tbuckley/cabot-search huggingface dataset:
Rugby World Cup 2015: World Rugby injury surveillance study
Authors: Colin W Fuller, Aileen Taylor, Simon P T Kemp, Martin Raftery
Journal: British Journal of Sports Medicine (2016)

To determine the incidence, severity and nature of injuries sustained during the Rugby World Cup (RWC) 2015 together with the inciting events leading to the injuries.A prospective, whole population study.639 international rugby players representing 20 countries.The study protocol followed the definitions and procedures recommended in the consensus statement for epidemiological studies in rugby union; output measures included players' age (years), stature (cm), body mass (kg) and playing position, and the group-level incidence (injuries/1000 player-hours), mean and median severity (days-absence), location (%), type (%) and inciting event (%) for match and training injuries.Incidence of injury was 90.1 match injuries/1000 player-match-hours (backs: 100.4; forwards: 81.1) and 1.0 training injuries/1000 player-training-hours (backs: 0.9; forwards: 1.2). The mean severity of injuries was 29.8 days-absence (backs: 30.4; forwards: 29.1) during matches and 14.4 days-absence (backs: 6.3; forwards: 19.8) during training. During matches, head/face (22.0%), knee (16.2%), muscle-strain (23.1%) and ligament-sprain (23.1%) and, during training, lower limb (80.0%) and muscle-strain (60.0%) injuries were the most common locations and types of injury. Being-tackled (24.7%) was the most common inciting event for injury during matches and rugby-skills-contact activities (70.0%) the most common during training.While the incidence, nature and inciting events associated with match injuries at RWC 2015 were similar to those reported previously for RWCs 2007 and 2011, there were increasing trends in the mean severity and total days-absence through injury.
Abstract 1021: Lipidomic analysis: a powerful tool for evaluating lipid metabolism in cultured cancer cells
Authors: Finnur F. Eiríksson, Manuela Magnusdottir, Skarphedinn Halldorsson, Margret Thorsteinsdottir, Helga M. Ögmundsdottir
Journal: Cancer Research (2016)

Abstract Lipids have numerous functions in biological processes, structural as well as regulatory. Cancer cells show differences from healthy normal cells in their metabolism, including lipid metabolism, which contribute to their survival and growth. Overexpression of fatty acid synthase (FASN) is commonly observed in cancer cells and there is also evidence of other lipid pathways being changed in tumor cells. The general aim of this project is to establish a lipidomic based UPLC-QToF method for evaluation of lipid composition in cultured cells of normal and cancerous origin using electrospray quadrupole traveling wave ion mobility Q-ToF mass spectrometry. Cell lines were selected based on their lipid metabolism, including three breast cancer cell lines: SK-Br-3 (overexpresses FASN), T47D (TP53-mutated), MCF7 (estrogen receptor-positive); and one pancreatic cancer cell line, ASPC-1(overexpresses 5-and 12-lipoxygenases). Furthermore, we analyzed the immortalized breast epithelial stem cell line D492 along with its subline, D492M, that has undergone epithelial to mesenchymal transition (EMT). Principal component analysis (PCA) revealed distinct differences in lipid composition between all the cell lines tested, each cell line showed a clear cluster of lipid components and patterns that were reproducible between experiments. The Sk-Br-3 was most clearly separated from the other two breast cancer cell lines. Further analysis revealed significant differences in levels of phosphocholins (PC) that are elevated in Sk-Br-3compared to other cell lines. Further investigations of the data have led to identification of certain PC that are different between cell lines. Significant differences were detected in the lipid composition of D492 and D492M. In conclusion, different levels of lipid-synthesizing enzymes are reflected in distinct lipid profiles in breast cancer cells. The observed differences in lipid profiles of the breast epithelial cell line and its mesenchymal-like subline may provide an insight into membrane changes associated with EMT and help evaluate lipidomes of tumor samples from patients in terms of invasive potential. Citation Format: Finnur F. Eiríksson, Manuela Magnusdottir, Skarphedinn Halldorsson, Margret Thorsteinsdottir, Helga M. Ögmundsdottir. Lipidomic analysis: a powerful tool for evaluating lipid metabolism in cultured cancer cells. [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 1021.
Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study
Authors: George Lau, Yves Benhamou, Guofeng Chen, Jin Li, Qing Shao, Dong Ji, Fan Li, Bing Li, Jialiang Liu, Jinlin Hou, Jian Sun, Cheng Wang, Jing Chen, Vanessa Wu, April Wong, Chris L P Wong, Stella T Y Tsang, Yudong Wang, Leda Bassit, Sijia Tao, Yong Jiang, Hui-Mien Hsiao, Ruian Ke, Alan S Perelson, Raymond F Schinazi
Journal: The Lancet. Gastroenterology & hepatology (2016)
Abstract 3111: Elevated expression of hyaluronan synthase 2 associates with poor prognosis in diffusely infiltrating astrocytomas
Authors: Mari J. Poukka, Hannu Haapasalo, Kirsi J. Rilla, Kristiina Tyynelä-Korhonen, Ylermi Soini, Sanna M. Pasonen-Seppänen
Journal: Cancer Research (2016)

