tbuckley/cabot-search huggingface dataset:
An outbreak of Legionnaires’ disease associated with a display spa pool in retail premises, Stoke-on-Trent, United Kingdom, July 2012
Authors: N Coetzee, H Duggal, J Hawker, S Ibbotson, T  G Harrison, N Phin, V Laza-Stanca, R Johnston, Z Iqbal, Y Rehman, E Knapper, S Robinson, N Aigbogun
Journal: Eurosurveillance (2012)

Twenty-one confirmed cases of Legionnaires’ disease (Legionella pneumophila serogroup 1) were identified in the Stoke-on-Trent area of England with onsets since 2 July 2012. Sequence-based typing results are available for nine cases; all are a unique type (ST1268). Initial interviews highlighted a number of possible environmental sources. Inspection of premises of interest revealed an operating spa pool on display, from which the outbreak strain was identified. All cases had visited the retail premise with this spa pool.
Abstract 783: Ponatinib demonstrates antitumor activity in RET- and FGFR-driven patient-derived xenografts
Authors: Joseph M. Gozgit, Youngchul Song, Victor M. Rivera
Journal: Cancer Research (2015)

Abstract Background: Ponatinib is a potent pan-BCR-ABL tyrosine kinase inhibitor (TKI) approved for patients (pts) with refractory or T315I+ chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia. We have previously shown that ponatinib also inhibits oncogenic variants of KIT, RET, and FGFR in vitro. Moreover, ponatinib induced complete regression of KIT-mutant tumors in a gastrointestinal stromal tumor (GIST) patient-derived xenograft (PDX), a finding consistent with the preliminary evidence of efficacy observed in pts with refractory GIST (NCT01874665). In this study, we evaluated ponatinib in a panel of PDXs harboring oncogenic variants of RET and FGFR. Methods: The efficacy of ponatinib (20 mg/kg once-daily oral dosing) was compared to that of vehicle in 10 PDXs derived from a variety of tumor types containing oncogenic RET or FGFR fusions, high-level FGFR amplification (amp), or no known oncogenic drivers (WT; Table 1). Chemotherapeutic comparators (cisplatin or 5-fluorouracil) were included in 6 models. To confirm target modulation, levels of RET or FGFR phosphorylation in tumors were analyzed 6 hrs post dosing. Results: Ponatinib induced tumor regression or ∼80% tumor growth inhibition (TGI) in the 4 RET fusion PDXs, and 62-98% TGI in the 3 FGFR PDXs (Table 1). Complete abrogation of target phosphorylation due to ponatinib treatment was verified in the 3 models examined. The efficacy of ponatinib exceeded that of the chemotherapy comparator in RET-driven but not WT PDXs, further suggesting this efficacy was driven primarily through inhibition of the driver oncogene. Conclusion: Ponatinib demonstrates marked efficacy across several PDX models with either RET fusion-, FGFR2/3 fusion-, or FGFR2 amp-driven cancers, in a target dependent manner. These results provide additional support for evaluating ponatinib in pts with cancers positive for these aberrations; such trials are planned or ongoing (NCT01813734, NCT02265341, NCT01935336, and NCT02272998). Table 1: Ponatinib's efficacy in PDX tumor modelsCancer TypeTargetTumor growth inhibition (%)Tumor regression (%)CRCCCDC6-RET-78CRCNCOA4-RET79-NSCLCKIF5B-RET80-NSCLCKIF5B-RET-12NSCLCMCU-FGFR290-GliomaTACC3-FGFR362-GastricFGFR2 amp98-CRCWT (control)41-CRCWT (control)24-NSCLCWT (control)51- Citation Format: Joseph M. Gozgit, Youngchul Song, Victor M. Rivera. Ponatinib demonstrates antitumor activity in RET- and FGFR-driven patient-derived xenografts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 783. doi:10.1158/1538-7445.AM2015-783
Abstract 15437: Replication of the Association of PSRC1 and MTHFD1L with Coronary Artery Disease: the Multi-Ethnic Study of Atherosclerosis
Authors: Matthew B Sellers, Yongmei Liu, Gregory Burke, Jasmin Divers, Pamela Ouyang, Walter Palmas, Wendy Post, Kurt Lohman, David Herrington
Journal: Circulation (2011)

