tbuckley/cabot-search huggingface dataset:
TMIC-64. THE ROLE OF TUMOR-DERIVED GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR (GM-CSF/CSF2) IN REGULATION OF MICROGLIA-DEPENDENT INVASION IN GLIOMAS
Authors: Katarzyna Poleszak, Maria Pasierbinska, Aleksandra Ellert-Miklaszewska, Bartosz Wojtaś, Kamil Wojnicki, Bozena Kaminska
Journal: Neuro-Oncology (2019)

Abstract Brain resident immune cells (microglia) and peripheral macrophages accumulate in malignant gliomas and constitute for 30–50% of the tumor mass. These immune cells are polarized by factors released by glioma and become the pro-invasive, immunosuppressive cells that support tumor progression. We have previously found that tumor-derived granulocyte macrophage colony stimulating factor (GM-CSF/CSF2) is a crucial factor controlling accumulation of microglia and macrophages in murine gliomas. The analysis of TCGA dataset revealed overexpression of the CSF2 gene (encoding GM-CSF) in a set of mesenchymal glioblastomas and its association with high immune gene expression. To study the role of GM-CSF in microglia-stimulated glioma invasion, we used a co-culture system, which mimics microglia interactions with tumor cells. We silenced the expression of CSF2 in glioma cells and found reduced microglia-dependent invasion of glioma cells. To translate those results into clinically relevant setting, we designed and tested humanized short peptides interfering with binding of GM-CSF to its receptor. Selected peptide effectively inhibited binding of GM-CSF to its receptor as demonstrated with different methods. We selected the non-cytotoxic peptides that potently blocked microglia-dependent glioma invasion in cell co-cultures. Blocking GM-CSF-receptor signaling pathway with a neutralizing antibody against a GM-CSF receptor also inhibited microglia-dependent invasion of glioma cells. Altogether, our results demonstrate that glioma-derived GM-CSF supports pro-tumorigenic polarization of microglia turning them into cells that facilitate glioma growth and shape the immune microenvironment. This work was supported by statutory budget of Nencki Institute of Experimental Biology and grant PBS3/B7/19/2015 from The National Centre for Research and Development, Poland.
TMIC-28. LONG NON-CODING RNA EXPRESSION DIFFERS BETWEEN GLIOBLASTOMA PATIENT IMMUNE CELLS AND HEALTHY VOLUNTEERS
Authors: Anthony Nwankwo, Victoria Sanchez, John Lynes, Xiang Wang, Gifty Dominah, Arnold Obungu, Nancy Edwards, Kwadwo Sarpong, Oluwatobi Ariyo, Kory Johnson, Edjah K Nduom
Journal: Neuro-Oncology (2019)

