tbuckley/cabot-search huggingface dataset:
Formate: The Neglected Member of One-Carbon Metabolism
Authors: Margaret E. Brosnan, John T. Brosnan
Journal: Annual Review of Nutrition (2016)

Formate, the only non-tetrahydrofolate (THF)-linked intermediate in one-carbon metabolism, is produced in mammals from a variety of metabolic sources. It occurs in serum of adults at a concentration of approximately 30 μM. Its principal function lies as a source of one-carbon groups for the synthesis of 10-formyl-THF and other one-carbon intermediates; these are primarily used for purine synthesis, thymidylate synthesis, and the provision of methyl groups for synthetic, regulatory, and epigenetic methylation reactions. Although formate is largely produced in mitochondria, these functions mostly occur in the cytoplasm and nucleus. Formate plays a significant role in embryonic development, as evidenced by the effectiveness of formate in the pregnant dam's drinking water on the incidence of neural tube defects in some genetic models. High formate concentrations in fetal lambs may indicate a role in fetal development and suggest that extracellular formate may play a role in the interorgan distribution of one-carbon groups.
Perceived Neighborhood Environmental Attributes Associated with Walking and Cycling for Transport among Adult Residents of 17 Cities in 12 Countries: The IPEN Study
Authors: Jacqueline Kerr, Jennifer A. Emond, Hannah Badland, Rodrigo Reis, Olga Sarmiento, Jordan Carlson, James F. Sallis, Ester Cerin, Kelli Cain, Terry Conway, Grant Schofield, Duncan J. Macfarlane, Lars B. Christiansen, Delfien Van Dyck, Rachel Davey, Ines Aguinaga-Ontoso, Deborah Salvo, Takemi Sugiyama, Neville Owen, Josef Mitáš, Loki Natarajan
Journal: Environmental Health Perspectives (2015)

Prevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions. The aim of this study was to examine the strength and shape of the relationship between adults' neighborhood perceptions and walking and cycling for transport across diverse environments. As part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18-65 years) living in physically and socially diverse neighborhoods in 17 cities across 12 countries. Neighborhood perceptions were measured using the Neighborhood Environment Walkability Scale, and walking and cycling for transport were measured using the International Physical Activity Questionnaire-Long Form. Generalized additive mixed models were used to model walking or cycling for transport during the last seven days with neighborhood perceptions. Interactions by city were explored. Walking-for-transport outcomes were significantly associated with perceived residential density, land use mix-access, street connectivity, aesthetics, and safety. Any cycling for transport was significantly related to perceived land use mix-access, street connectivity, infrastructure, aesthetics, safety, and perceived distance to destinations. Between-city differences existed for some attributes in relation to walking or cycling for transport. Many perceived environmental attributes supported both cycling and walking; however, highly walkable environments may not support cycling for transport. People appear to walk for transport despite safety concerns. These findings can guide the implementation of global health strategies.
Abstract 12858: Left Ventricular Dysfunction Switches Cardiac Mesenchymal Stem/Stromal Cells Toward a Pro-Inflammatory Phenotype
Authors: Nili Naftali-Shani, La-Paz Levin-Kotler, Dahlia Palevski, Uri Amit, Radka Holbova, Edith Hochhauser, Jonathan Leor
Journal: Circulation (2014)

