tbuckley/cabot-search huggingface dataset:
Associations Between End-of-Life Cancer Care Patterns and Medicare Expenditures
Authors: Shi-Yi Wang, Jane Hall, Craig E. Pollack, Kerin Adelson, Amy J. Davidoff, Jessica B. Long, Cary P. Gross
Journal: Journal of the National Comprehensive Cancer Network (2016)

The purpose of this study was to examine the extent to which patterns of intensive end-of-life care explain geographic variation in end-of-life care expenditures among cancer decedents.Using the SEER-Medicare database, we identified 90,465 decedents who were diagnosed with cancer in 2004-2011. Measures of intensive end-of-life care included chemotherapy received within 14 days of death; more than 1 emergency department visit, more than 1 hospitalization, or 1 or more intensive care unit (ICU) admissions within 30 days of death; in-hospital death; and hospice enrollment less than 3 days before death. Using hierarchical generalized linear models, we estimated risk-adjusted expenditures in the last month of life for each hospital referral region and identified key contributors to variation in expenditures.The mean expenditure per cancer decedent in the last month of life was $10,800, ranging from $8,300 to $15,400 in the lowest and highest expenditure quintile areas, respectively. There was considerable variation in the percentage of decedents receiving intensive end-of-life care intervention, with 41.7% of decedents receiving intensive care in the lowest quintile of expenditures versus 57.9% in the highest quintile. Regional patterns of late chemotherapy or late hospice use explained only approximately 1% of the expenditure difference between the highest and lowest quintile areas. In contrast, the proportion of decedents who had ICU admissions within 30 days of death was a major driver of variation, explaining 37.6% of the expenditure difference.Promoting appropriate end-of-life care has the potential to reduce geographic variation in end-of-life care expenditures.
Beyond ‘communication and control’: towards ethically complete rationales for brain-computer interface research
Authors: Laura Specker Sullivan, Judy Illes
Journal: Brain-Computer Interfaces (2016)

Rapid advances in neural engineering have led to an increasing use of human subjects in brain-computer interface (BCI) research. Here we ask whether the rationales articulated for this research have kept pace with related ethical requirements. To answer this question, we examined the content of peer-reviewed BCI research publications of studies involving human subjects. We analysed the publications for the rationale expressed for the research against a backdrop of journal type and study design. We discuss the results in the context of strategies that neural engineering researchers can adopt to ensure that the ethical dimensions of human subject research are not lost amid the technological drive for results.
Abstract 4262: Combined 3D quantitative imaging and 3D cell culture for cancer drug discovery
Authors: Guillaume Vidal, Valérie Lobjois, Zied Souguir, Pauline Pannetier, Elise Demange, Jean-Michel Lagarde
Journal: Cancer Research (2016)

Abstract Monitoring drug activity in multicellular tumor spheroid in vitro models is an important challenge as these 3D models have demonstrated their major relevance in pharmacological screening and anticancer drugs evaluation (1). Optical microscopy coupled to the selective plane illumination microscopy (SPIM)3D microscopy, and, and automatic automated images processing and quantitative analysis are promising approaches to process optimizes the evaluation of drug response in a 3D cell culture models with, in a high/mediumhigh throughput screening waycapabilities. BIOMIMESYS® used as a 3D cell model is based on hyaluronic to provide an in vivo like environment to the cells. The In this study the effects of the topoisomerase I inhibitor Topotecan were investigated on colon adenocarcinoma HCT-116 3D cell culture. Spheroids were prepared and grown in BIOMIMESYS® used as a 3D cell model isa matrix based on hyaluronic acid tothat provides an in vivo like environment to the cells. was monitored and coupled with mMorphometric parameters and with nuclei fluorescence markers were used to monitor analysis for drug activity. Data provideand to characterization characterize of both cytostatic and cytotoxic effects of this drug withon the basis of both quantitative 3D and imaging of the mechanisms. These data highlight the relevance of combining a biomimetic microenvironment for 3D cell culture recreating the the in vivo features of a tumor cell population biology, together with and high resolution content microscopy-based quantification for drug screening. This biomimetic model provides an innovative platform for the in-depth analysis of tumor development and for the discovery or the characterization of novel therapeutic targets. Ref: 1) Breslin S, O’Driscoll L. Drug Discov Today.18: 240-249 (2013) Citation Format: Guillaume Vidal, Valérie Lobjois, Zied Souguir, Pauline Pannetier, Elise Demange, Jean-Michel Lagarde. Combined 3D quantitative imaging and 3D cell culture for cancer drug discovery. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4262.
Detection of Fainters and Epileptics in Young Adult Population
Authors: R H Mewburn, W C Gibson
Journal: JAMA (1963)

