tbuckley/cabot-search huggingface dataset:
Defects of ATM Gene Involving Mutation Lead to Complete Elimination of ATM Function in Chronic Lymphocytic Leukemia
Authors: Veronika Navrkalova, Ludmila Sebejova, Jana Zemanova, Jana Kminkova, Blanka Kubesova, Michael Doubek, Yvona Brychtova, Jana Smardova, Jiri Mayer, Sarka Pospisilova, Martin Trbusek
Journal: Blood (2012)
Achievement a Negative 18-FDG/PET Status at the End of Procedure by Tailored Treatment According Pre-Transplantation Pet Status in Lymphomas Improve 5 Years-OS and EFS.
Authors: Dominique Bordessoule, Benoit Marin, Stéphane Girault, Fredericka Bompart, Julie Abraham, Natacha Dmytruck, Arnaud Jaccard, Jacques Monteil, Pascal Turlure
Journal: Blood (2008)
The Fas Ligand Inhibitor APG101 in Transfusion Dependent Patients with Low Risk MDS: Interim Results from a Phase I Study
Authors: Evi launiger-Lörsch, Thomas Luft, Stephanie Fey, Julia Obländer, Susanne Brendel, Jovita Pressler, Johann-Christoph Jann, Claudia Kunz, Anthony D. Ho, Harald Fricke, Maximilian Mossner, Georgia Metzgeroth, Daniel Nowak, Wolf-Karsten Hofmann, Florian Nolte
Journal: Blood (2014)
Vascular Endothelial-Cadherin Targeted Alpha-Particle Mediated Vascular Killing and Remodeling Augments Subsequent Chemotherapeutic Efficacy.
Authors: Freddy E Escorcia, Erik Henke, Michael R. McDevitt, Carlos Villa, Peter Smith-Jones, Ronald Blasberg, Robert Benezra, David A. Scheinberg
Journal: Blood (2009)
Annals Consult Guys – Measuring Lipids: To Fast or Not to Fast
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2017)

Web Exclusives17 January 2017Annals Consult Guys – Measuring Lipids: To Fast or Not to FastFREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0001 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Miki CsintalanUCI25 January 2017 Annals Consult Guys-Measuring Lipids: To Fast or Not to Fast Great discussion. Our patients will be much happier about not fasting. I am a bit confused after listening to Dr. Weitz' statements 11 min into the video. "there should be a national move toward the nonfasting lipid panel. Be aware that triglycerides will affect a calculated LDL, but many labs are doing direct LDL measurement. The effect of triglycerides on calculated LDL really only occurs when triglycerides are 400 mg/dl or higher. We think we should move toward the fasting test." Did Dr. Weitz really mean to say nonfasting test at the end of this quote? Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCorrection: Annals Consult Guys—Measuring Lipids: To Fast or Not to Fast 17 January 2017Volume 166, Issue 2Page: CG1KeywordsDisclosureLipidsResearch grantsResearch reporting guidelines ePublished: 17 January 2017 Issue Published: 17 January 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
The amyloidogenic light chain is a stressor that sensitizes plasma cells to proteasome inhibitor toxicity
Authors: Laura Oliva, Ugo Orfanelli, Massimo Resnati, Andrea Raimondi, Andrea Orsi, Enrico Milan, Giovanni Palladini, Paolo Milani, Fulvia Cerruti, Paolo Cascio, Simona Casarini, Paola Rognoni, Thierry Touvier, Magda Marcatti, Fabio Ciceri, Silvia Mangiacavalli, Alessandro Corso, Giampaolo Merlini, Simone Cenci
Journal: Blood (2017)
Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain
Authors: Kassandra Kisler, Amy R Nelson, Sanket V Rege, Anita Ramanathan, Yaoming Wang, Ashim Ahuja, Divna Lazic, Philbert S Tsai, Zhen Zhao, Yi Zhou, David A Boas, Sava Sakadžić, Berislav V Zlokovic
Journal: Nature Neuroscience (2017)
Precision medicine in allergic disease—food allergy, drug allergy, and anaphylaxis—<scp>PRACTALL</scp> document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology
Authors: A. Muraro, R. F. Lemanske, M. Castells, M. J. Torres, D. Khan, H.‐U. Simon, C. Bindslev‐Jensen, W. Burks, L. K. Poulsen, H. A. Sampson, M. Worm, K. C. Nadeau
Journal: Allergy (2017)