Introduction GWAS have identified thirty single nucleotide polymorphisms (SNPs) associated with coronary heart disease (CHD); however the majority of these analyses are in subjects of Caucasian anc...
Abstract 1839: MicroRNA-499 Promotes the Differentiation of Cardiac Progenitor Cells into Myocytes
Authors: Toru Hosoda, Konrad Urbanek, Adriana Bastos Carvalho, Claudia Bearzi, Silvana Bardelli, Roberto Rizzi, Domenico D’Amario, Cynthia Carrillo-Infante, Hanqiao Zheng, Federico Quaini, Marcello Rota, Piero Anversa, Annarosa Leri
Journal: Circulation (2008)

Myocardial regeneration mediated by cardiac progenitor cells (CPCs) results in the partial recovery of the infarcted heart but the newly formed myocytes within the necrotic tissue have fetal-neonatal characteristics. In contrast, CPC activation in the remote viable myocardium results in the formation of mature myocytes, suggesting that CPC differentiation is conditioned by the surrounding cells. Thus, the hypothesis is raised that microRNAs (miRs) that are highly expressed in myocytes and are absent in CPCs, may translocate through gap junctions to adjacent CPCs promoting their differentiation. By employing miR array and Q-RT-PCR, miR-499 was found to be ~500-fold more expressed in myocytes than CPCs. Additionally, we demonstrated that miR-499 translocates from neighboring cells to CPCs through the formation of gap junctions. The translocated miR-499 was functional and repressed the expression of target genes. Among 200 putative targets of miR-499, we have elected to study Sox6 and Rod1. The validation of these putative miR-499-targets was obtained by reporter assays; cells transfected with miR-499 together with plasmids carrying luciferase and the 3′-UTR region of Sox6 or Rod1 show the expected decrease in luciferase activity. Transcripts of Sox6 and Rod1 were measured by Q-RT-PCR in myocytes and CPCs; Sox6 mRNA was 2-fold higher and Rod1 mRNA was 98% lower in myocytes than CPCs. However, the protein levels of Sox6 and Rod1 were significantly lower in myocytes than CPCs suggesting that miR-499 promotes degradation and/or inhibition of translation of these target genes. To document miR-499 function, CPCs were transfected with a miR-499-expression vector and cell proliferation and differentiation were evaluated 3 days later. BrdU incorporation decreased 60% and the cells displayed a marked upregulation of the myocyte-specific transcription factors Nkx2.5 and MEF2C. Similar results were obtained when Sox6 and Rod1 were selectively blocked with siRNA. In both cases, the number of Nkx2.5- and MEF2C-positive cells increased 2–3-fold. Thus, our data indicate that miR-499 translocates via gap junction from myocytes to CPCs where miR-499 is a crucial modulator of the differentiation of CPCs into cardiomyocytes through the repression of Sox6 and Rod1.
Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. Italian Multicentre Breast Study with Epirubicin.
Authors: G Ambrosini, M Balli, G Garusi, R Demicheli, A Jirillo, G Bonciarelli, G Bruscagnin, G Fila, C Bumma, F Lacroix, F Buzzi, F Di Costanzo, D Padalino, M Brugia, F Calabresi, M Natali, G Cartei, G Chiesa, B Blasina, E Ciambellotti, G Moro, S D'Aquino, G Altavilla, V Adamo, D De Maria, A M Falchi, P Bertoncelli, A Farris, M Fiorentino, A Fornasiero, V Fosser, O Daniele, C M Foggi, G B Speranza, S Sartori, E Camilluzzi, L Gallo, R Poggio, V Secondo, A Gambi, F Grignani, E Capodicasa, M Lopez, P Papaldo, L Di Lauro, P Vici, G Marenco, U Folco, F Bonanni, P Marsilio, G Palazzotto, A Di Carlo, M P Cusimano, G Pastorino, C Puccetti, M Giusto, L Rausa, N Gebbia, S Palmeri, N D'Alessandro, F Saccani, G Becchi, G Schieppati, I Spinelli, A Tagliagambe, M Tonato, V Minotti, A Ardia, D Viaro, P De Micheli, G Zingali, G Sacchetti, C Intini
Journal: Journal of Clinical Oncology (1988)

