not alone on the erythrocyte surface. Instead, we show that it is exclusively found in one of two macromolecular complexes, bound predominantly to either plasma membrane Ca<sup>2+</sup>-ATPase 1/4, PMCA1/4, or monocarboxylate transporter 1, MCT1. PfRH5 binds to either of these complexes with a higher affinity than to isolated basigin ectodomain, making it likely that these are the physiological targets of PfRH5. PMCA-mediated Ca<sup>2+</sup> export is not affected by PfRH5, ruling this out as the mechanism underlying changes in calcium flux at the interface between an erythrocyte and the invading parasite. However, our studies rationalise the function of the most effective growth inhibitory antibodies targeting PfRH5. While these antibodies do not reduce the binding of PfRH5 to monomeric basigin, they do reduce its binding to basigin-PMCA and basigin-MCT complexes. This indicates that the most effective PfRH5-targeting antibodies inhibit growth by sterically blocking the essential interaction of PfRH5 with basigin in its physiological context.
Neuropathy with IgM Gammopathy: Incidence, Characteristics and Management, a Rory Morrison W.M.U.K Registry Analysis
Authors: Oliver Tomkins, Jindriska Lindsay, Stephen Keddie, Aisling Carr, Helen McCarthy, Dima El-Sharkawi, Charalampia Kyriakou, Kirsty Cuthill, Guy Pratt, Ali Rismani, Michael P Lunn, Shirley D'Sa
Journal: Blood (2020)
Roleof Allogeneic Stem Cell Transplant (ASCT) in Patients (Pts) with Relapsed/Refractory (R-R) Acute Lymphoblastic Leukemia (ALL) Treated with Inotuzumab Ozogamicin (INO) in Combination with Low-Intensity Chemotherapy (mini-hyper-CVD) with or without Blinatumomab (Blina): Results from a Phase 2 Study
Authors: Hind Rafei, Hagop M. Kantarjian, Koji Sasaki, Nicholas J. Short, Farhad Ravandi, Xuelin Huang, Joseph D. Khoury, Sa A Wang, Jeffrey L. Jorgensen, Issa F. Khouri, Partow Kebriaei, Richard E. Champlin, Nitin Jain, Bouthaina S. Dabaja, Ghayas C. Issa, Naveen Pemmaraju, Tapan M. Kadia, Shilpa Paul, Nadya Jammal, Guillermo Garcia-Manero, William G. Wierda, Courtney D. DiNardo, Naval Daver, Guillermo Montalban-Bravo, Rita Khouri, Patrice Nasnas, Philip A. Thompson, Jovitta Jacob, Meagan Rostykus, Rebecca Garris, Marina Konopleva, Susan M. O'Brien, Elias Jabbour
Journal: Blood (2020)
Efficacy of Ixazomib and Bortezomib with Lenalidomide Combination Regimens for Multiple Myeloma: A Systematic Review
Authors: Muhammad Khawar Sana, Syed Maaz Abdullah, Saad Javed, Hamid Ehsan, Unaiza Faizan, Farhan Khalid, Ali Jaan, Muhammad Tayyeb, Sikander Abdullah, Faiz Anwer
Journal: Blood (2020)
Author Correction: A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals
Authors: Philippos Demetriou, Enas Abu-Shah, Salvatore Valvo, Sarah McCuaig, Viveka Mayya, Audun Kvalvaag, Thomas Starkey, Kseniya Korobchevskaya, Lennard Y. W. Lee, Matthias Friedrich, Elizabeth Mann, Mikhail A. Kutuzov, Matteo Morotti, Nina Wietek, Heather Rada, Shamsideen Yusuf, Jehan Afrose, Anastasios Siokis, Michael Meyer-Hermann, Ahmed Ashour Ahmed, David Depoil, Michael L. Dustin
Journal: Nature Immunology (2020)