Abstract Diffusely infiltrating astrocytomas are central nervous system tumors originating from astrocytic glial cells or their precursor cells. In this retrospective study we investigated the content of hyaluronan and the expression of hyaluronan metabolizing enzymes and its cell surface receptor, CD44, in these aggressive tumors. Hyaluronan is a large extracellular matrix molecule synthesized by three hyaluronan synthases (HAS1-3) on the plasma membrane and degraded by two hyaluronidases (HYAL1-2). In many tumors, aberrant hyaluronan metabolism implicates aggressive disease progression and metastatic potential. Our material consisted of 165 diffusely infiltrating astrocytomas (WHO grades II-IV). Tumor samples were processed into tissue microarray (TMA) blocks. The TMA sections were stained for hyaluronan, CD44, HAS1, HAS2, HAS3 and HYAL2. The staining intensity of astrocytomas was evaluated with a four-level scoring (0-3; no color, weak, moderate and strong) by two independent observers. The immunostaining results were compared with χ2 -test or with Kruskal-Wallis test for correlation with clinicopathological parameters and survival analyses were done with Kaplan-Meier log rank test and Cox regression. Hyaluronan and CD44 were strongly expressed in astrocytic gliomas but their expression did not correlate with WHO grade, cell proliferation activity by Ki-67, p53 status, epidermal growth factor receptor (EGFR) amplification or IDH1 mutation. Whereas HAS2 staining intensity showed a significant correlation with IDH1 mutation. Tumors with high HAS2 expression were IDH1 negative (p = 0.003). In addition, in non-parametric tests increased HAS2 staining intensity showed association with increased cell proliferation (p = 0.013) and in log rank test with decreased overall survival of patients (p = 0.001). Variables included in the multivariable Cox regression analysis were HAS2 staining intensity, p53 status, EGFR amplification, IDH1 mutation and WHO tumor grade; in this analysis HAS2 expression turned out to be a significant independent prognostic factor (p = 0.008). This study indicates that elevated expression of HAS2 is associated with glioma progression and suggests that HAS2 has a prognostic significance in diffusely infiltrating astrocytomas. Citation Format: Mari J. Poukka, Hannu Haapasalo, Kirsi J. Rilla, Kristiina Tyynelä-Korhonen, Ylermi Soini, Sanna M. Pasonen-Seppänen. Elevated expression of hyaluronan synthase 2 associates with poor prognosis in diffusely infiltrating astrocytomas. [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 3111.
Abstract 1086: Elevated level of circulating microRNA-99a correlates with serous epithelial ovarian cancer and can be used as a potential biomarker
Authors: Akihiko Yoshimura
Journal: Cancer Research (2016)

