tbuckley/cabot-search huggingface dataset:
Majority of secondary school children buy tickets
Authors: E. Moran
Journal: BMJ (1995)

<h3>Background</h3> Many health systems across the globe have introduced arrangements to deny payment for patients readmitted to hospital as an emergency. The purpose of this study was to develop an exploratory categorisation based on likely causes of readmission, and then to assess the prevalence of these different types. <h3>Methods</h3> Retrospective analysis of 82 million routinely collected National Health Service hospital records in England (2004–2010) was undertaken using anonymised linkage of records at person-level. Numbers of 30-day readmissions were calculated. Exploratory categorisation of readmissions was applied using simple rules relating to International Classification of Diseases (ICD) diagnostic codes for both admission and readmission. <h3>Results</h3> There were 5 804 472 emergency 30-day readmissions over a 6-year period, equivalent to 7.0% of hospital discharges. Readmissions were grouped into hierarchically exclusive categories: potentially preventable readmission (1 739 519 (30.0% of readmissions)); anticipated but unpredictable readmission (patients with chronic disease or likely to need long-term care; 1 141 987 (19.7%)); preference-related readmission (53 718 (0.9%)); artefact of data collection (16 062 (0.3%)); readmission as a result of accident, coincidence or related to a different body system (1 101 818 (19.0%)); broadly related readmission (readmission related to the same body system (1 751 368 (30.2%)). <h3>Conclusions</h3> In this exploratory categorisation, a large minority of emergency readmissions (eg, those that are potentially preventable or due to data artefacts) fell into groups potentially amenable to immediate reduction. For other categories, a hospital9s ability to reduce emergency readmission is less clear. Reduction strategies and payment incentives must be carefully tailored to achieve stated aims.
Integrated safety findings with tesetaxel, an orally administered taxane, in patients (pts) with gastric, colon, breast, and nonsmall cell lung cancer: Phase II results
Authors: S. C. Novick, J. Wu, D. Ilson
Journal: Journal of Clinical Oncology (2009)

e13516 Background: The orally active taxane tesetaxel has potent cytotoxic activity against various human and murine cancer cell lines in vitro and in xenograft tumor models, including those that express P-glycoprotein (pgp). In a Phase 1 study, 48 pts with advanced solid tumors were treated at doses of 1.5 mg/m 2 to 40 mg/m 2 . AUC and C max increased in a dose-proportional manner. There was no dose-limiting toxicity (DLT) at doses ≤18 mg/m 2 . Above 18 mg/m 2 , Grade 4 neutropenia &gt; 5 days in duration was the most common DLT. The MTD was 27 mg/m 2 for heavily pretreated pts and 35 mg/m 2 for minimally pretreated pts. These doses were further evaluated in a Phase 2 program in 4 studies, and activity was demonstrated in gastric, colorectal, breast, and non-small cell lung cancers. To assess safety across all indications prior to beginning randomized trials, we conducted an integrated analysis of the safety of the 27 mg/m 2 dose as initial therapy in Phase 2. Methods: All pts had been previously treated with a nontaxane regimen. Tesetaxel was given on Day 1 of a 21-day cycle; the dose was rounded to the nearest 10 mg. Prophylactic treatment with such drugs as antiemetics and colony- stimulating factors (CSFs) was permitted only after Cycle 1. Results: A total of 142 subjects received tesetaxel 27 mg/m 2 as initial therapy. The most common Grade 3–4 adverse events were neutropenia (33%), leukopenia (22%), and anemia (11%). Grade 3–4 neuropathy was distinctly uncommon (3%). Conclusions: Taxanes are highly active in solid tumors, but most are associated with neurotoxicity and infusion reactions. Oral tesetaxel eliminates infusion reactions and consequent requirements for extended observation and premedication, is associated with a low incidence of Grade 3–4 neurotoxicity, and may be useful in diseases associated with high pgp expression. Like other taxanes, the most common adverse event is neutropenia, which can be ameliorated with appropriate monitoring and use of CSFs. These and other safety considerations will be incorporated into planned registration trials. [Table: see text]
P0920 : Specific modulation of hepatic Estrogen Receptor alpha prevents fatty liver but also obesity and insulin resistance induced by a high fat diet in mice
Authors: M. Guillaume, S. Handgraaf, I. Raymond-Letron, A. Fabre, E. Riant, A. Montagner, H. Guillou, C. Bureau, J.-F. Arnal, P. Gourdy
Journal: Journal of Hepatology (2015)
Identification and validation of biomarkers for autism spectrum disorders
Authors: Eva Loth, Will Spooren, Lindsay M. Ham, Maria B. Isaac, Caroline Auriche-Benichou, Tobias Banaschewski, Simon Baron-Cohen, Karl Broich, Sven Bölte, Thomas Bourgeron, Tony Charman, David Collier, Fernando de Andres-Trelles, Sarah Durston, Christine Ecker, Andre Elferink, Marion Haberkamp, Robert Hemmings, Mark H. Johnson, Emily J. H. Jones, Omar S. Khwaja, Sabine Lenton, Luke Mason, Valentina Mantua, Andreas Meyer-Lindenberg, Michael V. Lombardo, Laurence O'Dwyer, Koichi Okamoto, Gahan J. Pandina, Luca Pani, Antonio M. Persico, Emily Simonoff, Sitra Tauscher-Wisniewski, Jordi Llinares-Garcia, Spiros Vamvakas, Steve Williams, Jan K. Buitelaar, Declan G. M. Murphy
Journal: Nature Reviews Drug Discovery (2015)
Abstract 16231: Respiratory Failure After Cardiac Surgery: Evidence of Cardiopulmonary Bypass and Transfusion Interaction
Authors: Robert H Habib, Lama G Ghazi, Nathalie E Chalhoub, Ameer Kabour, Milo C Engoren, Thomas A Schwann
Journal: Circulation (2013)

