tbuckley/cabot-search huggingface dataset:
Rapid Clinical and Radiographic Response With Combined Dabrafenib and Trametinib in Adults With <i>BRAF</i> -Mutated High-Grade Glioma
Authors: Tanner M. Johanns, Cole J. Ferguson, Patrick M. Grierson, Sonika Dahiya, George Ansstas
Journal: Journal of the National Comprehensive Cancer Network (2018)

BRAF V600E mutations have been successfully treated with targeted therapy in melanoma, non–small cell lung cancer, and thyroid cancer. Interestingly, these mutations have also been identified in a subset of pediatric and adult brain tumors, with several cases reportedly responding to targeted therapy. However, these reports have been limited to single-agent BRAF inhibitor therapy and recurrent disease. Herein, we report dramatic clinical and radiographic responses to combination dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) in 2 adults with high-grade gliomas (HGGs), with 1 patient treated in the first-line setting. These observations, together with prior case reports, advocate for routine screening of BRAF point mutations in adult HGGs, and suggest that treatment with dual-targeted therapy, even in newly diagnosed cases, is safe and effective.
Erratum: Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway
Authors: Wouter J de Jonge, Esmerij P van der Zanden, Frans O The, Maarten F Bijlsma, David J van Westerloo, Roelof J Bennink, Hans-Rudolf Berthoud, Satoshi Uematsu, Shizuo Akira, Rene M van den Wijngaard, Guy E Boeckxstaens
Journal: Nature Immunology (2005)
Origin and Segmental Diversity of Spinal Inhibitory Interneurons
Authors: Lora B. Sweeney, Jay B. Bikoff, Mariano I. Gabitto, Susan Brenner-Morton, Myungin Baek, Jerry H. Yang, Esteban G. Tabak, Jeremy S. Dasen, Christopher R. Kintner, Thomas M. Jessell
Journal: Neuron (2018)
A Phase 1 Trial of the Combination of Ibrutinib and Azacitidine for the Treatment of Higher Risk Myelodysplastic Syndromes: University of California Hematologic Malignancies Consortium (UCHMC) Study 1503
Authors: Brian A Jonas, Aaron C. Logan, Deepa Jeyakumar, Mehrdad Abedi, Rafael Bejar, Matthew J. Wieduwilt, Leslie G. Oesterich, Peter T. Curtin
Journal: Blood (2017)
Geographic Variation in Cardiac Rehabilitation Participation in Medicare and Veterans Affairs Populations
Authors: Alexis L. Beatty, Michael Truong, David W. Schopfer, Hui Shen, Justin M. Bachmann, Mary A. Whooley
Journal: Circulation (2018)

Cardiac rehabilitation is strongly recommended after myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery, but it is historically underused. We sought to evaluate variation in cardiac rehabilitation participation across the United States.
Association of Noncigarette Tobacco Product Use With Future Cigarette Smoking Among Youth in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2015
Authors: Shannon Lea Watkins, Stanton A. Glantz, Benjamin W. Chaffee
Journal: JAMA Pediatrics (2018)

