tbuckley/cabot-search huggingface dataset:
Trends and Outcomes of Coronary Angiography and Percutaneous Coronary Intervention After Out-of-Hospital Cardiac Arrest Associated With Ventricular Fibrillation or Pulseless Ventricular Tachycardia
Authors: Nish Patel, Nileshkumar J. Patel, Conrad J. Macon, Badal Thakkar, Maheshkumar Desai, Pablo Rengifo-Moreno, Carlos E. Alfonso, Robert J. Myerburg, Deepak L. Bhatt, Mauricio G. Cohen
Journal: JAMA Cardiology (2016)

<h3>Importance</h3> The 2015 cardiopulmonary resuscitation and emergency cardiovascular care guidelines recommend performing coronary angiography in resuscitated patients after cardiac arrest with or without ST-segment elevation (STE). <h3>Objective</h3> To assess the temporal trends, predictors, and outcomes of performing coronary angiography and percutaneous coronary intervention (PCI) in patients resuscitated after out-of-hospital cardiac arrest (OHCA) with initial rhythms of ventricular tachycardia or pulseless ventricular fibrillation (VT/VF). <h3>Design, Setting, and Participants</h3> An observational analysis of the use of coronary angiography and PCI in 407 974 patients hospitalized after VT/VF OHCA from January 1, 2000, through December 31, 2012, from the Nationwide Inpatient Sample database. Multivariable analysis was used to assess factors associated with coronary angiography and PCI use. Data analysis was performed from December 12, 2015, to January 5, 2016. <h3>Main Outcomes and Measures</h3> Temporal trends of coronary angiography, PCI, and survival to discharge in patients with VT/VF OHCA. <h3>Results</h3> Among the 407 974 patients hospitalized after VT/VF OHCA, 143 688 (35.2%) were selected to undergo coronary angiography. The mean (SD) age of the total population was 65.7 (14.9) years, 37.9% were female, and 74.1% were white, 13.4% black, 6.8% Hispanic, and 5.7% other race. Use of coronary angiography increased from 27.2% in 2000 to 43.9% in 2012 (odds ratio, 2.47; 95% CI, 2.25-2.71;<i>P</i>for trend &lt; .001), and PCI increased from 9.5% in 2000 to 24.1% in 2012 (odds ratio, 4.80; 95% CI, 4.21-5.66;<i>P</i>for trend &lt; .001). From 2000 to 2012, coronary angiography and PCI after VT/VF OHCA increased in patients with STE (53.7% to 87.2%,<i>P</i>for trend &lt; .001, and 29.7% to 77.3%,<i>P</i>for trend &lt; .001, respectively) and those without STE (19.3% to 33.9%,<i>P</i>for trend &lt; .001, and 3.5% to 11.8%,<i>P</i>for trend &lt; .001, respectively). There was an associated increasing trend in survival to discharge in the overall population of patients with VT/VF OHCA (46.9% to 60.1%,<i>P</i>for trend &lt; .001) in those with STE (59.2% to 74.3%,<i>P</i>for trend &lt; .001) or without STE (43.3% to 56.8%,<i>P</i>for trend &lt; .001). <h3>Conclusions and Relevance</h3> Coronary angiography, PCI, and survival to discharge have increased in VT/VF OHCA survivors from event to hospitalization. However, a significant proportion of patients with VT/VF OHCA, especially those without STE, do not undergo coronary angiography and revascularization. Prospective studies are needed to determine whether this limitation has a survival effect.
Shwachman-Diamond Syndrome: Energetic Stress, Calcium Homeostasis and mTOR Pathway
Authors: Carlo Dufour, Silvia Ravera, Simone Cesaro, Roberta Bottega, Cesare Usai, Cipolli Marco, Anna Savoia, Paolo Degan, Michela Faleschini, Paola Cuccarolo, Marta Columbaro, Fabio Corsolini, Enrico Cappelli
Journal: Blood (2015)
Azacitidine/Decitabine Synergism with the NEDD8-Activating Enzyme Inhibitor MLN4924 in Pre-Clinical AML Models
Authors: Peter G Smith, Tary Traore, Steve Grossman, Usha Narayanan, Jennifer S Carew, Anya Lublinksky, Michael Kuranda, Michael Milhollen
Journal: Blood (2011)
Assessment of overdiagnosis in CT screening for lung cancer.
Authors: G. Veronesi, M. Bellomi, P. Maisonneuve, G. Pelosi, M. Casiraghi, C. Rampinelli, L. Spaggiari
Journal: Journal of Clinical Oncology (2010)

