tbuckley/cabot-search huggingface dataset:
Abstract P282: Cross-sectional Relationship Between Physical Activity and Cardiovascular Risk Factors in Kidney Transplant Patients: A Baseline Examination of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial
Authors: Augustine W Kang, Carol E Garber, Charles B Eaton, Patricia M Risica, Andrew G Bostom
Journal: Circulation (2018)

Introduction: Data characterizing the potential relationship between physical activity and cardiovascular disease (CVD) risk factors in kidney transplant recipients (KTRs) are limited in the published literature. Accordingly, we sought to: (1) describe the levels of physical activity (PA) in KTRs; and (2) analyze the associations between PA levels and CVD risk factors in KTRs. We report the largest cross-sectional study of PA levels and CVD risk factors in KTRs to date. Methods: Baseline data from the large multiethnic, multicenter trial (FAVORIT) were examined with n = 4034 participants (37% female; mean age 51.9 ± 9.4 years; 75% White; 97% with stage 2T-4T Chronic Kidney Disease; 20% with prevalent CVD). PA was categorized in tertiles (low, moderate, high) derived from a modified PA summary score from the Yale Physical Activity Survey (YPAS). CVD risk factors were examined across levels of PA by ANOVA, Kruskal-Wallis rank test and hierarchical multiple regression modeling. Results: Collectively, participants were less active (mean YPAS 39.9 ± 20.6) compared to similar-aged rheumatoid arthritis (48 ± 21) and osteoarthritis (51 ± 20) samples from other studies. Participants in the “high” PA tertile reported more vigorous PA and walking, compared to participants in moderate and low tertiles (both p &lt; .001). No differences were observed for daily household, occupational or sedentary activities (i.e., standing, sitting, moving about) across PA tertiles. More participants in the “low” PA tertile were overweight/obese and had a history of prevalent diabetes and/or CVD, compared with more active participants (all p &lt; .001). Hierarchical multiple regression revealed that lower age ( p = .002), having a cadaveric donor source ( p = .006), shorter transplant vintage ( p = .025), lower pulse pressure ( p &lt; .001) and no history of diabetes ( p &lt; .001) were significantly associated with higher PA scores. Conclusion: KTR participants appear to be less active than samples of other chronically ill participants. In our data, lower levels of PA were positively associated with the presence of most CVD risk factors in the KTR population. Furthermore, higher PA levels were associated with younger age and variables associated with more positive KTR outcomes. Future longitudinal analyses of this unique KTR cohort will examine whether higher PA levels are associated with reduced risk for the development of hard, centrally-adjudicated CVD outcomes.
Immunological Cytopenias Induced By Anti-Programmed Cell Death (ligand) 1 Antibodies
Authors: Jean-Marie Michot, Nicolas Delanoy, Thibault Comont, Nora Kramkimel, Romain Dupont, Julien Lazarovici, Stéphane Champiat, Caroline Robert, Charles Herbaux, Benjamin Besse, Claude Chahine, Aude Guillemin, Christine Mateus, Patricia Pautier, Philippe Saiag, Emmanuela Madonna, Marie Maerevoet, Jean-Christophe Bout, Charlotte Leduc, Pascal Biscay, Gilles Quere, Christophe Nardin, Mikael Ebbo, Laurence Albiges, Grégoire Marret, Virginie Levrat, Cécile Dujon, Salim Laghouati, Laure Croisille, Anne-Laure Voisin, Bertrand Godeau, Christophe Massard, Vincent Ribrag, Aurelien Marabelle, Marc Michel, Olivier Lambotte
Journal: Blood (2018)
Hematopoietic Stem-Cell Transplantation Does Not Improve the Poor Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group
Authors: Jennifer L. McNeer, Meenakshi Devidas, Yunfeng Dai, Andrew J. Carroll, Nyla A. Heerema, Julie M. Gastier-Foster, Samir B. Kahwash, Michael J. Borowitz, Brent L. Wood, Eric Larsen, Kelly W. Maloney, Leonard Mattano, Naomi J. Winick, Kirk R. Schultz, Stephen P. Hunger, William L. Carroll, Mignon L. Loh, Elizabeth A. Raetz
Journal: Journal of Clinical Oncology (2019)