Abstract [Objective] There is a critical need for improved diagnostic markers for ovarian high grade serous cancer (HGSC). Emerging evidence have shown that microRNAs (miRNAs) stably exist in circulating blood, reflecting tissue or organ conditions and these are present in circulating microvesicles such as exosomes. The purpose of this study was to identify which miRNAs are highly produced from HGSCs and to analyze whether circulating miRNA can discriminate patients with HGSC from healthy volunteers. [Methods] Secreted exosomes from serous ovarian cancer cell lines were collected and exosomal miRNAs were extracted. miRNA microarray was performed and several elevated miRNAs specific to ovarian cancer cells were picked-up. Among these, we focused on miR-99a in this study. Sera were collected from 9 consecutive patients with HGSC and 5 healthy volunteers. Expression level of miR-99a was determined by miRNA RT-qPCR. [Results] miRNA microarray revealed several miRNAs were highly expressed in exosomes in patients with HGSC. In patients, serum miR-99a levels were significantly increased (7.2 fold) compared with healthy controls. Receiver operating curve (ROC) analysis for miR-99a showed that at the cut-off of 2.1 times compared with control, the sensitivity and specificity of this marker were 77.8% and 100%, respectively for detecting HGSC (AUC = 0.84). Serum miR-99a levels decreased after surgery by 0.2 fold, indicating that serum miR-99a was originated from ovarian cancer. [Conclusion] Elevated serum miR-99a were detected in sera of patients with HGSC and reflected the disease condition. This miRNA profiling in serum can be used as a diagnostic biomarker, extending its utility to screening asymptomatic populations. Citation Format: Akihiko Yoshimura. Elevated level of circulating microRNA-99a correlates with serous epithelial ovarian cancer and can be used as a potential biomarker. [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 1086.
Abstract 2364: Spontaneous and vaccine-induced clearance of Mus Musculus Papillomavirus1 (MusPV1) infection
Authors: Rosie T. Jiang, Joshua W. Wang, Shiwen Peng, Chien-Fu Hung, Richard B.S Roden.
Journal: Cancer Research (2016)

Abstract Human papilloma virus (HPV) high risk (hr) types cause several cancers, including cervical, vaginal, penile, and oropharyngeal, whereas low risk types cause benign diseases such as skin warts, anogenital warts and recurrent respiratory papillomatosis. Although hrHPV infection is one of the most common sexually transmitted diseases most infections remain asymptomatic and are cleared while a sub-population develops persistent HPV-related pathologies including cancer. Further, immune-compromised populations, notably organ transplant and HIV-positive patients, are particularly vulnerable to HPV-related pathologies. Here, we describe the first establishment of mouse papillomavirus-1 (MusPV1) disease in outbred and immune competent SKH1-Elite mice (Crl:SKH1-Hrhr). Challenge of SKH1 mice with MusPV1 resulted in three clinical outcomes: 1) persistent (&amp;gt;2 months) papillomas (∼15%), 2) transient papillomas that spontaneously regress typically within 2 months (∼10%), 3) no visible papillomas and viral clearance (∼75%). SKH1 mice with persisitent papillomas were treated using a potentially preventive and therapeutic DNA vaccine composed of human calreticulin (hCRT) linked to MusPV1 early proteins, mE6 and mE7 and the late protein mL2 (hCRTmE6/mE7/mL2). Three intramuscular DNA vaccinations (15 μg in PBS) via in vivo electroporation were administered weekly and immune responses were measured, including mE6/mE7/mL2 serum antibody response and T-cell epitope mapping studies. Previously persistent papillomas disappeared within 2 months after final vaccination. Clearance of MusPV1 was confirmed by loss of mE6/mE7 transcript staining using RNA-CISH on formalin-fixed, paraffin-embedded tail sections. Vaccination induced a strong mE6 and mE7 CD8+ T cell response in all mice. Interestingly, mL2 antibody responses were faster and stronger in asymptomatic challenged mice and in those that spontaneously cleared their papillomas after challenge as compared to mice with persistent papillomas. In sum, MusPV1 challenge of outbred, immune-competent SKH1 mice represents a promising model to further study potential immunotherapies for HPV-related disease and the relationship between spontaneous clearance of papillomavirus and host genetics. Citation Format: Rosie T. Jiang, Joshua W. Wang, Shiwen Peng, Chien-Fu Hung, Richard B.S Roden. Spontaneous and vaccine-induced clearance of Mus Musculus Papillomavirus1 (MusPV1) infection. [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 2364.
Abstract 1375: An ultra-sensitive cell free DNA liquid biopsy assay for cancer treatment monitoring
Authors: Grace Zhao, Li Weng, Paul Tang, Johnny Sun, Yi Huang, Lingchen Guo, Hongyan Wang, Xiaozheng Kang, Wei Shen, Kang Ying, Shengrong Lin
Journal: Cancer Research (2016)

