tbuckley/cabot-search huggingface dataset:
Trends on clinical characteristics and medical service use of lung cancer in China 2005–14: a multicentre retrospective survey
Authors: Le Wang, Ju-Fang Shi, Ning Wu, Jun-Ling Li, Zhou-Guang Hui, Shang-Mei Liu, Bo-Yan Yang, Shu-Geng Gao, Jian-Song Ren, Hui-Yao Huang, Juan Zhu, De-Bin Wang, Yun-Chao Huang, Xian-Zhen Liao, Xiao-Jing Xing, Ling-Bin Du, Li Yang, Yu-Qin Liu, Yong-Zhen Zhang, Kai Zhang, You-Lin Qiao, Jie He, Min Dai
Journal: The Lancet (2017)
Abstract 17252: A Randomized Controlled Trial of the System CHANGE Intervention on Lifestyle Behaviors in HIV+ Adults
Authors: Allison R Webel, Shirley M Moore, Abdus Sattar, Chris T Longenecker, Jackson Currie, Christine Horvat Davey, Joseph Perazzo, Richard Josephson
Journal: Circulation (2017)

Introduction: HIV+ adults are twice as likely to develop cardiovascular disease (CVD) and approximately four times more likely to have a stroke than HIV-uninfected adults. Lifestyle behaviors (e.g....
There is no compelling evidence that human neonates imitate
Authors: Siobhan Kennedy-Costantini, Janine Oostenbroek, Thomas Suddendorf, Mark Nielsen, Jonathan Redshaw, Jacqueline Davis, Sally Clark, Virginia Slaughter
Journal: Behavioral and Brain Sciences (2017)

Abstract Keven &amp; Akins (K&amp;A) propose that neonatal “imitation” is a function of newborns' spontaneous oral stereotypies and should be viewed within the context of normal aerodigestive development. Their proposal is in line with the result of our recent large longitudinal study that found no compelling evidence for neonatal imitation. Together, these works prompt reconsideration of the developmental origin of genuine imitation.
Abstract B03: The EWS/FLI oncogene exerts pro-migratory and anti-apoptotic effects via dysregulation of focal adhesion kinase (FAK) signaling in Ewing sarcoma
Authors: Konrad Steinestel, Marcel Trautmann, Jan Rehkaemper, Eva Wardelmann, Uta Dirksen, Wolfgang Hartmann
Journal: Cancer Research (2017)

Abstract Ewing sarcoma (ES), an aggressive bone tumor of childhood and adolescence, is one of the most genetically normal tumors. The oncogenic potential is derived from chimeric fusions of EWS and ETS family transcription factors, with EWS-FLI1 rearrangements in 85% of cases. (Micro-) metastatic dissemination is the major threat for patients, and earlier studies have shown that cytoskeletal rearrangements upon EWS/FLI oncoprotein expression contribute to a migratory phenotype in ES cells. Using a patient-derived ES cell line with a stable EWS/FLI knockdown (A673-iEF), we show here that key tumorigenic effects of EWS/FLI are mediated via autophosphorylation of FAK on tyrosine 397, resulting in enhanced formation of focal adhesions and actin stress fibers as well as tumor cell migration, but impaired caspase-3-mediated anoikis (detachment-induced cell death) in vitro. This effect was not limited to A673 cells, but could also be observed in TC-32 and CADO-ES1 ES cells. Application of the FAK inhibitor 1, 2, 4, 5-Benzenetetraamine tetrahydrochloride (Y15) impaired cell migration and enhanced caspase-mediated apoptosis. Taken together, our results show that key oncogenic effects of EWS rearrangements are mediated via FAK autophosphorylation in ES and provide a rationale for the use of FAK inhibitors to impair metastatic dissemination of ES. Citation Format: Konrad Steinestel, Marcel Trautmann, Jan Rehkaemper, Eva Wardelmann, Uta Dirksen, Wolfgang Hartmann. The EWS/FLI oncogene exerts pro-migratory and anti-apoptotic effects via dysregulation of focal adhesion kinase (FAK) signaling in Ewing sarcoma [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B03.
Diagnosis and Treatment of Hypertension in the 2017 ACC/AHA Guidelines and in the Real World
Authors: John P. A. Ioannidis
Journal: JAMA (2017)

In this Viewpoint, John Ioannidis discusses implications of the 2017 hypertension guidelines for real-world management of blood pressure (BP), including labeling healthy people as having disease and possible adverse treatment effects at lower BP treatment targets..
“What” matters more than “Why” – Neonatal behaviors initiate social responses
Authors: Klaus Libertus, Melissa E. Libertus, Christa Einspieler, Peter B. Marschik
Journal: Behavioral and Brain Sciences (2017)