A screening procedure for the detection of fainters and of epileptics was tested on 212 university student volunteers. No subject in this series gave a history of epilepsy but four definitely abnormal electroencephalograms were recorded. As a supplement to routine electroencephalography various circulatory stresses were applied with the subject sitting upright. The application of needle electrodes to the scalp was itself a potent stimulus to fainting. Under these conditions 16 of the 21 subjects with a history of repeated fainting were detected by their cardiovascular response to electrode placement or ocular compression. The use of painless pad electrodes reduced the total stress and produced inferior results. By careful adjustment of total stress intensity the majority of habitual fainters can be detected.
Abstract 3295: Microbiome profiling and immunological characterization on gastrointestinal tract tumors
Authors: Chao Zhang, Kyle Cleveland, Felice Schnoll-Sussman, Bridget McClure, Michelle Bigg, Nikolaus Schultz, Manish A. Shah, Doron Betel
Journal: Cancer Research (2016)

Abstract Motivation: Conservative estimates are that around 20% of all malignancies may be attributed to microbiota. Especially in the gastrointestinal (GI) tract, infection can cause chronic inflammation and further influence immune response to create a proinflammatory microenvironment for cancer development. This can account in part for the reason that the immunotherapy in colon cancer is less efficacious than in non-GI tract cancers. We proposed a systematic computational study to profile the microbiome from next generation sequencing of gastric biopsy samples, and evaluate the relationships among microbiome composition, host immune response and genomic characterization. Method: Patients undergoing upper endoscopy without chronic inflammatory disease or chronic NSAID use were eligible for participation, including cancer/non-cancer, Helicobacter pylori positive and negative patients. In total, 62 endoscopic biopsies from 3 locations in the gastric antrum/body were freshly frozen for whole genome sequencing and transcriptome analysis. In addition, TCGA whole genome sequencing (WGS) data from 37 gastric cancer, 102 colon cancer, and 46 rectal cancer samples were analyzed for microbiome composition. Results: H. pylori was detected in all positive infection gastric biopsy samples by our pipeline, and the results were successfully validated by qPCR. Comparing to other traditional bacterial identification methods, our pipeline shows a strong capacity for profiling microbiome from low bacterial content biopsy samples. We observed a high positive correlation between the H. pylori content and total non-H. pylori bacteria content. And we also identified significantly differentially expressed immune-related genes between active H. pylori infection and negative samples. Finally, we analyzed collected TCGA WGS data, and identified the dominant species from the different cancer studies, such as Bacteroides fragilis in rectum adenocarcinoma, and Fusobacterium nucleatum in colon adenocarcinoma. The correlation among microbiome composition, the expression of immune-related genes and cancer genomic characterization were also demonstrated in this study. Citation Format: Chao Zhang, Kyle Cleveland, Felice Schnoll-Sussman, Bridget McClure, Michelle Bigg, Nikolaus Schultz, Manish A. Shah, Doron Betel. Microbiome profiling and immunological characterization on gastrointestinal tract tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3295.
The PI3K-δ Inhibitor TGR-1202 in Combination with Brentuximab Vedotin (SGN-35) Synergistically Inhibits Tubulin Polymerization and Exerts Potent Antitumor Effects in NOD/SCID Mice with Hodgkin Lymphoma Cell Line Xenografts
Authors: Silvia L Locatelli, Silvia Tartari, Luca Castagna, Rita Mazza, Srikant Viswanadha, Peter Sportelli, Swaroop Vakkalanka, Armando Santoro, Carmelo Carlo-Stella
Journal: Blood (2014)
Long Term Follow up of SWOG S0313: Ibritumomab Tiuxetan Consolidation after 3 Cycles of CHOP Plus Radiotherapy for High Risk Limited Stage Aggressive B-Cell Lymphoma
Authors: Daniel O Persky, Thomas P. Miller, Joseph M Unger, Catherine M. Spier, Soham D. Puvvada, B. Dino Stea, Oliver W. Press, Louis Constine, Kevin Barton, Michael LeBlanc, Sonali Smith, Richard I. Fisher, Jonathan W. Friedberg
Journal: Blood (2014)
Bloodstream infections caused by <i>Klebsiella pneumoniae</i> in onco‐hematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey
Authors: Enrico Maria Trecarichi, Livio Pagano, Bruno Martino, Anna Candoni, Roberta Di Blasi, Gianpaolo Nadali, Luana Fianchi, Mario Delia, Simona Sica, Vincenzo Perriello, Alessandro Busca, Franco Aversa, Rosa Fanci, Lorella Melillo, Federica Lessi, Maria Ilaria Del Principe, Chiara Cattaneo, Mario Tumbarello
Journal: American Journal of Hematology (2016)