Abstract In order to take advantage of the narrow time window for optimal treatment efficacy, highly sensitive disease monitoring is critical in the successful management of cancer. Currently, treatment efficacy is assessed by using a combination of protein cancer biomarkers and imaging. However, both methods present limitations with regard to specificity or sensitivity due to their dependency on tumor size. Recently, a number of studies have suggested that monitoring cell free DNA (cfDNA) may provide a more specific alternative for tracking cancer treatment with greatly improved sensitivity. Here we introduce a novel next-generation sequencing based mutation detection system aimed at improving the sensitivity, reliability, and clinical utility of cancer treatment monitoring. Our system, comprised of Nebula, a whole genome amplification technology that is capable of amplifying nanogram quantities of cfDNA &amp;gt;1000-fold, and Firefly, a proprietary technology combining molecular biology and computational algorithm for error-suppression, has reduced the rate of random sequencing errors to 10-6. As a result, we are able to detect 1.5 variant copies from 10ng of input cfDNA with a detection rate of 46%. We have validated the Nebula-Firefly assay on a patient cohort with either colorectal (CRC) or lung cancer. Here we report the successful detection of drug resistant mutations and various genomic alterations associated with minimal residual detection (MRD) in sample cfDNA. These initial findings have led to the exploration of Nebula-Firefly as the technological backbone for a noninvasive, scalable approach for the early detection, treatment, and monitoring of cancer. Citation Format: Grace Zhao, Li Weng, Paul Tang, Johnny Sun, Yi Huang, Lingchen Guo, Hongyan Wang, Xiaozheng Kang, Wei Shen, Kang Ying, Shengrong Lin. An ultra-sensitive cell free DNA liquid biopsy assay for cancer treatment monitoring. [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 1375.
Use of adjuvant chemotherapy and radiation in women with node-positive endometrial cancer: A National Cancer Database study.
Authors: Anna Everett Strohl, Nicholas Rydzewski, Eric Donald Donnelly, Margaux Jenna Kanis, Shohreh Shahabi, Jonathan Blake Strauss
Journal: Journal of Clinical Oncology (2016)

5588 Background: Women with node-positive endometrial cancer have higher rates of disease recurrence and decreased survival compared to those with early stage disease. Adjuvant treatment is considered a mainstay of treatment, yet no standard treatment approach exists. Using a large national cancer database, we aimed to investigate outcomes for women with node-positive endometrial cancer treated with chemotherapy (CT) alone, radiotherapy (RT) alone, or chemoradiotherapy (CRT), compared to patients that received no adjuvant treatment. Methods: The National Cancer Database was queried to identify women with surgically staged IIIC1 or IIIC2 node-positive endometrial cancer diagnosed between 2003 and 2011. Chi-square tests and multivariable logistic regression were performed to analyze factors associated with treatment type. Survival analysis was performed using log-rank test, Cox proportional hazards regression, and Kaplan-Meier estimates. Results: A total of 7,653 patients were identified, among whom 1,502 (19.6%) received no adjuvant treatment, 1,350 (17.6%) received RT, 1,939 (25.3%) received CT, and 2,862 (37.4%) received CRT. Patients were more likely to receive CRT if they were younger, had fewer comorbidities, lived closer to the hospital, had fewer number of positive nodes, had smaller tumor size, and if a single agent chemotherapy regimen was used. Use of CRT was associated with improved survival compared to no adjuvant treatment (HR 2.08, 95% CI 1.73-2.50, p < 0.001), RT only (HR 1.28, 95% CI 1.09-1.51, p = 0.003), and CT only (HR 1.34, 95% CI 1.15-1.56, p < 0.001). Receipt of any treatment was superior to no treatment. Conclusions: In women with node-positive endometrial cancer, modern multimodality CRT appears to confer an additional survival advantage beyond that achieved with CT or RT alone in this large cohort. Our findings suggest that CRT should be the preferred adjuvant treatment strategy in women with node-positive endometrial cancer who are expected to tolerate the toxicities of the combined approach.
Case 36-1982
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Reginald E. Greene, Eugene J. Mark
Journal: New England Journal of Medicine (1982)