Abstract To improve glioblastoma treatment, improved characterization of the tumor’s immune microenvironment is critical. Aberrant long non-coding RNA (LncRNA) expression has been implicated in the pathogenesis of many cancers, including glioblastoma. Other studies have discovered long non-coding RNAs which regulate immunity. However, lncRNA expression has not been systematically investigated glioblastoma patient immune cells. We aimed to investigate the differential expression of LncRNA and mRNs in the T lymphocytes and monocytes of glioblastoma patients when compared to healthy controls in an unbiased fashion. CD3 and CD14 cells were sorted from PBMC samples from 3 newly diagnosed glioblastoma patients and 3 normal donors, and RNA was extracted from them. These RNA samples were run on the Arraystar Human LncRNA microarray. We found 309 LncRNAs differentially expressed in glioblastoma patient T cells, and 316 in patient monocytes (fold change &gt;2 or £0.5, P£0.05). A preliminary review of this data has revealed upregulation of lncRNAs that have previously been reported to play a role in tumorigenesis, such as MIF12-AS1, VIM-AS1, and WEE2-AS1. Additionally, lncRNAs such as CCDC26 and Hoxa10 that have been implicated in immune cell differentiation and hyperactivity also show differential expression between the two groups. We also found differential expression of 203 mRNA in T cells and 467 in monocytes (fold change ³2 or £0.5, P£0.05). An analysis based on the Kyoto Encyclopedia of Genes and Genomes identified 42 biological pathways that have enrichment of these differentially expressed mRNAs (P£0.05), including the RIG-I-like receptor pathway and toll-like receptor pathway, both implicated in innate immunity in T-cells. This array data will form the template for future single-cell RNA sequencing of tumor-infiltrating immune cells; peripheral immune cells from glioblastoma patients; and immune cells from non-tumorous brain (epilepsy tissue) and blood samples to investigate these differences in greater detail.
Closing the Efficacy and Effectiveness Gap: Outcomes in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Treated with Ixazomib-Lenalidomide-Dexamethasone (IRd) in Routine Clinical Practice Remain Comparable to the Outcomes Reported in the Phase 3 Tourmaline-MM1 Study
Authors: Roman Hajek, Jiri Minarik, Jan Straub, Ludek Pour, Alexandra Jungova, Jesus G. Berdeja, Mario Boccadoro, Lucie Brožová, Andrew Spencer, Frits van Rhee, Jorge Vela-Ojeda, Michael A. Thompson, Rafat Abonour, Ajai Chari, Gordon Cook, Caitlin L. Costello, Faith E. Davies, Vania T.M. Hungria, Hans C. Lee, Xavier Leleu, Noemi Puig, Robert M. Rifkin, Evangelos Terpos, Saad Z. Usmani, Katja C. Weisel, Jeffrey A. Zonder, Magda Bařinová, Matyáš Kuhn, Jiri Silar, Lenka Capkova, Kenny Galvez, Jin Lu, Tomas Skacel, Jennifer Elliott, Brittany Demers, Dawn Marie Stull, Kaili Ren, Vladimir Maisnar
Journal: Blood (2019)
Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication
Authors: Chenyang Xiang, Yuxuan Zhang, Weisheng Guo, Xing-Jie Liang
Journal: Acta Pharmaceutica Sinica B (2019)

Nowadays, nanotechnology is revolutionizing the approaches to different fields from manufacture to health. Carbon nanotubes (CNTs) as promising candidates in nanomedicine have great potentials in developing novel entities for central nervous system pathologies, due to their excellent physicochemical properties and ability to interface with neurons and neuronal circuits. However, most of the studies mainly focused on the drug delivery and bioimaging applications of CNTs, while neglect their application prospects as therapeutic drugs themselves. At present, the relevant reviews are not available yet. Herein we summarized the latest advances on the biomedical and therapeutic applications of CNTs in vitro and in vivo for neurological diseases treatments as inherent therapeutic drugs. The biological mechanisms of CNTs-mediated bio-medical effects and potential toxicity of CNTs were also intensely discussed. It is expected that CNTs will exploit further neurological applications on disease therapy in the near future.
Imetelstat Sensitizes Hematopoietic Malignancy Cells to Genotoxic Agent Via Suppression of Telomerase Mediated DNA Repair Process
Authors: Daisuke Hidaka, Masahiro Onozawa, Naohiro Miyashita, Masao Nakagawa, Daigo Hashimoto, Takanori Teshima
Journal: Blood (2019)
Treatment of Phlebothrombosis
Authors: K. Ball
Journal: BMJ (1948)