Approximately 90% of adult smokers first tried a cigarette by 18 years of age, and even infrequent smoking in adolescence is associated with established adult smoking. Noncigarette tobacco use is increasing and could stimulate subsequent conventional cigarette smoking in youths.To estimate the longitudinal association between noncigarette tobacco use and subsequent cigarette smoking initiation among US youth.In this prospective cohort study of the Population Assessment of Tobacco and Health (PATH) waves 1 (September 12, 2013, to December 14, 2014) and 2 (October 23, 2014, to October 30, 2015), a nationally representative sample of youths who never smoked a conventional cigarette at baseline and completed wave 2 follow-up (N = 10 384) was studied. PATH retention at follow-up was 87.9%.Ever use and past 30-day use of electronic cigarettes (e-cigarettes), hookah, noncigarette combustible tobacco, or smokeless tobacco at baseline.Ever use and past 30-day use of cigarettes at follow-up.The present analysis was based on the 10 384 PATH youth respondents who reported never having smoked a cigarette in wave 1 and whose cigarette ever or past 30-day use was reported in wave 2 (mean [SD] age, 14.3 [1.7] years; age range, 12-17 years; 5087 [49.1%] female; 4829 [52.5%] white). At 1-year follow-up, 469 (4.6%) of all baseline never-smoking youths had tried a cigarette and 219 (2.1%) had smoked a cigarette within the past 30 days. Cigarette ever use at follow-up was higher among youths who had ever used e-cigarettes (78 [19.1%]), hookah (60 [18.3%]), noncigarette combustible tobacco (45 [19.2%]), or smokeless tobacco (29 [18.8%]) at baseline. After adjusting for sociodemographic, environmental, and behavioral smoking risk factors and for baseline ever use of other tobacco products, the odds of past 30-day cigarette use at follow-up were approximately twice as high among baseline ever users of e-cigarettes (odds ratio [OR], 1.87; 95% CI, 1.15-3.05), hookah (OR, 1.92; 95% CI, 1.17-3.17), noncigarette combustible tobacco (OR, 1.78; 95% CI, 1.00-3.19), and smokeless tobacco (OR, 2.07; 95% CI, 1.10-3.87). Youths who had tried more than 1 type of tobacco product at baseline had 3.81 (95% CI, 2.22-6.54) greater adjusted odds of past 30-day cigarette smoking at follow-up than did baseline never tobacco users.Any use of e-cigarettes, hookah, noncigarette combustible tobacco, or smokeless tobacco was independently associated with cigarette smoking 1 year later. Use of more than 1 product increased the odds of progressing to cigarette use.
Depression and anxiety associate with less remission after 1 year in rheumatoid arthritis
Authors: Aleid C Boer, Tom W J Huizinga, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2018)

Depression and anxiety have been considered to influence disease activity, and with great interest we read the recently published report by Michelsen et al .1 In this large, prospective, multicentre observational study, depression and anxiety reduced the likelihood of joint remission based on composite scores, in rheumatoid arthritis (RA) after 3 and 6 months. Differences were predominantly caused by subjective markers of disease activity rather than by C reactive protein or erythrocyte sedimentation rate. The study cannot prove causality; however, their findings imply that baseline depression/anxiety can impair the fulfilment of remission criteria during follow-up, influencing important treatment decisions.

As replication is a keystone in research, we aimed to validate their findings in an independent cohort, the Leiden Early Arthritis Clinic (EAC), to assess generalisability of the results. The EAC is a population-based inception cohort of patients with newly diagnosed arthritis that started in 1993; from 2010 onwards patients completed the Short Form-36 (SF-36) at …
Abstract 16940: Annular Dynamics After Mitral Valve Repair With Different Prosthetic Rings -Real-Time 3-Dimensional Transesophageal Echocardiography Study-
Authors: Hiroyuki Nishi, Koichi Toda, Shigeru Miyagawa, Yasushi Yoshikawa, Satsuki Fukushima, Daisuke Yoshioka, Tetsuya Saito, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2013)

Objective: We assessed the effects of mitral valve repair (MVr) with different types of prosthetic rings on mitral annular dynamics using real-time 3-dimensional echocardiography (RT3DE) in a singl...
Abstract 12037: Metabolite Profiles Associated With Variation in Visceral Adiposity: The Multi-Ethnic Study of Atherosclerosis
Authors: Ian J Neeland, Colby Ayers, Ioanna Tzoulaki, Ibrahim Karaman, Claire Boulange, Dhananjay Vaidya, Naresh Punjabi, Matthew Allison, David Herrington, Phil Greenland
Journal: Circulation (2016)

Introduction: Understanding the association between serum metabolites and variation in visceral adipose tissue (VAT) content could provide novel insights into the pathogenesis and prevention of obesity and obesity-associated diseases. Methods: We analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis who underwent untargeted metabolomics profiling of blood serum collected between 2000-2002 by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy on a Bruker DRX600 spectrometer at 600 MHz using a standard 1-D spectrum and subsequent assessment of VAT area (cm 2 ) between 2002-2005 by computed tomography. Multivariable linear regression was used to evaluate the associations between NMR metabolic features and VAT area. Metabolites were identified with spiking and peak connectivity and with spectral library verification. A false discovery rate threshold of 1% was applied for statistical significance. Results: 1,102 participants were included with median age 63 years; 52% male; 40% white; median BMI 27 kg/m 2 . 30,590 metabolomic spectral features were evaluated. After multivariable adjustment for age, sex, race, data acquisition phase (batch 1 or 2), socioeconomic status score, smoking, physical activity, and body mass index, 2,113 spectral variables representing 14 distinct metabolites were significantly associated with VAT area ( Figure ). After additional adjustment for fasting plasma glucose or diabetes status, all metabolites except glycerol remained statistically significant. Conclusions: Using an untargeted metabolomics approach, we found a distinct BMI and glucose independent metabolite profile associated with excess visceral adiposity. These findings provide insight into the pathophysiologic and metabolic mechanisms associated with variation in VAT burden. Further identification of unknown metabolites and external validation are needed.
Abstract 20605: Population Trends in the Incidence, Etiology and Outcomes of Infective Endocarditis
Authors: Nana Toyoda, Joanna Chikwe, Shinobu Itagaki, Anelechi Anyanwu, David H Adams, Natalia N Egorova
Journal: Circulation (2016)