Newborns are born into a social environment that dynamically responds to them. Newborn behaviors may not have explicit social intentions but will nonetheless affect the environment. Parents contingently respond to their child, enabling newborns to learn about the consequences of their behaviors and encouraging the behavior itself. Consequently, newborn behaviors may serve both biological and social-cognitive purposes during development.
Abstract IA31: Precision prevention: Leveraging genomics to improve cancer control
Authors: Timothy R. Rebbeck
Journal: Cancer Research (2017)

Abstract Most tumors are incurable once they reach an advanced (e.g., metastatic) stage. Even for those cancers with effective treatment options, prevention has the greatest potential to reduce the burden of cancer in the general population. Prevention has great potential to reduce the burden of cancer before it can cause illness and death. However, not all individuals respond to prevention strategies in the same way: an individual's unique genetic makeup and unique set of biological events that lead to cancer mean that each individual may require a personalized approach to prevention. Precision prevention can be defined as the use of biological, behavioral, socioeconomic, and epidemiological data to devise and implement strategies tailored to reducing cancer incidence and mortality in a specific individual or group of individuals. In order to develop a precision prevention approach, it is critical that we understand: 1) basic biology of early carcinogenesis (e.g., genomic susceptibility, drivers of cancer, timing of carcinogenic events, reversibility of biological events); 2) heterogeneity (e.g., Inter-individual differences in susceptibility and tumor phenotype, intra-tumor differences in terms of clonality and propensity to metastasize, and response to preventive interventions); 3) unintended Effects of preventive strategies; and 4) implementation and health economics of preventive interventions. The principles of precision prevention strategies include a focus on those individuals who are at highest risk of suffering or death from cancer (e.g., genetically high-risk individuals and individuals with pre-neoplasia), focus on interventions that are motivated by fundamental biological knowledge, have a favorable cost-benefit ratio, and benefit all populations, including underserved and minority groups. In order for precision prevention to be successful, research is required to generate fundamental knowledge about cancer etiology and mechanism through scientific discovery; develop novel prevention strategies based on these fundamental discoveries; improve existing prevention strategies by incorporating biological information, biomarkers, risk profiling, and molecular subtyping to optimize prevention efficacy; and understand and implement cost-effective prevention strategies in targeted populations who are most likely to benefit. Citation Format: Timothy R. Rebbeck. Precision prevention: Leveraging genomics to improve cancer control [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA31.
Prognostic Value of Strain by Tissue Tracking Cardiac Magnetic Resonance After ST-Segment Elevation Myocardial Infarction
Authors: Jose Gavara, Jose F. Rodriguez-Palomares, Filipa Valente, Jose V. Monmeneu, Maria P. Lopez-Lereu, Clara Bonanad, Ignacio Ferreira-Gonzalez, Bruno Garcia del Blanco, Julian Rodriguez-Garcia, Maria Mutuberria, Elena de Dios, Cesar Rios-Navarro, Nerea Perez-Sole, Paolo Racugno, Ana Paya, Gema Minana, Joaquim Canoves, Mauricio Pellicer, Francisco J. Lopez-Fornas, Jose Barrabes, Arturo Evangelista, Julio Nunez, Francisco J. Chorro, David Garcia-Dorado, Vicente Bodi
Journal: JACC. Cardiovascular imaging (2017)
Stool Donor Body Mass Index Does Not Affect Recipient Weight After a Single Fecal Microbiota Transplantation for Clostridium difficile Infection
Authors: Monika Fischer, Dina Kao, Zain Kassam, Justin Smith, Thomas Louie, Brian Sipe, Michelle Torbeck, Huiping Xu, Fangqian Ouyang, Dariush Mozaffarian, Jessica R. Allegretti
Journal: Clinical Gastroenterology and Hepatology (2017)
Progress on malaria stalls amid decline in funding
Authors: Sanjeet Bagcchi
Journal: BMJ (2017)

Malaria cases across the globe increased by 5 million during 2016, suggesting a slowdown in the progress of global malaria control initiatives, a new report suggests.1

The World Malaria Report 2017 by the World Health Organization says that global malaria cases have declined steadily since 2010 (237 million), but there was a significant increase in the number of cases in 2016 (216 million) compared with 2015 (211 million).