1516 Background: CT for screening lung cancer may result in overdiagnosis and overtreatment. We retrospectively assessed overdiagnosis in a single-centre CT screening trial. Methods: Between 2004 and 2005, 5203 high-risk persons were enrolled in a low-dose CT screening trial with CT annual scans for five consecutive years. A non-invasive protocol including PET and determination of volume doubling time (VDT) was used to assess indeterminate lung nodules. Lung cancers detected from the second screening round on were classified as new cancers or progressive cancers depending on the presence of the nodule on CT the year previously. The VDT of progressive cancers was calculated using the maximum diameter from the formula: log10(2)*(date of CT2 ‐ date of CT1) / 3* log10 (nodule size at CT2 / nodule size at CT1). Tumors were classified according to VDT: < 400 days (fast-growing), between 400 and 600 days (slow-growing) and > 600 days (indolent). Results: A total of 168 primary lung cancers were diagnosed and treated. Fifty-six cancers were diagnosed at baseline and 112 were identified at subsequent screening rounds. Of the 112 subsequent cancers, 29 (26%) were new, with median VDT 35 days (assuming a diameter of 1 mm the year previously); and 83 (74%) were progressive with median VDT 283 days. Among the progressive cancers, 60 (54%) were fast-growing, 10 (9%) were slow-growing and 13 (12%) were indolent. Stage 1 cases were 70% of baseline cancers, 59% of new cancer, 76% of fast-growing cancers and 100% of slow-growing and indolent tumors. Conclusions: Slow-growing and indolent tumors are potentially overdiagnosed cases. In the present series they formed about one fifth of the cancers detected after the baseline screening round. At least 80% of the screen detected lung cancers were clinically aggressive tumors, differently from screen detected prostate cancers. The role of limited resection versus follow-up only should be investigated in these potentially overdiagnosed cases. No significant financial relationships to disclose.
The Role of the Cytoplasmic RNA Sensor Retinoic Acid Inducible Gene- I (RIG-I) in Allogeneic Stem Cell Transplantation
Authors: Julius Clemens Fischer, Caroline A Lindemans, Chia-Ching Lin, Alexander Wintges, Michael Bscheider, Tobias Wertheimer, Simon Heidegger, Robert Jenq, Jarrod A Dudakov, Alan M. Hanash, Christian Peschel, Tobias Haas, Marcel R.M. van den Brink, Hendrik Poeck
Journal: Blood (2014)
The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells
Authors: Alejo Chorny, Sandra Casas-Recasens, Jordi Sintes, Meimei Shan, Nadia Polentarutti, Ramón García-Escudero, A. Cooper Walland, John R. Yeiser, Linda Cassis, Jorge Carrillo, Irene Puga, Cristina Cunha, Hélder Bastos, Fernando Rodrigues, João F. Lacerda, António Morais, Rebeca Dieguez-Gonzalez, Peter S. Heeger, Giovanni Salvatori, Agostinho Carvalho, Adolfo Garcia-Sastre, J. Magarian Blander, Alberto Mantovani, Cecilia Garlanda, Andrea Cerutti
Journal: The Journal of Experimental Medicine (2016)