Background: Data regarding the epidemiology of infective endocarditis in the United States are insufficient to allow effective evaluation of healthcare promotion efforts. Study aim: The aim of this...
Longitudinal Changes in Glucocorticoid Metabolism Are Associated with Later Development of Adverse Metabolic Phenotype
Authors: R K Crowley, B A Hughes, J Gray, T McCarthy, S Hughes, C H Shackleton, N Crabtree, P Nightingale, P M Stewart, J W Tomlinson
Journal: Endocrine Reviews (2014)

Objective: Dysregulation of enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistance; however, longitudinal changes in glucocorticoid metabolism have not been investigated. This study was performed to evaluate the role of glucocorticoid metabolism in the development of insulin resistance and obesity and to identify biomarkers for future development of metabolic disease. Design: This was a prospective longitudinal observation study conducted over 5 years. Methods: A 24-h collection was used to serially analyze urinary glucocorticoid and mineralocorticoid metabolites in 57 obese and overweight patients with no prior diagnosis of diabetes mellitus, recruited from the community. Results: Baseline higher 5a-reductase (5aR) activity, but not 11b-hydroxysteroid dehydrogenase type 1 activity, was predictive of increased fasting insulin at final visit (11.4 compared with 7.4 mU/l in subjects with lower 5aR activity, P!0.05), area under the curve insulin response to oral glucose tolerance test (176.7 compared with 89.1 mU/l.h, P!0.01), and homeostasis model assessment (HOMA2-IR; 1.3 compared with 0.8, P!0.01). Higher total glucocorticoid production was associated with abnormal glucose tolerance and increased BMI. During this study, systolic blood pressure increased (equivalent to w1 mmHg/year), as did plasma sodium levels; this evidence of increased mineralocorticoid activity was associated with increased aldosterone metabolites and decreased 11b-hydroxysteroid dehydrogenase type 2 activity. Conclusions: Increased 5aR activity and glucocorticoid secretion rate over time are linked with the development of metabolic disease, and may represent targets for therapeutic intervention, which merits further study.
Aging Significantly Drives Decision Making and Outcome in Immune Thrombocytopenia Patients: A Monocentre Study on 508 Patients
Authors: Francesca Palandri, Giuseppe Auteri, Daniela Bartoletti, Maria Letizia Bacchi Reggiani, Giovanni Martinelli, Michele Cavo, Lucia Catani, Nicola Vianelli
Journal: Blood (2017)
Activation of 4-1BB on Liver Myeloid Cells Triggers Hepatitis via an Interleukin-27–Dependent Pathway
Authors: Todd Bartkowiak, Ashvin R. Jaiswal, Casey R. Ager, Renee Chin, Chao-Hsien Chen, Pratha Budhani, Midan Ai, Matthew J. Reilley, Manu M. Sebastian, David S. Hong, Michael A. Curran
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Agonist antibodies targeting the T-cell costimulatory receptor 4-1BB (CD137) are among the most effective immunotherapeutic agents across preclinical cancer models. In the clinic, however, development of these agents has been hampered by dose-limiting liver toxicity. Lack of knowledge of the mechanisms underlying this toxicity has limited the potential to separate 4-1BB agonist–driven tumor immunity from hepatotoxicity. Experimental Design: The capacity of 4-1BB agonist antibodies to induce liver toxicity was investigated in immunocompetent mice, with or without coadministration of checkpoint blockade, via (i) measurement of serum transaminase levels, (ii) imaging of liver immune infiltrates, and (iii) qualitative and quantitative assessment of liver myeloid and T cells via flow cytometry. Knockout mice were used to clarify the contribution of specific cell subsets, cytokines, and chemokines. Results: We find that activation of 4-1BB on liver myeloid cells is essential to initiate hepatitis. Once activated, these cells produce interleukin-27 that is required for liver toxicity. CD8 T cells infiltrate the liver in response to this myeloid activation and mediate tissue damage, triggering transaminase elevation. FoxP3+ regulatory T cells limit liver damage, and their removal dramatically exacerbates 4-1BB agonist–induced hepatitis. Coadministration of CTLA-4 blockade ameliorates transaminase elevation, whereas PD-1 blockade exacerbates it. Loss of the chemokine receptor CCR2 blocks 4-1BB agonist hepatitis without diminishing tumor-specific immunity against B16 melanoma. Conclusions: 4-1BB agonist antibodies trigger hepatitis via activation and expansion of interleukin-27–producing liver Kupffer cells and monocytes. Coadministration of CTLA-4 and/or CCR2 blockade may minimize hepatitis, but yield equal or greater antitumor immunity. Clin Cancer Res; 24(5); 1138–51. ©2018 AACR.
Gene Expression Profiles and Methylation Analysis in Down Syndrome Related Acute Lymphoblastic Leukemia
Authors: Yasuo Kubota, Kumiko Uryu, Tomoko Kawai, Tatsuya Ito, Isamu Hanada, Tsutomu Toki, Masafumi Seki, Kenichi Yoshida, Keisuke Kataoka, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Akira Oka, Yasuhide Hayashi, Seishi Ogawa, Kiminori Terui, Atsushi Sato, Kenichiro Hata, Etsuro Ito, Junko Takita
Journal: Blood (2016)
Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology
Authors: Peter F. Coccia, Alberto S. Pappo, Lynda Beaupin, Virginia F. Borges, Scott C. Borinstein, Rashmi Chugh, Shira Dinner, Jeanelle Folbrecht, A. Lindsay Frazier, Robert Goldsby, Alexandra Gubin, Robert Hayashi, Mary S. Huang, Michael P. Link, John A. Livingston, Yousif Matloub, Frederick Millard, Kevin C. Oeffinger, Diane Puccetti, Damon Reed, Steven Robinson, Abby R. Rosenberg, Tara Sanft, Holly L. Spraker-Perlman, Margaret von Mehren, Daniel S. Wechsler, Kimberly F. Whelan, Nicholas Yeager, Lisa A. Gurski, Dorothy A. Shead
Journal: Journal of the National Comprehensive Cancer Network (2018)

