tbuckley/cabot-search huggingface dataset:
PD-1 inhibitor inducing exosomal miR-34a-5p expression mediates the cross talk between cardiomyocyte and macrophage in immune checkpoint inhibitor–related cardiac dysfunction
Authors: Wenzheng Xia, Hanbin Chen, Didi Chen, Yijia Ye, Congying Xie, Meng Hou
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immune checkpoint inhibitors (ICIs) have been an important therapeutic advancement in the field of cancer medicine. Recent reports provided greater insights into the cardiovascular adverse events, which prohibited the use of ICIs. Cardiovascular adverse events occur in different forms, such as myocarditis and cardiomyopathy, myocardial fibrosis, heart failure and pericardial disease. Cardiac aging overlapped with the occurrence of some cardiac diseases. Exosomes mediate cell–cell cross talk in cardiac diseases by transferring a variety of biomolecules, including microRNAs (miRs). miR-34a-5p is a well-known miR associated with the cardiac senescence. This study aimed to investigate whether cardiovascular adverse effects of the programmed cell death 1 (PD-1) inhibitor, a widely used ICI, were related to exosomal-transferred miR-34a-5p in cardiac senescence in a mouse model. Methods and results The upregulation of miR-34a-5p in cardiomyocytes induced by exosomes derived from PD-1 inhibitor–treated macrophages, accompanied by cardiac senescence, caused cardiac injury in mouse hearts. miR-34a-5p was identified as an exosomal transfer RNA to induce cardiac senescence–related injury. Inhibiting miR-34a-5p in macrophages attenuated the exosome PD-1 inhibitor -induced pro-senescent effect in cardiomyocytes. TargetScan and luciferase assay showed that miR-34a-5p targeted the serine/threonine-protein phosphatase 1 regulatory subunit 10 (PNUTS) 3′-untranslated region. Conclusions Exosomes derived from PD-1 inhibitor–treated macrophages exerted a pro-senescent effect by modulating the miR-34a-5p/PNUTS signaling pathway. The findings might supply new targets to ameliorate cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.
Quality of Life in Newly Diagnosed Patients with Multiple Myeloma Randomized to Either Krd or Ktd Induction Therapy Followed By Carfilzomib Maintenance or Control (AGMT MM 02 trial)
Authors: Heinz Ludwig, Thomas Melchardt, Johannes Andel, Eberhard Gunsilius, Siegfried Sormann, Axel Hinke, Bernd L. Hartmann, Klaus Podar, Wolfgang Willenbacher, Alexander Egle, Andreas Petzer, Niklas Zojer, Ewald Wöll, Reinhard Ruckser, Boris Bozic, Clemens A. Schmitt, Sigrid Machherndl-Spandl, Maria-Theresa Krauth, Martin Schreder, Hermine Agis, Christoph Tinchon, Michael Fillitz, Richard Greil
Journal: Blood (2020)
Biologically active indolizidine alkaloids
Authors: Junmin Zhang, Susan L. Morris‐Natschke, Di Ma, Xiao‐Fei Shang, Chen‐Jie Yang, Ying‐Qian Liu, Kuo‐Hsiung Lee
Journal: Medicinal Research Reviews (2020)

Abstract Indolizidine alkaloids are chemical constituents isolated from various marine and terrestrial plants and animals, including but not limited to trees, fungi, ants, and frogs, with a myriad of important biological activities. In this review, we discuss the biological activity and pharmacological effects of indolizidine alkaloids and offer new avenues toward the discovery of new and better drugs based on these naturally occurring compounds.