From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.
Abstract 720: Transthoracic Echocardiographic Parameters as Predictors of Atrial Fibrillation Recurrence: Data From the GISSI-AF Echocardiographic Study
Authors: Lidia Staszewsky, Roberto Latini, Maylene Wong, Alberto Volpi, Simona Barlera, Enrico Nicolis, Silvana Gramenzi, Filippo Taddei, Giovanni Cioffi, Silvana Boni, Prisca Zeni, Elena Raimondi, Maria Grazia Franzosi, Aldo Maggioni, Gianni Tognoni, Marcello Disertori
Journal: Circulation (2009)

Objective: The identification of echocardiographic predictors of recurrence of atrial fibrillation (AF) may represent a valuable step towards its prevention. This study was undertaken in an effort ...
Abstract 3393: The Common LQT1 Mutation KCNQ1/A341V Predicts High Risk of Cardiac Events in Different Ethnic Backgrounds
Authors: Peter J Schwartz, Carla Spazzolini, Lia Crotti, Alessandro Vicentini, Minoru Horie, Arthur J Moss, Wataru Shimizu, Eric Schulze-Bahr, Arthur A Wilde
Journal: Circulation (2006)

We recently suggested that the KCNQ1-A341V mutation, identified in a large LQT1 founder population in South Africa (SA), is associated with a risk of becoming symptomatic much higher than that repo...
Abstract 3075: The Chromosome 9p21 Risk Variant rs10757278 is Associated with Increased Arterial Stiffness
Authors: Riyaz S Patel, Ibhar Al Mheid, Jesse P Jorgensen, Irina Uphoff, Imrana Qureshi, Yusuf Ahmed, Konstantinos Aznaouridis, Jinying Zhao, Stephen D Clements, Anna Helgadottir, Jeffrey Gulcher, A Maziar Zafari, Viola Vaccarino, Arshed A Quyyumi
Journal: Circulation (2008)
Abstract 17367: Echogenic Liposomes for Clot Imaging and Combined Delivery of Thrombolytic/neuroprotective Agents with Ultrasound-Facilitated Drug Release for Stroke Treatment
Authors: George L Britton, Tao Peng, Hyunggun Kim, Melvin Klegerman, Susan Laing, David McPherson, Shaoling Huang
Journal: Circulation (2011)

Background: Currently, the only FDA-approved therapy for acute ischemic stroke is the administration of recombinant tissue plasminogen activator (tPA). However, the therapeutic application of tPA requires optimization. Combining thrombolytic treatment with administration of neuroprotective agents is a promising strategy under development. We have previously developed tPA-loaded echogenic liposomes (tPA-ELIP) as an improved thrombolytic formulation. We hypothesized that tPA-ELIP can co-encapsulate another agent for combined treatment with the potential for ultrasound-controlled drug release. MATERIALS AND METHODS: Calcein, a small (MW &lt; 1 kDa) molecular fluorophore, was used as a prototypic hydrophilic drug. Calcein-tPA-ELIP, comprising the fluorophore, protein thrombolytic, phospholipids and cholesterol, were prepared by a lipid drying-rehydration-lyophilization method. Clots were incubated with calcein-tPA-ELIP for 2 minutes in vitro. Transvascular ultrasound imaging was performed before and after the incubation to demonstrate tPA-fibrin binding. Color Doppler ultrasound was applied for 30 seconds to trigger the release of calcein from targeted calcein-tPA ELIP. The fluorescent intensity of calcein in solution was measured before and after ultrasound application. RESULTS: Fifteen percent of calcein was entrapped in tPA-ELIP with retention of ultrasound reflectivity. Transvascular B-mode ultrasound imaging demonstrated specific highlighting of clots by tPA-ELIP. The release of calcein from calcein-tPA-ELIP was triggered by application of Doppler ultrasound. CONCLUSIONS: We have demonstrated co-encapsulation of a hydrophilic drug surrogate and a protein thrombolytic agent into ELIP with targeted clot highlighting and in situ ultrasound-triggered drug release. Co-encapsulation of drugs in tPA-ELIP has potential for thrombus-targeted combination thrombolysis and neuroprotective treatment for stroke.
Abstract 14463: Associated Factors of Trajectories of Fatigue and Dyspnea in Patients Three Months After Coronary Artery Bypass Surgeries
Authors: Ming Fen Tsai, Po-Jung Yuan, Chen-Yen Chien, Tsuey-Yuan Huang
Journal: Circulation (2013)