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation-related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell-independent and T cell-dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens.
Nature and outcome of clinical trials conducted by the Eastern Cooperative Group (ECOG) from 1977 to 2006.
Authors: R. S. Go, C. M. Meyer, M. A. Mathiason, A. E. Emmel, K. A. Frisby, L. A. Meyer, J. E. Schroeder, D. L. Sieber, K. L. Crampton, S. R. Pingali
Journal: Journal of Clinical Oncology (2010)

6069 Background: Systematic analysis of trials conducted by ECOG is unavailable. Methods: From the National Cancer Institute and ECOG websites, we obtained a list of therapeutic trials conducted by ECOG between 1977 and 2006 that were terminated before September 1, 2007. A trial was considered positive if the treatment was recommended to be safe for further study (phase I), had a response rate of ≥ 20% (phase II), or if the primary endpoint was reached (phase III). We searched for abstract presentation and subsequent publication until September 1, 2008. Results: A total of 495 trials were included. Phase II trials predominated (65%) followed by phase III (31%) and I (4%). The top 5 disease sites were hematologic (24%), gastrointestinal (17%), genitourinary (15%), thoracic (14%), and breast (11%). Most trials (73%) completed accrual. The median times that the trials were open to accrual were 42, 25, and 39 months for phase I, II, and III trials, respectively. Characteristics of trial development, accrual, and data dissemination are shown in the Table. In terms of outcome, 33% were positive, while 45% were negative and 22% were unavailable or not applicable. To date, 68% of all trials had been published. The median follow-up time for unpublished trials was 95 months. For trials that completed accrual, 27% and 56% were published within 3 and 5 years, respectively. Independent predictors of trial accrual completion were nonhematologic studies, positive result, and activation prior to 1987. Independent predictors of full publication were achievement of accrual goal and activation prior to 1987. Conclusions: Over the last 30 years, ECOG conducted mostly phase II and III trials targeting a variety of malignancies. The process from trial development to publication was generally slow and could take up to a decade to complete. Over a quarter of the trials failed to achieve accrual goal and almost a third never got published. Equal efforts must be directed towards streamlining trial activation, promotion of accrual, and timely publication of results. Median time from concept approval (months) To activation To accrual termination To abstract presentation To full publication Phase I 12 54 56 91 Phase II 11 40 59 85 Phase III 11 55 83 116 No significant financial relationships to disclose.
Size Dependent Kinetics of Gold Nanorods in EPR Mediated Tumor Delivery
Authors: Xiao Tong, Zhantong Wang, Xiaolian Sun, Jibin Song, Orit Jacobson, Gang Niu, Dale O. Kiesewetter, Xiaoyuan Chen
Journal: Theranostics (2016)