The aim of this study was to identify risk factors for mortality in patients suffering from hematological malignancies (HMs) with bloodstream infections (BSIs) caused by Klebsiella pneumoniae (KP). We conducted a prospective cohort study on KP BSI in 13 Italian hematological units participating in the HEMABIS registry-SEIFEM group. The outcome measured was death within 21 days of BSI onset. Survivor and non-survivor subgroups were compared and Cox regression analysis was conducted to identify independent predictors of mortality. A total of 278 episodes of KP BSI were included in the study between January 2010 and June 2014. We found that 161 (57.9%) KP isolates were carbapenem resistant (CRKP). The overall 21-day mortality rate was 36.3%. It was significantly higher for patients with CRKP BSI (84/161, 52.2%) than for those with BSI caused by carbapenem susceptible KP (CSKP) (17/117, 14.5%; P < 0.001). Septic shock (HR 3.86), acute respiratory failure (HR 2.32), inadequate initial antimicrobial therapy (HR 1.87) and carbapenem resistance by KP isolates (HR 1.85) were independently associated with mortality. A subanalysis was conducted in only 149 patients with CRKP BSI who had received ≥48 hr of adequate antibiotic therapy, and combination therapy was independently associated with survival (HR 0.32). Our study shows that in recent years carbapenem resistance has dramatically increased in HM patients with KP BSI in Italy and is associated with a worse outcome. The optimal management of such infections and the definition of new empirical/targeted antimicrobial strategies in HM patients can still be considered unmet clinical needs. Am. J. Hematol. 91:1076-1081, 2016. © 2016 Wiley Periodicals, Inc.
PWE-014 Jesrey Flexible Sigmoidoscopy Bowel Cancer Programme: One Year’s Experience: Abstract PWE-014 Table 1
Authors: M Duku, D Ng, S De George, T Hughes, K Tierney, S Turnbull, L Diggle
Journal: Gut (2014)

