tbuckley/cabot-search huggingface dataset:
Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability
Authors: Ryan Rickels, Hans-Martin Herz, Christie C Sze, Kaixiang Cao, Marc A Morgan, Clayton K Collings, Maria Gause, Yoh-hei Takahashi, Lu Wang, Emily J Rendleman, Stacy A Marshall, Annika Krueger, Elizabeth T Bartom, Andrea Piunti, Edwin R Smith, Nebiyu A Abshiru, Neil L Kelleher, Dale Dorsett, Ali Shilatifard
Journal: Nature Genetics (2017)
RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo
Authors: Lorenz Fülle, Nancy Steiner, Markus Funke, Fabian Gondorf, Franziska Pfeiffer, Julia Siegl, Friederike V. Opitz, Silvana K. Haßel, Anna Belen Erazo, Oliver Schanz, H. James Stunden, Michael Blank, Carsten Gröber, Kristian Händler, Marc Beyer, Heike Weighardt, Eicke Latz, Joachim L. Schultze, Günter Mayer, Irmgard Förster
Journal: Molecular Therapy (2017)

The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4+ lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner. To study the effect of these aptamers in vivo, we used a murine model of contact hypersensitivity. Systemic application of the aptamers significantly prevented ear swelling and T cell infiltration into the ears of sensitized mice after challenge with the contact sensitizer. The results of this proof-of-principle study establish aptamers as potent inhibitors of CCL17-mediated chemotaxis. Potentially, CCL17-specific aptamers may be used therapeutically in humans to treat or prevent allergic and inflammatory diseases. The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4+ lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner. To study the effect of these aptamers in vivo, we used a murine model of contact hypersensitivity. Systemic application of the aptamers significantly prevented ear swelling and T cell infiltration into the ears of sensitized mice after challenge with the contact sensitizer. The results of this proof-of-principle study establish aptamers as potent inhibitors of CCL17-mediated chemotaxis. Potentially, CCL17-specific aptamers may be used therapeutically in humans to treat or prevent allergic and inflammatory diseases.
Omega-3 fatty acid epoxides are autocrine mediators that control the magnitude of IgE-mediated mast cell activation
Authors: Yuta Shimanaka, Nozomu Kono, Yoshitaka Taketomi, Makoto Arita, Yoshimichi Okayama, Yuki Tanaka, Yasumasa Nishito, Tatsuki Mochizuki, Hiroyuki Kusuhara, Alexander Adibekian, Benjamin F Cravatt, Makoto Murakami, Hiroyuki Arai
Journal: Nature Medicine (2017)
Brief Report: Rheumatoid Arthritis as the Underlying Cause of Death in Thirty‐One Countries, 1987–2011: Trend Analysis of World Health Organization Mortality Database
Authors: Aliasghar A. Kiadaliri, David T. Felson, Tuhina Neogi, Martin Englund
Journal: Arthritis & Rheumatology (2017)

Objective To examine trends in rheumatoid arthritis (RA) as an underlying cause of death (UCD) in 31 countries across the world from 1987 to 2011. Methods Data on mortality and population were collected from the World Health Organization mortality database and from the United Nations Population Prospects database. Age‐standardized mortality rates (ASMRs) were calculated by means of direct standardization. We applied joinpoint regression analysis to identify trends. Between‐country disparities were examined using between‐country variance and the Gini coefficient. Due to low numbers of deaths, we smoothed the ASMRs using a 3‐year moving average. Changes in the number of RA deaths between 1987 and 2011 were decomposed using 2 counterfactual scenarios. Results The absolute number of deaths with RA registered as the UCD decreased from 9,281 (0.12% of all‐cause deaths) in 1987 to 8,428 (0.09% of all‐cause deaths) in 2011. The mean ASMR decreased from 7.1 million person‐years in 1987–1989 to 3.7 million person‐years in 2009–2011 (48.2% reduction). A reduction of ≥25% in the ASMR occurred in 21 countries, while a corresponding increase was observed in 3 countries. There was a persistent reduction in RA mortality, and on average, the ASMR declined by 3.0% per year. The absolute and relative between‐country disparities decreased during the study period. Conclusion The rates of mortality attributable to RA have declined globally. However, we observed substantial between‐country disparities in RA mortality, although these disparities decreased over time. Population aging combined with a decline in RA mortality may lead to an increase in the economic burden of disease that should be taken into consideration in policy‐making.
Heterogenity of epigenetic and EMT marks observed in hepatocellular carcinoma with keratin 19 proficiency
Authors: T. Okada, T. Nagasaka, N. Yokomichi, F. Taniguchi, T. Toshima, K. Yasui, T. Fuji, Y. Mori, T. Kawai, Y. Umeda, T. Yagi, T. Fujiwara, A. Goel
Journal: Annals of Oncology (2017)