Gold nanorods (AuNR) have been intensively used in nanomedicine for cancer diagnostics and therapy, due to their excellent plasmonic photothermal properties.Tuning the size and aspect ratio of AuNR tailors the localized surface plasmon resonance (LSPR) in the NIR spectrum at which biological tissues are transparent, thus enables specific and effective treatment.The AuNR extravasates into tumor interstitium through enhanced permeation and retention (EPR) effect.Efficient AuNR based cancer therapy requires efficient AuNR tumor delivery.However, the size of AuNR can dramatically affect its blood circulation and tumor accumulation.Here we proposed for the first time a systematic framework to investigate the size-dependent kinetics of AuNRs during EPR mediated tumor delivery.By using 64 Cu-labeled AuNRs with positron emission tomography (PET) and kinetic modeling, the in vivo uptake and kinetics of 64 Cu-AuNR during its blood circulation, tumor accumulation and elimination were studied both in vitro and in vivo.The results of different sized AuNRs were compared and the optimum size of AuNR was suggested for EPR mediated tumor delivery.Our study provides a better understanding of the in vivo behavior of AuNR, which can help future design of nanomaterials for cancer imaging and therapy.
Weight-loss in obese insulin-resistant mice induces changes in the adipose tissue gene expression profile that are associated with reversal of hypertriglyceridemia, increase of insulin-sensitivity and glucose tolerance, prevention of atherosclerosis, and improvement of cardiac function
Authors: Wim Verreth, Peter Verhamme, Javier Ganame, A Mertens, Rozenn Quarck, N Benhabiles, G Marguerie, Marie-Christine Herregods, Paul Holvoet
Journal: Circulation (2003)
An International Multicenter Comparative Analysis of Tacrolimus Plus Sirolimus with or without Antithymocyte Globulin As Graft-Versus-Host Disease Prophylaxis in HLA-Mismatched Allogeneic Hematopoietic Cell Transplantation
Authors: Mohamed A. Kharfan-Dabaja, Rocio Parody, Janelle Perkins, Oriana Lopez-Godino, Lucia Lopez-Corral, Lourdes Vazquez, Dolores Caballero, Jose Falantes, Jamie Shapiro, Guillermo Orti, Pere Barba, David Valcárcel, Alber Esquirol, Rodrigo Martino, Jose Luis Piñana, Carlos Solano, Joseph A Pidala, Claudio Anasetti, Jose A. Perez-Simon
Journal: Blood (2015)
Cognitive, behaviour, and academic functioning in adolescent and young adult survivors of childhood acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study
Authors: Lisa M Jacola, Kim Edelstein, Wei Liu, Ching-Hon Pui, Robert Hayashi, Nina S Kadan-Lottick, Deokumar Srivastava, Tara Henderson, Wendy Leisenring, Leslie L Robison, Gregory T Armstrong, Kevin R Krull
Journal: The Lancet Psychiatry (2016)
Administration of Non-Torsadogenic human Ether-à-go-go-Related Gene Inhibitors Is Associated with Better Survival for High hERG–Expressing Glioblastoma Patients
Authors: Kelli B. Pointer, Paul A. Clark, Kevin W. Eliceiri, M. Shahriar Salamat, Gail A. Robertson, John S. Kuo
Journal: Clinical Cancer Research (2016)

Glioblastoma is the most malignant primary brain tumor, with a median survival of less than 2 years. More effective therapeutic approaches are needed to improve clinical outcomes.Glioblastoma patient-derived cells (GPDC) were isolated from patient glioblastomas and implanted in mice to form xenografts. IHC was performed for human Ether-à-go-go-Related Gene (hERG) expression and tumor proliferation. Sphere-forming assays with the hERG blocker E-4031 were performed on a high and low hERG-expressing lines. A glioblastoma tissue microarray (TMA; 115 patients) was used to correlate hERG expression with patient survival. Clinical data were analyzed to determine whether patient survival was affected by incidental administration of hERG inhibitory drugs and the correlative effect of patient glioblastoma hERG expression levels.hERG expression was upregulated in glioblastoma xenografts with higher proliferative indices. High hERG-expressing GPDCs showed a reduction in sphere formation when treated with hERG inhibitors compared with low hERG-expressing GPDCs. Glioblastoma TMA analysis showed worse survival for glioblastoma patients with high hERG expression versus low expression-43.5 weeks versus 60.9 weeks, respectively (P = 0.022). Furthermore, patients who received at least one hERG blocker had a better survival rate compared with patients who did not (P = 0.0015). Subgroup analysis showed that glioblastoma patients with high hERG expression who received hERG blockers had improved survival (P = 0.0458). There was no difference in survival for low hERG-expressing glioblastoma patients who received hERG blockers (P = 0.4136).Our findings suggest that hERG is a potential glioblastoma survival marker, and that already approved drugs with non-torsadogenic hERG inhibitory activity may potentially be repurposed as adjuvant glioblastoma therapy in high hERG-expressing glioblastoma patients. Clin Cancer Res; 23(1); 73-80. ©2016 AACRSee related commentary by Arcangeli and Becchetti, p. 3.
Hydroxyurea Therapy Reduces the Gene Expression of Adhesion Molecules VLA-4 and CD36 in Sickle Erythrocytes, with a Concomitant Decrease in Adhesion to Fibronectin.
Authors: Sheley Gambero, Nicola Conran, Dulcineia M. Albuquerque, Camila O. Santos, Sara T.O. Saad, Fernando F. Costa
Journal: Blood (2005)
P2-028: Aberrant methylation of IL-12Rβ2 gene in lung cancer
Authors: Makoto Suzuki, Toshihiko Iizasa, Takahiro Nakajima, Reiko Kubo, Akira Iyoda, Kenzo Hiroshima, Yukio Nakatani, Takehiko Fujisawa
Journal: Journal of Thoracic Oncology (2007)
Abstract 3802: Selective cytotoxicty and mechanism of Myrothamnus flabellifolius, an edible medicinal plant, on acute myeloid leukemia cells
Authors: Abeer Badiab, Jasjit Dhillon, Fizal Nabbie, Bela Peethambaran
Journal: Cancer Research (2015)

