tbuckley/cabot-search huggingface dataset:
Evolutionary Epigenomics of Retrotransposon-Mediated Methylation Spreading in Rice
Authors: Jae Young Choi, Michael D Purugganan
Journal: Molecular Biology and Evolution (2017)

Plant genomes contain numerous transposable elements (TEs), and many hypotheses on the evolutionary drivers that restrict TE activity have been postulated. Few models, however, have focused on the evolutionary epigenomic interaction between the plant host and its TE. The host genome recruits epigenetic factors, such as methylation, to silence TEs but methylation can spread beyond the TE sequence and influence the expression of nearby host genes. In this study, we investigated this epigenetic trade-off between TE and proximal host gene silencing by studying the epigenomic regulation of repressing long terminal repeat (LTR) retrotransposons (RTs) in Oryza sativa. Results showed significant evidence of methylation spreading originating from the LTR-RT sequences, and the extent of spreading was dependent on five factors: 1) LTR-RT family, 2) time since the LTR-RT insertion, 3) recombination rate of the LTR-RT region, 4) level of LTR-RT sequence methylation, and 5) chromosomal location. Methylation spreading had negative effects by reducing host gene expression, but only on host genes with LTR-RT inserted in its introns. Our results also suggested high levels of LTR-RT methylation might have a role in suppressing TE-mediated deleterious ectopic recombination. In the end, despite the methylation spreading, no strong epigenetic trade-off was detected and majority of LTR-RT may have only minor epigenetic effects on nearby host genes.
Annals Story Slam - Dr. Mom Gets Sick
Authors: Jacqueline W. Fincher
Journal: Annals of Internal Medicine (2017)

Web Exclusives7 November 2017Annals Story Slam - Dr. Mom Gets SickFREEJacqueline W. Fincher, MDJacqueline W. Fincher, MDMcDuffie Medical Associates, Thomson, Georgia (J.W.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0067 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Dr. Mom Gets Sick "Dr. Mom Gets Sick," by Dr. Jacqueline W. Fincher (Duration 5:49)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video. Here, Dr. Fincher relays her story of balancing doctoring and parenting.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: McDuffie Medical Associates, Thomson, Georgia (J.W.F.)Current Author Address: Jacqueline W. Fincher, MD, McDuffie Medical Associates, PO Box 900, 505 Mount Pleasant Road, Thomson, GA 30824; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 November 2017Volume 167, Issue 9Page: SS1 ePublished: 7 November 2017 Issue Published: 7 November 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
P1.17-002 Clinicopathological Significance of Epithelial Mesenchymal Transition in Thymic Cancer
Authors: Y. Shintani, S. Funaki, T. Kawamura, N. Ose, R. Kanzaki, K. Kimura, Y. Yamamoto, M. Minami, M. Okumura
Journal: Journal of Thoracic Oncology (2017)
Innate Genetic Evolution of Lung Cancers and Spatial Heterogeneity: Analysis of Treatment-Naïve Lesions
Authors: Kenichi Suda, Jihye Kim, Isao Murakami, Leslie Rozeboom, Masaki Shimoji, Shigeki Shimizu, Christopher J. Rivard, Tetsuya Mitsudomi, Aik-Choon Tan, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2018)

IntroductionData regarding the pre-treatment intertumor heterogeneity of potential biomarkers in advanced-stage lung cancers is limited. A finding of such heterogeneity between primary and metastatic lesions would prove valuable to determine if a metastatic lesion can be a surrogate for the primary tumor, as more biomarkers will likely be used in the future to inform treatment decisions.MethodsWe performed RNA sequencing to analyze intertumor heterogeneity in 30 specimens (primary tumors, intrathoracic, and extrathoracic metastatic lesions) obtained from five treatment-naïve lung cancer patients.ResultsThe global unsupervised clustering analysis showed that the lesions clustered at the individual patient level rather than on the metastatic sites, suggesting that the characteristics of specific tumor cells have a greater impact on the gene expression signature than the microenvironment in which the metastasis develops. The mutational and transcriptional data highlight the presence of intertumor heterogeneity showing that the primary tumors are usually distinct from metastatic lesions. Through a comparison between metastatic lesions and the primary tumors, we observed that pathways related to cell proliferation were upregulated, whereas immune-related pathways were downregulated in metastatic lesions.ConclusionThese data not only provide insight into the evolution of lung cancers, but also imply possibilities and limitations of biomarker-based treatment in lung cancers.
Radium-223 in metastatic castration-resistant prostate cancer (mCRPC): efficacy and safety in real-life experience
Authors: S.E. Rebuzzi, A. Prelaj, C. Pozzi, C. Ferrara, V. Frantellizzi, G.A. Follacchio, G. de Vincentis, S. Tomao, V. Bianco
Journal: Annals of Oncology (2017)
The value of conducting research with people
Authors: Nasrul Ismail
Journal: BMJ (2016)

