tbuckley/cabot-search huggingface dataset:
10-year performance of four models of breast cancer risk: a validation study
Authors: Mary Beth Terry, Yuyan Liao, Alice S Whittemore, Nicole Leoce, Richard Buchsbaum, Nur Zeinomar, Gillian S Dite, Wendy K Chung, Julia A Knight, Melissa C Southey, Roger L Milne, David Goldgar, Graham G Giles, Sue-Anne McLachlan, Michael L Friedlander, Prue C Weideman, Gord Glendon, Stephanie Nesci, Irene L Andrulis, Esther M John, Kelly-Anne Phillips, Mary B Daly, Saundra S Buys, John L Hopper, Robert J MacInnis
Journal: The Lancet Oncology (2019)
702. Concurrent Delivery of GM-CSF and B7-1 Using an Oncolytic Adenovirus Elicits Potent Anti-Tumor Effect on the Growth Established B16-F10 Tumor Model
Journal: Molecular Therapy (2005)

Oncolytic adenoviral vectors are currently being developed as biological anti-cancer therapeutic agents. Coupling the lytic function of oncolytic adenovirus with virus-mediated transgene delivery represents a powerful extension of this methodolgy. To increase the potential anti-tumor activity of oncolytic adenovirus, we constructed an E1B 55kDa deleted oncolytic adenoviral vector, YKL-GB, which expresses both GM-CSF and B7-1. The therapeutic efficacy of YKL-GB adenovirus was evaluated in immunocompetent mice bearing murine melanoma B16-F10 tumors. Significant inhibition of tumor growth was seen in mice treated with YKL-GB compared to those treated with an analogous vector, YKL-1, that lacks GM-CSF and B7-1. Moreover, YKL-GB oncolytic adenovirus demonstrated enhanced anti-tumor activity and a higher incidence of complete tumor regression compared to a replication-incompetent adenovirus, dl-GB, which co-expresses the GM-CSF and B7-1. Localized GM-CSF and B7-1 gene transfer also conferred long-lasting immunity against tumor rechallenge. To establish that anti-tumor effect is associated with the generation of tumor-specific immune response, we examined the cytolytic activity by IFN-|[gamma]| ELISpot assay. We observed that YKL-GB induced significantly higher T cell-mediated antitumor activity than YKL-1. Furthermore, immunohistochemical studies demonstrated robust CD4+ and CD8+ T-cell infiltration in these mice compared to the YKL-1 groups. In agreement with these results, splenocytes from tumor-bearing mice treated with YKL-GB expressed high levels of costimulatory and activation molecules. In conclusion, the findings of this study demonstrate the effectiveness of augmenting the immune response against tumors with oncolytic adenovirus expressing both GM-CSF and B7-1, which provide a potential therapeutic strategy for the management of neoplasia.
BRAF Mutant NSCLC and Immune Checkpoint Inhibitors: Results From a Real-World Experience
Authors: Karim Rihawi, Diana Giannarelli, Domenico Galetta, Angelo Delmonte, Marco Giavarra, Daniele Turci, Marina Garassino, Marcello Tiseo, Fausto Barbieri, Stefano Panni, Andrea Ardizzoni
Journal: Journal of Thoracic Oncology (2019)
Abstract 16875: Functional Analysis of Low Density Lipoprotein Receptor Variants in Lymphocytes to Assess the Effect of Evinacumab in Homozygous Familial Hypercholesterolemia Patients With a Spectrum of Low Density Lipoprotein Receptor Activity
Authors: Poulabi Banerjee, Shazia Ali, Michel Tarabocchia, Aurelie Bouzelmat, Ana Catarina Dos Santos Alves, Aitor Etxebarria, Asior Benito-Vicente, Mafalda Bourbon, Robert Pordy, Daniel Gipe, Daniel Gaudet, César Martin
Journal: Circulation (2017)