Children and young adults with hypodiploid B-lymphoblastic leukemia (B-ALL) fare poorly and hematopoietic stem-cell transplantation (HSCT) is often pursued in first complete remission (CR1). We retrospectively reviewed the outcomes of children and young adults with hypodiploid B-ALL who were enrolled in recent Children's Oncology Group (COG) trials to evaluate the impact of HSCT on outcome.
Inhibition of diacylglycerol kinase alpha to augment antitumor effector T cells in tumor-bearing host.
Authors: Naoki Okada, Ko Sugiyama, Hidemitsu Kitamura, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2019)

293 Background: Diacylglycerol kinases (DGKs), lipid kinases transforming diacylglycerol to phosphatidic acid, play important roles in intracellular signal transduction. Diacylglycerol kinase alpha (DGKa), an isozyme of DGKs, is well-known to promote proliferation of cancer cells by suppression of the apoptosis. Additionally, a previous report demonstrated that activation of DGKa induced anergy state of T lymphocytes in vivo. In this study, we investigated whether inhibition of DGKa not only suppress the tumorigenesis of cancer cells but also activate anti-tumor immunity. Methods: We first investigated the effect of DGKa inhibitor on in vitro proliferation of murine hepatoma cell lines (Hepa1-6) by cell proliferation assay. Cytokine and Granzyme B productions by CD8 + T cells from OT-1 mice after the OVA antigen stimulation were evaluated by ELISA and flowcytometry, respectively. Next, we established a tumor-bearing mice model by injection of mCherry-transfected Hepa1-6 cells into spleen. Tumorigenesis and tumor-infiltrating T cells in the liver were evaluated by in vivo imaging system, HE staining, and immunohistochemistry. CD8 + T cells were collected from the liver and stimulated with PMA and Ca 2+ ionophore and the IFN-g production levels were evaluated by flowcytometry. Results: Proliferation of Hepa1-6 cells were suppressed in the presence of DGKa inhibitor in vitro. IL-2 production levels of OT-1 CD8 T cells in control group was augmented by the addition of DGKa inhibitor (246 vs 579 pg/ml, p &lt; 0.05). Granzyme B-positive cells in OT-1 CD8 + T cells were increased by the treatment with DGKa inhibitor compared to the control group (4.4 vs 8.9 %, P &lt; 0.05) after the antigen stimulation. In vivo administration of DGKa inhibitor significantly suppressed the tumor size (fluorescence (AU) 2.0x10 10 vs 6.3x10 9 , area (μm 2 ) 1.5x10 7 vs 0.9x10 7 , p &lt; 0.05) in the liver of tumor bearing mice. Then, the number of tumor-infiltrating T cells (582 vs 1506, 5 HPF, p &lt; 0.05) and the IFN-g-producing cells (9.2 vs 16.0 %) in CD8 + T cells were elevated by the DGKa treatment. Conclusions: Inhibition of DGKa not only suppressed the proliferation of hepatoma but also activated anti-tumor effector T cells in vivo.
Executive Summary: Heart Disease and Stroke Statistics—2015 Update
Authors: Dariush Mozaffarian, Emelia J. Benjamin, Alan S. Go, Donna K. Arnett, Michael J. Blaha, Mary Cushman, Sarah de Ferranti, Jean-Pierre Després, Heather J. Fullerton, Virginia J. Howard, Mark D. Huffman, Suzanne E. Judd, Brett M. Kissela, Daniel T. Lackland, Judith H. Lichtman, Lynda D. Lisabeth, Simin Liu, Rachel H. Mackey, David B. Matchar, Darren K. McGuire, Emile R. Mohler, Claudia S. Moy, Paul Muntner, Michael E. Mussolino, Khurram Nasir, Robert W. Neumar, Graham Nichol, Latha Palaniappan, Dilip K. Pandey, Mathew J. Reeves, Carlos J. Rodriguez, Paul D. Sorlie, Joel Stein, Amytis Towfighi, Tanya N. Turan, Salim S. Virani, Joshua Z. Willey, Daniel Woo, Robert W. Yeh, Melanie B. Turner
Journal: Circulation (2015)
Response to Open Peer Commentaries on “Patenting Foundational Technologies: Lessons From CRISPR and Other Core Biotechnologies”
Authors: Oliver Feeney, Julian Cockbain, Michael Morrison, Lisa Diependaele, Kristof Van Assche, Sigrid Sterckx
Journal: The American Journal of Bioethics (2019)