been oedema, diarrhoea, or vomiting.No other drugs had been given and the patient's conduct prior to the commencement of treatment in hospital had been normal.i The patient was now a pleasant and co-operative individual who was rather vague about what had been happening to him during the days when his behaviour was abnormal.He scarcely ever touched alcohol because of his disability and had no previous history of mental aberration.
Validation of the PRIMA-Prognostic Index for Patients Treated with Rituximab Plus Chemotherapy and Refinement of Prognostic Parameters for Patients on Rituximab Plus Lenalidomide in the Phase III Relevance Trial
Authors: Edith Julia, Nathan H Fowler, Emmanuel Bachy, Pierre Feugier, Reda Bouabdallah, Herve Tilly, M. Lia Palomba, Christophe Fruchart, Edward N. Libby, Rene-Olivier Casasnovas, Ian W. Flinn, Corinne Haioun, Herve Maisonneuve, Loic Ysebaert, Nancy L. Bartlett, Kamal Bouabdallah, Pauline Brice, Vincent Ribrag, Nicolas Daguindau, Steven Le Gouill, Gian-Matteo Pica, Alejandro Martín, Armando Lopez-Guillermo, Jean-Francois Larouche, Kiyoshi Ando, Gomes da Silva Maria, Marc André, Ka Lung Wu, Laurie H Sehn, Kensei Tobinai, Guillaume Cartron, Richard Delarue, Myron Czuczman, Luc Xerri, Gilles A. Salles, Franck Morschhauser
Journal: Blood (2019)
Eltrombopag: More Than Just a Thrombopoietin Receptor Agonist (TPO-RA) in Immune Thrombocytopenia (ITP)
Authors: Anwar A. Sayed, Amna Malik, Grace Ayoola, Elisa Lucchini, Sasfia Candrianita, Michelle H Tan, Camelia Vladescu, Deena Paul, Alice C J Hart, Ahmad Khoder, Nesrina Imami, Nichola Cooper
Journal: Blood (2019)
UM171 Modified Cord Blood Achieves Excellent Survival and Disease Control after 2 Years of Follow-up in High and Very High Risk Malignancies
Authors: Sandra Cohen, Jean Roy, Jean-Sébastien Delisle, Nadia M. Bambace, Imran Ahmad, Silvy Lachance, Léa Bernard, Frederic Barabe, Thomas L. Kiss, Lambert Busque, Denis-Claude Roy, Filippo Milano, Guy Sauvageau
Journal: Blood (2019)
Doctor who worked as private GP is suspended for 12 months for excessive prescribing
Authors: Clare Dyer
Journal: BMJ (2019)

A doctor who trained in cardiology but worked for many years as a private practice GP has been suspended from the UK medical register for 12 months for exceeding his competence in prescribing risky drugs to a “complex” and addicted patient.

David Dighton, who qualified in 1966 and worked in academic medicine before becoming a sole practitioner in a private practice in Essex in 1982, admitted prescribing excessive quantities of the powerful pain drugs co-proxamol and dihydrocodeine and the sleeping pill zolpidem to a woman named only as Patient A. In some cases, he renewed prescriptions at a rate that would exceed the prescribed dosage.

A medical practitioners’ tribunal found that Dighton, who had no formal GP training, failed to adequately assess her mental state or suicide risk, or refer her to mental health services, although he also prescribed antidepressants while …
Haploidentical Stem Cell Transplantation in Advanced Stage Mycosis Fungoides and Sézary Syndrome: A Report of Four Consecutive Cases from a Single Center
Authors: Francesco Onida, Giorgia Saporiti, Viviana Beatrice Valli, Silvia Alberti Violetti, Federica Irene Grifoni, Maria Cecilia Goldaniga, Mariarita Sciumè, Luca Baldini, Emilio Berti
Journal: Blood (2019)
Alpine: Phase 3 Trial of Zanubrutinib (BGB-3111) Vs Ibrutinib in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Authors: Peter Hillmen, Jennifer R. Brown, John C. Byrd, Barbara F. Eichhorst, Nicole Lamanna, Susan M. O'Brien, Lugui Qiu, Tommi Salmi, James Hilger, Jane Huang, Constantine S. Tam
Journal: Blood (2019)
Post-myocardial-infarction Syndrome
Authors: C. Davidson, M. F. Oliver, R. F. Robertson
Journal: BMJ (1961)