Health-Related Quality of Life in Patients with AL Amyloidosis Treated with Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone: Results from the Phase 3 Andromeda Study
Authors: Vaishali Sanchorawala, Giovanni Palladini, Monique C. Minnema, Arnaud Jaccard, Hans C. Lee, Simon D. Gibbs, Peter Mollee, Christopher P. Venner, Jin Lu, Stefan Schönland, Moshe Gatt, Kenshi Suzuki, Kihyun Kim, M. Teresa Cibeira, Meral Beksac, Edward Libby, Jason Valent, Vania T. M. Hungria, Sandy W. Wong, Michael Rosenzweig, Naresh Bumma, Dominique Chauveau, Katharine S. Gries, John Fastenau, NamPhuong Tran, Xiang Qin, Sandra Y. Vasey, Brenda Tromp, Brendan M. Weiss, Jessica Vermeulen, Giampaolo Merlini, Raymond L. Comenzo, Efstathios Kastritis, Ashutosh D. Wechalekar
Journal: Blood (2020)
Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: From Recapitulation/Acquisition of Leukemogenic Hits to Immune Escape Due to Somatic Class I/ II HLA Mutations
Authors: Simona Pagliuca, Carmelo Gurnari, Sanghee Hong, Cassandra M Kerr, Sunisa Kongkiatkamon, Hassan Awada, Ashwin Kishtagari, Misam Zawit, Laila Terkawi, Valeria Visconte, Eric D. Hsi, Betty K. Hamilton, Hetty E. Carraway, Navneet S. Majhail, Jaroslaw P. Maciejewski
Journal: Blood (2020)
Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage
Authors: Yasutaka Kakui, Christopher Barrington, David J. Barry, Tereza Gerguri, Xiao Fu, Paul A. Bates, Bhavin S. Khatri, Frank Uhlmann
Journal: Genome biology (2020)

Abstract Background Structural maintenance of chromosomes (SMC) complexes are central organizers of chromatin architecture throughout the cell cycle. The SMC family member condensin is best known for establishing long-range chromatin interactions in mitosis. These compact chromatin and create mechanically stable chromosomes. How condensin contributes to chromatin organization in interphase is less well understood. Results Here, we use efficient conditional depletion of fission yeast condensin to determine its contribution to interphase chromatin organization. We deplete condensin in G2-arrested cells to preempt confounding effects from cell cycle progression without condensin. Genome-wide chromatin interaction mapping, using Hi-C, reveals condensin-mediated chromatin interactions in interphase that are qualitatively similar to those observed in mitosis, but quantitatively far less prevalent. Despite their low abundance, chromatin mobility tracking shows that condensin markedly confines interphase chromatin movements. Without condensin, chromatin behaves as an unconstrained Rouse polymer with excluded volume, while condensin constrains its mobility. Unexpectedly, we find that condensin is required during interphase to prevent ongoing transcription from eliciting a DNA damage response. Conclusions In addition to establishing mitotic chromosome architecture, condensin-mediated long-range chromatin interactions contribute to shaping chromatin organization in interphase. The resulting structure confines chromatin mobility and protects the genome from transcription-induced DNA damage. This adds to the important roles of condensin in maintaining chromosome stability.
