tbuckley/cabot-search huggingface dataset:
Meiotic crossovers are associated with open chromatin and enriched with Stowaway transposons in potato
Authors: Alexandre P. Marand, Shelley H. Jansky, Hainan Zhao, Courtney P. Leisner, Xiaobiao Zhu, Zixian Zeng, Emily Crisovan, Linsey Newton, Andy J. Hamernik, Richard E. Veilleux, C. Robin Buell, Jiming Jiang
Journal: Genome biology (2017)

Meiotic recombination is the foundation for genetic variation in natural and artificial populations of eukaryotes. Although genetic maps have been developed for numerous plant species since the late 1980s, few of these maps have provided the necessary resolution needed to investigate the genomic and epigenomic features underlying meiotic crossovers. Using a whole genome sequencing-based approach, we developed two high-density reference-based haplotype maps using diploid potato clones as parents. The vast majority (81%) of meiotic crossovers were mapped to less than 5 kb. The fine-scale accuracy of crossover detection was validated by Sanger sequencing for a subset of ten crossover events. We demonstrate that crossovers reside in genomic regions of "open chromatin", which were identified based on hypersensitivity to DNase I digestion and association with H3K4me3-modified nucleosomes. The genomic regions spanning crossovers were significantly enriched with the Stowaway family of miniature inverted-repeat transposable elements (MITEs). The occupancy of Stowaway elements in gene promoters is concomitant with an increase in recombination rate. A generalized linear model identified the presence of Stowaway elements as the third most important genomic or chromatin feature behind genes and open chromatin for predicting crossover formation over 10-kb windows. Collectively, our results suggest that meiotic crossovers in potato are largely determined by the local chromatin status, marked by accessible chromatin, H3K4me3-modified nucleosomes, and the presence of Stowaway transposons.
Inhibition of REDD1 Sensitizes Bladder Urothelial Carcinoma to Paclitaxel by Inhibiting Autophagy
Authors: Qinghai Zeng, Jianye Liu, Peiguo Cao, Jingjing Li, Xiaoming Liu, Xiaojun Fan, Ling Liu, Yan Cheng, Wei Xiong, Jigang Li, Hao Bo, Yuxing Zhu, Fei Yang, Jun Hu, Ming Zhou, Yanhong Zhou, Qiong Zou, Jianda Zhou, Ke Cao
Journal: Clinical Cancer Research (2017)

Purpose: Regulated in development and DNA damage response-1 (REDD1) is a stress-related protein and is involved in the progression of cancer. The role and regulatory mechanism of REDD1 in bladder urothelial carcinoma (BUC), however, is yet unidentified.Experimental Design: The expression of REDD1 in BUC was detected by Western blot analysis and immunohistochemistry (IHC). The correlation between REDD1 expression and clinical features in patients with BUC were assessed. The effects of REDD1 on cellular proliferation, apoptosis, autophagy, and paclitaxel sensitivity were determined both in vitro and in vivo Then the targeted-regulating mechanism of REDD1 by miRNAs was explored.Results: Here the significant increase of REDD1 expression is detected in BUC tissue, and REDD1 is first reported as an independent prognostic factor in patients with BUC. Silencing REDD1 expression in T24 and EJ cells decreased cell proliferation, increased apoptosis, and decreased autophagy, whereas the ectopic expression of REDD1 in RT4 and BIU87 cells had the opposite effect. In addition, the REDD1-mediated proliferation, apoptosis, and autophagy are found to be negatively regulated by miR-22 in vitro, which intensify the paclitaxel sensitivity via inhibition of the well-acknowledged REDD1-EEF2K-autophagy axis. AKT/mTOR signaling initially activated or inhibited in response to silencing or enhancing REDD1 expression and then recovered rapidly. Finally, the inhibited REDD1 expression by either RNAi or miR-22 sensitizes BUC tumor cells to paclitaxel in a subcutaneous transplant carcinoma model in vivoConclusions: REDD1 is confirmed as an oncogene in BUC, and antagonizing REDD1 could be a potential therapeutic strategy to sensitize BUC cells to paclitaxel. Clin Cancer Res; 24(2); 445-59. ©2017 AACR.
TCT-81 Hybrid Coronary Revascularization Vs Percutaneous Strategies in Unprotected Left Main Stenosis: A Propensity Match Study
Authors: Alberto Repossini, Alfonso Ielasi, Lorenzo Di Bacco, Claudio Gentilini, Antonio Saino, Giulietta Grigis, Davide Personeni, Claudio Muneretto, Maurizio Tespili
Journal: Journal of the American College of Cardiology (2017)
Excretion of the Herbicide Glyphosate in Older Adults Between 1993 and 2016
Authors: Paul J. Mills, Izabela Kania-Korwel, John Fagan, Linda K. McEvoy, Gail A. Laughlin, Elizabeth Barrett-Connor
Journal: JAMA (2017)