Introduction and Hypothesis: Mesenchymal stem/stromal cells (MSCs) are appealing candidates for cardiac cell therapy due to their ease of preparation, immunoprivilege properties, reparative potential and safety. We aimed to test the hypothesis that the inflammatory environment following myocardial infarction (MI) and left ventricular (LV) dysfunction could modulate the reparative properties of resident and transplanted MSCs. Methods and Results: To test this hypothesis, we isolated and cultured resident cardiac and subcutaneous (SC) fat tissue MSCs from mice, 28 days after MI (LVEF: 27.9%±3.8) or sham operation (LVEF: 54.9%±3.8). Proliferation rate was highest in cardiac MSCs after MI, compared with other groups (p&lt;0.001 after 96 hours). Next, we measured the levels of secreted cytokines in the medium collected from the different cells and found that MI polarized cardiac MSCs toward a pro-inflammatory profile and stimulated secretion of the inflammatory cytokines IL1α, IL1β, IL-12, IL-6 and TNF-α (p&lt;0.05), as well as the monocyte recruitment factors: MIP-1α, RANTES and MCP-1 (p&lt;0.05). In contrast, SC fat MSCs were less affected by MI and LV dysfunction and mainly decreased their macrophage recruitment and anti-inflammatory factors. Surprisingly, transplantation of cardiac and adipose tissue MSCs from both MI and sham operated animals, into mice hearts immediately after MI (n=5-8 per group), did not improve cardiac remodeling and function, compared with saline. To determine the mechanism behind MSC polarization, we stimulated cardiac MSCs from toll-like receptor 4 ( TLR4 ) deficient and wild-type mice, with the secretome of LPS-activated macrophages. Significantly, there was less inflammatory cytokine secretion in TLR4-deficient MSCs, compared with control suggesting that cardiac MSC polarization is mediated by TLR4 activation. Conclusions: Post MI inflammatory environment switches resident cardiac and implanted MSCs toward a pro-inflammatory phenotype and impair their reparative properties. This effect is mediated by TLR4 . Our findings are relevant to the pathogenesis and progression of LV remodeling, and could guide the selection and engineering of MSCs for heart repair.
Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials
Authors: Neal J. Meropol, Yu-Ning Wong, Terrance Albrecht, Sharon Manne, Suzanne M. Miller, Anne Lederman Flamm, Al Bowen Benson, Joanne Buzaglo, Michael Collins, Brian Egleston, Linda Fleisher, Michael Katz, Tyler G. Kinzy, Tasnuva M. Liu, Seunghee Margevicius, Dawn M. Miller, David Poole, Nancy Roach, Eric Ross, Mark D. Schluchter
Journal: Journal of Clinical Oncology (2015)

Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option.A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials.Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone.These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving knowledge and reducing attitudinal barriers.
Acute effects of heparin administration on the ischemic threshold of patients with coronary artery disease
Authors: Gabriele Fragasso, Pier Marco Piatti, Lucilla Monti, Altin Palloshi, Chunzeng Lu, Gianpietro Valsecchi, Emanuela Setola, Giliola Calori, Guido Pozza, Alberto Margonato, Sergio Chierchia
Journal: Journal of the American College of Cardiology (2002)
LP03 : Safety and efficacy of short-duration treatment with GS-9857 combined with sofosbuvir/GS-5816 in treatment-naïve and DAA-experienced genotype 1 patients with and without cirrhosis
Authors: E.J. Gane, R.H. Hyland, Y. Ying, E. Svarovskaia, L.M. Stamm, D.M. Brainard, G.M. Subramanian, J.G. McHutchison, C. Schwabe
Journal: Journal of Hepatology (2015)
Mutations of Cystic Fibrosis Transmembrane Conductance Regulator Gene Cause a Monocyte-Selective Adhesion Deficiency
Authors: Claudio Sorio, Alessio Montresor, Matteo Bolomini-Vittori, Sara Caldrer, Barbara Rossi, Silvia Dusi, Stefano Angiari, Jan E. Johansson, Marzia Vezzalini, Teresinha Leal, Elisa Calcaterra, Baroukh M. Assael, Paola Melotti, Carlo Laudanna
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Cystic fibrosis (CF) is a common genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Persistent lung inflammation, characterized by increasing polymorphonuclear leukocyte recruitment, is a major cause of the decline in respiratory function in patients with CF and is a leading cause of morbidity and mortality. CFTR is expressed in various cell types, including leukocytes, but its involvement in the regulation of leukocyte recruitment is unknown.We evaluated whether CF leukocytes might present with alterations in cell adhesion and migration, a key process governing innate and acquired immune responses.We used ex vivo adhesion and chemotaxis assays, flow cytometry, immunofluorescence, and GTPase activity assays in this study.We found that chemoattractant-induced activation of β1 and β2 integrins and of chemotaxis is defective in mononuclear cells isolated from patients with CF. In contrast, polymorphonuclear leukocyte adhesion and chemotaxis were normal. The functionality of β1 and β2 integrins was restored by treatment of CF monocytes with the CFTR-correcting drugs VRT325 and VX809. Moreover, treatment of healthy monocytes with the CFTR inhibitor CFTR(inh)-172 blocked integrin activation by chemoattractants. In a murine model of lung inflammation, we found that integrin-independent migration of CF monocytes into the lung parenchyma was normal, whereas, in contrast, integrin-dependent transmigration into the alveolar space was impaired. Finally, signal transduction analysis showed that, in CF monocytes, chemoattractant-triggered activation of RhoA and CDC42 Rho small GTPases (controlling integrin activation and chemotaxis, respectively) was strongly deficient.Altogether, these data highlight the critical regulatory role of CFTR in integrin activation by chemoattractants in monocytes and identify CF as a new, cell type-selective leukocyte adhesion deficiency disease, providing new insights into CF pathogenesis.
Prevalence and risk factors for COPD in farmers: a cross-sectional controlled study
Authors: Alicia Guillien, Marc Puyraveau, Thibaud Soumagne, Stéphanie Guillot, Fabrice Rannou, David Marquette, Patrick Berger, Stéphane Jouneau, Elisabeth Monnet, Frédéric Mauny, Jean-Jacques Laplante, Jean-Charles Dalphin, Bruno Degano
Journal: European Respiratory Journal (2015)