We express our sincere thanks to all those who submitted comments on our article and to the editors of AJOB for allowing us to comment in reply.Boggio and Ho’s (2018) comment is centered on the “hu...
Eosinophilic Esophagitis: Association with atopic diseases and IgE mediated Food Allergy
Authors: Pablo Torres, Andressa Zanandrea, Antonio Penido, Catherine Sonaly Ferreira Martins, Claudia Castilho Mouco, Joao Paulo de Assis, Mariele Morandin Lopes, Claudia Leiko Yonekura Anagusko, Fabio M. Castro, Ariana C. Yang
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract P092: Association of Social Isolation with Functional Status and Mental Health in Patients with Heart Failure
Authors: Alanna M Chamberlain, Lila J Finney Rutten, Sheila M Manemann, Cynthia M Boyd, Susan A Weston, Ruoxiang Jiang, Veronique L Roger
Journal: Circulation (2016)

Background: Social isolation has been shown to have a negative impact on psychosocial and physical health, particularly among older adults. However, these relationships have not been fully examined among patients with heart failure (HF). Methods: Residents from 11 southeast MN counties with a first-ever ICD-9 code 428 for HF between 1/1/2013 and 3/31/2014 (N=1649) were mailed a survey to measure social isolation (PROMIS Social Isolation Short Form) and functional status and mental health (PROMIS 29 Health Profile). A total of 778 patients returned the survey (response rate 47%), and among these, 645 completed all questions and were retained for analysis. Patients who returned a completed survey were similar on age (p=0.15), sex (p=0.80), and Charlson comorbidity index (p=0.28) to those who did not return or returned an incomplete survey. The relationship between social isolation and functional status and mental health was analyzed using linear regression, adjusted for age, sex, and Charlson comorbidity index. Results: Among 645 patients with HF, 53% were men, the mean age was 73 years, and the mean Charlson index was 2.2. The mean scores for each functional and mental health subscale and the total score increased with increasing severity of social isolation (Table). For example, the mean physical function scores were 8.6, 11.3, and 12.8 and the mean depression scores were 5.0, 7.3, and 9.8 for those with low, moderate, and high social isolation, respectively. In addition, the total score increased from 51.1 among those with low social isolation to 80.2 for those with high social isolation. Observed differences persisted after adjustment for age, sex, and comorbidity. Conclusion: In patients with HF, greater social isolation is associated with worse functional and mental health, independent of comorbidity. As functional status and mental health impact disease management, addressing social isolation may help with managing HF.
Cell-Free DNA Screening During Pregnancy
Authors: Anthony R. Gregg, Aleksandar Rajkovic
Journal: JAMA (2019)

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Abstract P187: Blood Pressure Control in Adults with Autistic Spectrum Disorders in a Large Integrated Medical Care Program is Better Than in a Demographically Matched Comparison Group
Authors: Stephen Sidney, Ousseny Zerbo, Michael E Sorel, Yinge Qian, Steve Rich, Joseph D Young, Lisa A Croen
Journal: Circulation (2016)