Background: HoFH is a rare disease characterized by markedly elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and an extremely high risk of premature atherosclerotic cardiovasc...
Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees
Authors: Martha J. Glenn, Michael J. Madsen, Ethan Davis, Cassandra D. Garner, Karen Curtin, Brandt Jones, Justin A. Williams, Michael H. Tomasson, Nicola J. Camp
Journal: Blood Cancer Journal (2019)

Abnormal serum immunoglobulin (Ig) free light chains (FLC) are established biomarkers of early disease in multiple B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL). Heavy chains have also been shown to be biomarkers in plasma cell disorders. An unanswered question is whether these Ig biomarkers are heritable, i.e., influenced by germline factors. CLL is heritable but highly heterogeneous. Heritable biomarkers could elucidate steps of disease pathogenesis that are affected by germline factors, and may help partition heterogeneity and identify genetic pleiotropies across malignancies. Relatives in CLL pedigrees present an opportunity to identify heritable biomarkers. We compared FLCs and heavy chains between relatives in 23 high-risk CLL pedigrees and population controls. Elevated IgM (eIgM) and abnormal FLC (aFLC) ratio was significantly increased in relatives, suggesting that these Ig biomarkers are heritable and could offer risk stratification in pedigree relatives. Within high-risk CLL pedigrees, B-cell lymphoid malignancies were five times more prevalent in close relatives of individuals with eIgM, prostate cancer was three times more prevalent in relatives of individuals with aFLC, and monoclonal B-cell lymphocytosis increased surrounding individuals with normal Ig levels. These different clustering patterns suggest Ig biomarkers have the potential to partition genetic heterogeneity in CLL and provide insight into distinct heritable pleiotropies associated with CLL.
BCL2 blockade overcomes MCL1 resistance in multiple myeloma
Authors: Ka Tat Siu, Cherrie Huang, Cristina Panaroni, Kenta Mukaihara, Keertik Fulzele, Rosemary Soucy, Cassandra Thorburn, Justin Cidado, Lisa Drew, Shrikanta Chattopadhyay, Noopur Raje
Journal: Leukemia (2019)
Abstract P2-04-01: Withdrawn
Authors: L Magnani, G Pruneri, DK Patten, G Corleone, B Győrffy, E Erdős, A Saiakhova, K Goddard, A Vingiani, S Shousha, LS Pongor, DJ Hadjiminas, G Schiavon, P Barry, C Palmieri, RC Coombes, P Scacheri
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
Money, Politics, and Firearm Safety
Authors: Rebecca M. Cunningham, Marc A. Zimmerman, Patrick M. Carter
Journal: JAMA Network Open (2019)

