tbuckley/cabot-search huggingface dataset:
A prospective genome-wide study of prostate cancer metastases reveals association of wnt pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate–prednisone
Authors: L. Wang, S.M. Dehm, D.W. Hillman, H. Sicotte, W. Tan, M. Gormley, V. Bhargava, R. Jimenez, F. Xie, P. Yin, S. Qin, F. Quevedo, B.A. Costello, H.C. Pitot, T. Ho, A.H. Bryce, Z. Ye, Y. Li, P. Eiken, P.T. Vedell, P. Barman, B.P. McMenomy, T.D. Atwell, R.E. Carlson, M. Ellingson, B.W. Eckloff, R. Qin, F. Ou, S.N. Hart, H. Huang, J. Jen, E.D. Wieben, K.R. Kalari, R.M. Weinshilboum, L. Wang, M. Kohli
Journal: Annals of Oncology (2017)

BackgroundGenomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known.Patients and methodsIn a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher's exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC.ResultsAt 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4–24.1). Genes in the Wnt/ß-catenin pathway were more frequently mutated and negative regulators of Wnt/ß-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17–3.80; P = 0.01).ConclusionsWnt/ß-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.
Versatile hyaluronic acid modified AQ4N-Cu(II)-gossypol infinite coordination polymer nanoparticles: Multiple tumor targeting, highly efficient synergistic chemotherapy, and real-time self-monitoring
Authors: Shihong Shen, Youshen Wu, Ke Li, Ya Wang, Jimin Wu, Yun Zeng, Daocheng Wu
Journal: Biomaterials (2017)
TCT-43 Bioresorbable Scaffold for the Treatment of Calcified Coronary Lesions: IVUS Insights from the ABSORB Japan Trial
Authors: Kozo Okada, Yasuhiro Honda, Hideki Kitahara, M. Brooke Hollak, Paul G. Yock, Hajime Kusano, Wai-Fung Cheong, Krishna Sudhir, Peter J. Fitzgerald, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2017)
TCT-230 Vascular healing response to biodegradable-polymer sirolimus-eluting stent, UltimasterTM, in comparison with durable-polymer everolimus-eluting stent, XienceTM/PromusTM, assessed by optical coherence tomography and angioscopy at 10 months
Authors: Amane Kozuki, Toshiro Shinke, Ryoji Nagoshi, Hiromasa Otake, Junya Shite
Journal: Journal of the American College of Cardiology (2017)
Phase II study of trastuzumab with irinotecan in HER2-positive gastric cancer previously treated with trastuzumab
Authors: Kazuteru Hatanaka, Yasuyuki Kawamoto, Satoshi Yuki, Takashi Meguro, Minoru Uebayashi, Masakazu Abe, Michio Nakamura, Hiroyuki Okuda, Yuh Sakata, Yoshito Komatsu
Journal: Annals of Oncology (2017)
TCT-329 Twelve-Month Follow-Up of a Novel Thin Strut (112 μm) Sirolimus-Eluting Absorbable Vascular Scaffold in Porcine Coronary Arteries
Authors: Yanping Cheng, Jenn McGregor, Stephen Rowland, Ike Juman, Nancy Zhang, Paul Wang, Gerard Conditt, Frank Kolodgie, Renu Virmani, Juan Granada, Greg Kaluza
Journal: Journal of the American College of Cardiology (2017)
TCT-462 Two-years Echocardiographic Changes After Neochord Procedure
Authors: Andrea Colli, Laura Besola, Erica Manzan, Eleonora Bizzotto, Roberto Bellu, Nicola Pradegan, Alessandro Fiocco, Matteo Nadali, Demetrio Pittarello, Gino Gerosa
Journal: Journal of the American College of Cardiology (2017)
Five-Year Effectiveness of the Multidisciplinary Risk Assessment and Management Programme–Diabetes Mellitus (RAMP-DM) on Diabetes-Related Complications and Health Service Uses—A Population-Based and Propensity-Matched Cohort Study
Authors: Eric Yuk Fai Wan, Colman Siu Cheung Fung, Fang Fang Jiao, Esther Yee Tak Yu, Weng Yee Chin, Daniel Yee Tak Fong, Carlos King Ho Wong, Anca Ka Chun Chan, Karina Hiu Yen Chan, Ruby Lai Ping Kwok, Cindy Lo Kuen Lam
Journal: Diabetes Care (2017)