Greenhalgh and colleagues’ invitation to BMJ’s editors to reconsider their policy on qualitative research highlights the continuing paradigm war between quantitative and qualitative research. This response seeks to support the invitation by highlighting the value of doing research with people – the patients, service users, families and carers, concerned others, and so forth – that can be catalysed by qualitative research.
GTIL: Um programa Europeu de vigilância da doença do legionário associada a viagens
Authors: E. J. Hutchinson, C Joseph, C L R Bartlett
Journal: Eurosurveillance (1996)

O Grupo de Trabalho das Infeccoes a Legionela (GTIL) foi criado em 1986 e integrado no Programa Europeu de Vigilância da Doenca do Legionario Associada a Viagens, em 1987. Os microbiologistas em exercicio nos laboratorios de referencia e os epidemiologistas envolvidos em programas nacionais de vigilância da doenca do legionario em paises membros, reconheceram que, atraves da troca de informacao, seria mais provavel que surtos de doenca do legionario fossem mais precocemente identificados. Nesta ordem de ideias, os objectivos do programa sao: identificar clusters (agrupamentos) de casos de doenca do legionario que podem indiciar a ocorrencia de surtos de origem comum; rapidamente alertar os centros colaboradores sobre os clusters; e manter e desenvolver continuamente uma base de dados Europeia.
A vigilância europeia da doença dos legionários associada a viagens
Authors: C Joseph
Journal: Eurosurveillance (2004)

Quando uma doenca e contraida num pais mas diagnosticada e notificada noutro, e necessaria a cooperacao internacional para o seu controlo, investigacao e a prevencao de outros casos. A rede europeia de vigilância da doenca dos legionarios associada a viagens (EWGLINET), estabelecida em 1987 para responder a estas situacoes tem actuado eficazmente na difusao de informacao e na coordenacao de accoes.
Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine
Authors: Steven D. Weisbord, Martin Gallagher, Hani Jneid, Santiago Garcia, Alan Cass, Soe-Soe Thwin, Todd A. Conner, Glenn M. Chertow, Deepak L. Bhatt, Kendrick Shunk, Chirag R. Parikh, Edward O. McFalls, Mary Brophy, Ryan Ferguson, Hongsheng Wu, Maria Androsenko, John Myles, James Kaufman, Paul M. Palevsky
Journal: New England Journal of Medicine (2017)

Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy.
High-resolution RNA-seq profiling of glioblastoma residual invasive cells isolated by a novel 5-ALA fluorescence based method
Authors: Jonathan Rowlinson, Maria de los Angeles Estevez-Cebrero, Anbarasu Lourdusamy, Ruman Rahman, Stuart Smith
Journal: Neuro-Oncology (2018)