medical specialties committed to reducing firearm violence, are indicators of the beginning of the end of the medical community's silence on the issue of firearm research and safety.Although such attention is urgently needed, the article by Schuur et al 5 highlights the disconnect that currently exists between physician organization political action committee (PAC) priorities and the positions of their membership when it comes to firearm injury prevention.The authors found that even among professional organizations that endorsed the 2015 Firearm-Related Injury and Death in the United States: A Call to Action, there was significant support for candidates with records in opposition to firearm safety policies.As the authors note, this is not a new issue in medicine.For many years, we saw a similar discrepancy between the American Medical Association's public calls to regulate the tobacco industry and their financial support of politicians who actively voted against such regulations. 10This history lesson serves as an important cautionary tale.Schuur et al 5 provide transparency in how medical PACs are aligned with this public health issue.Although it is, to our knowledge, a first in-depth assessment of this alignment and lack thereof, it is unlikely to be the last such examination in relation to firearm injury prevention goals of PACs and voices in the physician community.As greater transparency is brought to this issue by analyses such as in the article by Schuur et al, 5 medical PACs must consider the increasing physician voice on the need to address firearm-associated morbidity and mortality in the policy arena to reduce their experience with this issue in emergency bays, operating rooms, and clinics.
Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Barbara R Haight, Susan M Learned, Celine M Laffont, Paul J Fudala, Yue Zhao, Amanda S Garofalo, Mark K Greenwald, Vijay R Nadipelli, Walter Ling, Christian Heidbreder, James L. Andersen, Genie L. Bailey, Scott Robert Bartley, Michael J. Biunno, Brent Boyett, Jesse M. Carr, Eduardo Cifuentes, Sandra Daniela Duarte-Sckell, Otto R. Dueno, Boyde J. Harrison, David R. Hassman, Kent Steven Hoffman, Valentin Isacesu, Saleem Ishaque, Rishi Kakar, Kyle Kampman, Richard D. Knapp, George Konis, Jelena Kunovac, Joseph A. Kwentus, Lawrence S. Levinson, Shishuka Malhotra, Vishaal Mehra, Ricky Stuart Mofsen, Marvin Lane Peyton, Gita G. Pujari, Rakesh Ranjan, Daniel Rutrick, Gregory Seal, Scott Daniel Segal, Rajinder Shiwach, Haydn Mikel Thomas, Peter Paul Ventre, Amit K. Vijapura, David P. Walling, Katharina L. Wiest
Journal: The Lancet (2019)
A Novel mTORC1/2 Inhibitor (MTI-31) Inhibits Tumor Growth, Epithelial–Mesenchymal Transition, Metastases, and Improves Antitumor Immunity in Preclinical Models of Lung Cancer
Authors: Qianwen Zhang, Yan Zhang, Yaqing Chen, Jianchang Qian, Xuesai Zhang, Ker Yu
Journal: Clinical Cancer Research (2019)

Abstract Purpose: We aimed to investigate efficacy and mechanism of MTI-31 (LXI-15029), a novel mTORC1/mTORC2 inhibitor currently in human trial (NCT03125746), in non–small cell lung cancer (NSCLC) models of multiple driver mutations and tyrosine kinase inhibitor (TKI)-resistance. Experimental Design: Gene depletion, inhibitor treatment, immunological, flow cytometry, cellular, and animal studies were performed to determine in vitro and in vivo efficacy in NSCLC models of driver mutations and elucidate roles by mTOR complexes in regulating migration, epithelial–mesenchymal transition (EMT), metastasis, intracranial tumor growth, and immune-escape. Results: MTI-31 potently inhibited cell proliferation (IC50 &amp;lt;1 μmol/L) and in vivo tumor growth in multiple NSCLC models of EGFR/T790M, EML4-ALK, c-Met, or KRAS (MED &amp;lt;10 mg/kg). In EGFR-mutant and/or EML4-ALK-driven NSCLC, MTI-31 or disruption of mTORC2 reduced cell migration, hematogenous metastasis to the lung, and abrogated morphological and functional traits of EMT. Disruption of mTORC2 inhibited EGFR/T790M-positive tumor growth in mouse brain and prolonged animal survival correlating a diminished tumor angiogenesis and recruitment of IBA1+ microglia/macrophages in tumor microenvironment. MTI-31 also suppressed programmed death ligand 1 (PD-L1) in EGFR- and ALK-driven NSCLC, mediated in part by mTORC2/AKT/GSK3β-dependent proteasomal degradation. Depletion of mTOR protein or disruption of mTOR complexes profoundly downregulated PD-L1 and alleviated apoptosis in Jurkat T and primary human T cells in a tumor-T cell coculture system. Conclusions: Our results highlight mTOR as a multifaceted regulator of tumor growth, metastasis, and immune-escape in EGFR/ALK-mutant and TKI-resistant NSCLC cells. The newly characterized mechanisms mediated by the rapamycin-resistant mTORC2 warrant clinical investigation of mTORC1/mTORC2 inhibitors in patients with lung cancer.
Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score
Authors: Fazileh Hosseini Shamili, Mona Alibolandi, Houshang Rafatpanah, Khalil Abnous, Mahmoud Mahmoudi, Mahmoudreza Kalantari, Seyed Mohammad Taghdisi, Mohammad Ramezani
Journal: Journal of Controlled Release (2019)
Antibiotic prescription for febrile children in European emergency departments: a cross-sectional, observational study
Authors: Josephine van de Maat, Elles van de Voort, Santiago Mintegi, Alain Gervaix, Daan Nieboer, Henriette Moll, Rianne Oostenbrink, Henriette A. Moll, Rianne Oostenbrink, Mirjam van Veen, Jeroen G. Noordzij, Frank Smit, Anne-Marie van Wermeskerken, Francois Angoulvant, Francois Dubos, Christele Gras-Leguen, Marie Desmarest, Marie Aurel, Vincent Gajdos, Christelle Joffre, Santiago Mintegi, Yordana Acedo, Laura Herrero Garcia, Inmaculada Medina, Juan Alonso Cózar, Jose Luis Fernandez Arribas, Sara Pinto, Gabriela Sá, Patrícia Mação, Daniela Silva, Maria Zarcos, Michelle Seiler, Alain Gervaix, Ian Maconochie, Hanne Olesen, Christiane Bønnelykke, Niccolò Parri, Vito Fichera, Alberto Arrhigini, Silvia Bressan, Liviana Da Dalt, Diana Moldovan, Daniela-Maria Dreghiciu, Zsolt Bognar, Hayri L. Yilmaz, Sinem Sari Gökay
Journal: The Lancet Infectious Diseases (2019)
TCT-738 BIOTRONIK-Safety and Clinical Performance of the Drug Eluting Orsiro Stent in the Treatment of Subjects With Single De Novo Coronary Artery Lesions-II (BIOFLOW-II) – 5 Year Clinical Results
Authors: Ton Slagboom, Thierry Lefevre, Michael Haude, Michael Gross, Karl Stangl, Franz-Josef Neumann, Manel Sabate, Gert Richardt, Bela Merkely, Javier Goicolea, Paul Barragan, Ron Waksman, Stephan Windecker
Journal: Journal of the American College of Cardiology (2017)
<i>JAMA Internal Medicine</i>—The Year in Review, 2017
Authors: Rita F. Redberg
Journal: JAMA Internal Medicine (2018)