This study reports urinary levels of glyphosate, an herbicide sprayed onto genetically modified crops, among participants in the Rancho Bernardo Study of Healthy Aging between 1993 and 2016.
TCT-464 Percutaneous Transcatheter Mitral Valve Replacement via Transseptal or Transapical Approach In Patients Who Are Prohibitive Risk For Surgery: US Multicenter Registry
Authors: Divya Ratan Verma, Ashish Pershad, Michael Morse, Saibal Kar, Michael Morris, George Gellert, Brian Whisenant, Kapildeo Lotun, Yoshifumi Nakajima, Colin Barker, Richard Smalling, Abhijeet Dhoble, Tammy Querrey, Alexis Okoh, Chunguang Chen, Soundos Moualla, Marc Cohen, Steven Yakubov, Daniel Watson, Mark Russo, Michael J. Reardon, Michael Caskey, Timothy Byrne, Hao Fang
Journal: Journal of the American College of Cardiology (2017)
Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an Oncogenic Driver–Dependent Manner
Authors: Amanda E. Brinker, Carolyn J. Vivian, Devin C. Koestler, Trevor T. Tsue, Roy A. Jensen, Danny R. Welch
Journal: Cancer Research (2017)

Using a novel mouse model, a mitochondrial-nuclear exchange model termed MNX, we tested the hypothesis that inherited mitochondrial haplotypes alter primary tumor latency and metastatic efficiency. Male FVB/N-Tg(MMTVneu)202Mul/J (Her2) transgenic mice were bred to female MNX mice having FVB/NJ nuclear DNA with either FVB/NJ, C57BL/6J, or BALB/cJ mtDNA. Pups receiving the C57BL/6J or BALB/cJ mitochondrial genome (i.e., females crossed with Her2 males) showed significantly (P < 0.001) longer tumor latency (262 vs. 293 vs. 225 days), fewer pulmonary metastases (5 vs. 7 vs. 15), and differences in size of lung metastases (1.2 vs. 1.4 vs. 1.0 mm diameter) compared with FVB/NJ mtDNA. Although polyoma virus middle T-driven tumors showed altered primary and metastatic profiles in previous studies, depending upon nuclear and mtDNA haplotype, the magnitude and direction of changes were not the same in the HER2-driven mammary carcinomas. Collectively, these results establish mitochondrial polymorphisms as quantitative trait loci in mammary carcinogenesis, and they implicate distinct interactions between tumor drivers and mitochondria as critical modifiers of tumorigenicity and metastasis. Cancer Res; 77(24); 6941-9. ©2017 AACR.
TCT-731 Nine-month clinical outcomes in patients with diabetes treated with polymer free sirolimus-eluting stents and dual-anti platelet therapy (DAPT) for 6 months versus DAPT for 12 months
Authors: Markus Florian Krackhardt, Matt Waliszewski, Maxime Pons, Francois Verdun, Michel Pansieri, Xabobe Flores Rios, Fernando Lozano, Michael Boxberger, Behrouz Kherad
Journal: Journal of the American College of Cardiology (2017)
Demographics and patient characteristics of 1209 patients with Gaucher disease: Descriptive analysis from the Gaucher Outcome Survey (GOS)
Authors: Ari Zimran, Nadia Belmatoug, Bruno Bembi, Patrick Deegan, Deborah Elstein, Diego Fernandez‐Sasso, Pilar Giraldo, Ozlem Goker‐Alpan, Heather Lau, Elena Lukina, Zoya Panahloo, Ida Vanessa D. Schwartz
Journal: American Journal of Hematology (2017)