This consensus document summarizes the current knowledge on the potential for precision medicine in food allergy, drug allergy, and anaphylaxis under the auspices of the PRACTALL collaboration platform. PRACTALL is a joint effort of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology, which aims to synchronize the European and American approaches to allergy care. Precision medicine is an emerging approach for disease treatment based on disease endotypes, which are phenotypic subclasses associated with specific mechanisms underlying the disease. Although significant progress has been made in defining endotypes for asthma, definitions of endotypes for food and drug allergy or for anaphylaxis lag behind. Progress has been made in discovery of biomarkers to guide a precision medicine approach to treatment of food and drug allergy, but further validation and quantification of these biomarkers are needed to allow their translation into practice in the clinical management of allergic disease.
Addition of Hemoglobin Level Into the Prognostic Scoring System Together with White Blood Cell and Platelet Count Provides Better Prognostic Stratification for Treatment-Related Mortality and Overall Survival, but Not for Relapse Risk In Adult Patients with Acute Promyelocytic Leukemia
Authors: Jun Ho Yi, Chul Won Jung, Boram Han, Ha Yeon Lee, Jun Ho Jang, Kihyun Kim, Hyeoung Joon Kim, Yeo-Kyeoung Kim, Won-Sik Lee, Young-Don Joo, Min Kyoung Kim, Myung Soo Hyun, Hawk Kim, Jae Hoo Park, Dong Hwan (Dennis) Kim
Journal: Blood (2010)
Systematic Pan-Cancer Analysis Reveals Immune Cell Interactions in the Tumor Microenvironment
Authors: Frederick S. Varn, Yue Wang, David W. Mullins, Steven Fiering, Chao Cheng
Journal: Cancer Research (2017)

Abstract With the recent advent of immunotherapy, there is a critical need to understand immune cell interactions in the tumor microenvironment in both pan-cancer and tissue-specific contexts. Multidimensional datasets have enabled systematic approaches to dissect these interactions in large numbers of patients, furthering our understanding of the patient immune response to solid tumors. Using an integrated approach, we inferred the infiltration levels of distinct immune cell subsets in 23 tumor types from The Cancer Genome Atlas. From these quantities, we constructed a coinfiltration network, revealing interactions between cytolytic cells and myeloid cells in the tumor microenvironment. By integrating patient mutation data, we found that while mutation burden was associated with immune infiltration differences between distinct tumor types, additional factors likely explained differences between tumors originating from the same tissue. We concluded this analysis by examining the prognostic value of individual immune cell subsets as well as how coinfiltration of functionally discordant cell types associated with patient survival. In multiple tumor types, we found that the protective effect of CD8+ T cell infiltration was heavily modulated by coinfiltration of macrophages and other myeloid cell types, suggesting the involvement of myeloid-derived suppressor cells in tumor development. Our findings illustrate complex interactions between different immune cell types in the tumor microenvironment and indicate these interactions play meaningful roles in patient survival. These results demonstrate the importance of personalized immune response profiles when studying the factors underlying tumor immunogenicity and immunotherapy response. Cancer Res; 77(6); 1271–82. ©2017 AACR.
Aberrations of KIT, BRAF, NRAS, and PDGFRA in Chinese melanoma patients and their significance: Large, scale analysis of 644 patients.
Authors: Y. Kong, L. Si, J. Guo, Z. H. Chi, C. L. Cui, X. N. Sheng, B. X. Tang
Journal: Journal of Clinical Oncology (2011)