Abstract Current therapies for acute myeloid leukemia involve chemotherapy and radiation, which cause damage to normal and cancerous cells. There is a dire need to discover novel drugs that target only cancer cells. Myrothamnus flabellifolius is a South African resurrection plant known for its anti-viral, anti-microbial and anti-inflammatory properties. Human myeloid leukemia (HL-60) cells and normal (TK-6) lymphocytes were treated with the methanolic extract of M. flabellifolius. Cancer cells treated with extract depicted a significant reduction in viability as compared to normal cells. The first part of this project involved fractionation of the methanolic extract using HPLC and testing each fraction on the normal and leukemic cell lines to find a fraction that selectively killed the cancer cells. A phytochemical analysis was also conducted for characterization of the anticancer compounds. In terms of mechanism, the loss in HL-60 viability was accompanied by the induction of caspase dependent apoptosis by way of caspase-7 cleavage. Heat shock proteins are molecular chaperones that aid in protein reassembly under stressful conditions and protect cells from apoptosis. TK-6 cells express heat shock protein 70 at a high level while HL-60 cells do not express the protein under normal conditions. The expression of HSP70 exhibits a positive correlation with the viability of cells post treatment with extract, indicating that this vital protein plays an important role in the survival of cells post treatment with M. flabellifolius extract. Citation Format: Abeer Badiab, Jasjit Dhillon, Fizal Nabbie, Bela Peethambaran. Selective cytotoxicty and mechanism of Myrothamnus flabellifolius, an edible medicinal plant, on acute myeloid leukemia cells. [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 3802. doi:10.1158/1538-7445.AM2015-3802
Trial-level association between response-based endpoints (RBEs) and progression-free (PFS)/overall survival (OS) in first-line therapy for metastatic colorectal cancer (mCRC) in the ARCAD database.
Authors: Elisabeth Coart, Everardo D. Saad, Qian Shi, Dirkje Willemien Sommeijer, John Raymond Zalcberg, Tim Maughan, Richard M. Goldberg, Hans-Joachim Schmoll, Cornelis J. A. Punt, Eric Van Cutsem, Jean-Yves Douillard, Paulo Marcelo Hoff, Niall C. Tebbutt, Charles S. Fuchs, Alfredo Falcone, Christophe Tournigand, Aimery De Gramont, Daniel J. Sargent, Tomasz Burzykowski, Marc E. Buyse
Journal: Journal of Clinical Oncology (2015)