There are conflicting data regarding the magnitude and determinants of chronic obstructive pulmonary disease (COPD) risk in farmers. In a cross-sectional study of 917 nonfarming working controls and 3787 farmers aged 40–75 years, we assessed respiratory symptoms, tobacco exposure, job history (without direct exposure measurement) and lung function. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (post-bronchodilator forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) &lt;0.70) and by the Quanjer reference equation (post-bronchodilator FEV 1 /FVC &lt;lower limit of normal (LLN)). The prevalence (95% CI) of COPD according to the GOLD criterion was 5.1% (4.4–5.8%) and 2.9% (1.8–4.0%) in farmers and controls, respectively (p=0.005), and 3.1% (2.5–3.6%) and 1.5% (0.7–2.3%), respectively, for the LLN criterion (p&lt;0.01). For both COPD criteria after adjustment for age, sex and smoking status, COPD prevalence was similar in controls and crop farmers. Compared to controls, four job categories had a higher prevalence of COPD according to the GOLD criterion, namely, cattle breeders, swine breeders, poultry breeders and breeders of two or more livestock types. Among cattle breeders, only those from Franche-Comté had higher prevalence of COPD according to both GOLD and LLN criteria. The prevalence of COPD in farmers is higher than in nonfarming working controls, and depends on the farming activity, the region and the criterion used to define COPD.
Rationale and Design of the GUIDE-IT Study
Authors: G. Michael Felker, Tariq Ahmad, Kevin J. Anstrom, Kirkwood F. Adams, Lawton S. Cooper, Justin A. Ezekowitz, Mona Fiuzat, Nancy Houston-Miller, James L. Januzzi, Eric S. Leifer, Daniel B. Mark, Patrice Desvigne-Nickens, Gayle Paynter, Ileana L. Piña, David J. Whellan, Christopher M. O’Connor
Journal: JACC Heart Failure (2014)
Comment on Krul-Poel et al. Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial. Diabetes Care 2015;38:1420–1426
Authors: Giuseppe Bellastella, Maria Ida Maiorino, Katherine Esposito, Dario Giugliano
Journal: Diabetes Care (2015)

We read with interest the article by Krul-Poel et al. (1) that reported the results of a randomized controlled trial on the effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes. The authors did not find any significant improvement of HbA1c in the group receiving vitamin D supplementation (129 patients) as compared with the group receiving placebo (132 patients) …
Derangement of p53 and MDM2 is involved in transformation of differentiated into anaplastic thyroid cancer
Authors: S. M. Wiseman, H. Masoudi, P. Niblock, D. Turbin, A. Rajput, J. Hay, D. Filipenko, A. Melck, B. Gilks, D. Huntsman
Journal: Journal of Clinical Oncology (2006)

