tbuckley/cabot-search huggingface dataset:
Assessing the natural language processing capabilities of IBM Watson for oncology using real Australian lung cancer cases.
Authors: Dishan H. Herath, Dominic Wilson-Ing, Emeline Ramos, George Morstyn
Journal: Journal of Clinical Oncology (2016)

e18229 Background: Optimal treatment decisions require information from multiple sources and formats even in the context of electronic medical records. In addition, structured data such as that collected by cancer registries can be used for research and quality assurance purposes. IBM Watson for Oncology (WFO), developed in collaboration with Memorial Sloan Kettering Cancer Center, is a cognitive computing system able to extract structured data from free text documents using natural language processing (NLP). We evaluated the baseline NLP performance of WFO in Australian lung cancer patients. Methods: NLP performance was evaluated for 32 data elements including ECOG performance status, sites of metastasis, histological subtype, mutation status and T, N and M stage. De-identified text documents from lung cancer patients treated at 2 Australian hospitals in the last 2 years were entered into WFO, with each patient treated as an individual case for NLP. The documents used were: doctors’ letters, tumor board notes, radiology reports, histology or cytology reports and mutation test results. Patients were those assessed by a medical oncologist for suitability for either adjuvant chemotherapy following surgery or for 1st line systemic therapy for metastatic disease. Two clinicians checked each source document for the presence or absence of data elements. Results: 264 documents from 50 patients (7 adjuvant, 43 metastatic) were analyzed. WFO correctly identified 335 data elements (true positives) and correctly derived an additional 75 elements not explicitly stated in the source documents (e.g. derived M1 stage in a patient with bone metastases). There were 41 false negative data elements found by the readers, but not WFO, 61 false positive elements and 17 incorrectly derived elements. Overall per-patient results were: NLP precision 85%, NLP recall 89% and NLP accuracy 94%. For derived elements, accuracy was 82%. Conclusions: The NLP performance of WFO demonstrates its potential as a data collection tool. Local performance would be expected to improve with training of WFO capabilities using Australian cases.
Disparities in Adult Cigarette Smoking — United States, 2002–2005 and 2010–2013
Authors: Brandi N. Martell, Bridgette E. Garrett, Ralph S. Caraballo
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Although cigarette smoking has substantially declined since the release of the 1964 Surgeon General's report on smoking and health,* disparities in tobacco use exist among racial/ethnic populations (1). Moreover, because estimates of U.S. adult cigarette smoking and tobacco use are usually limited to aggregate racial or ethnic population categories (i.e., non-Hispanic whites [whites]; non-Hispanic blacks or African Americans [blacks]; American Indians and Alaska Natives [American Indians/Alaska Natives]; Asians; Native Hawaiians or Pacific Islanders [Native Hawaiians/Pacific Islanders]; and Hispanics/Latinos [Hispanics]), these estimates can mask differences in cigarette smoking prevalence among subgroups of these populations. To assess the prevalence of and changes in cigarette smoking among persons aged ≥18 years in six racial/ethnic populations and 10 select subgroups in the United States,(†) CDC analyzed self-reported data collected during 2002-2005 and 2010-2013 from the National Survey on Drug Use and Health (NSDUH) (2) and compared differences between the two periods. During 2010-2013, the overall prevalence of cigarette smoking among the racial/ethnic populations and subgroups ranged from 38.9% for American Indians/Alaska Natives to 7.6% for both Chinese and Asian Indians. During 2010-2013, although cigarette smoking prevalence was relatively low among Asians overall (10.9%) compared with whites (24.9%), wide within-group differences in smoking prevalence existed among Asian subgroups, from 7.6% among both Chinese and Asian Indians to 20.0% among Koreans. Similarly, among Hispanics, the overall prevalence of current cigarette smoking was 19.9%; however, within Hispanic subgroups, prevalences ranged from 15.6% among Central/South Americans to 28.5% among Puerto Ricans. The overall prevalence of cigarette smoking was higher among men than among women during both 2002-2005 (30.0% men versus 23.9% women) and 2010-2013 (26.4% versus 21.1%) (p<0.05). These findings highlight the importance of disaggregating tobacco use estimates within broad racial/ethnic population categories to better understand and address disparities in tobacco use among U.S. adults.
Management Considerations After Cystectomy for Bladder Cancer
Authors: Libni J. Eapen, Robert M. MacRae
Journal: Journal of Clinical Oncology (2016)

