tbuckley/cabot-search huggingface dataset:
Abstract 18408: The Impact of Anemia on 3-year Clinical Outcomes in Patients Undergoing Percutaneous Coronary Itervention Using Drug-eluting Stent: Insights from the CREDO-Kyoto PCI/CABG Registry Cohort-2
Authors: Neiko Ozasa, Takeshi Morimoto, Bingyuan Bao, Satoshi Shizuta, Hiroki Shiomi, Junichi Tazaki, Masahiro Natsuaki, Takeshi Kimura
Journal: Circulation (2012)

OBJECTIVES: We investigated the impact of anemia on outcomes after percutaneous coronary intervention (PCI) using drug-eluting stent (DES). BACKGROUND: Patients with anemia have a higher risk of adverse outcomes after PCI. However, long-term outcomes of anemia after contemporary PCI using DES have not been fully investigated. METHODS: We performed a retrospective cohort study of 5336 consecutive patients who underwent first PCI using DES between 2005 and 2007, to assess the impact of anemia on long-term outcomes. RESULTS: Anemia (hemoglobin &lt;13g/dl for men and 12g/dl for women, respectively) were observed in 33.5% of study patients. Patients with anemia were older and more frequently women and have comorbidities such as diabetes mellitus, hypertension, and chronic kidney disease (p&lt;0.0001). In addition, patients with anemia received more complex PCI using longer and smaller-size stents (p&lt;0.05). Cumulative incidence of all cause death, cardiac death, and sudden cardiac death was higher in patients with anemia compared to those without anemia (16.4% vs. 3.6%; p&lt;0.0001, 7.1% vs. 1.7%; p&lt;0.0001, and 3.0% vs. 0.9%; p&lt;0.0001, respectively). In adjusted analyses, anemia was associated with a significantly increased risk of all cause death (HR, 1.96; 95% CI, 1.49-2.58; p&lt;0.0001), a trend toward high risk of cardiac death (HR, 1.36; 95% CI, 0.90-2.06; p=0.1), and sudden cardiac death (HR, 1.69; 95% CI, 0.90-3.18; p=0.09). CONCLUSIONS: Anemia is frequent among patients undergoing PCI using DES and significantly associated with disease severity and worse prognosis.
Evidence for Camel-to-Human Transmission of MERS Coronavirus
Authors: Christian Drosten, Paul Kellam, Ziad A Memish
Journal: New England Journal of Medicine (2014)