8568 Background: Mutations in KIT, BRAF, NRAS and PDGFRA are common in melanoma, which have not been extensively studied in Asia. We examined these aberrations and correlated the aberrations to the clinical features and survival in Asian melanoma patients. Methods: This study involved samples from 644 melanoma patients in Peking University Cancer Hospital. Clinical data were collected. Tissue samples were analyzed for mutations in KIT (exons 9,11,13,17,18), BRAF (exons 11,15), NRAS (exons1,2) and PDGFRA (exons 12,14,18) genes by PCR amplification and Sanger sequencing. The copy numbers of KIT gene were analyzed by quantitative PCR. Results: The incidence of somatic mutations within the KIT, BRAF, NRAS and PDGFRA genes was 10.1% (58/573), 25.9% (121/468), 7.2% (33/459) and 4.8% (17/352), respectively. The incidence of increased KIT copy number was 7.6% (39/516). The highest KIT mutation frequency is within the CSD subgroup (27.3%, 9/33). Increased KIT gene copy number was comparatively more frequent in acral (8.0%, 14/176) and mucosal (11.5%, 17/148) melanomas than in CSD (3.2%, 1/31) and Non-CSD (1.9%, 2/104) melanomas. Surprisingly, BRAF mutations were detected in 17.9% (28/156) of acral melanomas and 12.5% (16/128) of mucosal melanomas. The most frequent mutation in BRAF was V600E (87.3%). The median follow-up period was 24 (3~229) months (n=473). No statistical differences were found for thickness and ulceration rates between melanomas with or without these mutations (P=0.6). The median survival for patients with KIT mutations (30 months) and BRAF (33m) were significantly shorter than for patients with WT tumors (53m; P=0.01, P=0.005 respectively). Overall survivals were similar in groups with or without NRAS and PDGFRA mutations. Conclusions: KIT and BRAF are important oncogenes in Asian melanomas. Mutations in the BRAF gene were more common than KIT mutations. For the first time, our study suggests that genetic KIT and BRAF aberration is an adverse prognostic factor for melanoma. These results suggest that the KIT inhibitor as well as BRAF V600E inhibitor might play their roles in Asian melanoma patients. Supported by the National Natural Science Foundation of China30973483.
Adverse events raise concerns over safety of new hepatitis C drugs
Authors: Michael McCarthy
Journal: BMJ (2017)

Newer antiviral drugs for treating hepatitis C virus (HCV) may be associated with liver failure and other severe side effects, a non-profit drug safety group in the US has warned in a report released on 25 January.1

The report, by the Institute for Safe Medication Practices, is based on a review of adverse drug event reports submitted to the US Food and Drug Administration that were associated with new direct acting HCV antivirals.1

The drugs found to be associated with adverse drug events included: daclatasvir …
Novel psychoactive substances: types, mechanisms of action, and effects
Authors: Derek K Tracy, David M Wood, David Baumeister
Journal: BMJ (2017)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Novel psychoactive substances: types, mechanisms of action, and effects Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
The art of pronunciation
Authors: Dharani Yerrakalva
Journal: BMJ (2017)

We are in full flow, and the bright eyed woman in her 80s in front of me is rising to the challenge I am presenting her with. A little memory test.

“How do you spell the word ‘world’ backwards?” I ask.

“Whirled? Like a whirlpool? D,E, L…” she looks at …
High-Dose Melphalan Versus Busulfan, Cyclophosphamide As Conditioning Regimens for Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma
Authors: Michael Styler, Pamela Ann Crilley, Maneesh Jain, Kristine Ward, David Topolsky, David Cho, Marc Kim
Journal: Blood (2015)
High Antileukemic Efficacy and Shortened Neutropenia of Dose-Dense Induction (Sequential-HAM Followed by Pegfilgrastim) in Primary Acute Myeloid Leukemia - Results of a Pilot Study of the German AML-CG.
Authors: Jan Braess, Karsten Spiekermann, Christian Buske, Peter Staib, Wolf-Dieter Ludwig, Andreas Gruneisen, Christa Sauerland, Michael Unterhalt, Michael Fiegl, Bernhard Wormann, Wolfgang Kern, Achim Heinicke, Wolfgang Berdel, Thomas Büchner, Wolfgang Hiddemann
Journal: Blood (2007)
A Novel Role of Coagulation Proteases on Viral-Based Gene Transfer Efficacy.
Authors: Joerg Schuettrumpf, Jianxiang Zou, Shin Jen Tai, Alexander Schlachterman, Kian Tian, Shyrie Edmonson, Jianhua Liu, Patricia Andrade-Gordon, Katherine High, Valder Arruda
Journal: Blood (2004)
Complex Karyotype Predicts Outcome Better Than Monosomal Karyotype In Patients with MDS/Secondary Acute Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): a Retrospective Survey on Behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Angelique .M. Brands-Nijenhuis, Michel van Gelder, Theo M. de Witte, Johannes Schetelig, Anja van Biezen, Nicolaus Kroeger
Journal: Blood (2010)
Fludarabine Plus Cyclophosphamide and Rituximab In Waldenström's Macroglobulinemia: Results In 55 Patients
Authors: Véronique Leblond, Laetitia Compain, Vincent Levy, Jérôme Tamburini, Alain Delmer, Jacques Vargaftig, Brigitte Pégourié-Bandelier, Beatrice Mahe, Steven Le Guill, Olivier Tournilhac, Elisabeth Brottier-Mancini, Richard Delarue, Agnès Buzyn, Michel Maigre, Claude Gardin, Sylvain Choquet
Journal: Blood (2010)
Advancing Symptom Science Through Symptom Cluster Research: Expert Panel Proceedings and Recommendations
Authors: Christine Miaskowski, Andrea Barsevick, Ann Berger, Rocco Casagrande, Patricia A. Grady, Paul Jacobsen, Jean Kutner, Donald Patrick, Lani Zimmerman, Canhua Xiao, Martha Matocha, Sue Marden
Journal: JNCI Journal of the National Cancer Institute (2016)