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment and management considerations for AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for AYA Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.
Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes
Authors: Niels Grarup, Ida Moltke, Mette K. Andersen, Maria Dalby, Kristoffer Vitting-Seerup, Timo Kern, Yuvaraj Mahendran, Emil Jørsboe, Christina V. L. Larsen, Inger K. Dahl-Petersen, Arthur Gilly, Daniel Suveges, George Dedoussis, Eleftheria Zeggini, Oluf Pedersen, Robin Andersson, Peter Bjerregaard, Marit E. Jørgensen, Anders Albrechtsen, Torben Hansen
Journal: Nature Genetics (2018)
Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia
Authors: Erika Tissino, Dania Benedetti, Sarah E.M. Herman, Elisa ten Hacken, Inhye E. Ahn, Kari G. Chaffee, Francesca Maria Rossi, Michele Dal Bo, Pietro Bulian, Riccardo Bomben, Elisabeth Bayer, Andrea Härzschel, Julia Christine Gutjahr, Massimiliano Postorino, Enrico Santinelli, Ayed Ayed, Francesco Zaja, Annalisa Chiarenza, Gabriele Pozzato, Alexandre Chigaev, Larry A. Sklar, Jan A. Burger, Alessandra Ferrajoli, Tait D. Shanafelt, Adrian Wiestner, Giovanni Del Poeta, Tanja Nicole Hartmann, Valter Gattei, Antonella Zucchetto
Journal: The Journal of Experimental Medicine (2018)

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors.
Abstract 15665: Fall Risk and Outcomes in Cardiovascular Disease - A Community Study
Authors: Sheila M Manemann, Alanna M Chamberlain, Cynthia Boyd, Susan A Weston, Ruoxiang Jiang, Veronique L Roger
Journal: Circulation (2016)