We describe the isolation and sequencing of Middle East respiratory syndrome coronavirus (MERS-CoV) obtained from a dromedary camel and from a patient who died of laboratory-confirmed MERS-CoV infection after close contact with camels that had rhinorrhea.Nasal swabs collected from the patient and from one of his nine camels were positive for MERS-CoV RNA.In addition, MERS-CoV was isolated from the patient and the camel.The full genome sequences of the two isolates were identical.Serologic data indicated that MERS-CoV was circulating in the camels but not in the patient before the human infection occurred.These data suggest that this fatal case of human MERS-CoV infection was transmitted through close contact with an infected camel.
Gestational weight gain standards based on women enrolled in the Fetal Growth Longitudinal Study of the INTERGROWTH-21<sup>st</sup>Project: a prospective longitudinal cohort study
Authors: Leila Cheikh Ismail, Deborah C Bishop, Ruyan Pang, Eric O Ohuma, Gilberto Kac, Barbara Abrams, Kathleen Rasmussen, Fernando C Barros, Jane E Hirst, Ann Lambert, Aris T Papageorghiou, William Stones, Yasmin A Jaffer, Douglas G Altman, J Alison Noble, Maria Rosa Giolito, Michael G Gravett, Manorama Purwar, Stephen H Kennedy, Zulfiqar A Bhutta, José Villar
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To describe patterns in maternal gestational weight gain (GWG) in healthy pregnancies with good maternal and perinatal outcomes. <b>Design</b>&nbsp;Prospective longitudinal observational study. <b>Setting</b>&nbsp;Eight geographically diverse urban regions in Brazil, China, India, Italy, Kenya, Oman, United Kingdom, and United States, April 2009 to March 2014. <b>Participants</b>&nbsp;Healthy, well nourished, and educated women enrolled in the Fetal Growth Longitudinal Study component of the INTERGROWTH-21<sup>st </sup>Project, who had a body mass index (BMI) of 18.50-24.99 in the first trimester of pregnancy. <b>Main outcome measures</b>&nbsp;Maternal weight measured with standardised methods and identical equipment every five weeks (plus/minus one week) from the first antenatal visit (&lt;14 weeks' gestation) to delivery. After confirmation that data from the study sites could be pooled, a multilevel, linear regression analysis accounting for repeated measures, adjusted for gestational age, was applied to produce the GWG values. <b>Results</b>&nbsp;13 108 pregnant women at &lt;14 weeks' gestation were screened, and 4607 met the eligibility criteria, provided consent, and were enrolled. The variance within sites (59.6%) was six times higher than the variance between sites (9.6%). The mean GWGs were 1.64 kg, 2.86 kg, 2.86 kg, 2.59 kg, and 2.56 kg for the gestational age windows 14-18<sup>+6</sup> weeks, 19-23<sup>+6</sup> weeks, 24-28<sup>+6</sup> weeks, 29-33<sup>+6</sup> weeks, and 34-40<sup>+0</sup> weeks, respectively. Total mean weight gain at 40 weeks' gestation was 13.7 (SD 4.5) kg for 3097 eligible women with a normal BMI in the first trimester. Of all the weight measurements, 71.7% (10 639/14 846) and 94.9% (14 085/14 846) fell within the expected 1 SD and 2 SD thresholds, respectively. Data were used to determine fitted 3rd, 10th, 25th, 50th, 75th, 90th, and 97th smoothed GWG centiles by exact week of gestation, with equations for the mean and standard deviation to calculate any desired centiles according to gestational age in exact weeks. <b>Conclusions</b>&nbsp;Weight gain in pregnancy is similar across the eight populations studied. Therefore, the standards generated in this study of healthy, well nourished women may be used to guide recommendations on optimal gestational weight gain worldwide.
Long-term survival in adult acute lymphoblastic leukemia: follow-up of a Southeastern Cancer Study Group trial.
Authors: G A Omura, M Raney
Journal: Journal of Clinical Oncology (1985)

Current observation was obtained for adults treated on a protocol for acute lymphoblastic leukemia, which was open from 1972 to 1978, in order to determine the long-term outcome and to evaluate potential prognostic factors. Long-term survival (five + years) was seen in 32% (25/79) of patients who achieved complete remission; 16/79 remain in first remission and 2/79 are currently in second remission. Young age (less than 40) and female sex were significant prognostic factors for long-term survival, but the basis for this advantage is unclear. Further improvements in chemotherapy are needed.
Quantitative determination of metaxalone in human plasma by LC-MS and its application in a pharmacokinetic study
Authors: Lanting Zhao, Qian Li, Chang Shu, Keli Wang, Li Ding
Journal: Asian Journal of Pharmaceutical Sciences (2016)