666 Background: Early tumor shrinkage (ETS; ≥20% decrease from baseline) and early objective tumor response (EOTR; CR/PR by RECIST) are associated with improved PFS/OS to a similar extent than best overall response (BOR), confirmed response (ConfR) and non-progression rate (NPR; CR/PR/SD by RECIST) at the individual level in first-line mCRC (ASCO 2014, abstr 3538/3578). We assessed these RBEs at the trial level. Methods: Data were available on 12,185 pts enrolled in a total of 17 randomized trials of chemotherapy (CT) alone or with targeted agents (TAs). ETS, EOTR and NPR were assessed at 6/8/9 and 12 weeks (wks), whereas BOR and ConfR were ascertained within 26 wks from randomization. Association between treatment effects on RBEs and on PFS/OS was assessed by coefficients of determination (R 2 , adjusted for estimation errors) using a copula model). Results: None of the RBEs had consistently strong correlations with PFS or OS (Table). The number of trials was insufficient to obtain reliable estimates for antiangiogenics and anti-EGFR separately. Conclusions: Despite their individual-level associations with PFS and OS, RBEs do not appear to be surrogate endpoints in first-line mCRC, given their poor predictive ability. [Table: see text]
P3-017: Characterization of efficacy and cellular signalling induced the novel melphalan pro-drug J1 and J3 in NSCLC cells
Authors: Kristina Viktorsson, Malin Wickström, Petra Häg, Birgitta Mörk, Rolf Larsson, Joachim Gullbo, Rolf Lewensohn
Journal: Journal of Thoracic Oncology (2007)
Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for controlled attenuation parameter values
Authors: Salvatore Petta, Vincent Wai‐Sun Wong, Calogero Cammà, Jean‐Baptiste Hiriart, Grace Lai‐Hung Wong, Fabio Marra, Julien Vergniol, Anthony Wing‐Hung Chan, Vito Di Marco, Wassil Merrouche, Henry Lik‐Yuen Chan, Marco Barbara, Brigitte Le‐Bail, Umberto Arena, Antonio Craxì, Victor de Ledinghen
Journal: Hepatology (2016)

Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). Controlled attenuation parameter (CAP) is a new parameter provided by the same machine used for LSM and associated with both steatosis and body mass index, the two factors mostly affecting LSM performance in NAFLD. We aimed to determine whether prediction of liver fibrosis by LSM in NAFLD patients is affected by CAP values. Patients (n = 324) were assessed by clinical and histological (Kleiner score) features. LSM and CAP were performed using the M probe. CAP values were grouped by tertiles (lower 132‐298, middle 299‐338, higher 339‐400 dB/m). Among patients with F0‐F2 fibrosis, mean LSM values, expressed in kilopascals, increased according to CAP tertiles (6.8 versus 8.6 versus 9.4, P = 0.001), and along this line the area under the curve of LSM for the diagnosis of F3‐F4 fibrosis was progressively reduced from lower to middle and further to higher CAP tertiles (0.915, 0.848‐0.982; 0.830, 0.753‐0.908; 0.806, 0.723‐0.890). As a consequence, in subjects with F0‐F2 fibrosis, the rates of false‐positive LSM results for F3‐F4 fibrosis increased according to CAP tertiles (7.2% in lower versus 16.6% in middle versus 18.1% in higher). Consistent with this, a decisional flowchart for predicting fibrosis was suggested by combining both LSM and CAP values. Conclusions: In patients with NAFLD, CAP values should always be taken into account in order to avoid overestimations of liver fibrosis assessed by transient elastography. (H epatology 2017;65:1145‐1155).
Sri Lanka declared malaria free
Authors: Sanjeet Bagcchi
Journal: BMJ (2016)

Sri Lanka has been declared free of malaria by the World Health Organization, fuelling hopes that the disease will be eliminated in 34 other countries where it is endemic.

Sri Lanka has now completed three years with no locally transmitted cases, enabling it to be certified malaria free.

Poonam Khetrapal Singh, WHO regional director, said that the country’s achievement was “truly remarkable.”

“In the mid-20th century it was among …
Adenoviral fibroblast growth factor-4 gene therapy in patients with stable angina. 12-month results of a double blind randomized multicenter trial
Authors: G Barbeau, K Beatt, A Betriu, Stefan Janssens, M Martinez-Rios, B Mautner, T O'Brien, P Paldanius, W Ruzyllo, P Smits, C Sylven, S Yla-Herttuala, B Annex, P Schofield
Journal: Journal of the American College of Cardiology (2006)