tbuckley/cabot-search huggingface dataset:
CCGs face legal threat for offering off-label drug for wet AMD
Authors: Deborah Cohen
Journal: BMJ (2017)

The drug companies Bayer and Novartis have threatened to take the NHS to court over a new policy to offer patients with wet age-related macular degeneration a choice of drugs to treat their condition, including details of price.

Twelve CCGs across northeast England and Cumbria are facing judicial review because they are planning to offer bevacizumab (Roche’s Avastin), which is not licensed for wet AMD, alongside ranibizumab (Lucentis, marketed by Novartis) and aflibercept (Eylea, Bayer), which are approved by the UK National Institute for Health and Clinical Excellence (NICE) for treating the condition in the NHS. The CCGs say that the policy will save them up to £13.5m (€15m; $18m) over the next five years.1

If hospital trusts in the area agree the plan, patients who receive a new diagnosis of wet AMD will be told that bevacizumab is the preferred choice, because it is as clinically effective as ranibizumab and …
Cistrome Cancer: A Web Resource for Integrative Gene Regulation Modeling in Cancer
Authors: Shenglin Mei, Clifford A. Meyer, Rongbin Zheng, Qian Qin, Qiu Wu, Peng Jiang, Bo Li, Xiaohui Shi, Binbin Wang, Jingyu Fan, Celina Shih, Myles Brown, Chongzhi Zang, X. Shirley Liu
Journal: Cancer Research (2017)

Abstract Cancer results from a breakdown of normal gene expression control, so the study of gene regulation is critical to cancer research. To gain insight into the transcriptional and epigenetic factors regulating abnormal gene expression patterns in cancers, we developed the Cistrome Cancer web resource (http://cistrome.org/CistromeCancer/). We conducted the systematic integration and modeling of over 10,000 tumor molecular profiles from The Cancer Genome Atlas (TCGA) with over 23,000 ChIP-seq and chromatin accessibility profiles from our Cistrome collection. The results include reconstruction of functional enhancer profiles, “super-enhancer” target genes, as well as predictions of active transcription factors and their target genes for each TCGA cancer type. Cistrome Cancer reveals novel insights from integrative analyses combining chromatin profiles with tumor molecular profiles and will be a useful resource to the cancer gene regulation community. Cancer Res; 77(21); e19–22. ©2017 AACR.
TCT-369 Initial experience with magnesium bioabsorbable scaffold (Magmaris) in coronary de-novo lesions. Acute and mid-term result in multicenter Italian study
Authors: Stefano Galli, Piero Montorsi, Sarah Troiano, Altin Palloshi, Claudio Rapetto, Franco Fabbiocchi, Giovanni Teruzzi, Massimo Leoncini, Michele Bianchi, Paolo Mario Ravagnani, Antonio Bartorelli
Journal: Journal of the American College of Cardiology (2017)
Arl2 content influences p53 phosphorylation and localization in a breast cancer cell line
Authors: Anne Beghin, Eva Matera, Marie Sylvie Negrier, Charles Dumontet
Journal: Cancer Research (2007)

5616   ADP-ribosylation factor like protein 2 (Arl2) has been shown to interact with tubulin binding cofactor D (TBCD), a key protein involved in the production of polymerization-competent αβ tubulin heterodimers, the basic building block of microtubules. Direct binding between Arl2 and the tumor suppressor protein phosphatase 2A (PP2A) has been also demonstrated. Variant of the human adenocarcinoma cell line MCF7 using stable transfection of pcDNA3 vectors containing the antisens construct of Arl2 (MA- cells) or the empty vector (MP cells) were produced and characterized. We have previously shown that alterations in Arl2 protein content were found to be associated with modifications in catalytic subunit of PP2A (PP2Ac) protein content in cancer cells. Given a possible role for Arl2 in the regulation of PP2A activity, we hypothesized that modifications of Arl2 expression could induce modifications of the phosphorylation status of the PP2A substrate and tumor suppressor p53. We therefore investigated the phosphorylation status and localization of p53 in various cell compartments under basal conditions and after incubation with drugs commonly used in breast cancer treatment. Using microtubule separation procedures and immunohistochemistry, we showed that the decrease of Arl2 in MA- cells induced an increase (+100%, p
Leveraging Molecular Genetic Approaches to Yield Insights Into Major Depression Etiology and Clinical Presentation
Authors: Roseann E. Peterson
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Phase 2 study of 1st-line modified FOLFIRINOX in unresectable advanced pancreatic cancer: Multicenter prospective study
Authors: Kensaku Yoshida, Takuji Iwashita, Shinya Uemura, Akinori Maruta, Masahito Shimizu, Keisuke Iwata, Tsuyoshi Mukai
Journal: Annals of Oncology (2017)
A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors
Authors: Luqiao Wang, Gayani Nanayakkara, Qian Yang, Hongmei Tan, Charles Drummer, Yu Sun, Ying Shao, Hangfei Fu, Ramon Cueto, Huimin Shan, Teodoro Bottiglieri, Ya-feng Li, Candice Johnson, William Y. Yang, Fan Yang, Yanjie Xu, Hang Xi, Weiqing Liu, Jun Yu, Eric T. Choi, Xiaoshu Cheng, Hong Wang, Xiaofeng Yang
Journal: Journal of Hematology & Oncology (2017)