OBJECTIVE To evaluate the 5-year effectiveness of a multidisciplinary Risk Assessment and Management Programme–Diabetes Mellitus (RAMP-DM) in primary care patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A 5-year prospective cohort study was conducted with 121,584 Chinese primary care patients with type 2 DM who were recruited between August 2009 and June 2011. Missing data were dealt with multiple imputations. After excluding patients with prior diabetes mellitus (DM)-related complications and one-to-one propensity score matching on all patient characteristics, 26,718 RAMP-DM participants and 26,718 matched usual care patients were followed up for a median time of 4.5 years. The effect of RAMP-DM on nine DM-related complications and all-cause mortality were evaluated using Cox regressions. The first incidence for each event was used for all models. Health service use was analyzed using negative binomial regressions. Subgroup analyses on different patient characteristics were performed. RESULTS The cumulative incidence of all events (DM-related complications and all-cause mortality) was 23.2% in the RAMP-DM group and 43.6% in the usual care group. RAMP-DM led to significantly greater reductions in cardiovascular disease (CVD) risk by 56.6% (95% CI 54.5, 58.6), microvascular complications by 11.9% (95% CI 7.0, 16.6), mortality by 66.1% (95% CI 64.3, 67.9), specialist attendance by 35.0% (95% CI 33.6, 36.4), emergency attendance by 41.2% (95% CI 39.8, 42.5), and hospitalizations by 58.5% (95% CI 57.2, 59.7). Patients with low baseline CVD risks benefitted the most from RAMP-DM, which decreased CVD and mortality risk by 60.4% (95% CI 51.8, 67.5) and 83.6% (95% CI 79.3, 87.0), respectively. CONCLUSIONS This naturalistic study highlighted the importance of early optimal DM control and risk factor management by risk stratification and multidisciplinary, protocol-driven, chronic disease model care to delay disease progression and prevent complications.
Efficacy of VDT PACE‐like regimens in treatment of relapsed/refractory multiple myeloma
Authors: Arjun Lakshman, Preet Paul Singh, S. Vincent Rajkumar, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, David Dingli, Yi Lisa Hwa, Amie L. Fonder, Miriam Hobbs, Suzanne R. Hayman, Steven R. Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S. Go, Yi Lin, Wilson I. Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, Shaji K. Kumar
Journal: American Journal of Hematology (2017)

Abstract Experience with intensive chemotherapy for relapsed/refractory multiple myeloma (RRMM) using VDT PACE regimen and its modifications (VDT PACE‐like regimens: VPLRs) outside TOTAL THERAPY trials is limited. We analyzed the outcomes of 141 patients with RRMM who received VPLRs at our center between 2006 and 2017 in an intent‐to‐treat analysis. Median age was 59.7 years and 66.7% of patients were male. A median of 2.2 years (range 0.02‐11.4) separated diagnosis of myeloma and inititation of VPLR. High‐risk cytogenetics were present in 52.4% patients. Patients received a median of 4 (range 1‐14) prior therapies, including stem cell transplant (SCT) in 66.7% patients. Ninety‐five (67.4%) patients received VDT PACE, 20 (14.2%) patients received VD PACE and 26 (18.4%) patients received other VPLRs. Patients received a median of 1 cycle (range 1‐9) of VPLR. We observed ≥ minimal response in 68.4%, ≥ partial response (PR) in 54.4% and ≥ very good PR in 10.3% patients. Median progression‐free survival was 3.1 months (95% CI, 1.9‐3.9) and median overall survival (OS) was 8.1 months (CI, 6.2‐9.9). One‐hundred and sixteen (82.3%) patients received some therapy after VPLR; 71 (61.2%) received systemic chemotherapy, while 45 (38.8%) underwent SCT. Median OS for those who received SCT after VPLR was 15.1 months (CI, 10.3‐20.8). Age ≥ 60 years (hazard ratio [HR] 2.3 [CI, 1.4‐3.7]; P = 0.0008) and R‐ISS III stage (HR‐ 2.4 [CI, 1.3‐4.0]; P = 0.003) predicted shorter OS in patients receiving VPLR. VPLRs are effective in heavily pre‐treated RRMM. In fit patients, SCT can be used to consolidate the response to VPLR.
TCT-763 Comparative Assessment of Infrainguinal CTO Crossing Devices
Authors: Kazeen Abdullah, Ehrin Armstrong, Haekyung Jeon-Slaughter, Nicolas W. Shammas, Khusrow Niazi, Scott Kinlay, Mazen Abu-Fadel, Anand Prasad, Houman Khalili, Bala Ramanan, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2017)
De la vigilancia epidemiológica a la integración europea
Authors: F Tissot
Journal: Eurosurveillance (1999)