Background: Respiratory Failure is an unpredictable complication of cardiac surgery with cardiopulmonary bypass (CPB) strongly implicated in its pathogenesis. Nearly half of CPB patients will recei...
Abstract 12609: Five-Year Outcomes Following Endovascular Therapy with Stenting in the Aorto-Iliac Artery
Authors: Tomoharu Dohi, Osamu Iida, Yoshimitsu Soga, Daizou Kawasaki, Yasutaka Yamauchi, Kenji Suzuki, Keisuke Hirano, Ryoji Koshida, Daisuke Kamoi, Junichi Tazaki, Masaaki Uematsu
Journal: Circulation (2012)

Background: Although with the advent of stenting, endovascular therapy (EVT) has been widely used in aorto-iliac (AI) lesions, long-term outcomes and factors affecting prognosis of patients after E...
Quantitative IFN-γ and IL-2 Response Associated with Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women
Authors: Jyoti S. Mathad, Ramesh Bhosale, Usha Balasubramanian, Savita Kanade, Vidya Mave, Nishi Suryavanshi, Nikhil Gupte, Samir Joshi, Ajay Chandanwale, Kathryn M. Dupnik, Vandana Kulkarni, Prasad Deshpande, Daniel W. Fitzgerald, Amita Gupta
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Pregnant women with latent tuberculosis infection (LTBI) are at high risk for development of TB, especially if infected with HIV.Objectives: To assess the performance of LTBI tests in pregnant and postpartum women infected with HIV, investigate the immunology behind discordance in pregnancy, and explore the implications for the development of postpartum TB.Methods: We screened pregnant women in their second/third trimester and at delivery for LTBI using the tuberculin skin test (TST) and IFN-γ release assay (IGRA) (QuantiFERON Gold). A subset of antepartum women had longitudinal testing, with repeat testing at delivery and postpartum and additional cytokines measured from the IGRA supernatant. The kappa statistic and Wilcoxon rank sum test were used to determine agreement and comparison of cytokine concentrations, respectively.Measurements and Main Results: Of 252 enrolled, 71 (28%) women had a positive IGRA but only 27 (10%) had a positive TST (P < 0.005). There was 75% agreement (kappa, 0.25). When stratified by pregnancy versus delivery, 20% had IGRA+/TST− discordance at each time point. A positive IGRA was associated with known TB contact (odds ratio, 3.6; confidence interval, 1.2–11.1; P = 0.02). Compared with IGRA+/TST+, women with IGRA+/TST− discordance had significantly less IFN-γ (1.85 vs. 3.48 IU/ml; P = 0.02) and IL-2 (46.17 vs. 84.03 pg/ml; P = 0.01). Five developed postpartum TB, of which three had IGRA+/TST− discordance during pregnancy.Conclusions: Choice of LTBI test in pregnant women infected with HIV affects results. Pregnant women with IGRA+/TST− discordance had less IFN-γ and IL-2 than those with concordant-positive results and may represent an especially high-risk subset for the development of active TB postpartum.
Arginine Methylation of SREBP1a via PRMT5 Promotes <i>De Novo</i> Lipogenesis and Tumor Growth
Authors: Liu Liu, Xiaoping Zhao, Li Zhao, Jiajin Li, Hao Yang, Zongping Zhu, Jianjun Liu, Gang Huang
Journal: Cancer Research (2016)