TO THE EDITOR: We write about the Grand Rounds case discussion by Sonpavde et al in a recent issue of Journal of Clinical Oncology. The discussion illustrates the twin challenges presented by locally advanced urothelial bladder cancer. The first challenge, which was covered well in the detailed review, is the risk of distant metastases. This risk is mitigated by a 5% survival gain with neoadjuvant chemotherapy and a disease-free survival gain with adjuvant chemotherapy. What is missing from the discussion is the second oncologic challenge of pelvic recurrence. In the presented patient case, the eventual pT3N1 stage gave the patient a 15% to 30% risk of pelvic recurrence either in isolation or, more likely, together with distant relapse. This pelvic failure rate has been demonstrated in multi-institutional case series, individual institutional series, and the two large randomized trials of neoadjuvant chemotherapy, which all demonstrated that chemotherapy unfortunately does not reduce the pelvic recurrence rate. This pelvic failure is an absolute ceiling on potential curability and also can be a source of significant clinical morbidity. Bladder cancer remains the one cancer for which optimization of locoregional control with multimodality therapy has not been studied rigorously. That is now set to change with the currently accruing NRG GU001 trial, which is a phase II randomized study of postoperative adjuvant radiotherapy in this setting. If all other solid tumors can be taken as an example, it is likely that bladder cancer too will benefit from the best of surgery, adjuvant radiotherapy, and systemic treatment. It is by offering patients the possibility of enrollment into this and other trials that we will improve the outlook for this disease. To finish by returning to the presented patient case: It so happens that, in the interest of safety, the NRG trial currently excludes patients with a neo bladder, so systemic treatment is the sole active, treatment option. If the patient did not have a neoadjuvant bladder, he would have been eligible for the radiation trial even if he received systemic adjuvant treatment postoperatively.
Polycomb Complex Group Gene Mutations and Their Prognostic Relevance In 5-Azacitidine Treated Myelodysplastic Syndrome Patients
Authors: Austin G Kulasekararaj, Azim M Mohamedali, Alexander E Smith, Nicholas C Lea, Aytug Kizilors, Atiyeh Abdallah, Erik E Nasser, Syed A Mian, Richard Yiu, Joop Gaken, Sabine Pomplun, Jie Jiang, Terry J Gaymes, Patience Pasipanodya, Janet Hayden, Robin M. Ireland, ZiYi Lim, Aloysius Y Ho, Judith C. W. Marsh, Ghulam J. Mufti
Journal: Blood (2010)
Case 50-1982
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, J. Thomas LaMont, Austin L. Vickery
Journal: New England Journal of Medicine (1982)

Presentation of CaseA 55-year-old woman was admitted to the hospital because of abnormal results of liver-function tests.She was apparently well until 30 years before entry, when sigmoidoscopic examination, done because of the discovery of multiple coloniC polyps in a sister, revealed similar findings in the patient. A total colectomy with ileoproctostomy was performed at another hospital. Microscopical examination of the excised specimen showed multiple polyps as well as focal fibrosis of the mesentery. The patient returned four times annually for evaluation.Four years before admission sigmoidoscopic examination revealed a tumor at the site of the anastomosis, and a . . .
Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
Authors: Marta Rava, Ismail Ahmed, Manolis Kogevinas, Nicole Le Moual, Emmanuelle Bouzigon, Ivan Curjuric, Marie-Hélène Dizier, Orianne Dumas, Juan R. Gonzalez, Medea Imboden, Amar J. Mehta, Pascale Tubert-Bitter, Jan-Paul Zock, Deborah Jarvis, Nicole M. Probst-Hensch, Florence Demenais, Rachel Nadif
Journal: Environmental Health Perspectives (2016)