Entre marzo y junio de 1999, llegaron a Albania 442.000 refugiados kosovares. El sistema de vigilancia nacional no estaba preparado para ello y se establecio un sistema de emergencia para la vigilancia de enfermedades transmisibles con el fin de detectar y controlar brotes potenciales en la poblacion refugiada. En este numero, Eurosurveillance publica un articulo que presenta los resultados de las nueve primeras semanas de vigilancia de las enfermedades transmisibles en los refugiados kosovares en Albania, cinco meses despues iniciarse el conflicto en la antigua Yugoslavia. Desde la llegada de los refugiados a Albania, epidemiologos del Institut de Veille Sanitaire (InVS), a peticion del gobierno frances, se unieron a los equipos humanitarios. La experiencia ha demostrado la importancia de una rapida intervencion para evaluar la salud de los refugiados, crear vinculos con la red local de vigilancia, implantar estrategias y labores de vigilancia e intervencion apropiadas.
Mid-term graft patency of right versus left internal mammary artery as arterial conduit usage for left anterior descending artery revascularisation: Insights from a single-centre study of propensity-matched data
Authors: Qiang Ji, LiMin Xia, YunQing Shi, RunHua Ma, JinQiang Shen, Hao Lai, WenJun Ding, ChunSheng Wang
Journal: International Journal of Surgery (2017)
Safety and Preliminary Efficacy Results of a Phase I First-in-Human Study of the Novel Notch-1 Targeting Antibody Brontictuzumab (OMP-52M51) Administered Intravenously to Patients with Hematologic Malignancies
Authors: Carla Casulo, Jia Ruan, Nam H. Dang, Lia Gore, Catherine Diefenbach, Anne W Beaven, Januario E. Castro, Pierluigi Porcu, Leonardo Faoro, Jakob Dupont, Ann Kapoun, Min Wang, Kristin McGuire, Ian W. Flinn
Journal: Blood (2016)
On the Preparations of the Indian Hemp, or Gunjah: Cannabis Indica Their Effects on the Animal System in Health, and their Utility in the Treatment of Tetanus and other Convulsive Diseases
Authors: W. B. O'Shaughnessy
Journal: BMJ (1843)

This pamphlet contains a detail of facts of a very important kind, which, we doubt not, will cause a great sensation among the members of the profession throughout the world.We feel it, therefore, to be a duty to give as full an account of its contents as our space will permit.It will appear clearly from what we shall state that Dr. O'Shaughnessy has the merit of having added to our materia medica a drug of great and un- equivocal powers, and, probably, a remedy of marked efficacy in diseases hitherto the most unmanageable.For the sake of accuracy, in a matter of so much consequence, we shall avail ourselves, as much as possible, of the author's own words, and endeavour to communicate all the more important facts in a series of extracts from his pamphlet."The narcotic effects of hemp are popularly known in the south of Africa, South America, Turkey, Egypt, Asia Minor, India, and the adjacent territories of the Malays, Burmese, and Siamese.In all these countries hemp is used in various forms, by the dissipated and depraved, as the ready agent of a pleasing intoxication.In the popular medicine of these nations we find it extensively employed for a multitude of affections.But in western Europe its use either as a stimulant or as a remedy is equally unknown Much difference of VOL.X.
Botulismo en el Reino Unido
Authors: M Brett
Journal: Eurosurveillance (1999)

Clostridium botulinum es una bacteria anaerobia productora de esporas que se desarrolla cuando no hay oxigeno y es responsable de las tres formas epidemiologicas principales de la enfermedad: botulismo transmitido por alimentos, del lactante y por heridas. El botulismo transmitido por alimentos es una intoxicacion causada por la ingestion de la neurotoxina preformada en alimentos a partir de la reproduccion de C. botulinum. Por el contrario, la causa del botulismo por heridas y del lactante es el desarrollo de organismos C. botulinum y liberacion de toxinas. El botulismo por heridas es el resultado de la reproduccion de organismos que producen la neurotoxina, bien en abscesos cutaneos en drogodependientes que utilizan jeringuilla, bien en tejidos con lesiones profundas. El botulismo del lactante tiene lugar cuando la espora ingerida de C. botulinum coloniza el intestino y produce la neurotoxina, que es absorbida desde el lumen intestinal.
PTK787/ZK 222584 enhances efficacy of cytostatics in human xenografts and does not interfere with their uptake in tumor tissue.
Authors: Karl H. Thierauch, Martin Haberey, Holger Hess-Stumpp, Klaus Bosslet, Andreas Reichel
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2373 