A simple and rapid method using liquid chromatography–mass spectrometry (LC-MS) for the determination of metaxalone in human plasma has been developed and validated. Letrozole was used as the internal standard (IS). The plasma samples were simply treated with acetonitrile which allowed the precipitation of plasma proteins. The chromatographic separation was achieved on a Sapphire C18 (2.1 mm × 150 mm, 5 µm, Newark, USA) column using the mobile phase (5 mM ammonium acetate containing 0.01% formic acid: acetonitrile (45:55, v/v)) at a flow rate of 0.3 ml/min. The selected ion monitoring (SIM) in the positive mode was used for the determination of [M + H]+ m/z 222.1 and 286.1 for metaxalone and letrozole, respectively. The standard curve obtained was linear (r2 ≥ 0.99) over the concentration range of 30.24−5040 ng/ml. Meanwhile, no interfering peaks or matrix effect was observed. The method established was simple and successfully applied to a pharmacokinetic study of metaxalone in healthy Chinese volunteers after a single oral dose administration of 800 mg metaxalone. The main pharmacokinetic parameters of metaxalone were as follow: Cmax, (1664 ± 1208) ng/ml and (2063 ± 907) ng/ml; AUC0−36, (13925 ± 6590) ng/ml h and (18620 ± 5717) ng/ml h; t1/2, (13.6 ± 7.7) h and (20.3 ± 7.7) h for the reference and test tablets, respectively. These pharmacokinetic parameters of metaxalone in healthy Chinese volunteers were reported for the first time.
Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party.
Authors: Enric Carreras, Hartmut Bertz, William Arcese, Jean-Paul Vernant, José-Francisco Tomás, Hans Hagglund, Giuseppe Bandini, Hèléne Esperou, James Russell, Javier de la Rubia, Gabriele Di Girolamo, Hilde Demuynck, Olivier Hartmann, Johannes Clausen, Tapani Ruutu, Veronique Leblond, Arturo Iriondo, Alberto Bosi, Isaac Ben-Bassat, Vladimir Koza, Alois Gratwohl, Jane F. Apperley
Journal: Blood (1998)
Tumor Promoter 12-&lt;italic&gt;O&lt;/italic&gt;-Tetradecanoylphorbol 13-Acetate: Effect on Complement and Epstein-Barr Virus Receptors in Human Lymphoblastoid Cell Lines&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: N Yamamoto, T Mitsuma, A Vogt
Journal: JNCI Journal of the National Cancer Institute (1982)

The effect of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) on the C3 and Epstein-Barr virus (EBV) receptors in various human Iymphoblastoid cells was investigated with the use of the erythrocyte-antibody-complement (EAC) rosette formation method and a quantitative bioassay for EBV receptors. TPA caused a significant decrease of C3 receptors in the cultures of both Raji and SB4 cells (by ≈50% of the C3 receptors in untreated cultures at 10 ng/ml). Kinetic studies revealed that the rate of reduction was rather moderate but progressive, reaching a maximum 5 days after treatment with TPA. Kinetic studies showed that EBV receptors also decreased, similar to the reduction seen with C3 receptors after TPA treatment. The effect of TPA on the reduction of C3 receptors was observed not only in these cells but also in other EBV-positive B-cells, subclones of SB4 cells, and MOLT-4 cells. However, in an EBV-negative B-cell line, BJAB, EAC rosette formation was significantly enhanced.
Abstract 353: Hdac Class I Inhibition Diminished Cd90+ Cardiac Fibroblast Activation Via Gsk3b/β-catenin Pathway.
Authors: Hikmet Nural-Guvener, Luidmila Zakharova, Diego Mastroeni, Mohamed Gaballa
Journal: Circulation Research (2013)