Abstract Dysregulation of the sterol regulatory element-binding transcription factors sterol regulatory element-binding protein (SREBP) and SREBF activates de novo lipogenesis to high levels in cancer cells, a critical event in driving malignant growth. In this study, we identified an important posttranslational mechanism by which SREBP1a is regulated during metabolic reprogramming in cancer cells. Mass spectrometry revealed protein arginine methyltransferase 5 (PRMT5) as a binding partner of SREBP1a that symmetrically dimethylated it on R321, thereby promoting transcriptional activity. Furthermore, PRMT5-induced methylation prevented phosphorylation of SREBP1a on S430 by GSK3β, leading to its disassociation from Fbw7 (FBXW7) and its evasion from degradation through the ubiquitin–proteasome pathway. Consequently, methylation-stabilized SREBP1a increased de novo lipogenesis and accelerated the growth of cancer cells in vivo and in vitro. Clinically, R321 symmetric dimethylation status was associated with malignant progression of human hepatocellular carcinoma, where it served as an independent risk factor of poor prognosis. By showing how PRMT5-induced methylation of SREBP1a triggers hyperactivation of lipid biosynthesis, a key event in tumorigenesis, our findings suggest a new generalized strategy to selectively attack tumor metabolism. Cancer Res; 76(5); 1260–72. ©2016 AACR.
Olfactory Receptor Subgenomes Linked with Broad Ecological Adaptations in Sauropsida
Authors: Imran Khan, Zhikai Yang, Emanuel Maldonado, Cai Li, Guojie Zhang, M. Thomas P. Gilbert, Erich D. Jarvis, Stephen J. O’Brien, Warren E. Johnson, Agostinho Antunes
Journal: Molecular Biology and Evolution (2015)

Olfactory receptors (ORs) govern a prime sensory function. Extant birds have distinct olfactory abilities, but the molecular mechanisms underlining diversification and specialization remain mostly unknown. We explored OR diversity in 48 phylogenetic and ecologically diverse birds and 2 reptiles (alligator and green sea turtle). OR subgenomes showed species- and lineage-specific variation related with ecological requirements. Overall 1,953 OR genes were identified in reptiles and 16,503 in birds. The two reptiles had larger OR gene repertoires (989 and 964 genes, respectively) than birds (182–688 genes). Overall, birds had more pseudogenes (7,855) than intact genes (1,944). The alligator had significantly more functional genes than sea turtle, likely because of distinct foraging habits. We found rapid species-specific expansion and positive selection in OR14 (detects hydrophobic compounds) in birds and in OR51 and OR52 (detect hydrophilic compounds) in sea turtle, suggestive of terrestrial and aquatic adaptations, respectively. Ecological partitioning among birds of prey, water birds, land birds, and vocal learners showed that diverse ecological factors determined olfactory ability and influenced corresponding olfactory-receptor subgenome. OR5/8/9 was expanded in predatory birds and alligator, suggesting adaptive specialization for carnivory. OR families 2/13, 51, and 52 were correlated with aquatic adaptations (water birds), OR families 6 and 10 were more pronounced in vocal-learning birds, whereas most specialized land birds had an expanded OR family 14. Olfactory bulb ratio (OBR) and OR gene repertoire were correlated. Birds that forage for prey (carnivores/piscivores) had relatively complex OBR and OR gene repertoires compared with modern birds, including passerines, perhaps due to highly developed cognitive capacities facilitating foraging innovations.
Abstract 16633: Differential Effects of Acute and Chronic Inflammation on the Release of Adiponectin By Human Adipose Tissue
Authors: Alexios S Antonopoulos, Rikhil Patel, Michael Demosthenous, Marios Margaritis, Janet Digby, Regent Lee, Rana Sayeed, Ravi De Silva, Mario Petrou, Keith M Channon, Charalambos Antoniades
Journal: Circulation (2012)

Background: Adiponectin (Adpn) is an anti-inflammatory adipokine. In cell culture studies, pro-inflammatory cytokines suppress adiponectin’s biosynthesis, however in clinical studies adiponectin le...
SCIMS: A new algorithm for associating anticancer drug mechanisms with gene ontology categories
Authors: Gabriel S. Eichler, Mark Reimers, John N. Weinstein
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1565 