Background: The expression of keratin 19 (K19) has been proposed as a novel predictor for poor prognosis in patients with hepatocellular carcinoma (HCC). However, the cell origin of K19-proficient HCC remains unclear. Herein we tried to reveal the cell origin of K19-proficient HCC by tracing epigenetic footprints in cultured cells and clinical materials. Methods: The KRT19 gene, which encodes K19, has a CpG island in promoter region and therefore implicates DNA methylation as a potential epigenetic process for K19 expression. Firstly, we examined epigenetic alterations in K19-positive HCC cell lines. Next, from a panel of 564 surgically resected HCCs, we clarify the clinicopathological relevance of K19-preficent HCCs by analyzing robust methylation analyses in KRT19 promoter region and LINE-1 in comparison with other cholangiocytic (K7), hepatocytic markers (HepPar-1 and Arginase-1), EMT markers (E-cadherin and vimentin), and a signal pathway associate with biliary differentiation (NOTCH-1). Results: In vitro, although methylation in KRT19 promoter was associated with K19 deficiency, 5-aza-dC treatment failed to re-expression of K19. From 564 surgically resected HCCs, a cohort of 125 HCC patients was selected and analyzed after exclusion of HCC with recurrence, TNM stage as IIIB or more, preoperative therapy, transplantation, and combined hepatocellular-cholangiocarcinoma. In this cohort, K19 expression was found in 29 HCCs (23.2%), and corresponded with poor survival following surgery (P = 0.025) and extrahepatic recurrence free survival (P = 0.017). Compared with K19-deficient HCCs, the lower methylation level in KRT19 promoter was observed in K19-proficient HCCs (P<.0001). Instead, HCC with genome-wide hypermethylation in LINE-1 was frequently observed in K19-proficient HCCs (P = 0.0079). Additionally, K19 proficiency was associated with K7 proficiency (P = 0.043), and reduced both E-cadherin and HepPar-1 expression (P = 0.043 and<.0001, respectively). Conclusions: K19-proficient HCC showed the poor prognosis owing to extrahepatic recurrence and the molecular signatures were different from K19-deficeint HCC, providing novel insights of heterogeneity underlying development of HCC with extrahepatic metastasis. Legal entity responsible for the study: Takeshi Nagasaka Funding: None Disclosure: All authors have declared no conflicts of interest.
Guías BICHAT para el manejo clínico del botulismo y del botulismo relacionado con el bioterrorismo
Authors: P Bossi, A Tegnell, A Baka, A Werner, F van Loock, J Hendriks, H Maidhof, G Gouvras
Journal: Eurosurveillance (2004)

El botulismo es una enfermedad paralizante poco frecuente pero muy grave debida a la toxina botulinica, producida por Clostridium botulinum. Esta toxina es la sustancia mas venenosa de cuantas se conocen. Es 100.000 veces mas toxica que el gas sarin. Ingerir o aspirar esta toxina es lo que produce la enfermedad en el hombre. Se han descrito cuatro formas clinicas diferentes: transmitida por alimentos, por heridas, infantil e intestinal. La quinta forma, el botulismo por inhalacion, se debe a la toxina botulinica aerosolizada que puede llegar a utilizarse como arma biologica. La emision intencionada asimismo puede producirse por la contaminacion de alimentos o del suministro de agua con la toxina o la bacteria C. Botulinum. Por inhalacion, la dosis que puede llegar a matar al 50% de las personas expuestas (LD50) es 0,003 g/kg de peso corporal. 
Los pacientes con insuficiencia respiratoria deben ser hospitalizados en cuidados intensivos y necesitan respiracion asistida prolongada. Debe administrarse antitoxinas equinas trivalentes (A,B,E) al paciente lo antes posible tras el diagnostico clinico. En algunos paises esta disponible la antitoxina humana heptavalente (A-G).
SPAZO2 (SOGUG): Comparative effectiveness of everolimus (Ev) vs axitinib (Ax) as second-line after first-line pazopanib (1stPz) in metastatic renal carcinoma (mRC)
Authors: J. Arranz Arija, B. Pérez-Valderrama, A. Rodriguez Sanchez, J. Puertas Alvarez, A. Pinto Marin, C. Maximiano Alonso, J.C. Villa Guzman, E.M. Fernandez Parra, E. Gallardo Diaz, J. Gonzalez-Larriba, J. Tafalla García, J. Lambea, M. Constenla Figueiras, M.J. Mendez Vidal, J.A. Virizuela Echaburu, F.J. Vazquez Mazon, O. Etxaniz Ulazia, M.T. Abad Villar, J. Cassinello, J.M. Jurado García
Journal: Annals of Oncology (2017)
Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape
Authors: Ellen M. Leitman, Christina F. Thobakgale, Emily Adland, M. Azim Ansari, Jayna Raghwani, Andrew J. Prendergast, Gareth Tudor-Williams, Photini Kiepiela, Joris Hemelaar, Jacqui Brener, Ming-Han Tsai, Masahiko Mori, Lynn Riddell, Graz Luzzi, Pieter Jooste, Thumbi Ndung’u, Bruce D. Walker, Oliver G. Pybus, Paul Kellam, Vivek Naranbhai, Philippa C. Matthews, Astrid Gall, Philip J.R. Goulder
Journal: The Journal of Experimental Medicine (2017)

Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in “shock-and-kill” cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to “corner” the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection.
Randomized phase III trial of ipatasertib vs. placebo, plus abiraterone and prednisone/prednisolone, in men with asymptomatic or mildly symptomatic previously untreated metastatic castrate-resistant prostate cancer (mCRPC)
Authors: J. de Bono, S. Bracarda, K. Chi, C. Massard, D. Olmos Hidalgo, S. Sandhu, C.N. Sternberg, S. Gendreau, N. Xu, T. Baney, D. Maslyar, C.J. Sweeney
Journal: Annals of Oncology (2017)
Integrating Proteomics and Transcriptomics for Systematic Combinatorial Chimeric Antigen Receptor Therapy of AML
Authors: Fabiana Perna, Samuel H. Berman, Rajesh K. Soni, Jorge Mansilla-Soto, Justin Eyquem, Mohamad Hamieh, Ronald C. Hendrickson, Cameron W. Brennan, Michel Sadelain
Journal: Cancer Cell (2017)

Highlights•We generated and annotated an extensive dataset of AML cell surface proteins•We designed an algorithm to identify candidate CAR targets•We defined six criteria for combinatorial pairing of CAR targets•We identified target combinations fulfilling stringent criteria for CAR therapySummaryChimeric antigen receptor (CAR) therapy targeting CD19 has yielded remarkable outcomes in patients with acute lymphoblastic leukemia. To identify potential CAR targets in acute myeloid leukemia (AML), we probed the AML surfaceome for overexpressed molecules with tolerable systemic expression. We integrated large transcriptomics and proteomics datasets from malignant and normal tissues, and developed an algorithm to identify potential targets expressed in leukemia stem cells, but not in normal CD34+CD38− hematopoietic cells, T cells, or vital tissues. As these investigations did not uncover candidate targets with a profile as favorable as CD19, we developed a generalizable combinatorial targeting strategy fulfilling stringent efficacy and safety criteria. Our findings indicate that several target pairings hold great promise for CAR therapy of AML.
Phase I/II study of S 49076, a MET/AXL/FGFR inhibitor, in combination with gefitinib in EGFR-mutated NSCLC patients who progress on EGFR tyrosine kinase inhibitor
Authors: K. Park, F. Ciardiello, T. Hida, W. Lim, C-C. Lin, H. Murakami, M. Nishio, F. Cantero, V. Cattan, C. Gabarroca, E. Gandossi, L. Paz-Ares
Journal: Annals of Oncology (2017)
Does hyper-progression exist among head and neck cancer patients treated with immunotherapy?
Authors: A. Ortega Franco, M. Plana, I. Braña, M. Taberna Sanz, M. Oliva Bernal, S. Vázquez, M. Domenech Vinyolas, G. Berenguer, E. Vilajosana, M. Bergamino, N. Baste, R. Mesia Nin
Journal: Annals of Oncology (2017)
A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer
Authors: Stephano S. Mello, Liz J. Valente, Nitin Raj, Jose A. Seoane, Brittany M. Flowers, Jacob McClendon, Kathryn T. Bieging-Rolett, Jonghyeob Lee, Danton Ivanochko, Margaret M. Kozak, Daniel T. Chang, Teri A. Longacre, Albert C. Koong, Cheryl H. Arrowsmith, Seung K. Kim, Hannes Vogel, Laura D. Wood, Ralph H. Hruban, Christina Curtis, Laura D. Attardi
Journal: Cancer Cell (2017)
State Intimate Partner Violence–Related Firearm Laws and Intimate Partner Homicide Rates in the United States, 1991 to 2015
Authors: Carolina Díez, Rachel P. Kurland, Emily F. Rothman, Megan Bair-Merritt, Eric Fleegler, Ziming Xuan, Sandro Galea, Craig S. Ross, Bindu Kalesan, Kristin A. Goss, Michael Siegel
Journal: Annals of Internal Medicine (2017)