The Gaucher Outcome Survey (GOS) is an international Gaucher disease (GD) registry established in 2010 for patients with a confirmed GD diagnosis, regardless of GD type or treatment status, designed to evaluate the safety and long-term effectiveness of velaglucerase alfa and other GD-related treatments. As of February 25, 2017, 1209 patients had enrolled, the majority from Israel (44.3%) and the US (31.4%). Median age at GOS entry was 40.4 years, 44.1% were male, and 13.3% had undergone a total splenectomy. Most patients had type 1 GD (91.5%) and were of Ashkenazi Jewish ethnicity (55.8%). N370S/N370S was the most prevalent genotype, accounting for 44.2% of genotype-confirmed individuals (n = 847); however, there was considerable variation between countries. A total of 887 (73.4%) patients had received ≥1 GD-specific treatment at any time, most commonly imiglucerase (n = 587), velaglucerase alfa (n = 507), and alglucerase (n = 102). Hematological and visceral findings at the time of GOS entry were close to normal for most patients, probably a result of previous treatment; however, spleen volume of patients in Israel was almost double that of patients elsewhere (7.2 multiples of normal [MN] vs. 2.7, 2.9 and 4.9 MN in the US, UK and rest of world), which may be explained by a greater disease severity in this cohort. This analysis aimed to provide an overview of GOS and present baseline demographic and disease characteristics of participating patients to help improve the understanding of the natural history of GD and inform the overall management of patients with the disease.
Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses Prostate Cancer Progression
Authors: Sungjin Kim, Omar Awad Alsaidan, Octavia Goodwin, Qianjin Li, Essilvo Sulejmani, Zhen Han, Aiping Bai, Thomas Albers, Zanna Beharry, Y. George Zheng, James S. Norris, Zdzislaw M. Szulc, Alicja Bielawska, Iryna Lebedyeva, Scott D. Pegan, Houjian Cai
Journal: Cancer Research (2017)

Protein N-myristoylation enables localization to membranes and helps maintain protein conformation and function. N-myristoyltransferases (NMT) catalyze co- or posttranslational myristoylation of Src family kinases and other oncogenic proteins, thereby regulating their function. In this study, we provide genetic and pharmacologic evidence that inhibiting the N-myristoyltransferase NMT1 suppresses cell-cycle progression, proliferation, and malignant growth of prostate cancer cells. Loss of myristoylation abolished the tumorigenic potential of Src and its synergy with androgen receptor in mediating tumor invasion. We identified the myristoyl-CoA analogue B13 as a small-molecule inhibitor of NMT1 enzymatic activity. B13 exposure blocked Src myristoylation and Src localization to the cytoplasmic membrane, attenuating Src-mediated oncogenic signaling. B13 exerted its anti-invasive and antitumor effects against prostate cancer cells, with minimal toxic side-effects in vivo Structural optimization based on structure-activity relationships enabled the chemical synthesis of LCL204, with enhanced inhibitory potency against NMT1. Collectively, our results offer a preclinical proof of concept for the use of protein myristoylation inhibitors as a strategy to block prostate cancer progression. Cancer Res; 77(24); 6950-62. ©2017 AACR.
Pfizer and Cipla plan to make cancer drugs affordable in Africa
Authors: Owen Dyer
Journal: BMJ (2017)

Pfizer and the Indian drug maker Cipla will sell 16 common cancer drugs at or near production cost price in six large African countries, in a programme that could save thousands of lives a year.

The programme will include Ethiopia, Kenya, Nigeria, Rwanda, Tanzania, and Uganda, which together account for about 44% of cancer cases in sub-Saharan Africa.

Under the agreement Pfizer will provide docetaxel, doxorubicin, epirubicin, fluorouracil, gemcitabine, leucovorin, methotrexate, and paclitaxel; Cipla will provide anastrozole, bleomycin, capecitabine, cytarabine, and vinblastine. Both companies will provide carboplatin, cisplatin, and oxaliplatin. These medicines together account for well over half the drug budget of a typical African oncology ward.

The deal, negotiated by the American Cancer Society and the Clinton Health Access …
Modelización en tiempo real de las epidemias de gripe: un análisis de regresión lineal
Authors: J. D. Mooney, E. Holmes, P Christie
Journal: Eurosurveillance (2002)

Las ondas epidemicas estacionales de gripe constituyen una carga considerable para los servicios de salud y se caracterizan por su gran variabilidad de ano en ano. El uso de los datos historicos que el Sistema Escoces de Vigilancia Centinela de la gripe recoge desde 1972 ha permitido establecer un modelo predictivo basado en la regresion lineal simple. Este modelo fue aplicado con un cierto exito en la temporada invernal 1999-2000.
Targeting acute myeloid leukemia by drug-induced c-MYB degradation
Authors: V Walf-Vorderwülbecke, K Pearce, T Brooks, M Hubank, M M van den Heuvel-Eibrink, C M Zwaan, S Adams, D Edwards, J Bartram, S Samarasinghe, P Ancliff, A Khwaja, N Goulden, G Williams, J de Boer, O Williams
Journal: Leukemia (2017)
TCT-496 Predictors of Residual Angina after Chronic Total Occlusion Percutaneous Coronary Intervention: External Validation of an Existing Model
Authors: Mohammed Qintar, Taishi Hirai, Christian Patterson, James Sapontis, J. Aaron Grantham, Kensey Gosch, Philip Jones, Yuanyuan Tang, John Spertus, Suzanne Arnold, Adam Salisbury
Journal: Journal of the American College of Cardiology (2017)
Reevaluation of chemotherapy for patients with advanced or recurrent colorectal cancer by RAS status and primary site
Authors: Kazuma Kobayashi, Fumihiko Fujita, Yuusuke Inoue, Izumi Yamaguchi, Yuka Mine, Masaaki Hidaka, Kengo Kanetaka, Kosho Yamanouchi, Mitsuhisa Takatsuki, Susumu Eguchi
Journal: Annals of Oncology (2017)
Intracardiac Metastases Detected by 18F-FSPG PET/CT
Authors: Meaghan A. Magarik, Ronald C. Walker, Jill Gilbert, H. Charles Manning, Pierre P. Massion
Journal: Clinical Nuclear Medicine (2017)