The biological mechanisms by which cleaning products and disinfectants-an emerging risk factor-affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (G × E) may help identify new genes related to adult-onset asthma.
Abstract 1441: Systems-level interrogation of resistance mechanisms to immunotherapy through pooled shRNA screens
Authors: Zhe Wang, Shruti Malu, Weiyi Peng, Jodi McKenzie, Rina Mbofung, Leila Williams, Sahil Seth, Tim Heffernan, Patrick Hwu
Journal: Cancer Research (2016)

Abstract Despite the impressive clinical efficacy of immunotherapy in some patients, many still do not respond or progress following an initial response. The molecular mechanisms underlying the tumor resistance in those non-responders remain largely undefined. To address this issue, we set out to perform high-throughput unbiased pooled shRNA screens to identify critical genes that confer immune resistance. Patient-derived melanoma cells were transduced with barcoded pooled lentiviral shRNA libraries that targeted the human kinome, followed by exposure to cytotoxicity mediated by autologous tumor infiltrating lymphocytes. Tumor cells were then subject to genomic deep sequencing and integrated analysis to identify depleted barcodes and corresponding genes. One identified candidate of particular interest is Aurora Kinase A (AURKA), a cell cycle regulator that has previously been shown to contribute to tumorigenesis and correlate with poor prognosis for cancer patients. Importantly, our independent screening with a bioactive compound library also implicated Aurora Kinase as an immune resistance candidate against T cell immunotherapy. Further studies showed that suppression of Aurora kinase activity with a pan inhibitor - AMG900, exhibited a synergistic cytotoxic effect with tumor infiltrating lymphocyte-mediated killing on autologous tumor cells from patients. Furthermore, our Nanostring analysis of tumor biopsies from patients that received adoptive T cell therapy revealed significantly increased expression of AURKA in tumors from non-responding patient when compared with responder counterparts. These results have substantiated the validity of our pooled shRNA screening platform. Further investigations are ongoing to elucidate the underpinnings of Aurora kinase-mediated tumor resistance to immunotherapy and to functionally and physiologically validate other putative targets we have identified. Citation Format: Zhe Wang, Shruti Malu, Weiyi Peng, Jodi McKenzie, Rina Mbofung, Leila Williams, Sahil Seth, Tim Heffernan, Patrick Hwu. Systems-level interrogation of resistance mechanisms to immunotherapy through pooled shRNA screens. [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 1441.
SGLT2 Inhibitors and the Diabetic Kidney
Authors: Paola Fioretto, Alberto Zambon, Marco Rossato, Luca Busetto, Roberto Vettor
Journal: Diabetes Care (2016)

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether SGLT2 inhibitors, in addition to their glycemic and blood pressure benefits, may provide nephroprotective effects.
Abstract 5051: Docosahexaenoic acid inhibits cancer cell invasion and migration by modifying focal adhesion complex structure and signaling
Authors: Michael Mouradian, Palvinder K. Bains, Ronald S. Pardini
Journal: Cancer Research (2016)