Nuclear receptors (NRs) can regulate gene expression; therefore, they are classified as transcription factors. Despite the extensive research carried out on NRs, still several issues including (1) the expression profile of NRs in human tissues, (2) how the NR expression is modulated during atherosclerosis and metabolic diseases, and (3) the overview of the role of NRs in inflammatory conditions are not fully understood. To determine whether and how the expression of NRs are regulated in physiological/pathological conditions, we took an experimental database analysis to determine expression of all 48 known NRs in 21 human and 17 murine tissues as well as in pathological conditions. We made the following significant findings: (1) NRs are differentially expressed in tissues, which may be under regulation by oxygen sensors, angiogenesis pathway, stem cell master regulators, inflammasomes, and tissue hypo-/hypermethylation indexes; (2) NR sequence mutations are associated with increased risks for development of cancers and metabolic, cardiovascular, and autoimmune diseases; (3) NRs have less tendency to be upregulated than downregulated in cancers, and autoimmune and metabolic diseases, which may be regulated by inflammation pathways and mitochondrial energy enzymes; and (4) the innate immune sensor inflammasome/caspase-1 pathway regulates the expression of most NRs. Based on our findings, we propose a new paradigm that most nuclear receptors are anti-inflammatory homeostasis-associated molecular pattern receptors (HAMPRs). Our results have provided a novel insight on NRs as therapeutic targets in metabolic diseases, inflammations, and malignancies.
Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy
Authors: Richard S. Finkel, Eugenio Mercuri, Basil T. Darras, Anne M. Connolly, Nancy L. Kuntz, Janbernd Kirschner, Claudia A. Chiriboga, Kayoko Saito, Laurent Servais, Eduardo Tizzano, Haluk Topaloglu, Már Tulinius, Jacqueline Montes, Allan M. Glanzman, Kathie Bishop, Z. John Zhong, Sarah Gheuens, C. Frank Bennett, Eugene Schneider, Wildon Farwell, Darryl C. De Vivo
Journal: New England Journal of Medicine (2017)

Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein.
Retrospective analysis of nivolumab in 15 patients with pretreated advanced non-small-cell lung cancer
Authors: Takayuki Takeda, Mayumi Takeuchi, Masahiko Saitoh, Takahiro Takemoto, Kuniaki Hirata, Toshiki Tanaka, Hiroshi Makihara, Sorou Takeda
Journal: Annals of Oncology (2017)
A gene signature to predict high tumor-infiltrating lymphocytes after neoadjuvant chemotherapy and outcome in patients with triple-negative breast cancer
Authors: C. Criscitiello, M.A. Bayar, G. Curigliano, F.W. Symmans, C. Desmedt, H. Bonnefoi, B. Sinn, G. Pruneri, C. Vicier, J.Y. Pierga, C. Denkert, S. Loibl, C. Sotiriou, S. Michiels, F. André
Journal: Annals of Oncology (2017)
Abstract 14593: Impact of Trans-Catheter Aortic Valve Implantation on Left Ventricular Systolic and Diastolic Properties: Real-time One-beat 3-dimensional Speckle Tracking Echocardiography Study
Authors: Itta Kawamura, Maki Saeki, Masanori Kawasaki, Ryuhei Tanaka, Takashi Kato, Takashi Yoshizane, Koji Ono, Shoko Watarai, Masanori Yamamoto, Maki Nagaya, Masazumi Arai, Kunihiko Tsuchiya, Hitoshi Matsuo, Toshiyuki Noda, Takahiko Suzuki, Hiroshige Ohashi, Shinya Minatoguchi
Journal: Circulation (2016)