Abstract PET/CT imaging is frequently used for cancer diagnosis and restaging as metabolically active cells, including cancer, utilize glucose for proliferation. 18 F-FDG is the most commonly utilized radiopharmaceutical in PET/CT imaging. Limitations of 18 F-FDG imaging include intense physiologic uptake in benign tissues such as the brain and myocardium. We present a case of non–small cell lung cancer with myocardial and pericardial metastases obscured by physiologic 18 F-FDG cardiac uptake but detected with the investigational PET radiotracer (4S)-4-(3- 18 F-fluoropropyl)- l- glutamate ( 18 F-FSPG), which targets a pathway associated with glutathione biosynthesis. This case demonstrates the added value of 18 F-FSPG PET/CT imaging.
Desarrollo de un protocolo para evaluar la calidad de los datos de la gripe recogidos por los médicos centinela en Europa
Authors: J F Aguilera, W J Paget, J Van Der Velden
Journal: Eurosurveillance (2002)

El EISS implanto un protocolo de evaluacion para valorar la calidad de los datos clinicos recogidos por redes centinela dedicadas a la vigilancia de la gripe. El protocolo fue aplicado en Belgica y tres regiones de Espana, dando lugar a la formulacion de recomendaciones para mejorar las redes de vigilancia nacionales y regionales.
NIH Funds “Tissue Chip” Models for Drug Screening
Authors: Jeff Lyon
Journal: JAMA (2017)

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Aumento significativo de la listeriosis en Alemania – caracteristicas epidemiológicas, 2001-2005
Authors: J Koch, K Stark
Journal: Eurosurveillance (2006)

En Alemania, la listeriosis es una enfermedad de notificacion obligatoria desde Enero de 2001. Los casos clinicos con aislamiento de Listeria monocytogenes procedentes de muestras esteriles o en recien-nacidos se notifican al instituto Robert Koch. La incidencia de la listeriosis aumento de forma significativa de 0,26 por 100.000 habitantes (217 casos) en 2001 a 0,62 por 100.000 habitantes (519 casos) en 2005. El aumento fue unicamente en infecciones no materno-neonatales y se debia principalmente a un aumento del numero de casos en el grupo de edad ≥60 anos. Las tasas de incidencia mas altas se detectaron en recien-nacidos y personas de edad ≥70 anos. Los varones fueron los mas afectados, excepto para casos de adultos en edad fertil. La tasa global de mortalidad fue del 9%. No se identifico ningun cluster de casos en el tiempo o el espacio, tampoco hubo brotes con una fuente de infeccion comun. 
En el 46% de los casos, un cancer como patologia subyacente fue el factor predisponente. Las razones del aumento de la listeriosis en Alemania aun no estan claras. Ni el nuevo programa de vigilancia ni los mejores diagnosticos parecen razones suficientes para explicar el aumento de la incidencia de la enfermedad entre 2004 y 2005. Es posible que la contaminacion creciente de los alimentos mas consumidos, la evolucion de las patologias subyacentes o las opciones terapeuticas hayan contribuido a dicho aumento. Un proyecto para reforzar la vigilancia de la listeriosis se llevo a cabo en 2005 para recoger informacion mas detallada sobre el desarrollo clinico, las patologias subyacentes, los tratamientos medicos, el conocimiento de la listeriosis y los eventuales factores de riesgo alimentarios de todos los casos recientemente diagnosticados. Para facilitar la deteccion de los brotes, es necesario un sistema nacional de sub-tipado molecular de las cepas de listeria aisladas en los humanos y en los productos alimentarios. Deberian extenderse las recomendaciones de prevencion a todos los grupos de riesgo que presenten condiciones predisponentes.
Inmunización contra la tos ferina en Europa: situación a finales de 1999
Authors: H Therre, S Baron
Journal: Eurosurveillance (2000)