Background: The prevalence of autism spectrum disorders (ASD) has been increasing, with a recent CDC estimate of 1 of 68 children. As this cohort ages, millions of individuals will advance into adulthood with this diagnosis. A recent report from Kaiser Permanente Northern California (KPNC), an integrated medical care program serving about 3.5 million members, showed that adults with ASD have a higher prevalence of hypertension (HTN), than a comparable group not known to have ASD (non-ASD). We are unaware of data regarding HTN control in persons with ASD. Hypothesis: HTN control rates will be lower in ASD than in non-ASD KPNC members because of communication difficulties associated with ASD. Methods: We identified 1,507 KPNC members, age &gt;18 years, with ASD (ICD-9-CM codes 299.0, 299.8. 299.9) during the time period, 1/1/2008-12/31/2012, of which 218 had HTN (2 outpatient diagnoses of HTN, or 1 outpatient diagnosis of HTN with a prescription for anti-hypertensive medication within 12 months of HTN identification). For each ASD patient, we identified 5 comparison KPNC non-ASD members with HTN, matched for age, sex, race, and year of HTN identification (n=1,090). We determined all primary care outpatient blood pressures (BP) recorded within 12 months after HTN identification and used the final BP obtained for analysis. We excluded 14 members with no BPs (1 ASD, 13 controls) and 39 members, age &gt;65 years (8 ASD, 31 controls). HTN control was defined as systolic BP &lt;140 and diastolic BP &lt;90 mm Hg. BP control rates were age-adjusted using weighting derived from the 2000 U.S. census. Results: The mean age was 43.6 years for ASD and 43.9 for controls (p=0.74). The HTN control rate was higher for ASD (84.2%; age-adjusted 84.9%) than for controls (73.5%, age-adjusted 71.7%) (p=0.001). Members with ASD had more BP measurements (mean 6.0, standard deviation [s.d.] 6.2) than controls (mean 4.8, s.d. 4.4) (p=0.0008). Conclusion: HTN was better controlled in adults with ASD than in non-ASD adults, possibly related to more frequent measurement of BP.
Cells with DNMT3A Mutations Are More Sensitive to Cytarabine-Induced DNA Damage
Authors: Kartika Venugopal, Jianping Li, Daniil E Shabashvili, Luisa M Posada, Yang Feng, Daphne Dupere-Richer, Aditya Bele, Jonathan D. Licht, Olga A Guryanova
Journal: Blood (2018)
Abstract 16078: SEEQ Mobile Cardiac Telemetry Associated With a High Yield of Clinically Relevant Arrhythmias in Patients With Suspected Arrhythmia
Authors: Shahrzad Shareghi, Morteza Tavakol, Katherine Lindborg, Carola Alfaro Vives, Leo Spaccavento
Journal: Circulation (2016)

Introduction: External cardiac monitoring through mobile cardiac telemetry (MCT) is frequently used to identify and monitor suspected arrhythmias for up to 30 days. The SEEQ™ MCT offers up to 4 wee...
Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries: a multicentre cohort study
Authors: Kathrin Zürcher, Marie Ballif, Lukas Fenner, Sonia Borrell, Peter M Keller, Joachim Gnokoro, Olivier Marcy, Marcel Yotebieng, Lameck Diero, E Jane Carter, Neesha Rockwood, Robert J Wilkinson, Helen Cox, Nicholas Ezati, Alash'le G Abimiku, Jimena Collantes, Anchalee Avihingsanon, Kamon Kawkitinarong, Miriam Reinhard, Rico Hömke, Robin Huebner, Sebastien Gagneux, Erik C Böttger, Matthias Egger, Kathrin Zürcher, Matthias Egger, Lukas Fenner, Marie Ballif, Frédérique Chammartin, Sebastien Gagneux, Sonia Borrell, Miriam Reinhard, Erik C. Boettger, Peter Keller, Rico Hömke, Alash'le Abimiku, Nicholas Ezati, Marcel Yotebieng, Landry Wenzi, Martine Tabala, Helen Cox, Neesha Rockwood, Robin Warren, Elizabeth Streicher, Robert J. Wilkinson, E. Jane Carter, Lameck Diero, Jimena Collantes, Carlos Zamudio, Robin Huebner, Annette Sohn, Anchalee Avihingsanon, Tor Petersen, Kamon Kawkitinarong, Naruporn Kasipong, Joachim Gnokoro, Kouassi N'Guessan, Olivier Marcy
Journal: The Lancet Infectious Diseases (2019)
BET Inhibitors Potentiate Chemotherapy and Killing of <i>SPOP</i>-Mutant Colon Cancer Cells via Induction of DR5
Authors: Xiao Tan, Jingshan Tong, Yi-Jun Wang, Rochelle Fletcher, Robert E. Schoen, Jian Yu, Liangfang Shen, Lin Zhang
Journal: Cancer Research (2019)