Background: Left ventricle (LV) with aortic stenosis (AS) has severe remodeling due to pressure overload, resulting in systolic and diastolic dysfunction. LV endocardium is most susceptible to dele...
The management of cancer pain
Authors: Judith A. Paice, Betty Ferrell
Journal: CA A Cancer Journal for Clinicians (2011)

The experience of pain in cancer is widely accepted as a major threat to quality of life, and the relief of pain has emerged as a priority in oncology care. Pain is associated with both the disease as well as treatment, and management is essential from the onset of early disease through long-term survivorship or end-of-life care. Effective relief of pain is contingent upon a comprehensive assessment to identify physical, psychological, social, and spiritual aspects and as a foundation for multidisciplinary interventions. Fortunately, advances in pain treatment and in the field of palliative care have provided effective treatments encompassing pharmacological, cognitive-behavioral, and other approaches. The field of palliative care has emphasized that attention to symptoms such as pain is integral to quality cancer care. CA Cancer J Clin 2011. © 2011 American Cancer Society, Inc.
TCT-816 Impact of Diabetes Mellitus on Percutaneous Coronary Intervention in Chinese Patients: A Large Single Center Data
Authors: Huan-Huan Wang, Zhan Gao, Ying Song, Jing-jing Xu, Ping Jiang, Lin Jiang, Jue Chen, Lijian Gao, Lei Song, Yuejin Yang, Run-Lin Gao, Bo Xu, Jin-qing Yuan
Journal: Journal of the American College of Cardiology (2017)
A Phase I Open-Label Study to Identify a Dosing Regimen of the Pan-AKT Inhibitor AZD5363 for Evaluation in Solid Tumors and in <i>PIK3CA</i>-Mutated Breast and Gynecologic Cancers
Authors: Udai Banerji, Emma J. Dean, J. Alejandro Pérez-Fidalgo, Gerald Batist, Philippe L. Bedard, Benoit You, Shannon N. Westin, Peter Kabos, Michelle D. Garrett, Mathew Tall, Helen Ambrose, J. Carl Barrett, T. Hedley Carr, S.Y. Amy Cheung, Claire Corcoran, Marie Cullberg, Barry R. Davies, Elza C. de Bruin, Paul Elvin, Andrew Foxley, Peter Lawrence, Justin P.O. Lindemann, Rhiannon Maudsley, Martin Pass, Vicky Rowlands, Paul Rugman, Gaia Schiavon, James Yates, Jan H.M. Schellens
Journal: Clinical Cancer Research (2017)

Abstract Purpose: This phase I, open-label study (Study 1, D3610C00001; NCT01226316) was the first-in-human evaluation of oral AZD5363, a selective pan-AKT inhibitor, in patients with advanced solid malignancies. The objectives were to investigate the safety, tolerability, and pharmacokinetics of AZD5363, define a recommended dosing schedule, and evaluate preliminary clinical activity. Experimental Design: Patients were aged ≥18 years with World Health Organization (WHO) performance status of 0 to 1. Dose escalation was conducted within separate continuous and intermittent [4 days/week (4/7) or 2 days/week (2/7)] schedules with safety, pharmacokinetic, and pharmacodynamic analyses. Expansion cohorts of approximately 20 patients each explored AZD5363 activity in PIK3CA-mutant breast and gynecologic cancers. Results: MTDs were 320, 480, and 640 mg for continuous (n = 47), 4/7 (n = 21), and 2/7 (n = 22) schedules, respectively. Dose-limiting toxicities were rash and diarrhea for continuous, hyperglycemia for 2/7, and none for 4/7. Common adverse events were diarrhea (78%) and nausea (49%) and, for Common Terminology Criteria for Adverse Events grade ≥3 events, hyperglycemia (20%). The recommended phase II dose (480 mg bid, 4/7 intermittent) was assessed in PIK3CA-mutant breast and gynecologic expansion cohorts: 46% and 56% of patients, respectively, showed a reduction in tumor size, with RECIST responses of 4% and 8%. These responses were less than the prespecified 20% response rate; therefore, the criteria to stop further recruitment to the PIK3CA-mutant cohort were met. Conclusions: At the recommended phase II dose, AZD5363 was well tolerated and achieved plasma levels and robust target modulation in tumors. Proof-of-concept responses were observed in patients with PIK3CA-mutant cancers treated with AZD5363. Clin Cancer Res; 24(9); 2050–9. ©2017 AACR. See related commentary by Costa and Bosch, p. 2029
Erratum to: Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma
Authors: Ashish M. Kamat, Joaquim Bellmunt, Matthew D. Galsky, Badrinath R. Konety, Donald L. Lamm, David Langham, Cheryl T. Lee, Matthew I. Milowsky, Michael A. O’Donnell, Peter H. O’Donnell, Daniel P. Petrylak, Padmanee Sharma, Eila C. Skinner, Guru Sonpavde, John A. Taylor, Prasanth Abraham, Jonathan E. Rosenberg
Journal: Journal for ImmunoTherapy of Cancer (2017)