The post-myocardial-infarction syndrome is character- ized by prolonged pericardial friction, persistent chest pain, continuing fever, and, in many instances, by pericardial and pleural effusion.These features develop during the first few weeks after myocardial infarction.The whole illness may pursue a relapsing course for months.The syndrome was first described by Dressler (1956), and in 1959 he reported its occurrence in 44 patients.He estimated that the syndrome complicates from 3 to 4% of cases of myocardial infarction, and it is therefore remarkable that it has escaped recognition until recent years.Weiser, Kantor, and Russell (1959) have described four similar cases, but, so far as we are aware, no series has been reported in the British literature.Two of the five cases described in this paper were seen early in 1960, and within six months two others were diagnosed.The remaining one was identified from a review of patients classified as having pericarditis complicating myocardial infarction; in this patient, the significance of the pericarditis and other features of the syndrome had not been appreciated at the time.A review of 500 consecutive patients admitted to the Edinburgh Royal Infirmary on account of acute myocardial infarction revealed only three who developed the features of the post-myocardial-infarction syndrome-an incidence of less than 1%.Case 1 A man aged 53 had increasing effort angina for two weeks.An acute myocardial infarct, with classical and severe precordial pain lasting for two hours, occurred immediately before admission.There was no history of previous vascular or other disease.On arrival in hospital he was shocked, with a blood-pressure of 100/80.With morphine, oxygen, and the relief of pain, the clinical features of shock dis- appeared but hypotension remained; on the fourth day after admission his blood-pressure fell to 80/50 and was subsequently in the region of 115/70.The first electro- cardiogram taken on the morning of admission showed an acute transmural posterior myocardial infarct with wide- spread myocardial ischaemia, and a further record taken later on the same day showed the development of atrial fibrillation with a ventricular rate of approximately 120 a B
100,000 genomes project: Integrating whole genome sequencing (WGS) data into clinical practice
Authors: A. Sosinsky, J. Ambrose, M. Zarowiecki, J. Mitchell, S. Henderson, N. Murugaesu, A. Hamblin, C. Turnbull, S. Walker, D. Perez-Gil, A. Rueda-Martin, T. Fowler, M. Caulfield, A. Rendon
Journal: Annals of Oncology (2019)
NLRP6 in Donor T Cells Separately Regulates CD4 and CD8 Mediated Graft-Versus-Host Disease in Experimental Murine BMT
Authors: Masahiro Suto, Eri Matsuki, Erika Sekiguchi, Hiroya Tamaki, Isao Tawara, Grace Chen, Kenichi Ishizawa, Pavan Reddy, Tomomi Toubai
Journal: Blood (2019)
Effect of Mailed Human Papillomavirus Test Kits vs Usual Care Reminders on Cervical Cancer Screening Uptake, Precancer Detection, and Treatment
Authors: Rachel L. Winer, John Lin, Jasmin A. Tiro, Diana L. Miglioretti, Tara Beatty, Hongyuan Gao, Kilian Kimbel, Chris Thayer, Diana S. M. Buist
Journal: JAMA Network Open (2019)