As we are accelerating into 2018, I want to take a moment to thank all of our readers, authors, reviewers and, of course, my incredible team of editors for the privilege of working with all on JAMA Internal Medicine.The journal could not exist without the generosity of our reviewers, who give their time and expertise to reviewing articles and offering suggestions for improvements.Again, I have learned so much from all of you and enjoyed every minute.We are grateful and energized to have a thoughtful and accomplished group of University of California, San Francisco housestaff working with us as JAMA Internal Medicine Editorial Fellows and Elective Residents.We will soon be accepting applications for a Teachable Moments Editorial Fellow position open to internal medicine chief residents across the United States.It is a privilege to be able to read our authors' work.We enjoy talking with you at conferences and hearing from youknowing that publishing in JAMA Internal Medicine opened new doors in your career makes our day.We hit a new record for submissions this year, at 2774 major manuscripts, with continued fast turnaround time (3 days), thanks to the hard work of the editors, with an overall acceptance rate of 11% and for research articles, 6% (Table ).We have a high rate of rejection without review (78%).This means that authors of manuscripts that we do not publish receive a decision within a few days, and we only use our reviewers' precious time for articles we know have a good chance of being published in our pages.We were also delighted to receive our highest impact factor ever-16.54.
Antiretroviral Therapy for HIV Infection in 1997
Authors: C C Carpenter, M A Fischl, S M Hammer, M S Hirsch, D M Jacobsen, D A Katzenstein, J S Montaner, D D Richman, M S Saag, R T Schooley, M A Thompson, S Vella, P G Yeni, P A Volberding
Journal: JAMA (1997)