Bromodomain and extraterminal domain (BET) family proteins such as BRD4 are epigenetic readers that control expression of a number of oncogenic proteins. Targeting this family of proteins has recently emerged as a promising anticancer approach. BET inhibitors (BETi), either alone or in combination with other anticancer agents, have exhibited efficacy in a variety of tumors. However, the molecular mechanisms underlying differential response to BETi are not well understood. In this study, we report that death receptor 5 (DR5), a key component of the extrinsic apoptotic pathway, is markedly induced in response to BRD4 depletion and BETi treatment in colorectal cancer cells. Induction of DR5, following BET inhibition, was mediated by endoplasmic reticulum stress and CHOP-dependent transcriptional activation. Enhanced DR5 induction was necessary for the chemosensitization and apoptotic effects of BETi and was responsible for increased BETi sensitivity in colorectal cancer cells containing a mutation in speckle-type POZ protein (SPOP), a subunit of BRD4 E3 ubiquitin ligase. In a colorectal cancer xenograft model, BETi combined with chemotherapy suppressed the tumor growth in a DR5-dependent manner and potently inhibited patient-derived xenograft tumor growth with enhanced DR5 induction and apoptosis. These findings suggest that BETi alone or in combination with chemotherapy is effective against colorectal cancer due to enhanced DR5 induction and apoptosis. DR5 induction may also serve as a useful marker for designing personalized treatment and improved colorectal cancer combination therapies.Significance: These findings reveal how BET inhibition sensitizes chemotherapy and kills a subset of colon cancer cells with specific genetic alterations and may provide a new molecular marker for improving colon cancer therapies.
Abstract 12988: Intermittent Hypoxia and Hypercapnia Induce Pulmonary Artery Atherosclerosis in Low Density Lipoprotein Receptor Deficient Mice by an NF-kappa B-dependent Mechanism
Authors: Toshihiro Imamura, Gabriel G Haddad
Journal: Circulation (2015)

Background: Obstructive sleep apnea (OSA) is a common sleep disorder characterized by intermittent hypoxia and hypercapnia (IHH). Clinical studies have shown that OSA is an independent risk factor for atherosclerosis. In spite of its clinical importance and relevance, the contribution of IHH to atherogenicity has not yet been fully examined compared to the role of intermittent hypoxia exposure alone, which has been relatively well documented. We previously reported that IHH increased pulmonary artery (PA) but not aortic atherosclerosis in low-density lipoprotein receptor deficient (Ldlr-/-) mice. The mechanism of this IHH-induced PA atherosclerosis is unknown; however, previous studies have shown that various inflammatory mediators, particularly in the NF-kappa B (NF-kB) pathway, could cause atherosclerosis in OSA patients. Furthermore, it is known that the macrophages in atherosclerotic lesions play an important role as inflammatory cells involved in this process. Therefore, we hypothesized that IHH-induced PA atherosclerosis is caused by a macrophage NF-kB-dependent mechanism. Methods: Myeloid restricted IKK-beta deleted (Ikk-bΔMye) mice were generated by a Cre/lox recombination system to inactivate the NF-kB pathway in macrophages, and then crossed to Ldlr-/- mice to generate a double knockout animal (Ldlr-/-_Ikk-bΔMye). Male mice were fed with high-fat diet for 8 weeks while being exposed to IHH for 10 h/day. Plasma lipid levels, PA and aortic atherosclerotic lesions were then assayed. Results: The IKK-beta intact (Ldlr-/-_Ikk-bflox/flox) mice exposed to IHH developed more PA atherosclerotic lesions as compared to room air (RA) exposed mice (IHH 10.45%±5.07 vs. RA 5.68%±1.73). However, this IHH-induced PA atherogenicity was partially abolished in IKK-beta deleted mice (IHH 7.38%±4.71 and RA 4.58%±3.42). There was no significant difference in aortic atherogenicity among these four animal groups. Serum total cholesterol and triacylglycerol were increased after the implementation of high-fat diet but showed no difference among the groups during the course of this experiment. Conclusion: The macrophage NF-kB pathway plays a critical role in IHH-induced PA atherosclerosis and inactivation of NF-kB ameliorats such atheogenicity.
The potential drug cost impact of nivolumab (N) in patients with advanced/metastatic gastric cancer (GC) or gastroesophageal junction cancer (GEJC) in Canada.
Authors: Kiran Virik, Robert B Wilson
Journal: Journal of Clinical Oncology (2019)