La evolucion de la tos ferina en los paises europeos ha demostrado claramente que la inmunizacion reduce la morbilidad asociada a la enfermedad. Las vacunas inactivadas de celulas completas contra la tos ferina se han utilizado en algunos programas de vacunacion nacional desde hace mas de 30 anos, pero las reacciones adversas, principalmente en ninos de mayor edad, se han convertido en motivo de gran preocupacion. Desde 1970, se han realizado importantes esfuerzos para identificar los principales factores de virulencia de Bordetella pertussis a fin de desarrollar nuevas vacunas acelulares contra la tos ferina. Estos factores son la toxina de la tos ferina (TP), responsable de casi todos los efectos toxicos de la bacteria, y factores de adhesion como la hemaglutininina filamentosa (FHA), la pertactina (PRN) y los aglutinogenos (AG). Las primeras vacunas acelulares simples se autorizaron en 1981 en Japon para ninos de 2 y mas anos de edad (1) y, posteriormente, se combinaron con los toxoides de la difteria y del tetanos (DTPa).
Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications
Authors: I. Kortekaas Krohn, M. M. Shikhagaie, K. Golebski, J. H. Bernink, C. Breynaert, B. Creyns, Z. Diamant, W. J. Fokkens, P. Gevaert, P. Hellings, R. W. Hendriks, L. Klimek, J. Mjösberg, H. Morita, G. S. Ogg, L. O'Mahony, J. Schwarze, S. F. Seys, M. H. Shamji, S. M. Bal
Journal: Allergy (2017)

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.
TCT-457 Impact of treatment strategy on angiographic outcomes and risk factors of restenosis after percutaneous coronary intervention for in-stent chronic total occlusion
Authors: Katsuya Miura, Hiroyuki Tanaka, Akimune Kuwayama, Masanobu Ohya, Takenobu Shimada, Hidewo Amano, Shunsuke Kubo, Seiji Habara, Yasushi Fuku
Journal: Journal of the American College of Cardiology (2017)
PVDOMICS
Authors: Anna R. Hemnes, Gerald J. Beck, John H. Newman, Aiden Abidov, Micheala A. Aldred, John Barnard, Erika Berman Rosenzweig, Barry A. Borlaug, Wendy K. Chung, Suzy A.A. Comhair, Serpil C. Erzurum, Robert P. Frantz, Michael P. Gray, Gabriele Grunig, Paul M. Hassoun, Nicholas S. Hill, Evelyn M. Horn, Bo Hu, Jason K. Lempel, Bradley A. Maron, Stephen C. Mathai, Mitchell A. Olman, Franz P. Rischard, David M. Systrom, W.H. Wilson Tang, Aaron B. Waxman, Lei Xiao, Jason X.-J. Yuan, Jane A. Leopold
Journal: Circulation Research (2017)
TCT-297 External elastic lamina vs luminal diameter for determination of stent diameter by optical coherence tomography
Authors: Yasir Parviz, Evan Shlofmitz, Bjorn Redfors, Mitsuaki Matsumura, Akiko Maehara, Khady Fall, Gary Mintz, Allen Jeremias, Fernando Sosa, Elizabeth Haag, Keyvan Karimi Galougahi, Dimitri Karmpaliotis, Ajay Jayant Kirtane, Jeffrey Moses, Ali Akhund, Ori Ben-Yehuda, Gregg Stone, Richard Shlofmitz, Ziad Ali
Journal: Journal of the American College of Cardiology (2017)
18F-FDG PET for Detection of Primary Tracheobronchial T-/Natural Killer–Cell–Derived Posttransplant Lymphoproliferative Disorder After Lung Transplantation
Authors: Thorsten Derlin, Peter Braubach, Hans Heinrich Kreipe, Katja Hueper
Journal: Clinical Nuclear Medicine (2017)

Posttransplant lymphoproliferative disorder (PTLD) is a rare, but potentially devastating complication of solid organ transplantation. Epstein-Barr virus-associated PTLDs of T-cell origin are exceedingly rare. We present the case of a 20-year-old man with extranasal T-/natural killer-cell-derived PTLD after lung transplantation who underwent an F-FDG PET/CT scan for staging of disease. The F-FDG-PET scan demonstrated an unusual pattern of lymphomatous involvement limited to the recipients tracheobronchial tree without concomitant involvement of the donor's bronchi. This case highlights the potential of F-FDG PET/CT for sensitive detection and staging of uncommon manifestations of PTLD.