5556 Background: Anaplastic thyroid cancer arises as a consequence of tumor progression, or transformation, from pre-existing differentiated thyroid cancer. Mutation of the p53 tumor-suppressor gene represents a common event in thyroid tumor progression. MDM2 encodes a protein that complexes with p53, downregulates its function, and leads to its degradation via a ubiquitin-proteasome pathway. The objective of this study was to evaluate the change in p53 and MDM2 expression in the transformation of differentiated to anaplastic thyroid carcinoma. Methods: Of 94 cases of anaplastic thyroid cancer diagnosed and treated in British Columbia Canada over a 20 year period (1984–2004) 32 cases (34%) had adequate tissue available for evaluation and 12 of these cases had associated foci of differentiated thyroid carcinoma. A tissue microarray was constructed from these 12 anaplastic thyroid tumors and their associated differentiated foci. Immunohistochemistry was utilized to evaluate expression of p53 and MDM2 by these tumors. Results: There was decreased expression of p53 and MDM2 by the anaplastic tumors when compared to the differentiated thyroid tumors from which they evolved. The expression of p53 and MDM2 was 17% and 8%, respectively, by the differentiated thyroid carcinoma, and 83% and 25%, respectively, by the anaplastic tumors. Evaluating the anaplastic cancers and the differentiated foci from which they evolved, p53 overexpression developed in 8 (67%) of tumors and MDM2 overexpression developed in 3 (25%) of tumors. All the anaplastic tumors that developed MDM2 overexpression also concurrently developed p53 overexpression. Conclusions: This report is the first to demonstrate derangement of p53, and its regulator, MDM2, is involved in the transformation of a subset of differentiated into anaplastic thyroid tumors. Isolated MDM2 overexpression does not appear to play an important role in anaplastic transformation of thyroid cancer. No significant financial relationships to disclose.
Role of Shape in Tumor Environment: Cubical Shape Enhances the Interaction of Layer‐by‐Layer Polymeric Particles with Breast Cancer Cells (Adv. Healthcare Mater. 17/2015)
Authors: Jenolyn F. Alexander, Veronika Kozlovskaya, Jun Chen, Thomas Kuncewicz, Eugenia Kharlampieva, Biana Godin
Journal: Advanced Healthcare Materials (2015)

Understanding the role of shape and elasticity in the behavior of objects in the tumor microenvironment is crucial for designing more efficient and less toxic therapies. On page 2657, E. Kharlampieva, B. Godin, and co-workers explore spherical and cubic biocompatible elastic microshells and their rigid core–shell precursors. The cover image, which is a superimposition of confocal (cells and particles) and scanning electron (particles) micrographs, illustrates how the cubic shape promotes the interaction of particles with breast cancer cells.
Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural Mesothelioma
Authors: Robin Cornelissen, Joost P. J. J. Hegmans, Alexander P. W. M. Maat, Margaretha E. H. Kaijen-Lambers, Koen Bezemer, Rudi W. Hendriks, Henk C. Hoogsteden, Joachim G. J. V. Aerts
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: We demonstrated previously that autologous tumor lysate–pulsed dendritic cell–based immunotherapy in patients with malignant pleural mesothelioma is feasible, well-tolerated, and capable of inducing immunologic responses against tumor cells. In our murine model, we found that reduction of regulatory T cells with metronomic cyclophosphamide increased the efficacy of immunotherapy.Objectives: To assess the decrease in number of peripheral blood regulatory T cells during combination therapy of low-dose cyclophosphamide and dendritic cell immunotherapy and determine the induction of immunologic responses with this treatment in patients with mesothelioma.Methods: Ten patients with malignant pleural mesothelioma received metronomic cyclophosphamide and dendritic cell–based immunotherapy. During the treatment, peripheral blood mononuclear cells were analyzed for regulatory T cells and immunologic responses.Measurements and Main Results: Administration of dendritic cells pulsed with autologous tumor lysate combined with cyclophosphamide in patients with mesothelioma was safe, the only side effect being moderate fever. Dendritic cell vaccination combined with cyclophosphamide resulted in radiographic disease control in 8 of the 10 patients. Overall survival was promising, with 7 out of 10 patients having a survival of greater than or equal to 24 months and two patients still alive after 50 and 66 months. Low-dose cyclophosphamide reduced the percentage of regulatory T cells of total CD4 cells in peripheral blood from 9.43 (range, 4.34–26.10) to 4.51 (range, 0.27–10.30) after 7 days of cyclophosphamide treatment (P = 0.02).Conclusions: Consolidation therapy with autologous tumor lysate–pulsed dendritic cell–based therapy and simultaneously reducing the tumor-induced immune suppression is well-tolerated and shows signs of clinical activity in patients with mesothelioma.Clinical trial registered with www.clinicaltrials.gov (NCT 01241682).
Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event
Authors: David M. Burns, Rose Tierney, Claire Shannon-Lowe, Jo Croudace, Charlotte Inman, Ben Abbotts, Sandeep Nagra, Christopher P. Fox, Sridhar Chaganti, Charles F. Craddock, Paul Moss, Alan B. Rickinson, Martin Rowe, Andrew I. Bell
Journal: Blood (2015)
Triple-Negative versus Non–Triple-Negative Breast Cancers in High-Risk Women: Phenotype Features and Survival from the HIBCRIT-1 MRI-Including Screening Study
Authors: Franca Podo, Filippo Santoro, Giovanni Di Leo, Siranoush Manoukian, Clelia de Giacomi, Stefano Corcione, Laura Cortesi, Luca A. Carbonaro, Rubina M. Trimboli, Anna Cilotti, Lorenzo Preda, Bernardo Bonanni, Matilde Pensabene, Laura Martincich, Antonella Savarese, Alma Contegiacomo, Francesco Sardanelli
Journal: Clinical Cancer Research (2015)

