tbuckley/cabot-search huggingface dataset:
Abstract 11761: Association of Red Blood Cell Microparticles With Biomarker-Defined Infarct Size in Acute Myocardial Infarction
Authors: Georgios Giannopoulos, Spyridon Deftereos, Christos Angelidis, Dimitrios Tsiachris, John Lekakis, Christodoulos Stefanadis
Journal: Circulation (2015)

Background: Red blood cell microparticles (RBCm) have drawn research attention as to their potential prothrombotic and vasoconstrictive effects in experimental settings. Our group has previously reported elevated RBCm counts in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI). Methods: Circulating microparticles were quantified with flow cytometry in blood samples from consecutive STEMI patients after primary PCI. Creatine kinase myocardial-brain fraction (CK-MB) was measured every 6 hours during the first 3 days and every 12 hours thereafter until discharge. The area under the CK-MB concentration curve (CKMB-AUC), calculated with Simpson’s summing rule, was used as a biochemical measure of infarction size. Results: 51 STEMI patients (age 59.8±8.8 years) were enrolled. RBCm concentration was 33740±21169 /μl. The median values [25th-75th percentile] of CKMB-AUC according to RBCm quartile were (from the lower to the upper quartile) 3351 [2550-4060] ng.h.ml-1, 4883 [4179-5348] ng.h.ml-1, 6932 [5464-13229] ng.h.ml-1, and 8784 [7216-12605] ng.h.ml-1, respectively (Kruskal-Wallis p&lt;0.001) (see Figure). In a multivariable regression analysis, RBCm quartile remained associated with CKMB-AUC, after adjustment for total RBC count, age, serum creatinine, presence of diabetes and Killip class on admission (adjusted p&lt;0.001). Conclusions: Erythrocyte microparticles appear to be related to total myocardial damage biomarker output, which is a parameter known to reliably reflect infarct size in patients with STEMI. This finding may be explained by rheologic and vasoactive properties of RBCm (close interaction of the heavily oxidative heme with the endothelium, depletion of NO etc.), which may act deleteriously on coronary vasculature, resulting in increased myocardial damage.
Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor–Redirected T Cells Against Multiple Myeloma
Authors: Xiuli Wang, Miriam Walter, Ryan Urak, Lihong Weng, Christian Huynh, Laura Lim, ChingLam W. Wong, Wen-Chung Chang, Sandra H. Thomas, James F. Sanchez, Lu Yang, Christine E. Brown, Flavia Pichiorri, Myo Htut, Amrita Y. Krishnan, Stephen J. Forman
Journal: Clinical Cancer Research (2017)