After the publication of the article [[1][1]], the treatment algorithm for advanced/metastatic bladder cancer in Fig. [3][2] was updated to reflect the current use of immunotherapy in this setting. The correct Fig. [3][2] can be seen here and the original article has been updated to reflect this
DeepPhe: A Natural Language Processing System for Extracting Cancer Phenotypes from Clinical Records
Authors: Guergana K. Savova, Eugene Tseytlin, Sean Finan, Melissa Castine, Timothy Miller, Olga Medvedeva, David Harris, Harry Hochheiser, Chen Lin, Girish Chavan, Rebecca S. Jacobson
Journal: Cancer Research (2017)

Precise phenotype information is needed to understand the effects of genetic and epigenetic changes on tumor behavior and responsiveness. Extraction and representation of cancer phenotypes is currently mostly performed manually, making it difficult to correlate phenotypic data to genomic data. In addition, genomic data are being produced at an increasingly faster pace, exacerbating the problem. The DeepPhe software enables automated extraction of detailed phenotype information from electronic medical records of cancer patients. The system implements advanced Natural Language Processing and knowledge engineering methods within a flexible modular architecture, and was evaluated using a manually annotated dataset of the University of Pittsburgh Medical Center breast cancer patients. The resulting platform provides critical and missing computational methods for computational phenotyping. Working in tandem with advanced analysis of high-throughput sequencing, these approaches will further accelerate the transition to precision cancer treatment. Cancer Res; 77(21); e115-8. ©2017 AACR.
Abstract 18164: Obesity Paradox in the Extremely Obese: Evaluaion of In-Hospital and Long Term Clinical Outcomes After Percutaneous Coronary Interventions
Authors: Maninder Singh, Abhishek Mishra, Daniel Sporn
Journal: Circulation (2014)

Introduction: Data regarding "obesity paradox" in patients with extreme obesity undergoing percutaneous coronary interventions (PCI) is limited and conflicting. We assessed clinical outcomes in patients with extreme obesity (Ex-Ob) compared to lean patients. Methods: From a single center prospective observational registry data, we assessed 1366 patients who underwent PCI from 01'-12'. We compared in-hospital and long term clinical outcomes between lean (body mass index (BMI ≤ 25kg/m2 , N=923) and Ex-Ob (BMI ≥40 kg/m2, N=443) patients. Results: The mean follow up duration was 3.6±2 yrs. Baseline characteristics are shown in table 1. Ex-Ob patients were younger, included fewer males and had higher frequency of cardiovascular co-morbidities (diabetes, hypertension, hyperlipidemia). There was no significant difference between the two groups with regards to in-hospital outcomes (death, major adverse cardiovascular events (MACE) or bleeding events). After multivariate adjustment for baseline differences, Ex-Ob patients had better long term overall (adj OR-0.63, 95%CI=0.41-0.95, p=0.029) and MACE free survival (adj OR-0.62, 95%CI=0.44 - 0.87, p=0.006) as compared to lean patients (Table 2 &amp; Fig 1). Conclusion: Although there was no difference in short term outcomes, obesity paradox was observed in patients with extreme obesity with regards to long term clinical outcomes after PCI.
Surto de legionelose em dois grupos de turistas acampados em França e Espanha, Junho de 1996
Authors: A Infuso, B Hubert, D Dumas, M Reyrolle, S De Mateo, C Pelaz, C Hemery, I Pérez
Journal: Eurosurveillance (1997)