B-Cell Precursor Acute Lymphoblastic Leukemia Instructs Mesenchymal Stromal Cells to Alter Interferon-Related Gene Expression and Cyto/Chemokine Secretion
Authors: Mandy W.E. Smeets, Femke Stalpers, Myrthe M.P. Vermeeren, Alex Q. Hoogkamer, Stefan Nierkens, Cesca Van De Ven, Monique L. Den Boer
Journal: Blood (2020)
Biological and Clinical Impact of JAK2/mTOR Blockade in Gvhd Prevention: Preclinical and Phase I Trial Results
Authors: Joseph Pidala, Kelly Walton, Hany Elmariah, Jongphil Kim, Asmita Mishra, Nelli Bejanyan, Taiga Nishihori, Farhad Khimani, Lia Perez, Rawan Faramand, Marco L. Davila, Michael Nieder, Nicholas Lawrence, Harshani Lawrence, Claudio Anasetti, Said Sebti, Brian C. Betts
Journal: Blood (2020)
Trends in Race/Ethnicity Among Applicants and Matriculants to US Surgical Specialties, 2010-2018
Authors: Edwin Nieblas-Bedolla, John R. Williams, Briana Christophers, Christopher Y. Kweon, Estell J. Williams, Nathalia Jimenez
Journal: JAMA Network Open (2020)

Surgical programs across the US continue to promote and invest in initiatives aimed at improving racial/ethnic diversity, but whether this translates to changes in the percentage of applicants or matriculants from racial/ethnic minority groups remains unclear.To examine trends in the percentage of applicants and matriculants to US surgical specialties who identified as part of a racial/ethnic group underrepresented in medicine from the 2010-2011 to 2018-2019 academic years.This cross-sectional study examined trends in self-reported racial/ethnic identity among applicants and matriculants to US residency programs to evaluate demographic changes among surgical programs from 2010 to 2018. Data were obtained from the Association of American Medical Colleges.The study population consisted of a total of 737 034 applicants and 265 365 matriculants to US residency programs, including 134 158 applicants and 41 347 matriculants to surgical programs. A total of 21 369 applicants (15.9%) and 5704 matriculants (13.8%) to surgical specialties identified as underrepresented in medicine. There was no statistically significant difference in the percentage of applicants underrepresented in medicine based on race/ethnicity for all surgical specialties combined in 2010 vs 2018 (15.3% [95% CI, 14.7%-15.9%] vs 17.5% [95% CI, 16.9%-18.1%]; P = .63). Thoracic surgery was the only surgical specialty in which there was a statistically significant change in the percentage of applicants (8.1% [95% CI, 4.9%-13.2%] vs 14.6% [95% CI, 10.2%-20.4%]; P = .02) or matriculants (0% [95% CI, 0%-19.4%] vs 10.0% [95% CI, 4.0%-23.1%]; P = .01) underrepresented in medicine based on race/ethnicity. Obstetrics and gynecology had the highest mean percentage of applicants (20.2%; 95% CI, 19.4%-20.8%) and matriculants (19.0%; 95% CI, 18.2%-19.8%) underrepresented in medicine among surgical specialties. Thoracic surgery had the lowest mean percentage of applicants (12.5%; 95% CI, 9.46%-15.4%) and otolaryngology the lowest mean percentage of matriculants (8.5%; 95% CI, 7.2%-9.9%) underrepresented in medicine.In this cross-sectional study, overall US surgical programs had no change in the percentage of applicants or matriculants who self-identified as underrepresented in medicine based on race/ethnicity, but the proportion remained higher than in nonsurgical specialties. Reevaluation of current strategies aimed at increasing racial/ethnic representation appear to be necessary to help close the existing gap in medicine and recruit a more racially/ethnically diverse surgical workforce.
Fairness and transparency in medical journals
Authors: Dirk M. Elston, Jane M. Grant-Kels, Nikki Levin, Murad Alam, Emily M. Altman, Robert T. Brodell, Anthony P. Fernandez, M. Yadira Hurley, John Maize, Desiree Ratner, Julie Schaffer, Jonathan Kantor
Journal: Journal of the American Academy of Dermatology (2020)
<i>FLT3</i> Internal Tandem Duplication Quantitation and Length Analysis By Digital PCR Paired with High-Speed AFM
Authors: Sean Koebley, Andrey Mikheikin, Kevin Leslie, Wendy McConnell-Wells, Joshua H Lehman, Daniel Guest, Taha Al Juhaishi, Xiaojie Zhang, Catherine H Roberts, Loren Picco, Amir Ahmed Toor, Alden Chesney, Jason Reed
Journal: Blood (2020)
FRI0061 Anakinra arrests joint destruction in patients with ra and established erosions
Authors: B Bresnihan, D McCabe, I Watt, H Genant, S Robbins, RD Newmark
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Patients with active RA and manifest erosive disease (at least 1 joint erosion) are likely to develop further joint damage. <h3>Objectives</h3> The aim of this study was to evaluate the effect of anakinra on progressive joint damage in patients with erosive disease. <h3>Methods</h3> Serial radiographs were obtained during a 24 week randomised placebo controlled study of 30 mg, 75 mg or 150 mg anakinra daily. Joint damage was quantified using both the Larsen and modified Sharp methods (Genant A&amp;R, 41:1583, 98). Patients with at least 1 erosion at baseline were selected for study. <h3>Results</h3> Approximately 75% of the 472 patients enrolled in the study had erosive disease (range 71–78% for each treatment group). The mean changes from baseline were highly significant for each anakinra dose group, when compared with placebo for reduction in the rate of joint destruction. The 75 and 150 mg dose groups arrested joint destruction (no radiographic progression) in a higher proportion of patients compared with placebo. A dose response was observed with regard to both the mean change from baseline of the modified Sharp scores and proportion of patients in whom joint destruction was arrested after 24 weeks of treatment. <h3>Conclusion</h3> In patients with erosive disease, the rate of deterioration was significantly less in those who received anakinra. Significantly more patients with erosive RA who received anakinra for 24 weeks demonstrated an arrest of progressive joint damage. Moreover, an increasing benefit was associated with increasing dosages.