Myofibroblast activation is one of the major mechanisms of scar formation and interstitial myocardial fibrosis after myocardial infarction (MI) and subsequent heart failure. Elucidating the mechanisms of myofibroblast activation will provide a strategy to treat heart failure. Histone Deacetylases (HDAC) were reported to regulate myofibroblast differentiation and extracellular matrix deposition in lung, kidney and liver fibrosis. Furthermore, HDAC inhibitors were shown to retard myocardial remodeling, interstitial fibrosis and improve cardiac function after MI. However, the mechanisms are unclear. Here we examined whether HDAC1/2 are up-regulated after MI, identify which myocardial cell type is predominately expressing HDAC, and examine the effects of HDAC inhibition on myocardial fibrosis. MI was created in rats by ligation of the left coronary artery. We found that, in sham rats, HDACs were uniformly expressed in both right and left ventriculars. On the other hand, we observed up-regulation of both HDAC1 and 2 in the infarcted LV following MI. In addition, HDAC1 and 2 were co-localized with cardiac fibroblast markers CD90, Vimentin, and αSMA in the infarcted area. Treatment of CD90+ cells isolated from both CHF and sham atrial culture with pan HDAC inhibitor (100 nM, or 300 nM) TSA diminished cardiac fibroblasts activation as indicated by the decrease in αSMA and the increase in E-cadherin gene expressions. Similarly, treatment of CD90 cells with a specific HDAC class I inhibitor (2 μM, Mocetinostat) upregulated E-cadherin and diminished the markers of fibrosis (αSMA, MMP-2, and Collagen III).The decrease in fibroblast activation by HDAC inhibition was associated with increase in p-Gsk3β/Gsk3β ratio and β-catenin protein content. In addition, Mocetinostat treatment of CD90+ cells up-regulated cleaved-Caspase3, an indicator of apoptosis. Taken together, diminishing cardiac fibroblast activation using HDAC class I inhibitor appears to be dependent on Gsk3β/β-catenin pathway.
PO47OVERALL SURVIVAL (OS) IN PATIENTS WITH 1P19Q CO-DELETED WHO GRADE 3 GLIOMAS MATCHES OR EXCEEDS SURVIVAL IN GRADE 2 DISEASE
Authors: M.B. Pinkham, G.A. Whitfield, N. Telford, F. O'Neill, H.R. Gattamaneni, A. Tran, C.A. McBain
Journal: Neuro-Oncology (2015)