An overview of proceedings, findings, and recommendations from the workshop on "Advancing Symptom Science Through Symptom Cluster Research" sponsored by the National Institute of Nursing Research (NINR) and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, is presented. This workshop engaged an expert panel in an evidenced-based discussion regarding the state of the science of symptom clusters in chronic conditions including cancer and other rare diseases. An interdisciplinary working group from the extramural research community representing nursing, medicine, oncology, psychology, and bioinformatics was convened at the National Institutes of Health. Based on expertise, members were divided into teams to address key areas: defining characteristics of symptom clusters, priority symptom clusters and underlying mechanisms, measurement issues, targeted interventions, and new analytic strategies. For each area, the evidence was synthesized, limitations and gaps identified, and recommendations for future research delineated. The majority of findings in each area were from studies of oncology patients. However, increasing evidence suggests that symptom clusters occur in patients with other chronic conditions (eg, pulmonary, cardiac, and end-stage renal disease). Nonetheless, symptom cluster research is extremely limited and scientists are just beginning to understand how to investigate symptom clusters by developing frameworks and new methods and approaches. With a focus on personalized care, an understanding of individual susceptibility to symptoms and whether a "driving" symptom exists that triggers other symptoms in the cluster is needed. Also, research aimed at identifying the mechanisms that underlie symptom clusters is essential to developing targeted interventions.
The Novel Akt Inhibitor Perifosine Induces Apoptosis, Cell Cycle Arrest and Synergizes with Chemotherapeutic Drugs in Acute Myelogenous Leukemia Cells by a JNK Dependent Mechanism - A Novel Therapeutic Approach for Leukemia Displaying Elevated Akt Signaling.
Authors: Alberto M. Martelli, Veronica Papa, Pier Luigi Tazzari, Francesca Chiarini, Alessandra Cappellini, Francesca Ricci, Anna Maria Billi, Camilla Evangelisti, Steve L. Abrams, Emanuela Ottaviani, Giovanni Martinelli, James A. McCubrey
Journal: Blood (2007)
Identification of SEC23B as the Gene Responsible for Congenital Dyserythropoietic Anemia Type II using a Proteomic-Genomic Approach.
Authors: Paola Bianchi, Elisa Fermo, Cristina Vercellati, Carla Boschetti, Wilma Barcellini, Alessandra Iurlo, Anna Paola Marcello, Pier Giorgio Righetti, Alberto Zanella
Journal: Blood (2009)
The Allosteric Inhibitor ABL001 Is Susceptible to Resistance in Vitro Mediated By Overexpression of the Drug Efflux Transporters ABCB1 and ABCG2
Authors: Laura N Eadie, Verity A Saunders, Tamara M Leclercq, Susan Branford, Deborah L White, Timothy P. Hughes
Journal: Blood (2015)
Mechanisms of malignant STS progression: Insights from a feline model
Authors: Nilanjana Banerji, Sagarika Kanjilal
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