To provide current recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease. The original International AIDS Society-USA 13-member panel representing international expertise in antiretroviral research and care of patients with HIV infection. The following were considered: Newly available clinical and basic science study results, including phase 3 controlled trials; clinical, virological, and immunologic end-point data; interim analyses of studies presented at national and international research conferences; studies of HIV pathophysiology; and expert opinions of panel members. Recommendations were limited to the drugs available in mid 1997. The full panel met on a regular basis (July 1996, September 1996, November 1996, January 1997, and April 1997) since the publication of its initial recommendations in mid 1996 to review new research reports and interim results. The panel discussed whether and how new information changed its initial recommendations. The recommendations contained herein were determined by group consensus. New data have provided a stronger rationale for earlier initiation of more aggressive therapy than previously recommended and reinforce the importance of careful selection of initial drug regimen for each patient for optimal long-term clinical benefit and adherence. The plasma viral load is a crucial element of clinical management for assessing prognosis and the effectiveness of therapy, and such testing must be done properly. Treatment failure is most readily indicated by a rising plasma HIV RNA level and should be confirmed prior to a change of treatment. Therapeutic approaches must be updated as new data, particularly on the long-term clinical effect of aggressive antiretroviral treatment, continue to emerge.
c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis
Authors: Christian Neumann, Jonas Blume, Urmi Roy, Peggy P. Teh, Ajithkumar Vasanthakumar, Alexander Beller, Yang Liao, Frederik Heinrich, Teresita L. Arenzana, Jason A. Hackney, Celine Eidenschenk, Eric J. C. Gálvez, Christina Stehle, Gitta A. Heinz, Patrick Maschmeyer, Tom Sidwell, Yifang Hu, Derk Amsen, Chiara Romagnani, Hyun-Dong Chang, Andrey Kruglov, Mir-Farzin Mashreghi, Wei Shi, Till Strowig, Sascha Rutz, Axel Kallies, Alexander Scheffold
Journal: Nature Immunology (2019)
Abstract 19120: Minimally Invasive Delivery of Engineered Stromal Cell-Derived Factor 1-a via a Dynamic, Dual Crosslinking Hydrogel Limits Left Ventricular Remodeling After Myocardial Infarction
Authors: Amanda N Steele, Huiyuan Wang, Anahita Eskandari, Vi N Truong, Lyndsay M Stapleton, Michael J Paulsen, Akshara D Thakore, Frederick Grady, Masashi Kawamura, Daniel von Bornstaedt, Justin M Farry, Kevin J Jaatinen, Sarah C Heilshorn, Y. Joseph Woo
Journal: Circulation (2017)

Objective: Shear-thinning hydrogels are promising vehicles for minimally invasive drug delivery. Continued development of advanced hydrogels is necessary to maximize their therapeutic potential. In this study, we encapsulated an engineered angiogenic cytokine, stromal cell-derived factor 1-α (ESA) in a novel, injectable hydrogel which undergoes a dual crosslinking mechanism. The first crosslinking step occurs ex situ via dynamic covalent bonds. The second step occurs in situ via thermal phase transition at body temperature to enforce the network, extending ESA release. We hypothesized that delivery of ESA via this novel, bioengineered hydrogel would facilitate targeted, sustained intramyocardial release, thereby prolonging endothelial progenitor cell (EPC) homing and improving left ventricular (LV) function in a rat model of myocardial ischemia. Methods: Cytoprotective and migratory effects of ESA on human EPCs were assessed via WST1 viability and QCM chemotaxis assays. Hydrogel release was monitored usin...
Once-Daily Plazomicin for Complicated Urinary Tract Infections
Authors: Florian M.E. Wagenlehner, Daniel J. Cloutier, Allison S. Komirenko, Deborah S. Cebrik, Kevin M. Krause, Tiffany R. Keepers, Lynn E. Connolly, Loren G. Miller, Ian Friedland, Jamie P. Dwyer
Journal: New England Journal of Medicine (2019)