Abstract Purpose: To compare phenotype features and survival of triple-negative breast cancers (TNBC) versus non-TNBCs detected during a multimodal annual screening of high-risk women. Experimental Design: Analysis of data from asymptomatic high-risk women diagnosed with invasive breast cancer during the HIBCRIT-1 study with median 9.7-year follow-up. Results: Of 501 enrolled women with BRCA1/2 mutation or strong family history (SFH), 44 were diagnosed with invasive breast cancers: 20 BRCA1 (45%), 9 BRCA2 (21%), 15 SFH (34%). Magnetic resonance imaging (MRI) sensitivity (90%) outperformed that of mammography (43%, P &amp;lt; 0.001) and ultrasonography (61%, P = 0.004). The 44 cases (41 screen-detected; 3 BRCA1-associated interval TNBCs) comprised 14 TNBCs (32%) and 30 non-TNBCs (68%), without significant differences for age at diagnosis, menopausal status, prophylactic oophorectomy, or previous breast cancer. Of 14 TNBC patients, 11 (79%) were BRCA1; of the 20 BRCA1 patients, 11 (55%) had TNBC; and of 15 SFH patients, 14 (93%) had non-TNBCs (P = 0.007). Invasive ductal carcinomas (IDC) were 86% for TNBCs versus 43% for non-TNBCs (P = 0.010), G3 IDCs 71% versus 23% (P = 0.006), size 16 ± 5 mm versus 12 ± 6 mm (P = 0.007). TNBC patients had more frequent ipsilateral mastectomy (79% vs. 43% for non-TNBCs, P = 0.050), contralateral prophylactic mastectomy (43% vs. 10%, P = 0.019), and adjuvant chemotherapy (100% vs. 44%, P &amp;lt; 0.001). The 5-year overall survival was 86% ± 9% for TNBCs versus 93% ± 5% (P = 0.946) for non-TNBCs; 5-year disease-free survival was 77% ± 12% versus 76% ± 8% (P = 0.216). Conclusions: In high-risk women, by combining an MRI-including annual screening with adequate treatment, the usual reported gap in outcome between TNBCs and non-TNBCs could be reduced. Clin Cancer Res; 22(4); 895–904. ©2015 AACR.
Transthoracic Needle Biopsies: It's More than Just Hitting the Bull's-eye
Authors: Joachim G. Aerts
Journal: Clinical Cancer Research (2015)

Spectroscopy has shown to be of value in determining benign from malignant tissue. Incorporation of spectroscopic measurements may increase the diagnostic yield of transthoracic needle biopsies. Given the increasing amount of incidentally found lung lesions, such a technique may prevent unnecessary invasive procedures and uncertainty for the patient.