Objectives: There is limited information about developmental trajectories of fatigue and dyspnea in CABG patients over the first three months postoperatively. The aims of the study are to identify ...
Suicide in young men needs multiagency solutions
Authors: Susan Mayor
Journal: BMJ (2000)

Young men need to be encouraged to make contact with a wide range of services—not just mental health services—if the high rate of suicide in this age group is to be reduced, according to a report published this week by a UK men's health group.

The report was commissioned by the Men's Health Forum, an organisation that aims to disseminate and promote good practice in men's health and which is funded by an educational grant from the pharmaceutical company Pfizer. The report argues that there is no simple solution for this multifaceted problem. The main recommendation is that suicide prevention should involve a much broader range …
Abstract 20027: Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Exerts Anti-Inflammatory Effect and Prevents Pressure Overload Induced Cardiac Left Ventricular Dysfunction
Authors: Monika K Duda, Pawel Dobrzyn, Urszula Mackiewicz, Agnieszka Dobrzyn, Michał Maczewski
Journal: Circulation (2010)

Omega-3 polyunsaturated fatty acids - docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) - suppress inflammatory pathways that could prevent development and progression of heart failure. Wh...
Abstract 5307: Cardiomyocyte Sodium Accumulation Promotes Diastolic Dysfunction in Serca2 Knockout Mice
Authors: William Louch, Karina Hougen, Magnus Aronsen, Halvor K Mork, Ivar Sjaastad, Kristin B Andersson, Geir Christensen, Ole M Sejersted
Journal: Circulation (2008)

Terminal decompensation during heart failure involves deterioration of diastolic function. We investigated the mechanisms underlying this functional decline in mice with cardiomyocyte-specific, conditional excision of the Serca2 gene (KO). At 4 weeks following gene deletion, SERCA levels in KO cardiomyocytes were reduced by more than 95% from flox-flox (FF) controls. Surprisingly, echocardiographic measurements indicated only moderate impairment of in vivo function, as systolic and diastolic tissue velocities were 62% and 72% of FF values, respectively. Diastolic heart failure developed in KO between 6 and 7 weeks, as diastolic tissue velocity rapidly declined to 51% of FF values. We compared cardiomyocyte contractions and Ca 2+ cycling at the 4 and 7 week time points. In KO cells, contractions were reduced between 4 and 7 weeks (from 40% to 14% of FF values), and the rate of relaxation was slowed (from 11% to 3% of FF values). Similar alterations were observed in Ca 2+ transients. Sarcoplasmic reticulum (SR) Ca 2+ content was markedly reduced in 4-week KO, although a minute thapsigargin-sensitive SR Ca 2+ release could be induced. SR content was further decreased in 7-week KO and SR Ca 2+ release was not detectable, although Western blots showed no difference in SERCA levels between 4 and 7 week KO. Ca 2+ influx via Ca 2+ channels was enhanced in KO (integrated current ≈200% of FF) at both time points. However, greater NCX-mediated Ca 2+ extrusion in 4-week KO was partially reversed in 7-week KO due to elevation in cytosolic [Na + ] (34 mM vs 25 mM in FF). Normalizing cytosolic [Na + ] using patch clamp increased the rate of decline of the Ca 2+ transient in 7-week KO to 4-week KO values. Thus, KO mice compensate for loss of SR function by increasing trans-sarcolemmal Ca 2+ flux. However, in the longer term, cytosolic Na + accumulation impairs NCX-mediated Ca 2+ extrusion, which promotes development of diastolic heart failure.
NCCN Task Force Report: Adjuvant Therapy for Breast Cancer
Authors: Robert W. Carlson, Elizabeth Brown, Harold J. Burstein, William J. Gradishar, Clifford A. Hudis, Charles Loprinzi, Eleftherios Paul Mamounas, Edith A. Perez, Kathleen Pritchard, Peter Ravdin, Abram Recht, George Somlo, Richard L. Theriault, Eric P. Winer, Antonio C. Wolff, _ _
Journal: Journal of the National Comprehensive Cancer Network (2006)