<h3>Importance</h3> In the United States, more than 50% of cervical cancers are diagnosed in underscreened women. Cervical cancer screening guidelines now include primary human papillomavirus (HPV) testing as a recommended strategy. Home-based HPV self-sampling is a viable option for increasing screening compliance and effectiveness; however, US data are needed to inform health care system implementation. <h3>Objective</h3> To evaluate effectiveness of mailed HPV self-sampling kits vs usual care reminders for in-clinic screening to increase detection and treatment of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and uptake of cervical cancer screening. <h3>Design, Setting, and Participants</h3> Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Women aged 30 to 64 years with health plan enrollment for 3 years and 5 months or more, a primary care clinician, no Papanicolaou test within 3 years and 5 months, and no hysterectomy were identified through electronic medical records and enrolled from February 25, 2014, to August 29, 2016, with follow-up through February 26, 2018. <h3>Interventions</h3> The control group received usual care (annual patient reminders and ad hoc outreach from primary care clinics). The intervention group received usual care plus a mailed HPV self-sampling kit. <h3>Main Outcomes and Measures</h3> Two primary outcomes were (1) CIN2+ detection within 6 months of screening and (2) treatment within 6 months of CIN2+ detection. Screening uptake within 6 months of randomization was a secondary outcome. <h3>Results</h3> A total of 19 851 women (mean [SD] age, 50.1 [9.5] years) were included, with 9960 randomized to the intervention group and 9891 randomized to the control group. All women randomized were included in analysis. In the intervention group, 12 participants with CIN2+ were detected compared with 8 in the control group (relative risk, 1.49; 95% CI, 0.61-3.64) and 12 cases were treated vs 7 in the control group (relative risk, 1.70; 95% CI, 0.67-4.32). Screening uptake was higher in the intervention group (2618 participants [26.3%] vs 1719 participants [17.4%]; relative risk, 1.51; 95% CI, 1.43-1.60). <h3>Conclusions and Relevance</h3> Mailing HPV kits to underscreened women increased screening uptake compared with usual care alone, with no significant differences in precancer detection or treatment. Results support the feasibility of mailing HPV kits to women who are overdue for screening as an outreach strategy to increase screening uptake in US health care systems. Efforts to increase kit uptake and follow-up of positive results are warranted to maximize detection and treatment of CIN2+. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT02005510
Geriatric Assessment Identifies Impairments in Younger Candidates for Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Meagan V. Lew, Yi Ren, Yen P. Lowder, Kristi M. Romero, Jillian C. Thompson, Lauren M. Bohannon, Harvey Cohen, David A. Bartlett, Amy M. Pastva, Miriam Morey, Katherine Hall, Patrick Smith, Katherine B. Peters, Tamara Somers, Sarah Kelleher, Sophia Smith, Paul Wischmeyer, Pao-Hwa Lin, Glynnis Thorpe, Kerry Minor, Allison Adler, Kristi Wiggins, Therese Hennig, Tanya Helms, Renee Welch, Whitney Hicks, Margaret Eren, Rebecca Porter, Brittany Matthews, JoAnn Liu, Jill Burleson, Whitney Andrew, Thomas Aberant, Ashley K. Engemann, Bethany Henshall, Maurisa Darby, Renea Valea, Christina Proch, Michelle Dellascio, Alyssa Pittman, Taewoong Choi, Cristina Gasparetto, Gwynn D. Long, Richard D. Lopez, David A. Rizzieri, Stefanie Sarantopoulos, Mitchell E. Horwitz, Nelson J. Chao, Anthony D. Sung
Journal: Blood (2019)
Tumor Circulating Plasma Cells Detected By Flow Cytometric Single Platform Method Correlate with Clinical Response to Therapy and Unfavorable Patients' Characteristics
Authors: Vittorio Emanuele Muccio, Milena Gilestro, Elona Saraci, Andrea Capra, Alessandro Costa, Marina Ruggeri, Simona Caltagirone, Daniela Oddolo, Chiara Mussatto, Pellegrino Musto, Lucia Pantani, Vincenzo Pavone, Sonia Ronconi, Iolanda Donatella Vincelli, Anna Maria Cafro, Claudia Cellini, Vanessa Innao, Eugenio Piro, Francesca Gay, Mario Boccadoro, Paola Omedé
Journal: Blood (2019)
PATH-31. BUILDING A RAMAN SPECTROSCOPY REFERENCE DATABASE FOR TUMOR IDENTIFICATION AND CLASSIFICATION
Authors: Felix Kleine Borgmann, Andreas Husch, Redouane Slimani, Finn Jelke, Giulia Mirizzi, Karoline Klein, Michel Mittelbronn, Frank Hertel
Journal: Neuro-Oncology (2019)

Abstract Brain tumor resection requires careful assessment of the nature and malignancy of the tumor tissue during intervention, as this is the basis for the decision as to how radical surgery has to be. Typically, there is no tissue available for analysis prior to the surgery. Intraoperative histopathological examination of tumor samples is time consuming and puts the patient to a significant amount of strain due to ongoing anesthesia and prolonged surgery, thus there is a need to develop faster methods for thorough diagnostics. Raman spectroscopy allows for a fast analysis of samples without the need for labeling and sample preparation, making it a useful tool for peri- and intrasurgical application. We collect Raman spectra and correlated histopathological results to build a database of different tumor types. As intrasurgical use of Raman spectroscopy will typically be applied to native specimens, the respective database has to be based on native samples as well. We collected several thousands of measurements from more than 100 patients and continue to assemble a native database. Tumors that do not occur with a high frequency are not sufficiently represented in the database. Therefore, we investigate whether it is possible to integrate fixed and frozen specimens in the collection of Raman spectra and the classifier. Fixation results in characteristic changes to the biochemistry of biological tissues. We collect pairs of spectra from native and fixed as well as from native and frozen specimens and use the difference of the spectra to create an algorithm for filtering of the specific changes in the spectra. These data can be used to train a classifier for the identification of native samples. This opens the way for assessing large collections of pathological samples in fixed and frozen state to cover any type of neoplastic disease in the database.
Using Childhood International Prognostic Scoring in Pediatric Hodgkin Lymphoma Patients Treated with ABVD Can Mitigate Use of Interim PET in LMIC
Authors: Reham Khedr, Hanaa Rashad, Asmaa Mohammed Hamoda, Eman Khorshed, Madeha Elwakeel, Mohamed Saad, Engy Mohamed, Emad Moussa
Journal: Blood (2019)
TMIC-51. GBP1 RECRUITS MACROPHAGES TO PROMOTE GLIOBLASTOMA GROWTH
Authors: Lili Chen, Ming Li
Journal: Neuro-Oncology (2019)