Thanks to global control initiatives, the incidence rate for the disease decreased significantly—from 76 per 1000 population in …
Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas
Authors: Stephen J Schuster, Jakub Svoboda, Elise A Chong, Sunita D Nasta, Anthony R Mato, Özlem Anak, Jennifer L Brogdon, Iulian Pruteanu-Malinici, Vijay Bhoj, Daniel Landsburg, Mariusz Wasik, Bruce L Levine, Simon F Lacey, Jan J Melenhorst, David L Porter, Carl H June
Journal: New England Journal of Medicine (2017)

Patients with diffuse large B-cell lymphoma or follicular lymphoma that is refractory to or that relapses after immunochemotherapy and transplantation have a poor prognosis. High response rates have been reported with the use of T cells modified by chimeric antigen receptor (CAR) that target CD19 in B-cell cancers, although data regarding B-cell lymphomas are limited.We used autologous T cells that express a CD19-directed CAR (CTL019) to treat patients with diffuse large B-cell lymphoma or follicular lymphoma that had relapsed or was refractory to previous treatments. Patients were monitored for response to treatment, toxic effects, the expansion and persistence of CTL019 cells in vivo, and immune recovery.A total of 28 adult patients with lymphoma received CTL019 cells, and 18 of 28 had a response (64%; 95% confidence interval [CI], 44 to 81). Complete remission occurred in 6 of 14 patients with diffuse large B-cell lymphoma (43%; 95% CI, 18 to 71) and 10 of 14 patients with follicular lymphoma (71%; 95% CI, 42 to 92). CTL019 cells proliferated in vivo and were detectable in the blood and bone marrow of patients who had a response and patients who did not have a response. Sustained remissions were achieved, and at a median follow-up of 28.6 months, 86% of patients with diffuse large B-cell lymphoma who had a response (95% CI, 33 to 98) and 89% of patients with follicular lymphoma who had a response (95% CI, 43 to 98) had maintained the response. Severe cytokine-release syndrome occurred in 5 patients (18%). Serious encephalopathy occurred in 3 patients (11%); 2 cases were self-limiting and 1 case was fatal. All patients in complete remission by 6 months remained in remission at 7.7 to 37.9 months (median, 29.3 months) after induction, with a sustained reappearance of B cells in 8 of 16 patients and with improvement in levels of IgG in 4 of 10 patients and of IgM in 6 of 10 patients at 6 months or later and in levels of IgA in 3 of 10 patients at 18 months or later.CTL019 cells can be effective in the treatment of relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. High rates of durable remission were observed, with recovery of B cells and immunoglobulins in some patients. Transient encephalopathy developed in approximately one in three patients and severe cytokine-release syndrome developed in one in five patients. (Funded by Novartis and others; ClinicalTrials.gov number, NCT02030834 .).
A first-in-human phase I study of MORAb-004 (M4), a humanized monoclonal antibody recognizing endosialin (TEM-1), in patients with solid tumors.
Authors: Luis A. Diaz, Nilofer Saba Azad, Mrinal M. Gounder, Christina Marie Coughlin, Jean Fishel, Daniel O'Shannessy, Luigi Grasso, Jason Wustner, Jagadeesh Aluri, Jeff Parno, Richard D. Carvajal
Journal: Journal of Clinical Oncology (2012)