Presentation of CaseA 69-year-old woman was admitted to the hospital because of a pulmonary mass.She was well until five months earlier, when she began to experience fatigue and dryness of the throat. A physician heard an expiratory wheeze over the left lung. An x-ray film of the chest showed slight elevation of the left hemidiaphragm and depression of the left hilus; no parenchymal opacity was seen; the heart and pleural spaces appeared normal. A film of the chest obtained two weeks later was unchanged. Examination two weeks before admission revealed persistence of the wheeze. X-ray films of the . . .
Abstract 3803: Development of genetic and chemical tools for understanding the recruitment of DOT1L in MLL-fusion driven leukemia and normal hematopoiesis
Authors: Sierrah Grigsby, Jennifer Chase, James Ropa, Justin Serio, Chenxi Shen, Martha Larsen, Preston Donover, Melvin Reichman, Andrew Muntean, Ivan Maillard, Zaneta Nikolovska-Coleska
Journal: Cancer Research (2016)

Abstract Leukemias harboring rearrangements of mixed-lineage leukemia gene (MLL1) are associated with poor clinical outcomes, and new therapeutic approaches are needed. Rearrangements of the MLL1 gene generate fusion oncoproteins which drive the high expression of the clustered homeobox (HOX) genes and induce leukemic transformation. Genome wide histone methylation studies have revealed that the abnormal expression of MLL1 fusion target genes is associated with high levels of histone H3 lysine 79 (H3K79) methylation. Recruitment of DOT1L (disruptor of telomeric silencing 1-like), a unique histone methyltransferase that catalyzes methylation of H3K79, proved to be essential for the transforming activity of multiple MLL fusion proteins. To gain insights into the unique functions of DOT1L in MLL-driven leukemia, we elucidated the mechanisms of DOT1L recruitment to the MLL fusion partners. The binding site was mapped to a short segment of 10 amino acids in DOT1L and peptides derived from this region disrupted the interaction between DOT1L and MLL-AF9. DOT1L mutants lacking these 10 residues did not support transformation by MLL-AF9. This discovery has established a foundation for disease-specific therapies that target chromatin modifications in highly malignant leukemias. Applying high throughput screening approach several different chemical classes of small molecules that disrupt the protein-protein interactions between DOT1L and oncogenic MLL-fusion proteins were identified and validated. To evaluate if the AF9-binding domain of DOT1L is critical for its functions in normal hematopoietic stem cells as opposed to leukemias driven by MLL fusion proteins, genetic tools were developed to functionally investigate the importance of the DOT1L AF9-binding domain in MLL-AF9-driven leukemia and its role in the physiological functions of DOT1L in normal hematopoiesis. Our findings demonstrate that pharmacological inhibition of the DOT1L complex through disrupting the AF9-DOT1L interactions may provide therapeutic benefits in an array of malignancies with abnormal HOXA gene expression. Citation Format: Sierrah Grigsby, Jennifer Chase, James Ropa, Justin Serio, Chenxi Shen, Martha Larsen, Preston Donover, Melvin Reichman, Andrew Muntean, Ivan Maillard, Zaneta Nikolovska-Coleska. Development of genetic and chemical tools for understanding the recruitment of DOT1L in MLL-fusion driven leukemia and normal hematopoiesis. [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 3803.
Abstract 10842: Incremental Prognostic Value of Left Ventricular Function Analysis over Non-Invasive Coronary Angiography using Multidetector Computed Tomography
Authors: Fleur R de Graaf, Jacob M van Werkhoven, Joella van Velzen, Mark Boogers, Louisa Antoni, Lucia Kroft, Albert de Roos, Martin J Schalij, J. Wouter Jukema, Ernst E van der Wall, Joanne D Schuijf, Jeroen J Bax
Journal: Circulation (2010)