To prevent intimate partner homicide (IPH), some states have adopted laws restricting firearm possession by intimate partner violence (IPV) offenders. "Possession" laws prohibit the possession of firearms by these offenders. "Relinquishment" laws prohibit firearm possession and also explicitly require offenders to surrender their firearms. Few studies have assessed the effect of these policies.To study the association between state IPV-related firearm laws and IPH rates over a 25-year period (1991 to 2015).Panel study.United States, 1991 to 2015.Homicides committed by intimate partners, as identified in the Federal Bureau of Investigation's Uniform Crime Reports, Supplementary Homicide Reports.IPV-related firearm laws (predictor) and annual, state-specific, total, and firearm-related IPH rates (outcome).State laws that prohibit persons subject to IPV-related restraining orders from possessing firearms and also require them to relinquish firearms in their possession were associated with 9.7% lower total IPH rates (95% CI, 3.4% to 15.5% reduction) and 14.0% lower firearm-related IPH rates (CI, 5.1% to 22.0% reduction) than in states without these laws. Laws that did not explicitly require relinquishment of firearms were associated with a non-statistically significant 6.6% reduction in IPH rates.The model did not control for variation in implementation of the laws. Causal interpretation is limited by the observational and ecological nature of the analysis.Our findings suggest that state laws restricting firearm possession by persons deemed to be at risk for perpetrating intimate partner abuse may save lives. Laws requiring at-risk persons to surrender firearms already in their possession were associated with lower IPH rates.Robert Wood Johnson Foundation.
Surto de Escherichia Coli O157 na Escócia, Novembro-Dezembro de 1996
Authors: J M Cowden
Journal: Eurosurveillance (1997)

Na tarde de sexta-feira, 22 de Novembro de 1996, o Departamento de Saude Publica do Health Board de Lanarkshire tomou conhecimento de 15 casos de possivel infeccao a Escherichia Coli O157 (5 dos quais tinham confirmacao microbiologica) em residentes da cidade de Wishaw na regiao central da Escocia. Todos os casos haviam ingerido, quer carnes frias ou sanduiches de carne fornecidos por um talho local, quer bifes com molho, num almoco paroquial a 17 de Novembro de 1996, fornecido pelo mesmo talho. Nesta fase podia-se pensar que a associacao entre os casos e a carne desse talho era apenas uma coincidencia, tanto mais que o talho tinha ganho, recentemente, o premio de melhor talho escoces do ano. No entanto, face a gravidade da infeccao, foi pedido ao talhante que deixasse de fornecer produtos de carne cozinhada, a partir da manha de 23 de Novembro de 1996.
A study of REOLYSIN in combination with pembrolizumab and chemotherapy in patients (pts) with relapsed metastatic adenocarcinoma of the pancreas (MAP).
Authors: Devalingam Mahalingam, Christos Fountzilas, Jennifer L. Moseley, Nicole Noronha, Karol Cheetham, Adrian Dzugalo, Gerard Nuovo, Andres Gutierrez, Sukeshi Patel Arora
Journal: Journal of Clinical Oncology (2017)