3016 Background: Endosialin (TEM-1) is a membrane glycoprotein on the cell surface of activated mesenchymal cells (e.g. pericytes, fibroblasts and mesenchymal tumor cells) and on a subset of human cancers. It is involved in the development of tumor vasculature, stromal/tumor organization and PDGFRb signaling. M4 is a humanized IgG monoclonal antibody which targets TEM-1. Preclinical studies suggest that M4 may have single agent activity via inhibition of the tumor microenvironment and by direct effects on tumors expressing this target. Methods: A phase I dose escalation study in patients (pts) with advanced solid tumors was conducted to evaluate the safety, pharmacokinetic profile and preliminary efficacy of M4 administered intravenously on a weekly schedule; final results are presented. Results: 36 pts refractory to therapy were treated at 10 dose levels (0.0625 to 16 mg/kg administered i.v. on a weekly schedule). Drug-related adverse events (AE) observed were primarily infusion toxicity (grade 1 and 2 fever, chills, headache, myalgia). The MTD was determined to be 12 mg/kg. DLT of grade 3 vomiting was observed at 16 mg/kg. Preliminary pharmacokinetic (PK) analyses demonstrate M4 accumulation beginning at 4 mg/kg, and that elimination mechanisms are saturable beginning at 0.25 mg/kg. Exposure (AUC) increases in a greater than dose-proportional manner, with the apparent t1/2 increasing proportionally with dose. Tumor shrinkage (Minor/mixed tumor responses, mR) were seen in four pts (soft tissue sarcoma (2), hepatocellular carcinoma, pancreatic neuroendocrine tumor). Each mR was associated with prolonged disease stabilization in these pts (6-14 months). A cohort (n=4) of pts with refractory colorectal carcinoma demonstrated disease stabilization (15-24 weeks). Analysis of archival tumor revealed TEM-1 stromal staining in all cases with tumor cell expression noted on a subset of tumors of mesenchymal origin. Conclusions: In this phase I study, M4 was tolerated up to 12 mg/kg (MTD) and early signs of potential activity were observed. Expanded cohorts of 1-12 mg/kg are ongoing to further define an optimal dose.
No evidence that CD33 splicing SNP impacts the response to GO in younger adults with AML treated on UK MRC/NCRI trials
Authors: Rosemary E. Gale, Teodora Popa, Melissa Wright, Naeem Khan, Sylvie D. Freeman, Alan K. Burnett, Nigel H. Russell, Robert K. Hills, David C. Linch
Journal: Blood (2017)
Synthetic Cannabinoid and Mitragynine Exposure of Law Enforcement Agents During the Raid of an Illegal Laboratory — Nevada, 2014
Authors: Loren Tapp, Jessica G. Ramsey, Anita Wen, Roy Gerona
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Synthetic cannabinoids (SCs), commonly known by the street name "Spice," are designer drugs of abuse that mimic the psychoactive effects of marijuana. Intentional SC use has resulted in multiple toxicities (1,2), but little is known about occupational SC exposure. After a federal agency's law enforcement personnel in Nevada reported irritability and feeling "high" after raiding illegal SC laboratories and processing seized SCs, a request for a health hazard evaluation was made by the agency to CDC's National Institute for Occupational Safety and Health (NIOSH) in 2014 to evaluate agents' occupational SC exposures. After making the request for a health hazard evaluation, federal agents conducted a raid of an illegal SC laboratory, with assistance from local law enforcement and Drug Enforcement Administration (DEA) personnel and with NIOSH investigators observing from a distance. After the raid, agents collected and processed material evidence. NIOSH investigators tested agents' urine for SC levels before and after the raid and measured SCs in the air and on surfaces after the raid. DEA determined that AB-PINACA (an SC compound) and mitragynine (a plant material with opium-like effects, also known as "kratom") were present in the illegal laboratory. AB-PINACA, its metabolites, and mitragynine were not detected in agents' urine before the raid; however, one or more of these substances was found in the urine of six of nine agents after the raid and processing of the SC evidence. AB-PINACA was detected in one surface wipe sample from the SC laboratory; none was detected in the air in the laboratory or in the offices of the law enforcement agency where the materials were processed after the raid. No policies were in place regarding work practices and use of personal protective equipment (PPE) during raids and evidence processing. To protect agents from SC exposures, NIOSH recommended that the agency require agents to wear a minimum level of PPE (e.g., protective gloves and disposable clothing) and undergo training in PPE and in handling and storing of contaminated evidence from SC laboratory raids. Showers and locker rooms also need to be provided so that agents can reduce contamination and prevent take-home exposure.
Abstract 55: SET protein as a therapeutic target in head and neck squamous cell carcinoma
Authors: Renata Nishida Goto, Karina Stringhetta-Padovani, Michael Vitek, Carlos Curti, Andreia Machado Leopoldino
Journal: Clinical Cancer Research (2017)