Introduction: In recent years, our research group has performed a number of experimental and computer studies that integrate different types of molecular data on the NCI-60, a diverse panel of human cancer cells from 9 tissues of origin. The NCI-60 panel has been used by the Developmental Therapeutics Program (DTP) of the NCI to screen >100,000 chemical compounds for anticancer activity since 1990. Using Pearson’s correlation as a metric, we previously shed light on the mechanisms and potential medical uses of a number of anticancer agents, including L-asparaginase, oxaliplatin, ‘MDR1-inverse’ compounds, and the ellipticiniums. The present study improves on that type of analysis by computing a more robust multi-gene correlation metric between drug growth inhibition data and biologically associated groups of genes, such as those in Gene Ontology (GO) categories or those with common Protein Family (Pfam) domains. Methods: To quantify the strength of association between anticancer drug activity patterns and mRNA transcriptional profiles, we developed a new algorithm (SCIMS) based on a stratified correlation metric and shrunken scoring scheme, with statistical significance computed using a false discovery rate (FDR) which adjusts for multiple comparisons. First, we validated the approach on a synthetic dataset of 100 drugs and 2000 genes. Then, we applied it to Affymetrix U133A microarray profiles of the NCI-60 and DTP GI50 data for 118 drugs with putatively known mechanisms of action. Because the program is compute-intensive, we ran it on the NIH’s Biowulf supercomputing cluster. Results: The results for the synthetic datasets showed >95% sensitivity and specificity for prediction of known associations. When applied to the NCI-60 cell line data, the SCIMS algorithm identified a number of robust associations that coincide with previously documented mechanisms of action, including a particularly strong one between the activity patterns of antifols and the ‘DNA processing’ GO category (FDR =.05). Conclusion: The results on the synthetic dataset suggest that the new algorithm is highly sensitive and specific, and the prediction of known mechanisms of action indicates utility of the algorithm for real data.
Abstract 15576: Long-Term Catheter Ablation Outcome in Females with Metabolic Syndrome
Authors: Sanghamitra Mohanty, Prasant Mohanty, Luigi Di Biase, Rong Bai, Chintan Trivedi, Pasquale Santangeli, Agnes Pump, David Burkhardt, Rodney Horton, Joseph Gallinghouse, Javier Sanchez, Jason Zagrodzky, Shane Bailey, Andrea Natale
Journal: Circulation (2012)

Introduction: Female gender and metabolic syndrome (MS) are two well-known risk factors of atrial fibrillation (AF). This study examined the combined impact of both risk factors on ablation outcome...
A Phase I Study to Assess the Safety and Tolerability of the Selective Akt Inhibitor Azd5363 in Japanese Patients with Advanced Solid Tumours
Authors: T. Esaki, T. Seto, F. Hirai, S. Arita, G. Toyokawa, J. Hashimoto, Y. Tanabe, M. Kodaira, K. Yonemori, Y. Hoshino, H. Yamamoto, T. Kawata, J. Lindemann, K. Tamura
Journal: Annals of Oncology (2014)
Hematopoietic Stem Cell Transplantation In Relapsed ALK + Anaplastic Large Cell Lymphoma Of Children and adolescent : A Study On Behalf Of The Sfce and SFGM-TC
Authors: Marion Strullu, Caroline Thomas, Nicole Raus, Catherine Paillard, Yves Bertrand, Charlotte Jubert, Regis Peffaut De La Tour, Patrick Lutz, Jean-Hugues Dalle, Laurence Lamant, Gerard Michel, Laurence Brugieres
Journal: Blood (2013)
Oncolytic Virus-Mediated Immunotherapy: A Combinatorial Approach for Cancer Treatment
Authors: Sean E. Lawler, E. Antonio Chiocca
Journal: Journal of Clinical Oncology (2015)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2015.62.5244 Journal of Clinical Oncology - published online before print July 27, 2015 PMID: 26215964 Oncolytic Virus-Mediated Immunotherapy: A Combinatorial Approach for Cancer Treatment Sean E. LawlerxSean E. LawlerSearch for articles by this author , E. Antonio ChioccaxE. Antonio ChioccaSearch for articles by this author Show More Brigham and Women's Hospital, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2015.62.5244 First Page Full Text PDF Figures and Tables © 2015 by American Society of Clinical Oncology
The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group.
Authors: J A Levi, D Raghavan, V Harvey, D Thompson, T Sandeman, G Gill, R Stuart-Harris, R Snyder, M Byrne, Z Kerestes
Journal: Journal of Clinical Oncology (1993)