e15753 Background: REOLYSIN is an immuno-oncology-reoviral agent that induces an inflamed tumor phenotype secondary to viral infection of cancer cells. In combination with chemotherapy, it achieves 1 &amp; 2 year-survival rates of 46% &amp; 24% in MAP pts, respectively. Tumor analysis from pts showed reovirus protein replication, T-cell infiltration and upregulation of PD-L1. Similarly, the combination of REOLYSIN with anti-PD-1 antibody documented survival benefit in a pre-clinical model. We hypothesized that REOLYSIN in combination with chemo and pembrolizumab in pts with MAP would be clinically efficacious. Methods: A phase 2 study (NCT02620423) enrolled MAP pts who progressed after first line treatment. Pts received REOLYSIN (4.5 x 10 10 TCID 50 IV, D1 &amp; D2), plus pembrolizumab (2mg/kg IV, D8) plus either 1)5-FU (LV (200 mg/m 2 /5-FU 200 mg /m 2 IV bolus, 5-FU 1200mg/m 2 continuous IV infusion D1) or 2) gemcitabine (1000 mg/m 2 IV, D1), or 3) irinotecan (125 mg/m 2 IV, D1) q3w, until disease progression/unacceptable toxicity. The primary endpoint was safety. Secondary objectives included tumor response &amp; evaluation for reovirus replication/immune analysis. We report results of safety cohort analysis. Results: 11 pts were enrolled with REOLYSIN, pembrolizumab and gem (n = 6), 5-FU (n = 3), or iri (n = 2). Grade 1 or 2 TEAEs occurred in all pts: fever (64%), headache (55%), chills (46%), fatigue (46%), dehydration (27%), and nausea (27%). In one pt (gem arm), transient Gr 2 increased transaminases was reported on two occasions. Grade 3 or 4 TEAEs occurred in 8 pts (73%): abdominal pain, anemia, arthralgias, biliary obstruction, chills, DVT, diarrhea, fever, hyperglycemia, leukopenia, myalgias, nausea, neutropenia, pulmonary emboli, vomiting. Of the 5 efficacy evaluable pts, one had PR (6 m duration) and 2 SD (lasting 126 and 221 days). Seven died secondary to PD. On-treatment biopsy show reovirus infection in cancer cells and immune infiltrates. Conclusions: The combination therapy showed manageable safety profiles and antitumor activity in previously treated MAP pts. Further evaluation of anti-tumor activity of REOLYSIN and anti-PD-1 antibody ± chemotherapy combos is planned. Clinical trial information: NCT02620423.
Comprehensive genomic profiling (CGP) and tumor mutational burden (TMB) assessment in subtypes of metastatic melanoma
Authors: J.S. Ross, J.A. Carlson, J.A. Elvin, J.-A. Vergilio, J. Suh, S. Ramkissoon, E. Severson, S. Daniel, S.M. Ali, A.B. Schrock, D. Fabrizio, G.M. Frampton, V.A. Miller, P.J. Stephens, L.M. Gay, D.B. Johnson
Journal: Annals of Oncology (2017)
Is chemotherapy worthwhile in patients with FIGO stage 1B, lymph nodes negative, grade 3 endometrial cancer?
Authors: C. Fontanella, S. Lepori, A. Barcellini, G. Maltese, C. Andreetta, E. Tripodi, F. Martinelli, A. Cerrotta, G. Bogani, A. Ditto, M. Signorelli, C. Scaffa, C. Sacco, F. Raspagliesi, D. Lorusso
Journal: Annals of Oncology (2017)
Cabazitaxel plus prednisone and prophylaxis of neutropenia complications in the treatment of metastatic castration-resistant prostate cancer after failure to docetaxel: A multicenter, non-comparative, open-label, phase IV study
Authors: F.C. Maluf, D. Cubero, F.A.M. de Oliveira, P.E.R. Liedke, L. Brust, C.G. Inocêncio, F.S.M. Monteiro
Journal: Annals of Oncology (2017)
Genotyping and mRNA profiling reveal actionable targets in biliary tract cancers
Authors: K. Papadopoulou, S. Murray, K. Manousou, I. Tikas, C. Dervenis, J. Sgouros, D. Rontogianni, S. Lakis, C. Poulios, S. Pervana, G. Lazaridis, G. Fountzilas, V. Kotoula
Journal: Annals of Oncology (2017)
Modulation of Risk and Prognosis of Cutaneous Melanoma Patients by Genetic Polymorphisms on PDCD1 Gene
Authors: G.V.B. Gomez, J.A. Rinck-Junior, D.H.L. Da Silva, R.L. Mamoni, G.J. Lourenço, A.M. Moraes, C.S.P. Lima
Journal: Annals of Oncology (2017)
Long term quality of life among epithelial ovarian cancer patients: The GINECO case/control VIVROVAIRE Study
Authors: F. Joly Lobbedez, A. Floquet, E. Kalbacher, N. Heutte, D. Berton-Rigaud, O. Tredan, M. Fabbro, A.M. Savoye, J.E. Kurtz, J. Alexandre, P. Follana, V. Delecroix, N. Dohollou, C. Roemer-Becuwe, A. Lesoin, A. Lortholary, G. De Rauglaudre, J-M. Grellard, D. Ahmed-Lecheheb, C. Lhomme
Journal: Annals of Oncology (2017)