Abstract The extracellular matrix (ECM) is responsible for the regulation of many cellular processes, including survival, proliferation, migration and invasion. Cellular-ECM contact induces a coordinated process recruiting functional protein complexes, consisting of scaffold, adapter, linking and docking proteins, to form focal adhesion (FA) structures. Once formed, FA complexes then recruit signaling proteins to activate downstream cellular pathways. Aberrations in FA structure and signaling have shown to contribute to cancer initiation, progression and cellular motility. Studies investigating the molecular mechanisms accounting for FA structure and function in cancer cells have demonstrated unique growth behavior and migratory properties in vitro. While docosahexaenoic acid (DHA), an omega-3 PUFA, has been shown to inhibit growth of a number of cancer cell lines, the effects of DHA on FA dynamics and signaling have not been investigated. In the present study, we show that DHA induced changes in the morphological growth phenotype in cancer cell lines grown in Matrigel™. DHA treatment also inhibited planar cell movement (cell migration) and amoeboid motility (invasion) in breast and lung cancer cell lines. Associated with the observed morphological changes and inhibited growth, were changes in the expression of a number of proteins involved in the FA complex. Upon further characterization, cell line specific changes in protein expression levels and protein localization of FAK, e-cadherin, paxillin and vinculin were observed with DHA treatment, which suggests that DHA is modifying FA complex structure. Additionally, changes in the phosphorylation patterns of major signaling pathways associated with the FA complex, like EGFR, ERK and c-Myc, were also observed with DHA treatment. Overall, these results provide new insight into FA activation and signaling and demonstrate a new mechanism for DHA treatment in cancer. Citation Format: Michael Mouradian, Palvinder K. Bains, Ronald S. Pardini. Docosahexaenoic acid inhibits cancer cell invasion and migration by modifying focal adhesion complex structure and signaling. [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 5051.
Abstract 2541: Preclinical results of SGN-CD19A in combination with R-ICE or R-CHOP in non-Hodgkin lymphoma models
Authors: Heather A. Van Epps, Kerry Klussman, Martha Anderson, Weiping Zeng, Devra Olson, Maureen Ryan, Tina Albertson, Che-Leung Law
Journal: Cancer Research (2015)

Abstract SGN-CD19A is an antibody drug conjugate (ADC) that recognizes CD19, a B-cell specific marker expressed in B-cell malignancies including non-Hodgkin lymphoma (NHL). SGN-CD19A is currently in a phase I clinical trial for adult patients with relapsed refractory B-cell NHL (CT.gov NCT01786135) in which it has shown evidence of single-agent activity (1). This ADC binds CD19, internalizes, and releases cys-mcMMAF, which ultimately induces apoptosis in targeted cells (2). Lymphoma tumor xenografts treated with SGN-CD19A show growth delay in a dose dependent manner. Here we show that SGN-CD19A in combination with standard of care [rituximab/ifosfamide/carboplatin/etoposide (R-ICE), rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP), or components] exceeds the activity of SGN-CD19A alone and results in impressive anti-tumor activity in multiple xenograft models. It was notable that in some xenograft models, SGN-CD19A + R-CHOP or SGN-CD19A + R-ICE yielded activity that was similar to SGN-CD19A plus rituximab alone. This strong interaction between rituximab and SGN-CD19A was modeled in vitro. SGN-CD19A synergized with rituximab, in the absence of cross-linking, to cause decreased cell viability in NHL cell lines. These data suggest that cell autonomous signaling contributes to the unique interaction between rituximab and SGN-CD19A. Our in vivo and in vitro data support R-CHOP, R-ICE, or rituximab as viable combination therapies for NHL patients with SGN-CD19A. 1) Uma Borate et al. A first-in-human phase 1 study of the antibody-drug conjugate SGN-CD19A in relapsed or refractory B-lineage acute leukemia and highly aggressive lymphoma. Blood 2013 122:1437 2) Che-Leung Law et al. Preclinical characterization of an auristatin-based anti-CD19 drug conjugate, SGN-19A. Abstract number 625. In: Proceedings of the 102th Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Citation Format: Heather A. Van Epps, Kerry Klussman, Martha Anderson, Weiping Zeng, Devra Olson, Maureen Ryan, Tina Albertson, Che-Leung Law. Preclinical results of SGN-CD19A in combination with R-ICE or R-CHOP in non-Hodgkin lymphoma models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2541. doi:10.1158/1538-7445.AM2015-2541
Expression of Differentiation Antigens on Bone Marrow Myeloid Cells of the Patients with Myelodysplastic Syndromes and it's Clinical Significances
Authors: Zonghong Shao, Lijuan Li, Rong Fu, Huaquan Wang, Lanzhu Yue, Hui Liu, Jun Wang, Honglei Wang, Erbao Ruan, Wen Qu, Yong Liang, Guojin Wang, Xiaoming Wang, Hong Liu, Jia Song, Yuhong Wu, Limin Xing, Jing Guan
Journal: Blood (2010)
Purification and characterization of the soluble interleukin-6 receptor from human plasma and identification of an isoform generated through alternative splicing
Authors: Radovan Keul, S. Matern, Christian Köhne, Margreet Hart, Just P. Just Brakenhoff, Ulrike Hemmann, Peter C. Heinrich, Gerhard Müller-Newen, Werner Müller-Esterl, John Wijdenes
Journal: Hepatology (1996)