PURPOSE In an effort to maintain the excellent long-term results achieved with combination chemotherapy for good-prognosis germ cell carcinoma, but to reduce the toxicities encountered, a randomized trial was conducted comparing cisplatin and vinblastine with or without bleomycin. PATIENTS AND METHODS Two hundred eighteen assessable patients with a good prognosis were randomized to receive induction chemotherapy with cisplatin 100 mg/m2 intravenously (IV) day 1 and vinblastine 6 mg/m2 IV days 1 and 2 every 3 weeks (PV) with or without bleomycin 30 mg intramuscularly (IM) weekly (PVB) for a maximum of 12 weeks. Once maximum response was achieved, patients with a complete remission (CR) received two courses of consolidation chemotherapy, while those with residual abnormalities and normal tumor markers underwent surgical resection whenever possible. RESULTS Toxicities encountered in this study were clearly greater for those patients who received bleomycin, with significantly more leukopenia, thrombocytopenia, anemia, alopecia, and renal and pulmonary toxicities. The proportion of patients who achieved CR and had no evidence of disease (resection of all viable malignancy) was 89% for PV and 94% for PVB (P = .29). After a minimum of 4 years of follow-up, relapses have occurred in 7% of patients who received PV and 5% who received PVB. A total of five patients on each therapy arm were successfully treated with further salvage chemotherapy and surgery. Thus, deaths from progressive malignancy have occurred in 15% of patients on PV and 5% on PVB (P = .02), a rate that was partly offset by the higher proportion of toxic deaths with PVB (P = .06). CONCLUSION Despite the toxicities encountered with bleomycin in cisplatin-based combination chemotherapy for these patients, complete deletion of this drug compromises therapeutic efficacy.
Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial
Authors: Lale Erdem-Eraslan, Martin J. van den Bent, Youri Hoogstrate, Hina Naz-Khan, Andrew Stubbs, Peter van der Spek, René Böttcher, Ya Gao, Maurice de Wit, Walter Taal, Hendrika M. Oosterkamp, Annemiek Walenkamp, Laurens V. Beerepoot, Monique C.J. Hanse, Jan Buter, Aafke H. Honkoop, Bronno van der Holt, René M. Vernhout, Peter A.E. Sillevis Smitt, Johan M. Kros, Pim J. French
Journal: Cancer Research (2016)

Abstract The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva), a humanized monoclonal antibody against circulating VEGF-A, when added to CCNU chemotherapy in patients with recurrent glioblastoma (GBM). In this study, we performed gene expression profiling (DASL and RNA-seq) of formalin-fixed, paraffin-embedded tumor material from participants of the BELOB trial to identify patients with recurrent GBM who benefitted most from beva+CCNU treatment. We demonstrate that tumors assigned to the IGS-18 or “classical” subtype and treated with beva+CCNU showed a significant benefit in progression-free survival and a trend toward benefit in overall survival, whereas other subtypes did not exhibit such benefit. In particular, expression of FMO4 and OSBPL3 was associated with treatment response. Importantly, the improved outcome in the beva+CCNU treatment arm was not explained by an uneven distribution of prognostically favorable subtypes as all molecular glioma subtypes were evenly distributed along the different study arms. The RNA-seq analysis also highlighted genetic alterations, including mutations, gene fusions, and copy number changes, within this well-defined cohort of tumors that may serve as useful predictive or prognostic biomarkers of patient outcome. Further validation of the identified molecular markers may enable the future stratification of recurrent GBM patients into appropriate treatment regimens. Cancer Res; 76(3); 525–34. ©2016 AACR.
Abstract 17408: Left Ventricle Internal Dimension in Diastole Strongly Predicts Long-term Survival Following Continuous Flow Left Ventricular Assist Device Implantation
Authors: Steve K Singh, Rohan M Shah, Ryan W Fairchild, Jatin Anand, Ruben Hernandez, Elena Sandoval, Andrew C Baldwin, Leo Simpson, Andrew Civitello, William E Cohn, O H Frazier, Hari R Mallidi
Journal: Circulation (2014)

Introduction: Left ventricular assist devices (LVADs) are seldom implanted in small hearts, determined by left ventricle internal diameter in diastole (LVIDD), to avoid suction events thought to impact flows, arrhythmias and LVAD function. No published evidence has confirmed this theory. Hypothesis: We aimed to determine if LVIDD impacts outcomes following LVAD insertion. Methods: A single center, retrospective review was performed of all patients (N=449) implanted with a continuous flow (CF) LVAD between 12/1999-12/2013. Demographics, preoperative and operative data, perioperative outcomes, echocardiographic and right heart catheterization data, and late survival were determined. Univariate and survival analyses were performed. Multivariable regression identified independent predictors of survival. Results: Patient characteristics, baseline echocardiographic and hemodynamic data, operative characteristics and clinical outcomes are summarized in Table 1. Patients with smaller LVIDD were more likely female...