Malignant brain cancer Glioblastoma (GBM) kills 3500 people per year in the UK with an average survival of 6 months. The intra-tumour heterogeneity of GBM has meant tailored therapies based on the genetic mutations within the cancer cells have so far failed to replicate in vitro promise in clinical trials. Previous research has focused on the core of the tumour; however this is removed by surgery and doesn’t reflect the residual cancer cells left in the patient’s brain. The aim of this study is to generate new potential targets from looking at the expression of those residual cancer cells left behind after surgery that ultimately lead to tumour recurrence. 5-aminolevulinic acid (5-ALA) is a clinically used drug that makes cancer cells glow (fluoresce) pink, allowing more complete removal of brain tumours. 10 Tumour samples were dissociated and fluorescent activated cell sorting (FACS) was used to separate the residual fluorescent cancer cells (1%) from normal brain at the tumour’s edge. Samples from 3 distinct tumour regions, core, rim and invasive margin without FACS sorting from the same patients were also included for comparison to the FACS samples. Gene expression was analysed by RNA-seq and validated by qPCR. High-resolution RNA-seq profiles were generated for distinct tumour regions and the fluorescently isolated invasive cell population, allowing potential targetable abnormalities to be identified and validated. This study shows that pure tumour cells can be separated from normal cells using fluorescence generated from tumour metabolism of 5-ALA. Further optimisation of FACS is required to increase RNA yield from FACS sorted samples. Our approach gives hope that we can interrogate the true residual disease, and for the first time gain insight into the source of tumour recurrence.
Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging
Authors: Andreas I. Jensen, Gregory W. Severin, Anders E. Hansen, Frederikke P. Fliedner, Rasmus Eliasen, Ladan Parhamifar, Andreas Kjær, Thomas L. Andresen, Jonas R. Henriksen
Journal: Journal of Controlled Release (2017)
Adjuvant treatment in elderly cancer patients: a multicenter real-life experience
Authors: M. Bassanelli, A. Ceribelli, D. Giannarelli, S. Giacinti, A. Viterbo, M. Siringo, G. Poti, M. Roberto, S. Macrini, R. Falcone, A. Giuli, F.R. Di Pietro, A.M. Aschelter, P. Marchetti
Journal: Annals of Oncology (2017)
NIMG-30. ASSESSING TREATMENT RESPONSE OF GLIOBLASTOMA TO AN HDAC INHIBITOR, BELINOSTAT (PXD101)
Authors: Saumya Gurbani, Soma Sengupta, Alfredo Voloschin, Zhongxing Liang, Younghyoun Yoon, Jose Enrique Velazquez Vega, Chad A Holder, Jeffrey J Olson, Hui-Kuo Shu, Hyunsuk Shim
Journal: Neuro-Oncology (2017)

The current standard of care for glioblastoma (GBM; WHO grade IV glioma) is maximal safe resection followed by radiation therapy (RT) with concurrent and adjuvant chemotherapy. Despite this aggressive treatment, the median survival remains only 15 months. Thus, there is a need for better treatment options. Histone deacetylases (HDAC) are proteins with broad impact on many cellular functions implicated in oncogenesis. Belinostat (PXD101; Spectrum Pharmaceuticals) is a pan-HDAC inhibitor (HDACi) with increased blood-brain barrier uptake compared to the previous HDACi’s. In this work, we evaluate the mechanism of belinostat in vitro and its anti-tumor effect in an in vivo orthotic rat glioma model. The data show that belinostat has an excellent dose-dependent anti-tumor effect as evaluated by behavioral changes and tumor volume, and that it restores MR-spectroscopy-detectable metabolism of N-acetylaspartate and myo-insolitol in vitro better than other HDACi’s. We also present data from several representative cases of patients treated with belinostat in addition to standard chemoradiation as part of an ongoing clinical trial (NCT02137759), assessing their metabolic response on spectroscopic MRI (sMRI) using the ratio of choline to N-acetylaspartate (Cho/NAA). It is observed that a patient who weakly stained acetyl H4 immunohistochemical analysis (IHC) showed an increase in metabolically-active tumor volume (as measured by Cho/NAA > twice contralateral white matter) at one month post-radiation, indicative of tumor proliferation, whereas two patients with strong acetylated H4 IHC showed sMRI signal decrease, indicative of tumor reduction. A patient with intermediate acetyl H4 IHC showed a small decrease in tumor volume. In summary, the preclinical data and these cases suggest that acetyl H4 can be a good biomarker for predicting HDACi treatment efficacy, and that its early response can be reliably monitered non-invasively using sMRI.
P2.01-027 Clinical Significance of Topoisomerase-II Expression in Patients with Non-Small Cell Lung Cancer Treated with Amrubicin
Authors: R. Sakurai, K. Kaira, Y. Miura, Y. Tomizawa, Y. Tsukagoshi, T. Masuda, N. Kasahara, N. Sunaga, R. Saito, T. Hisada
Journal: Journal of Thoracic Oncology (2017)
MA 20.02 Pleural Dye Marking of Lung Nodules by Electromagnetic Navigation Bronchoscopy in the Prospective, Multicenter NAVIGATE Study
Authors: C. Anciano, E. Folch, S. Khandhar, D. Arenberg, O. Awais, D. Minnich, M. Pritchett, O. Rickman, E. Sztejman, M. Bowling
Journal: Journal of Thoracic Oncology (2017)
RARE-08. MALIGNANT TRANSFORMATION OF NEUROCUTANEOUS MELANOCYTOSIS (NCM) FOLLOWING IMMUNOSUPPRESSION
Authors: Lauren Schaff, Ashfaq Marghoob, Rina Meyer, Yasmin Khakoo
Journal: Neuro-Oncology (2017)