A 11 de Junho de 1996, 3 casos suspeitos de Doenca dos legionarios num grupo de 42 turistas holandeses foram notificados a autoridade de saude local pelo hospital de Millau no sudoeste de Franca. O grupo (grupo 1) viajava, desde 15 de Maio, em caravanas, acampando em diversos parques em Franca e Espanha. A 15 de Junho foram internados no hospital de Millau com pneumonia, duas pessoas de um segundo grupo de 52 turistas holandeses (grupo 2), que faziam o mesmo percurso do primeiro grupo, mas com uma semana de intervalo. O presente relatorio sumariza as investigacoes epidemiologicas e ambientais levadas a cabo para identificar a fonte de infeccao.
Combretastatin A4/poly( L -glutamic acid)-graft-PEG conjugates self-assembled to nanoparticles
Authors: Yang Ou, Zhao-hui Tang, Lu Sun, Hai-yang Yu, Jia Li, Mei-hui Zhao, Hui Xu
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Combretastatin A4 (CA4) possesses varying ability to cause vascular disruption in tumors, while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4 (CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol (PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by 1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80~120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.
Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice
Authors: Chao Li, Yiping Lu, Sitong Du, Siyi Li, Yiting Zhang, Fangwei Liu, Ying Chen, Dong Weng, Jie Chen
Journal: Theranostics (2017)

Inhalation of crystalline silica particles leads to pulmonary fibrosis, eventually resulting in respiratory failure and death. There are few effective drugs that can delay the progression of this disease; thus, patients with silicosis are usually only offered supportive care. Dioscin, a steroidal saponin, exhibits many biological activities and health benefits including its protective effects against hepatic fibrosis. However, the effect of dioscin on silicosis is unknown.We employed experimental mouse mode of silicosis. Different doses of dioscin were gavaged to the animals 1 day after crystalline silica instillation to see the effect of dioscin on crystalline silica induced pulmonary fibrosis. Also, we used RAW264.7 and NIH-3T3 cell lines to explore dioscin effects on macrophages and fibroblasts. Dioscin was also oral treatment but 10 days after crystalline silica instillation to see its effect on established pulmonary fibrosis.Dioscin treatment reduced pro-inflammation and pro-fibrotic cytokine secretion by modulating innate and adaptive immune responses. It also reduced the recruitment of fibrocytes, protected epithelial cells from crystalline silica injury, inhibited transforming growth factor beta/Smad3 signaling and fibroblast activation. Together, these effects delayed the progression of crystalline silica-induced pulmonary fibrosis. The mechanism by which dioscin treatment alleviated CS-induced inflammation appeared to be via the reduction of macrophage, B lymphocyte, and T lymphocte infiltration into lung. Dioscin inhibits macrophages and fibroblasts from secreting pro-inflammatory cytokines and may also function as a modulator of T helper cells responses, concurrent with attenuated phosphorylation of the apoptosis signal-regulating kinase 1-p38/c-Jun N-terminal kinase pathway. Also, dioscin could block the phosphorylation of Smad3 in fibroblast. Oral treatment of dioscin could also effectively postpone the progression of established silicosis.Oral treatment dioscin delays crystalline silica-induced pulmonary fibrosis and exerts pulmonary protective effects in mice. Dioscin may be a novel and potent candidate for protection against crystalline silica-induced pulmonary fibrosis.
TCT-152 Early Versus Delayed Percutaneous Coronary Intervention for Non-ST Elevation Acute Coronary Syndromes in Patients with End Stage Renal Disease: A Nationwide Analysis from 2010 to 2014
Authors: Bing Yue, Chayakrit Krittanawong, Xin Wei, Mariam Khandaker, Shuyang Fang, Abel Casso
Journal: Journal of the American College of Cardiology (2017)
Blood Eosinophilia Neither Reflects Tissue Eosinophils nor Worsens Clinical Outcomes in Chronic Obstructive Pulmonary Disease
Authors: Graziella Turato, Umberto Semenzato, Erica Bazzan, Davide Biondini, Mariaenrica Tinè, Nerea Torrecilla, Marta Forner, Josè M. Marin, Manuel G. Cosio, Marina Saetta
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Procoagulant Profile in Primary Antiphospholipid Syndrome Is Not Dependent upon Increased Inflammatory Response
Authors: Lais Quinteiro, Bruna Mazetto, Sabrina Saraiva, Marina Pereira Colella, Erich Vinicius De Paula, Simone Appenzeller, Joyce Maria Annichino-Bizzacchi, Fernanda Andrade Orsi
Journal: Blood (2016)