<h3>Introduction</h3> Randomised control trials (RCTs) have demonstrated that once-only flexible sigmoidoscopy (FS) between ages of 55 to 64 reduces both incidence and mortality from colorectal cancer. A key marker of quality in FS screening is adenoma detection rate (ADR), which relies on effective bowel preparation and good technique. The States of Jersey introduced once-only FS at age 60 in February 2013. This study aims to evaluate the one-year outcomes of the programme. <h3>Methods</h3> Jersey residents aged 60 were invited by post to participate in the programme. Responders were telephone pre-assessed for eligiblity and bowel habit and assigned one of two bowel cleansing regimes; two fleet enemas + senna/bisacodyl or moviprep. FS were performed, unsedated, by two experienced gastroenterologists using paediatric colonoscopes, with the aim of visualising at least 60cm (straightened endoscope) of the left colon. Clients with poor bowel preparation had additional fleet enema and re-scoped on the same day or returned on a later day following moviprep. All polyps =1 cm were removed during FS. Indication for colonoscopy was the presence of high-risk lesions (adenoma =1 cm, adenoma with high grade dysplasia or a villous component and = 3 adenomas). After FS, clients were given a questionnaire, which included a pain score. <h3>Results</h3> 768 clients were invited. 60 were ineligible. 453 had the FS. The uptake was 69.2% and overall ADR was 15.7% (Table 1) which are higher than in the RCTs. FS was well tolarated. Only 36 (13.9%) required entonox. 79% reported no or mild discomfort and only 1% reported severe discomfort. 1 client had an incomplete examination due to pain. 435 (96.03%) had 2 fleet enemas plus senna or bisacodyl and 18 (3.97%) had moviprep as the first bowel prep. The quality was excellent or good in 83%. Only 32 (7%) had poor prep and needed repeat bowel preperation. There were no major complications during bowel preperation or the FS. 1 patient reported abdominal cramps during bowel preparation and 2 and vasovagal episodes immediately after the FS. None required hospital admission. <h3>Conclusion</h3> FS screening using two enemas is acceptable and safe. Better bowel preparation and complete examination of the left colon contributed to the high ADR. The impact of the uptake and high ADR on the incidence and mortality of CRC in Jersey will likley be greater than that seen in the RCTs. <h3>Disclosure of Interest</h3> None Declared.
Abstract 4738: The BET family bromodomain inhibitor ABBV-075 is a promising therapeutic agent for acute myeloid leukemia and myelodysplastic syndrome
Authors: Mai H. Bui, Xiaoyu Lin, Xiaoli Huang, Leiming Li, Aparna Sarthy, Daniel Albert, Terry Magoc, Lloyd Lam, Paul Hessler, Tamar Uziel, Steven Elmore, Keith McDaniel, Warren Kati, Yu Shen
Journal: Cancer Research (2016)

Abstract Small molecule inhibitors of the bromodomain and extraterminal domain (BET) proteins exhibit interesting activities in preclinical models of various cancer indications, and several of these inhibitors are currently under clinical investigation. ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered Phase 1 studies. Upon characterizing cellular responses to BET inhibitors across a large panel of cancer cell lines, we identified AML/MDS as one of the few cancer indications where BET inhibitors triggered robust apoptosis in cancer cell lines and in patient-derived cancer cells. The induction of apoptosis by BET inhibitors in AML/MDS cells may be partly attributed to their abilities to down regulate Bcl-XL and Bcl-2, and combining BET inhibitors with the Bcl-2 inhibitor venetoclax (ABT-199) resulted in robust cytotoxicity in AML/MDS cells. ABBV-075 exhibited significant antitumor efficacy as a monotherapy in flank xenograft models of AML and MDS. Furthermore, combining low doses of ABBV-075 with the standard of care agent azacitidine in the SKM1 model led to significant tumor regression, and the combination regimen was better tolerated than BETi monotherapy at doses that produced a similar degree of therapeutic benefit. Expression profiling of SKM1 tumors from mice treated with the ABBV-075/azacitidine combination or each of these agents as monotherapies revealed that ABBV-075 and azacitidine regulated a common set of biologic pathways. The combination of ABBV-075/azacitidine led to a more robust impact on these common pathways, which may partially contribute to the enhanced efficacy of the ABBV-075/azacitidine combination in the SKM-1 model. Citation Format: Mai H. Bui, Xiaoyu Lin, Xiaoli Huang, Leiming Li, Aparna Sarthy, Daniel Albert, Terry Magoc, Lloyd Lam, Paul Hessler, Tamar Uziel, Steven Elmore, Keith McDaniel, Warren Kati, Yu Shen. The BET family bromodomain inhibitor ABBV-075 is a promising therapeutic agent for acute myeloid leukemia and myelodysplastic syndrome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4738.
Abstract 4628: The RSK inhibitor SL0101 impairs the proliferation of glioblastoma cell lines
Authors: Martín Roffe, Fernanda C. Lupinacci, Luana C. Soares, Glaucia N. Hajj, Vilma R. Martins
Journal: Cancer Research (2016)