Neurocutaneous melanocytosis (NCM) is a rare disorder of melanocyte deposition in the leptomeninges and brain parenchyma. Rarely, cells undergo malignant transformation to leptomeningeal melanoma. We report the case of a 16 year old boy with malignant transformation of NCM following immunosuppression. He had a large congenital nevus and magnetic resonance imaging (MRI) at age three months demonstrating T1 shortening of the left pontomedullary junction and cerebellum. Subsequent MRI (age 12) revealed T1 hyperintensity of the left temporal lobe. MRI spine (age 13) was unremarkable. He was neurologically asymptomatic throughout childhood. At age 16, he developed hemorrhagic diarrhea. A colonoscopy diagnosed inflammatory bowel disease. His symptoms improved with balsalazide, an anti-inflammatory agent, before he developed hypersensitivity. He was then treated with adalimumab, a tumor necrosis factor (TNF) inhibitor (discontinued after severe headache), followed by infliximab and prednisone. Due to refractory disease, he underwent colectomy two months later. He was tapered off immunosuppressants peri-operatively. Two weeks following surgery, he developed severe headache along with nausea, vomiting, neck and back pain, diplopia, leg numbness, word finding difficulty, and lethargy. Neuraxial imaging demonstrated right cerebellar leptomeningeal enhancement with nodular T1 signal along the spinal cord and cauda equina. A lumbar puncture revealed elevated opening pressure and cytology positive for melanoma. Genetic sequencing of cells in the cerebrospinal fluid was negative for alterations in 49 commonly mutated genes including BRAF and NRAS. Placement of a ventriculoperitoneal shunt alleviated symptoms of increased intracranial pressure. Ultimately, the patient and family declined tumor-directed therapy. He died approximately 12 weeks after symptom onset. Immunosuppression, particularly anti-TNF therapy, is associated with increased incidence of melanoma and an aggressive disease course. To our knowledge, this is the first reported case of malignant transformation of NCM after anti-TNF therapy. We would caution against the use of anti-TNF agents in patients with NCM.
DRES-05. IDENTIFYING DRIVERS OF CHEMORESISTANCE IN GROUP 3 MEDULLOBLASTOMA THROUGH A GENOME-WIDE CRISPR/Cas9 ACTIVATION SCREEN
Authors: Anne Song, Stephen Mack, Jeremy Rich
Journal: Neuro-Oncology (2017)

Medulloblastoma (MB) is the most common malignant brain tumor in children, accounting for nearly 20% of all pediatric brain cancers. Based on transcriptional profiling studies, MB has been characterized into four molecular subgroups--WNT, SHH, Group 3, and Group 4--that have distinct genetics, patient demographics, histology, and clinical outcomes. Group 3 MB carries the worst prognosis, with 5-year survival rates of 50%. Current therapy for MB consists of maximal safe surgical resection, radiation, and chemotherapy, with cisplatin and cyclophosphamide as mainstays in many chemotherapy regimens. However, Group 3 MB commonly develops resistance and becomes refractory to standard therapy. As these mechanisms of resistance remain poorly understood, I used the CRISPR/Cas9-based synergistic activation mediator (SAM) system to conduct a genome-wide, gain-of-function, positive selection screen to identify the specific drivers of chemoresistance in Group 3 MB. I cloned and sequenced a library consisting of 70,290 single-guide RNAs (sgRNAs) targeting each of the 23,430 coding isoforms from the human RefSeq database. I transduced this library into a Group 3 MB patient-derived model stably expressing the other SAM components (dCas9, VP64, MS2, p65, and HSF1) and then selected with cisplatin and 4-hydroperoxycyclophosphamide. Modulators of chemotherapy sensitivity will be prioritized by sgRNAs that have activated genes conferring chemoresistance, and I have performed next-generation sequencing to identify these sgRNAs. I will validate the top hits from our screen and also cross-reference them with recently published whole-genome sequencing data on six pairs of human diagnostic and post-therapy Group 3 MBs. These findings will provide insights into the mechanisms of resistance in Group 3 MB and inform novel therapeutic targets that may sensitize the tumor to chemotherapy and improve future treatment response.
The Need for Better Data Breach Statistics—Reply
Authors: Ge Bai, John (Xuefeng) Jiang, Renee Flasher
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
CBIO-26. SUBPOPULATIONS OF CIRCULATING EXTRACELLULAR VESICLES OF GLIOBLASTOMA PATIENTS CAN BE DISTINGUISHED BY IMAGING FLOW CYTOMETRY
Authors: Franz Ricklefs, Cecile Maire, Katharina Kolbe, Mareike Holz, Rudolph Reimer, Markus Glatzel, E Antonio Chiocca, Manfred Westphal, Katrin Lamszus
Journal: Neuro-Oncology (2017)