Pioglitazone corrects dysregulation of skeletal muscle mitochondrial proteins involved in ATP synthesis in type 2 diabetes
Authors: Teresa Vanessa Fiorentino, Adriana Monroy, Subash Kamath, Rosa Sotero, Michele Dei Cas, Giuseppe Daniele, Alberto O. Chavez, Muhammad Abdul-Ghani, Marta Letizia Hribal, Giorgio Sesti, Devjit Tripathy, Ralph A. DeFronzo, Franco Folli
Journal: Metabolism (2020)
Abstract 383: Cavβ2a Transgenic Mouse as a Hfpef Model With Hypercontractile Cardiomyocytes
Authors: Yijia Li, Xiaoying Zhang, Jianguo Jin, Jeffery Molkentin, Steven Houser, Xiongwen Chen
Journal: Circulation Research (2020)

Objective: Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by a preserved cardiac EF, the presence of HF symptoms and diastolic dysfunction. There is a lack of animal models for exploring the mechanisms and treatments of HFpEF. This study aimed to test if cardiomyocyte (CMs) specific, inducible Cavβ2a transgenic (Cavβ2a TG) mice, having hypercontractile CMs, could be a model for HFpEF. Methods: High (HE) and low (LE) expression Cavβ2a TG mice were studied since transgene expression at the age of 2m till the age of 8m monthly to evaluate the systolic and diastolic function. At 8m, animals were euthanized for intra-left ventricular hemodynamic measurement, myocyte function and histological analyses, and Western blotting measurements. Results: LE and HE TG ventricular myocytes (VMs) had greater Ca2+ currents at the age of 2m (LE increased by 95.5%; HE increased by 171.9% ) and maintained at a similar level at the age of 8m. VM contraction and calcium transients had greater amplitudes in TG than in control VMs while the time from the peak contraction to 90% relaxation and the tau of Ca2+ transient decay of VMs were not different between groups probably due to enhanced NCX expression and increased SERCA activity because of increased phospholamban phosphorylation at the Thr17 site. Till 8m, LE and HE mice had a higher level of mortalities than control mice (LE: 32%, HE: 15%, control:5%), but more HE (87.5%) mice showed pleural effusion. The EF was highest in LE mice at the age of 2m but decreased to the same (&gt;60%) as in HE and control mice at 8m. The ratio of mitral E to mitral inflow A wave velocities (E/A) was increased significantly at 3 and 4m then decreased to the lowest in HE at 5m followed by a rise at 6-8m, while LE mice had the lowest E/A at 5m and 6m and increased at 8m. E wave to mitral annulus e’ velocity (e’ wave) was higher in LE and HE groups than control mice. More fibrosis of the LV tissue, cardiomyocyte necrosis was observed in HE than in LE hearts. LE and HE mice had greater left ventricular wall relaxation rates, as indicated by larger reversed radial and longitudinal strain rates. Conclusion: LE and HE mice showed progression of diastolic dysfunction, from impaired relaxation to restrictive filling pattern. Cavβ2a TG mouse is a model for HFpEF for exploring HF pathobiology and mechanisms.
COVID-19 Associated Coagulopathy: A Comprehensive Assessment of the Coagulation Profile in Critically and Non-Critically Ill Patients
Authors: Reyes María Martín-Rojas, Maite Chasco, Sara Casanova, Valeria Estefanía Delgado-Pinos, Gloria Perez-Rus, Patricia Duque, Milagros Sancho, Jose L. Diez-Martin, Cristina Pascual Izquierdo
Journal: Blood (2020)
Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Hematopoietic Stem Cells in <i>JAK2</i>-Mutant Myeloproliferative Neoplasms
Authors: Debra Van Egeren, Javier Escabi, Maximilian Nguyen, Shichen Liu, Christopher R. Reilly, Sachin Patel, Baransel Kamaz, Maria Kalyva, Daniel J. DeAngelo, Ilene Galinsky, Martha Wadleigh, Eric S. Winer, Marlise R Luskin, Richard M. Stone, Jacqueline S. Garcia, Gabriela S. Hobbs, Fernando D Camargo, Franziska Michor, Ann Mullally, Isidro Cortes-Ciriano, Sahand Hormoz
Journal: Blood (2020)
Abstract 14873: Integrated Cross-Sectional Modeling for the Prediction of 30-Day Unplanned Readmissions or All-Cause Mortality in Primary Heart Failure
Authors: Subhi J Al’Aref, Zhuoran Xu, Manasa Gummalla, Evan Sholle, Yiye Zhang, Ruth M Creber, Yongkang Zhang, Kelly Michalak, Kristina Dolan, Ashley Beecy, Benjamin C Lee, Gabriel Maliakal, Mohit Pandey, Gurpreet Singh, Thomas R Campion, Leslee J Shaw, Lohendran Baskaran, James K Min
Journal: Circulation (2019)

Introduction: Heart failure (HF) is a chronic condition that is associated with exacerbations and progressive decline in cardiac function, leading to frequent and unpredictable inpatient admissions...