The inhibition of neo-angiogenesis is a new treatment paradigm in cancer therapy intended to stop the disease progress and to shift the disease from an acute to a chronic state. Favourable in vitro and animal experiments with PTK787/ZK222584 (PTK/ZK), an angiogenesis inhibitor blocking the known VEGF receptor kinases, were translated in phase I and I/II studies and revealed encouraging efficacy associated with a favourable side effect profile in patients after once daily oral treatment. Two double blind, controlled phase III studies in first and second line colon cancer therapy have started recently (CONFIRM 1 and CONFIRM 2). The efficacy and low side effect profile of the compound is explained by its high selectivity for VEGFR 1, 2 and 3, c-fms, c-kit, and PDGFR. VEGF receptors were inhibited in cellular assays with IC50s between 20-50 nM; c-fms, c-kit and PDGFR kinases are inhibited 10 fold weaker. Other kinases were not inhibited up to 100-fold concentrations. VEGF receptor kinase inhibition blocks endothelial cell proliferation and migration without affecting tumor cells directly. PDGFR inhibition destabilizes the interaction of endothelium with the pericytes and the smooth muscle cells. The anti angiogenic effects of PTK/ZK resulted in efficacious inhibition of tumor growth in various models, without impairing animal weights. Since combination therapy is predominant for the majority of cancer indications, we performed a number of experiments combining a cytostatic agent and PTK/ZK for therapy. In the hormone-dependent prostate tumor model CWR22 we used a combination with an anti androgen (CPA) and measured the prostate specific antigen (PSA) as a biomarker. The drug combination inhibited tumor growth similarly well as orchiectomy and led to a simultaneous decrease of the PSA levels. PTK/ZK combined with taxol in the lung tumor model A 549 neither influenced toxicity nor weight gain compared to taxol treatment alone, whereas the efficacy in tumor growth inhibition was additive. Similar results were obtained with models for mammary and colon carcinomas as well as melanoma (MATU, HT29 and B16F10). To analyze the role of permeability reduction (VEGF= V ascular P ermeability F actor) by PTK/ZK in more detail, we investigated the consequences of a pretreatment with PTK/ZK followed by an application of cytostatic agents: We found no change of the uptake of the cytostatics in tumors after pretreatment with PTK/ZK using two independent analytical methods.In conclusion, combinations of PTK/ZK with cytostatics and antihormones were superior to a single agent treatment. There was no change in tolerability. Thus, PTK/ZK is well tolerated and may represent an additional treatment option for solid tumors either as single agent or in combination therapy. * PTK787/ZK 222584 is being co-developed by Schering AG, Germany and Novartis, Switzerland
TCT-248 Absorb bioresorbable vascular scaffold in patients with or without diabetes mellitus: a sub-analysis of the Italian multicenter RAI Registry ( ClinicalTrials.gov Identifier: NCT02298413)
Authors: Marco Mojoli, Giuseppe Tarantini, Giulia Masiero, Bruno Loi, Bernardo Cortese, Alfonso Ielasi, Attilio Varricchio, Luciano Moretti, Leonardo Misuraca, Giampaolo Pasquetto, Paolo Calabro', Donatella Corrado, Giuseppe Steffenino
Journal: Journal of the American College of Cardiology (2017)
A phase I/II study of Carboplatin plus Nab-Paclitaxel in PS 2 pts with advanced non-small-cell lung cancer
Authors: Takashi Niwa, Kazuhisa Nakashima, Hiroshige Yoshioka, Yasuo Iwamoto, Hiroaki Akamatsu, Haruyasu Murakami, Keita Mori, Toshiaki Takahashi
Journal: Annals of Oncology (2017)
Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium
Authors: Amy L Dapper, Bret A Payseur
Journal: Molecular Biology and Evolution (2017)