777 

Malignant soft-tissue sarcomas (STS) of adult onset are highly invasive tumors of mesenchymal origin that afflict ∼8,000 individuals each year in the US. Although this number represents only about 1% of adult malignancies, effective management of the disease is an extremely challenging task. While great progress has been made in preserving function through surgical advances and high dose radiation therapy, local recurrences appear at a median interval of 18 months for about a third of extremity tumors and about 60% of abdominal cases. While time to recurrence is improved with the use of adjuvant chemotherapy, patient survival is not significantly affected by such treatment and close to 50% of patients with primary soft tissue sarcoma die within 5 years due to the development of lung metastases. Hence, there is a clear need to gain a better understanding of the basic mechanisms involved in the pathogenesis of malignant STS and to develop new targets for therapeutic intervention. However, well-characterized sets of tissue samples appropriate for conducting such comprehensive analyses are not readily available for this relatively infrequent disease. In order to overcome this obstacle and develop a model for studying STS, we have investigated the development and progression of sarcomas that spontaneously arise from inflammatory granulomas at vaccination sites in domestic cats; a species whose genome bears a remarkable degree of syntenic conservation with that of humans. In order to characterize the model, we have established a comprehensive information and tissue bank of the vaccine associated feline sarcomas (VAFS) and our studies indicate that these tumors resemble human soft tissue sarcomas in a number of characteristics including pathologies and propensity for local post-surgical recurrence as well as distant metastasis. Similarities between the human disease and feline model also extend to p53 tumor suppressor gene alterations (which are associated with a poor prognosis in both species). In order to gain a further understanding of the molecular and cellular alterations that occur during disease progression, comparative studies have also been conducted on matched sets of cell lines from primary VAFS tumors and corresponding local recurrences. The results of these studies provide strong evidence for an increase in the intrinsic levels of chemo-resistance during disease progression even in absence of any prior exposure to chemotherapeutic agents. Concurrent gene expression analyses of disease progression using the matched tissues and cell-lines have also provided a rich harvest of “novel” targets for molecular classification and future investigations on therapeutic intervention. Overall, VAFS is proving to be an excellent model for studying disease progression in STS and has great potential for enhancing our understanding of the role of inflammation in tumor development.
MEIS1 Regulates Early Erythroid and Megakaryocytic Lineage Decision
Authors: Sabrina Zeddies, Sjoert Jansen, Franca di Summa, Sofieke Klamer, Marion Kleier, Jaap Jan Zwaginga, Marieke von Lindern, C. Ellen Van der Schoot, Daphne C Thijssen-Timmer
Journal: Blood (2011)
Fludarabine, but Not Mitoxantrone, Increases the Risk of a Poor Stem Cell Harvest and Treatment-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia (tMDS/AML) after Autologous Stem Cell Transplantation (ASCT) in Patients with Follicular Lymphoma (FL).
Authors: Jason Waterman, Lisa Rybicki, Brian Bolwell, Ronald Sobecks, Brad Pohlman, Edward Copelan, John Sweetenham, Robert Dean, Josephine Chan, Matt Kalaycio
Journal: Blood (2008)
Frequency of Clonal Evolution by FISH in Untreated, Early Stage Patients with CLL: A Prospective, Longitudinal Study with Long Clinical Follow-Up.
Authors: Tait D. Shanafelt, Stephanie Fink, Tom E. Witzig, Sarah F. Paternoster, Stephanie Smoley, Kim Stockero, Heather C. Flynn, Christine Almer, Robert Jenkins, Susan Geyer, Neil E. Kay, Gordy Dewald
Journal: Blood (2005)
Decreased Frequency of Circulating CD34+ Hematopoietic Stem/Progenitor Cells in Preterm Infants with Late-Onset Systemic Bacterial Infection
Authors: Kam Tong Leung, Hugh Simon Lam, Kathy Yuen Yee Chan, Raymond Pui On Wong, Karen Li, Chi Kong Li, Pak Cheung Ng
Journal: Blood (2014)
Single-cell epigenomic variability reveals functional cancer heterogeneity
Authors: Ulrike M. Litzenburger, Jason D. Buenrostro, Beijing Wu, Ying Shen, Nathan C. Sheffield, Arwa Kathiria, William J. Greenleaf, Howard Y. Chang
Journal: Genome biology (2017)

Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity but is difficult to detect and assess functionally.We develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using single-cell chromatin accessibility and RNA-seq data in K562 leukemic cells, we identify the cell surface marker CD24 as co-varying with chromatin accessibility changes linked to GATA transcription factors in single cells. Fluorescence-activated cell sorting of CD24 high versus low cells prospectively isolated GATA1 and GATA2 high versus low cells. GATA high versus low cells express differential gene regulatory networks, differential sensitivity to the drug imatinib mesylate, and differential self-renewal capacity. Lineage tracing experiments show that GATA/CD24hi cells have the capability to rapidly reconstitute the heterogeneity within the entire starting population, suggesting that GATA expression levels drive a phenotypically relevant source of epigenomic plasticity.Single-cell chromatin accessibility can guide prospective characterization of cancer heterogeneity. Epigenomic subpopulations in cancer impact drug sensitivity and the clonal dynamics of cancer evolution.