We previously demonstrated that extracellular vesicles (EV) from glioblastomas reflect the molecular subtype of the original tumor and mediate an exchange of pro-oncogenic signals. EV are commonly characterized by nanoparticle analysis (NTA), electron microscopy and immunoblot detection of tetraspanin markers, including CD9, CD81 and CD63. It is unclear, however, to what extent marker profiles overlap and how useful they are at distinguishing different cell types of origin. With the goal of defining markers that allow distinction and enrichment of glioma EVs from patient blood, we utilized Imaging Flow Cytometry (IFC) to discriminate single EVs via multiple surface markers. EVs were isolated from blood of glioblastoma patients (n=25), healthy controls (n=20), PALM-GFP-GL261 and PALM-GFP-CT2A tumor-bearing mice (n=5), glioblastoma (GSC) cultures (n=4), neural stem cells (NSC), cerebral endothelial cells (cEC) and T-cells (n=4) and analyzed by IFC, immunoblotting, electron microscopy and NTA. IFC allows the detection of up to 4 different markers on single EV below 200nm, including CD9, CD81, CD63 and AnnexinV. Glioblastoma patients display significantly increased levels of circulating EV compared to healthy controls (p<0.001), as measured by NTA and IFC. In particular, the proportion of double positive CD9+/CD81+ EVs is elevated in glioblastoma patients (p=0.018) vs. healthy controls, while single positive CD9+ or CD81+ EVs are not. In accordance, GSC excrete increased levels of CD9+/CD81+ EVs in vitro, while NSCs and cEC primarily produce CD9+ EVs, and T-cell EVs are predominantly CD81+. In syngeneic murine PALM-GFP glioma models, only 0.1-0.01% of circulating plasma EVs are derived from intracranial tumors, underlining the need to identify markers that can enrich tumor-specific EVs for molecular profiling. Glioma patients display increased levels of circulating plasma EV that can be characterized by IFC, which is a unique technique that allows discrimination of different EV subpopulations.
PATH-22. BRAINGENEEXPRESS: A WEB APPLICATION FOR DATA VISUALIZATION OF BRAIN TUMOR RESEARCH
Authors: Meijing Wu, Ting Xiao, Jason Miska, J Robert Kane, Deepak Kanojia, Xi Li, Maciej S Lesniak
Journal: Neuro-Oncology (2017)

During the past decade, several public databases have provided researchers with an unparalleled amount of data on brain tumors, like The Cancer Genome Atlas, Gene Expression Omnibus, and the recent MSK-IMPACT project. How to comprehensively integrate and easily visualize these data becomes crucial for researchers to extract any meaningful information for the benefit of translational research. We aim to build a web application, BrainGeneExpress, for visualization of data relevant to glioblastoma study to help researchers rapidly access the results by selecting genes of interest, available databases, and appropriate methods. Our web application will consolidate a large amount of data analysis results from both clinical and bioinformatics perspectives, which are not available in already existing web portals. We used Shinny by Rstudio to build the web application. It currently includes: 1) Survival analysis on overall survival and time-to-recurrence using Cox proportional hazards model with and without restricted cubic spline with adjustment of user-selected clinical factors. Different variable selection and missing data imputation methods were also available; 2) Correlation analysis: including correlation between two gene sets using canonical correlation analysis; correlation between one gene and a selected array of genes or the entire gene pool, with significant correlated genes filtered by different criteria, and visualized in both table and heatmap, and clustering analysis was also applied; 3) Gene set enrichment analysis; 4) Recursive partitioning analysis. All results can be easily obtained, and downloaded into different formats, with table notes and figure legends included. Successful completion of this web application will trigger the exploration of more brain tumor types, databases, and analysis methods aimed at including lower grade gliomas, pediatric gliomas, more GSE databases, and machine learning methods. It will greatly enhance the knowledge of glioma for researchers through data mining from different perspectives and make brain tumor research more efficient.