Abstract Glioblastoma (GBM) is the most common and lethal type of brain tumor. The most frequently altered signaling pathway in this tumor is the RTKs-PI3K-Akt-mTORC1 (88% of cases). However, clinical trials for GBM using inhibitors of this pathway exhibited poor clinical responses. One of the main responsibles for this resistance is the compensatory activation of the Ras-ERK1/2 pathway. In fact, GBMs can also present alterations in the Ras-ERK1/2 pathway, such as mutation of NF1 in 18% of the cases. RSK is a direct target of ERK1/2 and has been shown to regulate important functions in different types of tumors, such as prostate and breast. RSK is a family of kinases comprised by four highly-homologous isoforms in humans (RSK1-4) and nothing is known about their functions in GBMs. Here we show that RSK1 levels are highly variable between cells, the levels of RSK2 are less variable, and RSK3 and RSK4 were not detected. To gain insight into the function of RSK, we studied the effects of the RSK inhibitor, SL0101, on the proliferation of four different GBM cell lines (LN18, LN229, U87MG and A172). A suboptimal concentration of SL0101 (50 μM) was able to inhibit basal and EGF-stimulated proliferation, and it was more potent than 100 nM rapamycin in some of the cells. In 3 of the cell lines, SL0101 inhibited serum-stimulated proliferation, and in 2 of them, it was more potent than rapamycin. We have previously shown that SL0101 can inhibit mTORC1 signaling in an ERK1/2-RSK independent manner. However, SL0101 showed a synergistic interaction with rapamycin in all of the cell lines, which suggests that other effects besides RSK-mTORC1 inhibition might be involved in the effect of SL0101. This was further suggested by the modest synergistic interaction between rapamycin and the RSK inhibitor, fmk. Altogether, these results indicate that SL0101 is a potent inhibitor of proliferation in a manner not related with the RSK1 status of GBM cells. Further studies to define the molecular mechanism of the effects of SL0101 are necessary to understand which pathways are indeed modulated. Citation Format: Martín Roffe, Fernanda C. Lupinacci, Luana C. Soares, Glaucia N. Hajj, Vilma R. Martins. The RSK inhibitor SL0101 impairs the proliferation of glioblastoma cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4628.
Abstract LB-320: Obligate lesions and diverse evolutionary patterns drive small cell bladder cancer
Authors: Alexander Penson, Matthew T. Chang, Neil Desai, Nicholas D. Socci, Ronglai Shen, Venkatraman E. Seshan, Ritika Kundra, Adam Abeshouse, Agnes Viale, Eugene K. Cha, Bernard H. Bochner, Jonathan E. Rosenberg, Dean F. Bajorin, Nikolaus Schultz, Michael F. Berger, Gopa Iyer, David B. Solit, Hikmat Al-Ahmadie, Barry S. Taylor
Journal: Cancer Research (2016)

Abstract Small cell bladder cancer (SCBC) is a rare and aggressive neuroendocrine tumor with a dismal prognosis and limited treatment options. As SCBC is histologically indistinguishable from small cell lung cancer, a shared pathogenesis and cell of origin has been proposed. To determine whether SCBCs arise from a pre-existent urothelial carcinoma or share a molecular pathogenesis in common with small cell lung cancer, we performed integrative analysis of 61 SCBC patients to identify histology- and organ-specific similarities and differences with urothelial carcinomas and small cell lung cancers. SCBC has a high somatic mutational burden driven predominantly by an APOBEC-mediated mutational process. Obligate mutations in TP53, RB1, or the TERT promoter were present in nearly all samples. While these events arose early in all affected tumors, reflecting an evolutionary branch point that drove small cell lineage differentiation, they were not the founding transforming event, as they were often preceded by diverse and less common driver mutations many of which are common in bladder urothelial cancers but not small cell lung tumors. The majority of patient tumors (72%) also underwent whole-genome duplication (WGD). While arising at different chronological points in the evolution of the disease, WGD was often preceded by biallelic mutations in TP53 with retention of two intact copies. Together, our findings indicate that small cell cancers of the bladder and lung have a convergent but distinct pathogenesis and SCBCs likely arise from a cell of original shared with urothelial bladder cancer. Citation Format: Alexander Penson, Matthew T. Chang, Neil Desai, Nicholas D. Socci, Ronglai Shen, Venkatraman E. Seshan, Ritika Kundra, Adam Abeshouse, Agnes Viale, Eugene K. Cha, Bernard H. Bochner, Jonathan E. Rosenberg, Dean F. Bajorin, Nikolaus Schultz, Michael F. Berger, Gopa Iyer, David B. Solit, Hikmat Al-Ahmadie, Barry S. Taylor. Obligate lesions and diverse evolutionary patterns drive small cell bladder cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-320.