Gerhard MULLER-NEWEN', Christian KOHNE', Radovan KEUL', Ulrike HEMMANN', Werner MULLER-ESTERL', John WIJDENES ', Just P. J . BRAKENHOFF4, Margreet H. L. HART4 and Peter C. HEINRICH' ' Institut fur Biochemie der Rheinisch-Westfalischen Technischen Hochschule Aachen, Germany Institut fur Physiologische Chemie und Pathobiochemie, Johannes Gutenberg Universitat, Mainz, Germany Innotherapie Laboratoires, Besancon, France Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, The Netherlands
Manganese in Drinking Water and Cognitive Abilities and Behavior at 10 Years of Age: A Prospective Cohort Study
Authors: Syed Moshfiqur Rahman, Maria Kippler, Fahmida Tofail, Sven Bölte, Jena Derakhshani Hamadani, Marie Vahter
Journal: Environmental Health Perspectives (2016)

Cross-sectional studies have indicated impaired neurodevelopment with elevated drinking water manganese concentrations (W-Mn), but potential susceptible exposure windows are unknown.
Abstract 521: c-MYC as a differentiating marker between angiosarcoma and atypical vascular lesion
Authors: Ipshita Kak, Bekim Sadikovic, Guillaume Pare, Tom Corbett, Snezana Popovic
Journal: Cancer Research (2016)

Abstract Introduction: Angiosarcoma is a rare, aggressive malignancy that accounts for less than 1% of all sarcomas, characterized by a dismal 5 year survival of 20-30% at best. In striking contrast, atypical vascular lesion (AVL), which typically occurs secondary to radiation, follows for the most part, a benign course. However, debate rages over the true nature of AVL with reports describing both benign and malignant behavior. Further compounding the issue is the fact that overlapping histological features make the important differentiation between AVL and angiosarcoma difficult, especially on limited biopsy specimens. There have been a number of recent studies of c-MYC expression in vascular tumors in relation to this question, yielding varied results. Objectives: This pilot study aimed to investigate c-MYC expression in atypical vascular lesions and angiosarcomas (primary and secondary) to evaluate the clinical utility of c-MYC testing as an adjunct to the histological diagnosis. Methods: A retrospective search for biopsy, resection specimens and internal consult cases with diagnosis of angiosarcoma and/or atypical vascular lesion from January 2008- February 2014 was performed. A total of 32 cases (including controls) obtained after review were stained by dual colour c-MYC copy number probe set. The expression of c-MYC was read by two independent evaluators and final data was collated along with histology findings, follow-up and survival data. Results: c-MYC amplification was found to be a major differentiating factor (p value: 0.00002, 68% sensitivity, 96% specificity) between AVL and angiosarcoma(median c-MYC expression 1.0 vs. 12.14, 95% confidence interval: 0.8-1.9 vs. 9.2-22.3 respectively). The amplification levels of primary (median c-MYC expression:10.9, 95% confidence interval: 3.8-16.6) and secondary angiosarcoma (median c-MYC expression:13.2, 95% confidence interval: 9.0-25.5) were statistically not found to be significantly different (p = 0.07). Although no correlation was found between level of c-MYC amplification and outcome, the study was underpowered to accurately evaluate this relation. Conclusion: Amplification of c-MYC can be used as a reliable ancillary test to differentiate between diagnostically challenging cases of angiosarcoma and AVL. Citation Format: Ipshita Kak, Bekim Sadikovic, Guillaume Pare, Tom Corbett, Snezana Popovic. c-MYC as a differentiating marker between angiosarcoma and atypical vascular lesion. [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 521.