Abstract Guanylate binding protein 1 (GBP1) is an interferon-inducible large GTPase which plays a key role in tumor development, but the molecular mechanism is poorly understood. Here we investigated whether GBP1 could influence the tumor microenvironment in glioblastoma, the most common and malignant brain tumor. We found that forced expression of GBP1 in glioblastoma cells induced macrophage polarization toward an M2 phenotype via upregulating Chemokine (C-C motif) ligand 2 (CCL2). CCL2 acted via its receptor C-C chemokine receptor 2 (CCR2) to enhance macrophage cell migration in vitro. The M2 macrophages in turn promoted glioblastoma cell proliferation and migration. The orthotopic mouse model showed that GBP1 recruited M2 macrophages into tumor to promote glioblastoma progression, and targeting CCL2/CCR2 signaling axis with a small molecule inhibitor RS504393 led to decreased macrophage attraction and M2 polarization and a significant tumor growth retardation and prolonged survival of tumor-bearing mice. Clinically, GBP1 expression positively correlated with M2 macrophage numbers and CCL2 expression in glioblastoma. Taken together, our results reveal that GBP1 modulates the tumor immune microenvironment through CCL2 induction to promote glioblastoma infiltrating growth, and targeting tumor-associated macrophages may represent a new therapeutic strategy against glioblastoma.
Effect of Cyclophosphamide on Hemorrhagic Cystitis Following Haploidentical Related Compared to Matched Related/Unrelated Donor Hematopoietic Stem Cell Transplantation: A 7-Year Tertiary Center Analysis
Authors: Guldane Cengiz Seval, Nergis Ozturk, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Pervin Topcuoglu, Onder Arslan, Muhit Özcan, Taner Demirer, Gunhan Gurman, Osman Ilhan, Hamdi Akan, Meral Beksac, Selami Kocak Toprak
Journal: Blood (2019)
Severe Infections and Antibiotic Use Negatively Impact Progression Free and Overall Survival of Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
Authors: Marshall McKenna, Rena Feinman, Jaeil Ahn, Shuqi Wang, Elli Gourna Paleoudis, David H. Vesole, Stuart L. Goldberg, Jun Chih Wang, Abdul Rehman, Giselle Alexandra Suero-Abreu, Phyllis McKiernan, Michele L. Donato, Scott D. Rowley, David S. Siegel, Noa Biran
Journal: Blood (2019)
Pharmacokinetics of Ticagrelor in Infants and Toddlers Aged &lt;24 Months with Sickle Cell Disease
Authors: Baba PD Inusa, Adlette Inati, Philip Maes, Jessie Githanga, Miguel R. Abboud, Maurizio Miano, Elena Cela, Videlis Nduba, Mohammad Niazi, Magnus Åstrand, Kevin Persson, Anders Rikard Berggren, Glenn Carlson
Journal: Blood (2019)
Genomic Characterization of Diffuse Large B-Cell Lymphoma Transformation from Nodular Lymphocyte Predominant Hodgkin Lymphoma
Authors: Joo Y. Song, Caoimhe Egan, Alyssa Bouska, Weiwei Zhang, Qiang Gong, Girish Venkataraman, Alex F. Herrera, Lu Chen, Rebecca Ottesen, Joyce Niland, Victoria Bedell, Maria Valle-Catuna, Joyce Murata-Collins, Dennis D. Weisenburger, Javeed Iqbal, Elaine S. Jaffe, Wing C. Chan
Journal: Blood (2019)