Pretransplant Plasma Brain Natriuretic Peptide and N-Terminal Pro-Brain Natriuretic Peptide Are More Useful Prognostic Markers of Overall Survival after Allogeneic Hematopoietic Cell Transplantation Than Echocardiography
Authors: Naonori Harada, Hiroshi Okamura, Takahiko Nakane, Shiro Koh, Satoru Nanno, Mitsutaka Nishimoto, Asao Hirose, Mika Nakamae, Yasuhiro Nakashima, Hideo Koh, Masayuki Hino, Hirohisa Nakamae
Journal: Blood (2020)
Failures and Successes in Pediatric Patients with Acute Myeloid Leukemia with First Relapse: A Large International Report on Current Treatment Strategies and Outcome
Authors: Mareike Rasche, Martin Zimmermann, Emma Steidel, Todd A. Alonzo, Richard Aplenc, Jean-Pierre Bourquin, Heidrun Boztug, Alan S. Gamis, Robert B. Gerbing, Iveta Janotová, Thomas Lehrnbecher, Nora Muehlegger, Nils Von Neuhoff, Naghmeh Niktoreh, Lucie Sramkova, Jan Stary, Christiane Walter, Ursula Creutzig, Michael Dworzak, Edward A. Kolb, Dirk Reinhardt
Journal: Blood (2020)
Single-Cell Characterization of Acute Myeloid Leukemia (AML) and Its Microenvironment Identifies Signatures of Resistance to PD-1 Blockade Based Therapy
Authors: Hussein A Abbas, Dapeng Hao, Katarzyna Tomczak, Praveen Barrodia, Jin S. Im, Patrick K Reville, Zoe Alaniz, Wei Wang, Ruiping Wang, Feng Wang, Koichi Takahashi, Jing Ning, Maomao Ding, Jairo A. Matthews, Latasha Little, Jianhua Zhang, Sreyashi Basu, Courtney D. DiNardo, Tapan M. Kadia, Farhad Ravandi, Gautam Borthakur, Marina Konopleva, Guillermo Garcia-Manero, Michael R Green, Gheath Alatrash, Padmanee Sharma, James P Allison, Steven M. Kornblau, Kunal Rai, Linghua Wang, P Andrew Futreal, Naval Daver
Journal: Blood (2020)
CD-19 Specific CAR-T Cell Therapy in Relapsed/Refractory ALL in Pediatrics and Young Adults; Safety and Efficacy Outcomes: A Systematic Review and Meta-Analysis
Authors: Sobia Aamir, Muhammad Ashar Ali, Sana Irfan Khan, Abdul Jabbar Dar, Farhan Khalid, Muhammad Yasir Anwar, Muhammad Tayyeb, Anam Khan, Atif Irfan Khan, Syeda Sabeeka Batool, Arshia Akbar, Seemal Iftikhar, Faiz Anwer
Journal: Blood (2020)
Abstract PO-043: Plexiform neurofibroma microenvironment at single-cell resolution
Authors: Leah J. Kershner, Jianqiang Wu, Nathan Salomonis, Nancy Ratner
Journal: Cancer Research (2020)

Abstract Plexiform neurofibromas (PN) are benign nerve sheath Schwann cell tumors, which occur in at least 50% of individuals with loss of function mutations in the NF1 tumor suppressor gene, an off signal for RAS-GTPases. Tumors form, at least in part, through activation of the RAS-MAPK pathway in Schwann cells. Though benign, PN can cause significant morbidity and are often inoperable due to integration with vital peripheral nerves. Recent clinical trials have shown that MEK inhibition can shrink most PN, but continued MEK inhibition is required for sustained response. It is recognized that PN contain many cell types in addition to Schwann cells, and that Schwann cells are present in varying proportions. However, biomarkers for many cell types have not yet been identified, and it is not known whether subpopulations of certain cell types exist within neurofibromas. To address these issues, we performed single cell RNA sequencing on PN using a genetically engineered mouse model which closely recapitulates human PN. We have characterized tumor composition, and identified PN Schwann cells, satellite glial cells, endothelial cells, fibroblasts, macrophages, T cells, dendritic cells, and other previously unreported cell types. We identified multiple subpopulations of Schwann cells, macrophages and fibroblasts within benign PN. Cluster by cluster comparison of PN to age-matched healthy nerve and to pretumor nerve tissue from the same mouse model revealed gene regulatory networks that are significantly altered in PN, after loss of NF1 function. Further, inference of cell-cell communication networks shows robust changes in PN that are absent before tumors form, and that are potentially targetable. Comparison to MEK inhibitor treated PN and to human PN sc-RNASeq is ongoing. Taken together, these approaches characterize PN, provide potential biomarkers for cell populations and identify targets for drug treatment. Supported by NIH (NINDS-28840) and the DOD Program on Neurofibromatosis. LK is supported by NIH Ruth L. Kirschstein T32. Citation Format: Leah J. Kershner, Jianqiang Wu, Nathan Salomonis, Nancy Ratner. Plexiform neurofibroma microenvironment at single-cell resolution [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-043.
Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19
Authors: Yu Zuo, Shanea K. Estes, Ramadan A. Ali, Alex A. Gandhi, Srilakshmi Yalavarthi, Hui Shi, Gautam Sule, Kelsey Gockman, Jacqueline A. Madison, Melanie Zuo, Vinita Yadav, Jintao Wang, Wrenn Woodard, Sean P. Lezak, Njira L. Lugogo, Stephanie A. Smith, James H. Morrissey, Yogendra Kanthi, Jason S. Knight
Journal: Science Translational Medicine (2020)

Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions. Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease. Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies). Case series have recently detected aPL antibodies in patients with COVID-19. Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19. These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti-β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM. We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples. Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer's threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units). Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate. Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals. Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models. These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.
A multivariable prognostic score to guide systemic therapy in early-stage HER2-positive breast cancer: a retrospective study with an external evaluation
Authors: Aleix Prat, Valentina Guarneri, Laia Paré, Gaia Griguolo, Tomás Pascual, Maria V Dieci, Núria Chic, Blanca González-Farré, Antonio Frassoldati, Esther Sanfeliu, Juan M Cejalvo, Montserrat Muñoz, Giancarlo Bisagni, Fara Brasó-Maristany, Loredana Urso, Maria Vidal, Alba A Brandes, Barbara Adamo, Antonino Musolino, Federica Miglietta, Benedetta Conte, Mafalda Oliveira, Cristina Saura, Sònia Pernas, Jesús Alarcón, Antonio Llombart-Cussac, Javier Cortés, Luis Manso, Rafael López, Eva Ciruelos, Francesco Schettini, Patricia Villagrasa, Lisa A Carey, Charles M Perou, Federico Piacentini, Roberto D'Amico, Enrico Tagliafico, Joel S Parker, Pierfranco Conte
Journal: The Lancet Oncology (2020)
Final Results of a Dual-Institution Phase I Clinical Trial of Targeted Marrow Irradiation (TMI) Intensification of Reduced-Intensity Fludarabine/Busulfan (Flu/Bu) Conditioning for Allogeneic Hematopoietic Cell Transplantation for Medically Frail Patients with High-Risk Hematological Malignancies
Authors: Naveed Ali, Ana Carolina Pires de Rezende, Folashade Otegbeye, Mariana Nassif Kerbauy, Brenda W. Cooper, David Mansur, Gisele Pereira, Roberto Sakuraba, Benjamin K. Tomlinson, Kirsten M Boughan, Cinthya Correa Silva, Leland Metheny, Andreza Feitosa Ribeiro, Molly M Gallogly, Ehsan Malek, EDuardo Weltman, Marcos de Lima, Nelson Hamerschlak, Paolo F Caimi
Journal: Blood (2020)
Ventriculostomy-Related Infections
Authors: C. Glen Mayhall, Nancy H. Archer, V. Archer Lamb, Alice C. Spadora, Jane W. Baggett, John D. Ward, Raj K. Narayan
Journal: New England Journal of Medicine (1984)