In some species, meiotic recombination is concentrated in small genomic regions. These "recombination hotspots" leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots.
Surto de infecções por Clostridium histolyticum nos utilizadores de drogas injectavéis em Inglaterra e Escocia
Authors: J S Brazier, M Gal, V Hall, T E Morris
Journal: Eurosurveillance (2004)

As infeccoes por Clostridium histolyticum em utilizadores de drogas injectaveis no Reino Unido representam um fenomeno relativemente recente que apareceu em 2000 com a identificacao de casos serios da doenca e de obidos devidos a Clostridium novyi. Entre dezembro 2003 e abril 2004, o laboratorio de referencia dos anaerobios recebeu doze isolados de um patogene extrememente raro, Clostridium histolyticum, provindo de utilizadores de drogas injectaveis. As amostras provinham de nove hospitais differentes em Inglaterra e Escocia. A tipagem molecular dos isolamentos por dois metodos differentes de electroforese em campo pulsado e ribotipificacao por PCR revelou que todos eram indistinguiveis, indicando a existencia de uma fonte comum das infeccoes, provavelmente uma remessa de heroina recentemente distribuida em todo Reino Unido.
Association of rhinovirus species with common cold and asthma symptoms and bacterial pathogens
Authors: Hiba Bashir, Kristine Grindle, Rose Vrtis, Fue Vang, Teresa Kang, Lisa Salazar, Elizabeth Anderson, Tressa Pappas, Ronald Gangnon, Michael D. Evans, Daniel J. Jackson, Robert F. Lemanske, Yury A. Bochkov, James E. Gern
Journal: Journal of Allergy and Clinical Immunology (2017)
Characterization of CAMTA1, a putative 1p36 cancer gene: effects on cell cycle and gene expression
Authors: Lu Wang, Violetta Barbashina, Adam Olshen, Marc Ladanyi
Journal: Cancer Research (2007)

519   Hemizygous deletion of chromosome 1p is common in many cancers, including many oligodendrogliomas (where it is a favorable prognostic marker) and neuroblastomas (NB) (where it is a negative prognostic marker), and some Ewing sarcomas (EWS). We have previously shown that the  CAMTA1  (calmodulin-binding transcription activator 1) gene spans a minimal region of 1p36 loss in gliomas with oligodendrial differentiation but is not subject to somatic mutations (Clin Cancer Res 11:1119, 2005). CAMTA1 expression is cell cycle dependent, being higher in the S and M phases. To begin to characterize its role in human cancers, we knocked down  CAMTA1  using siRNA transfection in various cell lines with defined  CAMTA1  copy number by LOH analysis and by fluorescence in situ hybridization (FISH).  CAMTA1  knockdown (to approx. 40-50% of control) had moderate to profound effects on BrdU incorporation in cell lines with hemizygous loss of  CAMTA1  and low baseline expression, especially A172 glioma cells, but had little effect on cell lines without  CAMTA1  deletion. Western blotting of a panel of cell cycle proteins in A172 and SK-PN-DW (EWS cell line) demonstrated that  CAMTA1  knockdown was associated with decreased expression of CCND1, while the negative regulators p21 and p27 were significantly increased. A gene expression profile of  CAMTA1  knockdown was obtained using SK-PN-DW cells transiently transfected with specific or control siRNA and profiled at 48h and 72h on Affymetrix U133-Plus 2.0 arrays. Among 1039 probe sets significant at q CAMTA1  itself, confirming the knockdown, as well as  CCND1 , confirming the western blot data; other notable downregulated genes included  CSDA  (cold shock domain protein A),  FAS , and  NFIB  (nuclear factor I/B). Notable genes upregulated by  CAMTA1  knockdown included  CREM ,  TFEC , and  TCF3 . Gene ontology analysis of the expression profile showed a significant representation of genes implicated in regulation of signal transduction, calcium ion binding, and cell proliferation. These data suggest that CAMTA1 functions primarily as a transactivator and that it may be involved in positive transcriptional regulation of cell cycle progression. Further validation of potentially relevant  CAMTA1  target genes is in progress.
TCT-323 Length of Stay Following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction: Association With 30-Day Readmissions and Implications for Healthcare Costs
Authors: Dhaval Kolte, Poonam Velagapudi, Kashif Ather, Sahil Khera, Tanush Gupta, Gregg Fonarow, Deepak Bhatt, Herbert Aronow, David Cohen, J. Dawn Abbott
Journal: Journal of the American College of Cardiology (2017)