Abstract Introduction: The study of cancer molecular profiles allowed the development of several targeting agents, such as OP449 and FTY720/Fingolimod drugs, that can act as PP2A activators. OP449 is a synthetic peptide with antineoplastic action and FTY720 is a potent inhibitor of tumor growth and angiogenesis. SET/I2PP2A, a multifunctional protein, is a potent and specific inhibitor of PP2A and is upregulated in head and neck squamous cell carcinoma (HNSCC). SET has been proposed to be an oxidative stress sensor, promoting cell survival and apoptosis. Both OP449 and FTY720 bind to SET and destabilize SET/PP2A complex, reactivating the PP2A function. Objectives: The aim was to evaluate the antitumoral effect, in vitro and in vivo, of the association OP449 plus FTY720, in HNSCC. Material and Methods: HNSCC lineages were analyzed for SET protein status by Western blotting and for cancer stem cell population by using aldehyde dehydrogenase 1 (ALDH1) activity assay. Alterations in SET targets were confirmed by Western blotting. The cytotoxic effects of OP449 and/or FTY720, under different concentrations, were determined after 72 hours through the resazurin assay. The coefficient of drug interaction (CDI) was used to analyze the synergistic inhibitory effect of drug combination. Xenograft tumor model in Balb/c nude mice (n=5 per group), by subcutaneous injection of cells into the flank of the mouse, was used to investigate the antitumoral potential of treatment with OP449 and/or FTY720, every 48 h, for 15 days. Results and Discussion: HN12 cells were selected due to the higher levels of SET and higher ALDH1 activity compared to other HNSCC cells. The treatment of HN12 cells with OP449 altered the levels of SET targets. A significant synergistic effect was observed when cells were pre-treated with 2 μM OP449 followed by 15 μM FTY720 (CDI=0.27 ± 0.088). Nude mice bearing HN12 human xenograft tumors treated with OP449 (5 mg/kg) and/or FTY720 (2 mg/kg) showed reduction in tumor growth compared to either control (vehicle) or compounds isolated. Conclusion: Our results indicate that OP449 and FTY720 have a synergistic antitumoral effect, opening perspectives for either alternating or combined therapies in HNSCC, having SET protein as a target. Financial support: FAPESP, CNPq and CAPES. Citation Format: Renata Nishida Goto, Karina Stringhetta-Padovani, Michael Vitek, Carlos Curti, Andreia Machado Leopoldino. SET protein as a therapeutic target in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 55.
pH-sensitive polymeric nanoparticles with antioxidant and anti-inflammatory properties against cisplatin-induced hearing loss
Authors: Sergio Martín-Saldaña, Raquel Palao-Suay, María Rosa Aguilar, Luis García-Fernández, Humberto Arévalo, Almudena Trinidad, Rafael Ramírez-Camacho, Julio San Román
Journal: Journal of Controlled Release (2017)
Analysis of long-term survival in patients with glioblastoma treated in the wide area of romagna (AVR).
Authors: Elisabetta Melegari, Monia Dall'Agata, Serenella Cerasoli, Claudio Dazzi, Alessandro Gamboni, Giuseppe Pasini, Antonio Polselli, Toni Ibrahim, Flavia Foca, Giovanni Brigliadori, Marina Faedi
Journal: Journal of Clinical Oncology (2014)

e13006 Background: Adult glioblastoma (GBM) is the most common type of malignant primary brain tumor. Despite advances in treatment, median survival is between 12 and 15 months. Standard care is concomitant radiotherapy (RT)/chemotherapy (CT) and adjuvant temozolomide (TMZ) for 6 cycles. At progression, subsequent treatments are at the discretion of the patient’s physician. Methods: We retrospectively analyzed data from 174 patients (pts) with GBM treated from 2003 to 2011 in the oncology network of AVR, Italy, evaluating those with longer survival (> 24 months) in terms of treatment and methylated MGMT levels. Results: 44 (25.3%) pts treated showed long-term survival: 27 underwent radical macroscopic neurosurgery, 15 non radical surgery and 2 biopsy. All but 1 pt had a KPS between 70% and 100%. 11 pts were treated before the EORTC/NCIC trial and 33 after the study ended. 10 pts in the former group were treated with RT followed by TMZ and 1 received only RT. The latter group received standard care. To date only 6 /44pts have not progressed. Of the entire group, 25 pts underwent first-line treatment after progression and of these, 13 received second-line therapy. MGMT methylation status was re-analzyed in all cases by pyrosequencing and classified into 3 ranges: non methylated 0-9% pts (no. 4) had a median overall survival (mOS) of 53 months (95%IC, range 25-NS) and the median progression-free survival (mPFS) was not reached; methylated 10-29% pts (9) had an mOS of 29% (95%IC, range 25-42) and an mPFS of 16 (95%IC, range 3-26); methylated 30-100% pts(30) had an mOS of 36 months (95%IC, range 28-42) and an mPFS of 23 months (95%IC, range 17-32). Regardless of MGMT status, pts who received concomitant RT/CT had an mOS of 35 months (95%IC, range 28-48), while those who underwent sequential therapy had an mOS of 36 months (95%IC, range 26-42). Conclusions: Our results indicate that the long-term survival of pts was not determined by MGMT status or by concurrent or sequential therapy. Tumor methylation was not homogeneous. In non methylated pts, single CpG island hypermethylation was detected. Further studies are warranted to confirm these findings.
Influence of Ground Glass Opacity and the Corresponding Pathological Findings on Survival in Patients with Clinical Stage I Non–Small Cell Lung Cancer
Authors: Keiju Aokage, Tomohiro Miyoshi, Genichiro Ishii, Masahiro Kusumoto, Shogo Nomura, Shinya Katsumata, Keigo Sekihara, Kenta Tane, Masahiro Tsuboi
Journal: Journal of Thoracic Oncology (2017)