We concluded a prospective epidemiologic study of ventriculostomy-related infections (ventriculitis or meningitis) in 172 consecutive neurosurgical patients over a two-year period to determine the incidence, risk factors, and clinical characteristics of the infections. Ventriculitis or meningitis developed in 19 of 172 patients (11 per cent) undergoing a total of 213 ventriculostomies. When data from all these cases plus five cases of nonventriculostomy-related infection were combined, cerebrospinal-fluid pleocytosis was more significantly associated with the diagnosis of ventriculitis or meningitis (P less than 0.0001) than were fever and leukocytosis (P = 0.07). Risk factors for ventriculostomy-related infections included intracerebral hemorrhage with intraventricular hemorrhage (P = 0.027), neurosurgical operations (P = 0.016), intracranial pressure of 20 mm Hg or more (P = 0.019), ventricular catheterization for more than five days (P = 0.017), and irrigation of the system (P = 0.021). Previous ventriculostomy did not increase the risk of infection with subsequent procedures. We conclude that ventriculostomy-related infections may be prevented by maintenance of a closed drainage system and by early removal of the ventricular catheter. If monitoring is required for more than five days, the catheter should be removed and inserted at a different site.
SAT0129 Antalgic effects of u69593, a kappa agonist, do not implicate adenosine release
Authors: T Pham, JC Peragut, H Rochat, P Lafforgue, R Guieu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> There is evidence that endogenous adenosine (ADO) is impicated in the modulation of opiate action in central and peripheral nervous system, via both A1 and A2A receptors. <h3>Objectives</h3> However, little is know about the interaction between opioid receptor agonist subtype and ADO release at the supraspinal level. We sought to answer two questions: first, what subtype of opioid receptor is more particularly implicated in the modulation of ADO uptake by the supraspinal central nervous system cells? Second, is there a relationship between the modulation of extracellular ADO concentration by opioid agonist-subtype and the antalgic effects? <h3>Methods</h3> We evaluated the effects of caffeine, a non specific ADO receptor antagonist on the hot-plate and tail pinch test latency increase that is induced by i.c.v. administration of oxymorphone hydrochloride, SNC 80 or U69593(respectively μ, ∂ and k agonist). We also evaluated the effects of these opioid receptor agonists on the uptake of ADO by whole brain synaptosomes (HPLC). <h3>Results</h3> Tail-pinch test and Hot-plate latencies Opioïds and ADO agonists induce an increase both in tail-pinch test and hot-plate latencies in a dose dependant manner and in the rank order as follows: Oxymorphone hydrochloride &gt; CCPA &gt;SNC80 &gt;CGS21680 = U69593. No increase in tail-pinch test and hot-plate latencies was observed ten minutes after i.c.v injection whatever the drug tested. Opioïds and ADO agonists have synergistic effects when coinjected. The rank order was: CCPA + Oxymorphone &gt; CCPA + SNC80 = CGS21680 + Oxymorphone &gt; CCPA+ U69593 = CGS21680 + SNC80 &gt; CGS21680 + U69593. The increase in latencies induced by Oxymorphone and SNC80 (but not U69593) was partly reversed by coinjection of caffeine. Caffeine alone had no effect on latencies. ADO uptake ADO uptake was evaluate by measuring the decrease in adenosine concentration in the supernatant as a function of time. Oxymorphone hydrochloride at 10 μM increased ADO concentration by a mean of 16, 21 and 25% at times 5, 30, and 60 s respectively. SNC80 (10 μM) increased ADO concentration by 17, 16 and 40% at times 5, 30 and 60 s. At 100 μM, SNC80 increased ADO concentration by 26, 24 and 60% at times 5, 30 and 60 s. U69593 did not significantly modify ADO concentration in the supernatant whatever the dose used. Finally, none of the opioïds tested had a significant effect on ADO uptake at 1 μM concentration. <h3>Conclusion</h3> In summary, we found that oxymorphone and SNC80, but not U69593 (respectively μ, ∂ and k agonist) inhibits ADO uptake by brain cells. Furthermore, caffeine which is a non specific ADO receptor antagonist, failed to reverse antalgic effect obtained with U69593 in a acute pain model. These results suggest that the antalgic effects of k opioïd agonist does not implicate ADO release.