The increasing multidrug resistance among gram-negative uropathogens necessitates new treatments for serious infections. Plazomicin is an aminoglycoside with bactericidal activity against multidrug-resistant (including carbapenem-resistant) Enterobacteriaceae.
Right Ventricular Fibrosis
Authors: Stine Andersen, Jens Erik Nielsen-Kudsk, Anton Vonk Noordegraaf, Frances S. de Man
Journal: Circulation (2019)

The role of right ventricular (RV) fibrosis in pulmonary hypertension (PH) remains a subject of ongoing discussion. Alterations of the collagen network of the extracellular matrix may help prevent ventricular dilatation in the pressure-overloaded RV. At the same time, fibrosis impairs cardiac function, and a growing body of experimental data suggests that fibrosis plays a crucial role in the development of RV failure. In idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, the RV is exposed to a ≈5 times increased afterload, which makes these conditions excellent models for studying the impact of pressure overload on RV structure. With this review, we present clinical evidence of RV fibrosis in idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, explore the correlation between fibrosis and RV function, and discuss the clinical relevance of RV fibrosis in patients with PH. We postulate that RV fibrosis has a dual role in patients with pressure-overloaded RVs of idiopathic pulmonary arterial hypertension and chronic thromboembolic PH: as part of an adaptive response to prevent cardiomyocyte overstretch and to maintain RV shape for optimal function, and as part of a maladaptive response that increases diastolic stiffness, perturbs cardiomyocyte excitation-contraction coupling, and disrupts the coordination of myocardial contraction. Finally, we discuss potential novel therapeutic strategies and describe more sensitive techniques to quantify RV fibrosis, which may be used to clarify the causal relation between RV fibrosis and RV function in future research.
Localization and age distribution of telangiectases in children and adolescents with hereditary hemorrhagic telangiectasia: A retrospective cohort study
Authors: Cristian D. Gonzalez, Sarah D. Cipriano, Christina A. Topham, David A. Stevenson, Kevin J. Whitehead, Sheryll Vanderhooft, Angela P. Presson, Jamie McDonald
Journal: Journal of the American Academy of Dermatology (2019)
Update in Rheumatology: Evidence Published in 2010
Authors: Atul Deodhar
Journal: Annals of Internal Medicine (2011)

Updates5 April 2011Update in Rheumatology: Evidence Published in 2010Atul Deodhar, MDAtul Deodhar, MDFrom Oregon Health & Science University, Portland, Oregon.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-154-7-201104050-00008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This update in rheumatology highlights important articles and promising findings published in 2010 that are likely to affect practice or lead to larger-scale trials. These articles cover a broad array of topics, including the potential harms of calcium supplements and fructose-rich beverages; treatments for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, rheumatoid arthritis, reactive arthritis, and psoriasis; and a new classification system for rheumatoid arthritis.OsteoporosisCalcium Supplementation May Increase Risk for Myocardial Infarction Bolland MJ , ...References1. Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008;336:262-6. [PMID: 18198394] CrossrefMedlineGoogle Scholar2. Choi HK, Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ. 2008;336:309-12. [PMID: 18244959] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Oregon Health & Science University, Portland, Oregon.Article relevant to primary care general internistsDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-0131.Corresponding Author: Atul Deodhar, MD, Division of Arthritis and Rheumatic Diseases (OP09), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239; e-mail, [email protected]edu.Author Contributions: Conception and design: A. Deodhar.Analysis and interpretation of the data: A. Deodhar.Drafting of the article: A. Deodhar.Critical revision of the article for important intellectual content: A. Deodhar.Final approval of the article: A. Deodhar.Administrative, technical, or logistic support: A. Deodhar.Collection and assembly of data: A. Deodhar. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 April 2011Volume 154, Issue 7Page: 495-499KeywordsCalciumCyclophosphamideDrugsGoutPsoriasisReactive arthritisRheumatoid arthritisUveitisVasculitis ePublished: 5 April 2011 Issue Published: 5 April 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...