INTRODUCTION: Management of gliomas is becoming increasingly individualised. We evaluated outcomes of patients treated at The Christie NHS Foundation Trust in the era of 1p19q analysis. METHOD: Patients with WHO grade 2 and 3 gliomas referred for 1p19q co-deletion status from 2006-2014 were identified. Clinicopathologic data were collected retrospectively. EORTC low (0-2 risk factors) and high (3-5) risk disease was defined by >40yr, size >6cm, crosses midline, neurologic deficit, no oligodendroglial component. Co-deletion (co-del) was defined as FISH probe ratio ≤0.8 for both chromosomes. RESULTS: 243 patients were identified. Median age 46yr (range 18-83), median follow-up 2.3yr (range 0.5-7.8).151 tumours were WHO grade 2; 88 co-del, 63 non-co-del. Overall, 43% had surgery alone, 42% adjuvant RT, 3% adjuvant chemo, 11% adjuvant chemo-RT, 1 died before. Median survival (MS) & 10yr OS were 13.5yr & 65% and 12.1yr & 63%, respectively. For low versus high risk disease, MS and 10yr OS were 13.5yr & 71% and 6.7yr & 39%, respectively.92 tumours were WHO grade 3; 41 co-del, 51 non-co-del. Overall, 2% had surgery alone, 32% adjuvant RT, 62% adjuvant chemo-RT, 4% died before. Adjuvant chemo-RT was used in 71% co-del and 55% non-co-del, predating definitive guidance. MS & 10yr OS were 12.9yr & 96% and 2yr & 24% for co-del and non-co-del, respectively. On multivariate analysis, co-deletion and WHO PS (p < 0.00002), grade, RT use, chemotherapy use and age (p < 0.01) were statistically significant. CONCLUSION: Outcomes in grade 3 co-deleted patients treated before published conclusive evidence matched or exceeded that in WHO grade 2 disease. These results emphasise the evolving nature of this area and the importance of individualising care.
An Update On The Robust Clinical Activity Of SL-401, a Targeted Therapy Directed To The Interleukin-3 Receptor On Cancer Stem Cells and Tumor Bulk, In Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Arthur E. Frankel, Jung H. Woo, Jeremy P. Mauldin, Hetty E. Carraway, Olga Frankfurt, Stephen J. Forman, Sumithira Vasu, Naveen Pemmaraju, Marina Konopleva, Donna E. Hogge, Francine Garanache-Ottou, Fanny Angelot-Delettre, Christopher Brooks, Michael Szarek, Ivan Bergstein, Eric Rowinsky
Journal: Blood (2013)
Re: Daniel M. Geynisman. Anti-programmed Cell Death Protein 1 (PD-1) Antibody Nivolumab Leads to a Dramatic and Rapid Response in Papillary Renal Cell Carcinoma with Sarcomatoid and Rhabdoid Features. Eur Urol 2015;68:912–4
Authors: Francesco Piva, Matteo Santoni, Marina Scarpelli, Alberto Briganti, Antonio Lopez-Beltran, Liang Cheng, Rossana Berardi, Francesco Montorsi, Rodolfo Montironi
Journal: European Urology (2016)
PD-1 Blockade Boosts Radiofrequency Ablation–Elicited Adaptive Immune Responses against Tumor
Authors: Liangrong Shi, Lujun Chen, Changping Wu, Yibei Zhu, Bin Xu, Xiao Zheng, Mingfen Sun, Wen Wen, Xichao Dai, Min Yang, Quansheng Lv, Binfeng Lu, Jingting Jiang
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Radiofrequency ablation (RFA) has been shown to elicit tumor-specific T-cell immune responses, but is not sufficient to prevent cancer progression. Here, we investigated immune-suppressive mechanisms limiting the efficacy of RFA. Experimental Design: We performed a retrospective case-controlled study on patients with synchronous colorectal cancer liver metastases who had received primary tumor resection with or without preoperative RFA for liver metastases. Tumor-infiltrating T cells and tumoral PD-L1 expression in human colorectal cancer tissues were analyzed by immunohistochemistry. T-cell immune responses and PD-1/PD-L1 expression were also characterized in an RFA mouse model. In addition, the combined effect of RAF and PD-1 blockade was evaluated in the mouse RFA model. Results: We found that RFA treatment of liver metastases increased not only T-cell infiltration, but also PD-L1 expression in primary human colorectal tumors. Using mouse tumor models, we demonstrated that RFA treatment of one tumor initially enhanced a strong T-cell–mediated immune response in tumor. Nevertheless, tumor quickly overcame the immune responses by inhibiting the function of CD8+ and CD4+ T cells, driving a shift to higher regulatory T-cell to Teff ratio, and upregulating PD-L1/PD-1 expression. Furthermore, we established that the combined therapy of RFA and anti–PD-1 antibodies significantly enhanced T-cell immune responses, resulting in stronger antitumor immunity and prolonged survival. Conclusions: The PD-L1–PD-1 axis plays a critical role in dampening RFA-induced antitumor immune responses, and this study provides a strong rationale for combining RFA and the PD-L1/PD-1 blockade in the clinical setting. Clin Cancer Res; 22(5); 1173–84. ©2016 AACR.
Abstract 313: Effects of Therapeutic Hypothermia on Myocardial Oxygen Demand and Coronary Flow Velocity
Authors: Nicola Gasparetto, Luisa Cacciavillani, Daniele Scarpa, Francesco Tona, Martina Perazzolo Marra, Armando Marzari, Sabino Iliceto
Journal: Circulation (2012)

Therapeutic hypothermia (TH) has been recently introduced as a therapeutic strategy for brain protection in comatose patients after cardiac arrest (CA). It has been hypothesized that TH could be also useful for myocardial protection thanks to the temporary reduction of myocardial oxygen demand. We aimed to evaluate the effects of mild TH on myocardial oxygen demand and coronary flow velocity (CFV). Material and methods: We studied 11 comatose patients (9 male, aged 59 ± 12) treated with TH after CA of cardiac origin, and with angiographically normal left descending coronary artery (LAD). Rest CFV in the LAD was detected by transthoracic Doppler echocardiography at TH maintenance phase (32.7 ± 0.8 °C) and after rewarming (36.9 ± 0.5 °C).At same time we evaluated the rate-pressure product as a simple way for the estimation of myocardial oxygen demand. Results: During TH, CFV was lower than in normothermic condition (11.5± 2.3 vs. 18.4 ± 4.8, p=0.007) as rate-pressure product (6476 ± 1261 vs. 9565 ± 2332, p=0.021). At linear unadjusted regression analysis the relationships between CFV in LAD and rate-pressure product during TH and after rewarming were close (R2=0.598, p=0.0001, figure). Furthermore, TH reduced CFV by 8.8 ± 6.9% for each 1°C reduction in body temperature. Conclusions: TH reduces rate-pressure product and CFV thus suggesting its potential in reducing myocardial oxygen demand. CFV reduction, induced by hypothermia, parallels that of oxygen demand reduction and is related to the entity of temperature decrease. TH has a potential in protecting myocardium from ischemic damage.
Oncornavirus-Like Particles in Squirrel Monkey (Saimiri sciureus) Placenta and Placenta Culture2
Authors: G. C. Smith, R. L. Heberling, R. J. Helmke, S. T. Barker, S. S. Kalter
Journal: JNCI Journal of the National Cancer Institute (1977)