Background: As the population with cardiovascular disease (CVD) ages, fall risk is an increasing clinical concern. Whether fall risk is associated with outcomes is not well determined. Methods: Olm...
The Vitiligo Extent Score (VES) and the VESplus are responsive instruments to assess global and regional treatment response in patients with vitiligo
Authors: Nanja van Geel, Marcel Bekkenk, Janny E. Lommerts, Khaled Ezzedine, John Harris, Iltefat Hamzavi, Viktoria Eleftheriadou, Mauro Picardo, Alain Taieb, Cecilia A.C. Prinsen, Albert Wolkerstorfer, Reinhart Speeckaert
Journal: Journal of the American Academy of Dermatology (2018)
Recurrent ECSIT mutation encoding V140A triggers hyperinflammation and promotes hemophagocytic syndrome in extranodal NK/T cell lymphoma
Authors: Haijun Wen, Huajuan Ma, Qichun Cai, Suxia Lin, Xinxing Lei, Bin He, Sijin Wu, Zifeng Wang, Yan Gao, Wensheng Liu, Weiping Liu, Qian Tao, Zijie Long, Min Yan, Dali Li, Keith W. Kelley, Yongliang Yang, Huiqiang Huang, Quentin Liu
Journal: Nature Medicine (2018)
Development and Preclinical Validation of a Cysteine Knottin Peptide Targeting Integrin αvβ6 for Near-infrared Fluorescent-guided Surgery in Pancreatic Cancer
Authors: Willemieke S. Tummers, Richard H. Kimura, Lotfi Abou-Elkacem, C. Beinat, Alexander L. Vahrmeijer, Rutger-Jan Swijnenburg, Juergen K. Willmann, Sanjiv S. Gambhir
Journal: Clinical Cancer Research (2018)

Purpose: Intraoperative near-infrared fluorescence (NIRF) imaging could help stratification for the proper primary treatment for patients with pancreatic ductal adenocarcinoma (PDAC), and achieve complete resection, as it allows visualization of cancer in real time. Integrin αvβ6, a target specific for PDAC, is present in >90% of patients, and is able to differentiate between pancreatitis and PDAC. A clinically translatable αvβ6-targeting NIRF agent was developed, based on a previously developed cysteine knottin peptide for PET imaging, R01-MG, and validated in preclinical mouse models.Experimental Design: The applicability of the agent was tested for cell and tissue binding characteristics using cell-based plate assays, subcutaneous, and orthotopic pancreatic models, and a transgenic mouse model of PDAC development (Pdx1-Cretg/+;KRasLSL G12D/+;Ink4a/Arf-/-). IRDye800CW was conjugated to R01-MG in a 1:1 ratio. R01-MG-IRDye800, was compared with a control peptide and IRDye800 alone.Results: In subcutaneous tumor models, a significantly higher tumor-to-background ratio (TBR) was seen in BxPC-3 tumors (2.5 ± 0.1) compared with MiaPaCa-2 (1.2 ± 0.1; P < 0.001), and to the control peptide (1.6 ± 0.4; P < 0.005). In an orthotopic tumor model, tumor-specific uptake of R01-MG-IRDye800 was shown compared with IRDye800 alone (TBR 2.7 vs. 0.86). The fluorescent signal in tumors of transgenic mice was significantly higher, TBR of 3.6 ± 0.94, compared with the normal pancreas of wild-type controls, TBR of 1.0 ± 0.17 (P < 0.001).Conclusions: R01-MG-IRDye800 shows specific targeting to αvβ6, and holds promise as a diagnostic and therapeutic tool to recognize PDAC for fluorescence-guided surgery. This agent can help improve the stratification of patients for a potentially curative, margin-negative resection. Clin Cancer Res; 24(7); 1667-76. ©2018 AACR.
Use of Proton Pump Inhibitors and Risk of Major Depressive Disorder: A Nationwide Population-Based Study
Authors: Wei-Sheng Huang, Ya-Mei Bai, Ju-Wei Hsu, Kai-Lin Huang, Chia-Fen Tsai, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Shih-Jen Tsai, Tai-Long Pan, Tzeng-Ji Chen, Mu-Hong Chen
Journal: Psychotherapy and Psychosomatics (2018)