The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.
Diagnostic criteria in childhood depression
Authors: Elva Poznanski, Hartmut B. Mokros, Janet Grossman, Linda N. Freeman
Journal: American Journal of Psychiatry (1985)

Comparison of diagnoses of childhood depression from four sets of criteria (i.e., Research Diagnostic Criteria, DSM-III, and those of Poznanski and Weinberg) used with 65 children referred to a psychiatric clinic showed complete agreement in 56 (86%) of the cases. The major disagreement resulted from differences between the clinician's rating of dysphoria based on the child's nonverbal behavior and the child's and parent's verbal report of no dysphoria. Analyses of the essential symptoms of depression among the four criteria sets indicated that the nonverbal rating was most strongly associated with a diagnosis of depression and the best predictor of the severity of depression.
Recently acquired HIV infection in men who have sex with men (MSM) in France, 2003-2008
Authors: C Semaille, F Cazein, F Lot, J Pillonel, S Le Vu, Y Le Strat, V Bousquet, A Velter, F Barin
Journal: Eurosurveillance (2009)

An increase in the number of new HIV diagnoses among men who have sex with men (MSM) was observed in several countries in the early 2000s. In this article, we explore the trends among MSM in France between 2003 and 2008. To estimate the number of MSM newly diagnosed with HIV, we take into account the reporting delay, underreporting and missing data for HIV case notification. To identify recent infections (RI) (acquired an average of six months before diagnosis), we used an enzyme immunoassay for recent HIV-1 infections (EIA-RI) which has been performed routinely for new HIV diagnoses since 2003. Multivariate analysis was used to identify factors associated with RI. We estimate that between 1,900 and 2,400 MSM have been newly diagnosed with HIV every year: the proportion of MSM among all newly diagnosed with HIV cases has increased from 25.2% (95% confidence interval (CI): 23.3-27.1) in 2003 to 37.0% (95% CI: 35.2-38.7) in 2008 and was stable during the period 2006-2008. In 2008, the rate of newly diagnosed HIV cases per 10,000 MSM living in France was 72.5. The proportion of non-B subtypes of HIV-1 among cases diagnosed in MSM was 11.7% (2003-2008). The assessment of RI was performed for 4,819 MSM newly diagnosed with HIV in 2003-2008. Of these, 47.6% (95%CI = 46.2-49.0) (2,295 cases) were shown to have been recently infected. The risk of RI was greater for those of French nationality (adjusted odds ratio (aOR) =1.6 [95% CI: 1.4-1.9]), those with high economic status (aOR =1.4 [95% CI: 1.2-1.8]), those tested after a risk exposure (aOR =1.6[95% CI: 1.3-1.8]) or after presenting with clinical symptoms or abnormal biological markers (aOR =1.8 [95% CI: 1.5-2.0]), those who had tested for HIV three or more times during their life-time (aOR =4.2 [95% CI: 3.4-5.2]) and those living in the Paris area (aOR =1.2 [95% CI: 1.0-1.3]). The risk of RI decreased with age. The HIV situation among MSM living in France is a cause of concern, despite the prevention campaigns dedicated to this highly educated sub-population.
Abstract 4177: Safety and Efficacy of Subintimal Angioplasty in Patient With Chronic Total Occlusion Lesions in Ilio-femoral Artery
Authors: Seung Woon Rha, Ji Young Park, Lin Wang, Kanhaiya L. Poddar, Byoung Geol Choi, Ji Bak Kim, Seung Yong Shin, Un-Jung Choi, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2009)

Background:Endovascular therapy (EVT) is considered as an effective treatment in pts with chronic total occlusion (CTO) lesion in ilio-femoral artery. Recently, subintimal angioplasty (SA) has been...
Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy
Authors: Stephan B Felix, Alexander Staudt, Wolf V Dörffel, Verena Stangl, Kurt Merkel, Manfred Pohl, Wolf D Döcke, Stanislao Morgera, Hans H Neumayer, Klaus D Wernecke, Gerd Wallukat, Karl Stangl, Gert Baumann
Journal: Journal of the American College of Cardiology (2000)