Oncornavirus-like particles similar in morphology to type D particles were observed in 1 of 2 squirrel monkey (Saimiri sciureus) placentas. Intracytoplasmic type A particles, immature virus particles, and mature viruses with eccentric or occasionally centric nucleoids were associated with placental syncytiotrophoblasts. A spike layer typical of type B viruses was not detected in viral envelopes. Onvornaviruses, identical to those previously isolated from squirrel monkey tissues and similar to Mason-Pfizer monkey virus, were seen in cultures derived from the virus-positive squirrel monkey placenta cocultivated with a mink lung culture. The major morphologic difference between the in vivo and the in vitro squirrel monkey virus was in the nucleoid position of mature virus particles.
FOLFOXIRI plus bevacizumab as first-line treatment of <i>BRAF</i>-mutant metastatic colorectal cancer patients.
Authors: Lisa Salvatore, Fotios Loupakis, Chiara Cremolini, Marta Schirripa, Gianluca Masi, Carlotta Antoniotti, Lorenzo Fornaro, Elisa Sensi, Cristiana Lupi, Francesca Bergamo, Sara Lonardi, Vittorina Zagonel, Gabriella Fontanini, Alfredo Falcone
Journal: Journal of Clinical Oncology (2012)

3585 Background: BRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC) patients, leading to a median PFS of 4-6 months with first-line conventional treatments. Recently, results from a retrospective exploratory analysis suggested that an up-front intensive treatment with FOLFOXIRI plus bevacizumab could improve the outcome of BRAF mutant mCRC. Methods: Fifteen consecutive BRAF mutant mCRC patients treated with first-line FOLFOXIRI plus bevacizumab were included in a validation set. The primary endpoint was 6-months progression free rate (6m-PFR). Secondary endpoints were: overall survival, response rate and the pooled analysis of all main outcome parameters in both the exploratory and validation set. Results: In the validation set, 11 out 15 patients included were progression-free at 6 months, for a 6m-PFR of 73.3%. Primary endpoint was met. At a median follow-up of 21.6 months, median progression-free survival was 9.2 months while median OS has not yet been reached. In the pooled data analysis of the validation set and the initial retrospective cohort 24 out 25 total patients were evaluable for response: partial or complete response was obtained in 17 (68%) and in 1 (4%) patient, respectively, for an overall response rate of 72%. At a median follow-up of 34.1 months, the pooled set of patients showed a median PFS of 11.8 months and a median OS of 23.8 months. Conclusions: These data suggest that FOLFOXIRI plus bevacizumab could be a reasonable option for the first-line treatment of BRAF mutant metastatic colorectal cancer patients.
Multicolor Immunofluorescent Imaging of Complex Cellular Mixtures on Micropallet Arrays Enables the Identification of Single Cells of Defined Phenotype
Authors: Trisha M. Westerhof, Guann‐Pyng Li, Mark Bachman, Edward L. Nelson
Journal: Advanced Healthcare Materials (2016)

A Micropallet-Array-based strategy allowing the identification of cells of defined phenotype in complex mixtures, such as would be obtained from a tissue biopsy, is presented. Following the distribution of single adherent cells from the mixture on individual pedestals, termed "micropallets", immunofluorescent confocal imaging is applied to interrogate the expression of five cell surface molecules.