Hospitalized Infections in Lupus: A Nationwide Study of Types of Infections, Time Trends, Health Care Utilization, and In‐Hospital Mortality
Authors: Jasvinder A. Singh, John D. Cleveland
Journal: Arthritis & Rheumatology (2020)

To examine the time trends in hospitalized infections in patients with systemic lupus erythematosus (SLE), and the factors associated with health care utilization and in-hospital mortality.US National Inpatient Sample data from 1998-2016 were used to examine the epidemiology, time trends, and outcomes of 5 common hospitalized infections in patients with SLE, namely, pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections (SSTIs), and opportunistic infections (OIs). Time trends were compared using the Cochran-Armitage test. Multivariable-adjusted logistic regression models were used to examine the factors associated with health care utilization (hospital stay >3 days, hospital charges above the median, or discharge to a nonhome setting) and in-hospital mortality.Hospitalization rates per 100,000 claims among SLE patients in 1998-2000 versus in 2015-2016 were as follows: for OIs, 1.13 versus 1.61 (1.2-fold increase); for SSTIs, 4.78 versus 12.2 (2.5-fold increase); for UTI, 1.94 versus 6.12 (3.2-fold increase); for pneumonia, 15.09 versus 17.05 (1.1-fold increase); and for sepsis, 6.31 versus 39.64 (6.3-fold increase). In 2011-2012, sepsis surpassed pneumonia as the most common hospitalized infection in patients with SLE. In multivariable-adjusted models, a diagnosis of sepsis, older age, a Deyo-Charlson common comorbidities score of ≥2, having Medicare or Medicaid insurance, and urban hospital location were significantly associated with increased odds of in-hospital mortality and with all health care utilization outcomes. African American race was significantly associated with increased odds of health care utilization.The results of this study indicate that the rates of hospitalized infections increased over time in patients with SLE, and that pneumonia was surpassed by sepsis as the most common hospitalized infection. In addition, associations of risk factors with poorer outcomes were identified. These findings may help inform patients, providers, and policy makers with regard to the burden of infection in SLE, and could lead to interventions/pathways to improve outcomes.
FRI0081 Improvement of disability in ra patients with early vs established disease after treatment with enbrel® (etanercept)
Authors: R Fleischmann, S Baumgartner, L Moreland, M Schiff, J Markenson, G Spencer-Green
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Functional health status declines and disability increases early in patients with RA, with half of affected patients developing moderate loss of functional ability within 2 years of diagnosis.<sup>1</sup> Early initiation of aggressive treatment has been suggested as a means to improve long-term outcomes. <h3>Objectives</h3> To evaluate the impact of early therapy with ENBREL on disability. <h3>Methods</h3> In this analysis, we compared the improvement in Health Assessment Questionnaire (HAQ) disability scores over 2 years in 207 patients with early disease (mean duration of RA was 1 year) to 563 patients with long-standing disease (mean duration of RA 12 years) who were treated with 25 mg ENBREL SC twice weekly. Mean baseline patient characteristics in the early vs. late groups were similar, including HAQ (1.5 vs 1.6), number of tender (31 vs 32) and swollen (24 vs 26) joints, CRP (3.3 vs 4.4 mg/dL), presence of RF (87% vs 81%), and age (51 vs 53 years). Patients with early disease had been treated with fewer DMARDS (0.5 vs 3.3). <h3>Results</h3> Patients with both early and late RA achieved rapid and sustained clinical responses and improvement in HAQ scores, but the magnitude of improvement in HAQ was greater in patients with early disease. At 2 years, mean HAQ scores declined from 1.5 to 0.6 in the early RA group and from 1.6 to 1.0 in patients with established disease. The proportion