101 Background: Advanced/metastatic GC and GEJC is associated with poor survival outcomes. Systemic treatment options are limited in patients having had at least two lines of chemotherapy. Immune checkpoint inhibitors (ICIs) appear to be a promising therapeutic option in these patients. The role of predictive biomarkers to response to ICIs remains to be fully elucidated. This may ultimately inform the utility and thus potentially the drug cost incurred by ICIs. The ATTRACTION-2 phase III study using N in heavily pretreated advanced GC and GEJC patients improved outcomes. The use of ICIs has an anticipated budgetary impact on health care systems within the context of this potentially funded utilization of N. Methods: An estimation of the N drug cost alone for advanced de novo and relapsed cases diagnosed in 2017 and subsequently treated in the third line in Canada was undertaken. A cost estimate for N treatment in earlier lines was also evaluated. N cost per patient was calculated based on treatment indication, duration of treatment, standard dose/schedule. The analysis was performed in Canadian dollars ($) and assumed complete drug delivery and uncomplicated cycles. The cost of N was obtained from the pan Canadian Oncology Drug Review (PCODR) cost for N in lung cancer. The number of target patients and N utilization was derived from constructed schema to give a budget impact estimate. Results: Estimated N cost per treated patient is $15,770. The N drug cost in the third line setting is estimated at $5.9 million (M) for GC and $2.4M for GEJC, total $8.4M (IQR $3.9M-$18.7M). For first line and second line N in eligible pts respectively: potential drug cost is $23.7M, $11.8M for GC and $9.7M, $4.9M for GEJC. A sensitivity analysis was performed. Conclusions: ICIs potentially add a drug cost burden to the publically funded Canadian healthcare system. As biomarkers predictive of response evolve and patients are treated accordingly, the drug cost burden may lessen. Potential earlier line use and a longer duration of therapy will add to the estimated budgetary impact.
Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor for Overall Survival in Patients with Diffuse Large B-Cell Lymphoma Treated with Standard Chemoimmunotherapy
Authors: Chieh-Lung Cheng, Erin Huang, Ming-Kai Chuang, Wen-Chien Chou, Hwei-Fang Tien
Journal: Blood (2018)
Clinical Outcomes of Isolated Distal Deep Vein Thrombosis Associated with Cancer: The Cleveland Clinic Experience
Authors: Shyam K. Poudel, Xuefei Jia, Deborah Y. Park, Mailey Lynn Wilks, Vicki Pinkava, Meghan O'Brien, Barbara Tripp, Jung-Min Song, Keith R. McCrae, Alok A. Khorana, Dana E. Angelini
Journal: Blood (2018)
ARID1A Is Critical for Maintaining Normal Hematopoiesis in Mice
Authors: Lin Han, Vikas Madan, Anand Mayakonda, Pushkar Dakle, Weoi Woon Teoh, Pavithra Shyamsunder, Hazimah Binte Mohd Nordin, Zeya Cao, Janani Sundaresan, Ienglam Lei, Zhong Wang, H. Phillip Koeffler
Journal: Blood (2018)