of patients who achieved zero HAQ scores was greater for patients with early disease (29%) compared to patients with late disease (14%) (p &lt; 0.001). <h3>Conclusion</h3> While patients with early or long-standing disease had significant improvement in disability with ENBREL therapy, patients with early disease had greater benefit. Aggressive therapy in patients with early RA has greater potential to improve disability as measured by HAQ than in patients with more established disease who have failed multiple DMARDs. <h3>Reference</h3> Wolfe F. A Reappraisal of HAQ disability in rheumatoid arthritis. Arthritis Rheum. 2000;43:2751–61
RNA and TCR Sequencing Shed Light on Mechanisms of Treg Suppression in a Murine Model of Acute GvHD
Authors: Juliane K. Lohmeyer, Toshihito Hirai, Mustafa Turkoz, Natalie Koehler, Jeanette Baker, Stephane Buhler, Jean Villard, Xuhuai Ji, Federico Simonetta, Robert S. Negrin
Journal: Blood (2020)
Allogeneic Transplant Can Abrogate the Relapse Risk in the Patients with Detectable Measureable Residual Disease By Multicolor Flow-Cytometry at the Time of Assessment of Acute Myeloid Leukemia Patients in First Remission
Authors: Muhned Alhumaid, Georgina S. Daher-Reyes, Arjun Law, Auro Viswabandya, Armin Gerbitz, Fotios Michelis, Igor Nicolas Novitzky-Basso, Jeffrey H. Lipton, Jonas Mattson, Ivan Pasic, Rajat Kumar, Wilson Lam, Zeyad Al-Shaibani, Hassan Sibai, Dennis Dong Hwan Kim
Journal: Blood (2020)
Abstract 544: Increase in Isoflurane-mediated Blood-brain-barrier (bbb) Permeability is Regulated by Mmp3 via the Erk Signal Pathway
Authors: Rongxue Wu, Mei Zheng, Lifeng Liu, Cristian Betancourt, Albert Sitikov, Qiong Zhao, James K Liao, Rongxue Wu
Journal: Circulation Research (2020)

Introduction: The blood-brain barrier (BBB) normally maintains the CNS microenvironment. The effect of isoflurane, widely used in clinical anesthesia, on the BBB permeability has not been well studied. Matrix metalloproteinase 3 (MMP3) is implicated in the disruption of BBB. However, the direct role for MMP3 in regulating BBB and the underlying molecular mechanism has not yet been elucidated. We hypothesized that MMP3 plays a critical role in isoflurane mediated increase in BBB permeability. Methods: We used MMP3 deficient (MMP3 -/- ) mice and its littermate, wild-type (MMP3 +/+ ), as a control. Animals were assigned to either vehicle-air or isoflurane in 3 different groups: control, MMP3 -/- and control+MMP3 administration. We evaluated the anesthetic effect of isoflurane by the time of anesthesia induction, emergency time and volume of isoflurane. MMP3 levels were measured in different organs. We monitored the permeability of mouse BBB through in vivo (Evans blue dye extravasation, Sodium-FITC, and brain water content) and an in vitro model of BBB (Electrical cell impedance sensor assay and transwell permeability assay). To determine the mechanism of MMP3 on BBB permeability, we also used an ERK-inhibitor. Expression of the endothelial tight junctional protein was detected by both western blot and immunofluorescence staining. Results: The use of MMP3 increased the anesthetic sensitivity of isoflurane compared with the control group. In contrast, MMP3 KO mice displayed significantly longer induction time, higher isoflurane usage volume, and lower emergency time. Data showed that MMP3 increased BBB permeability in both in vivo and in vitro experiments, which is associated with a reduction in occluding, ZO-1 and claudin-5. We found mmp3 levels had negative correlations with tight junctional proteins and positive associations with p-ERK. Moreover, the use of an ERK-inhibitor abolished the effect of MMP3 on the junctional protein and in vitro BBB permeability. Conclusion: Our data suggest that MMP3 is required for modulation of isoflurane mediated BBB permeability by the reduction of tight junctional protein expression via the ERK pathway. Thus, mmp3 enhances the anesthetic effect of isoflurane, while the deletion of MMP3 protects against BBB disruption.