Purpose: Multiple myeloma remains an incurable malignancy of plasma cells despite considerable advances in treatment. The purpose of the study was to develop novel chimeric antigen receptors (CAR) for the treatment of multiple myeloma and explore combinatorial therapy using CAR T cells and immunomodulatory drugs such as lenalidomide for increasing treatment efficacy.Experimental Design: We redirected central memory T cells to express second-generation CAR-specific for CS1 and adoptively transferred them into multiple myeloma tumor-bearing mice to test their anti-multiple myeloma activity. CS1 CAR T cells were transduced and expanded in the presence of lenalidomide in vitro The phenotype and effector function of CS1 CAR T cells treated with and without lenalidomide were compared. Finally, CS1 CAR T cells and lenalidomide were administered to treat multiple myeloma-bearing mice as combinatorial therapy.Results: CS1 CAR T cells exhibited efficient antitumor activity when adoptively transferred into mice. Mechanistic studies indicated that the addition of lenalidomide during CS1 CAR T-cell expansion in vitro enhanced the immune functions of CS1 CAR T cells, including cytotoxicity, memory maintenance, Th1 cytokine production, and immune synapse formation. Furthermore, lenalidomide enhanced the antitumor activity and persistence of adoptively transferred CS1 CAR T cells in vivoConclusions: The study demonstrates that lenalidomide improves the anti-multiple myeloma properties of CS1-directed CAR T cells and provides a basis for a planned clinical trial using the combination of lenalidomide with engineered T cells against CS1 in relapsed myeloma. Clin Cancer Res; 24(1); 106-19. ©2017 AACR.
Treatment strategy for prostate cancer patients with bone metastases
Authors: Hiroyoshi Suzuki, Seiji Kato, Ken Wakai, Lee Fang-ching, Ryo Oka, Daisuke Nishimi, Takumi Endo, Masashi Yano, Shuichi Kamijima, Naoto Kamiya
Journal: Annals of Oncology (2017)
Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence
Authors: Joan L. Luby, Deanna Barch, Diana Whalen, Rebecca Tillman, Andy Belden
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Adverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood. <h3>Objective</h3> To investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes. <h3>Design, Setting, and Participants</h3> A prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit. <h3>Exposure</h3> Early life adversity. <h3>Main Outcomes and Measures</h3> Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years. <h3>Results</h3> The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively. <h3>Conclusions and Relevance</h3> Study findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.
Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial
Authors: Jean-Frederic Colombel, Remo Panaccione, Peter Bossuyt, Milan Lukas, Filip Baert, Tomas Vaňásek, Ahmet Danalioglu, Gottfried Novacek, Alessandro Armuzzi, Xavier Hébuterne, Simon Travis, Silvio Danese, Walter Reinisch, William J Sandborn, Paul Rutgeerts, Daniel Hommes, Stefan Schreiber, Ezequiel Neimark, Bidan Huang, Qian Zhou, Paloma Mendez, Joel Petersson, Kori Wallace, Anne M Robinson, Roopal B Thakkar, Geert D'Haens
Journal: The Lancet (2017)
TCT-70 Influence of microcirculatory resistance on the assessment of coronary stenosis severity with Quantitative Flow Ratio (QFR): Results of an international multicentre study
Authors: Hernan Mejia-Renteria, Francesco Lauri, Joo Myung Lee, Nina van der Hoeven, Guus de Waard, Alfonso de Hoyos, Fernando Macaya, Nicola Ryan, Nieves Gonzalo, Pilar Jimenez-Quevedo, Luis Nombela Franco, Ivan Nuñez-Gil, Pablo Salinas, Maria Del Trigo, Maria Perez-Vizcayno, Antonio Fernandez-Ortiz, Carlos Macaya, Bon-Kwon Koo, Niels van Royen, Javier Escaned
Journal: Journal of the American College of Cardiology (2017)
TCT-705 The Prognostic Value of Residual Coronary Stenosis After “Functionally” Complete Revascularization in Acute Coronary Syndrome: Insights from the DANAMI-3-PRIMULTI, FAME, and FAMOUS-NSTEMI
Authors: Yuhei Kobayashi, Jacob Lonborg, Andy Jong, Takeshi Nishi, Bernard De Bruyne, Dan Eik Høfsten, Henning Kelbæk, Jamie Layland, Chang-Wook Nam, Nico Pijls, Pim Tonino, Julie Warnøe, Keith Oldroyd, Colin Berry, Thomas Engstroem, William Fearon
Journal: Journal of the American College of Cardiology (2017)
Les infections à méningocoque en Ecosse, 1995 à 1997
Authors: S. J. O’Brien, L. E. Smart
Journal: Eurosurveillance (1997)

En Ecosse, l'incidence des infections a meningocoque est passee de 3,8 cas pour 100 000 personnes en 1995 a 4,1/100 000 en 1996 (193 cas rapportes en 1995 contre 210 en 1996). En 1996, le taux brut de letalite etait de 6,7% avec 14 deces, taux pratiquement identique a celui de 1995. Le taux de letalite associe a une septicemie a meningocoque etait au moins deux fois plus eleve que celui associe a la meningite a meningocoque seule (1).
Updated survival outcomes of NEJ005/TCOG0902, a randomized PII of gefitinib and chemotherapy in EGFR-mutant NSCLC
Authors: Eisaku Miyauchi, Satoshi Oizumi, Koichi Minato, Shunichi Sugawara, Toshiyuki Harada, Yuka Fujita, Makoto Maemondo, Satoshi Watanabe, Minoru Kurihara, Toshihiro Nukiwa
Journal: Annals of Oncology (2017)
Transmission inter-humaine du virus A/H7N7 de la grippe aviaire, Pays-Bas, 2003
Authors: M Du Ry van Beest Holle, A Meijer, M Koopmans, C M de Jager
Journal: Eurosurveillance (2005)

Une epidemie de virus de grippe aviaire hautement pathogene de type A de sous-type H7N7 s’est declaree dans un elevage de volailles aux Pays-Bas en 2003. L’infection par ce virus a ete detectee par RT-PCR (reverse transcriptase-polymerase chain reaction) chez 86 personnes travaillant dans cette ferme et chez trois membres de leur famille. La plupart des infections etait associee a une conjonctivite. Afin de determiner l’amplitude et les facteurs de risque d’une transmission inter-humaine de grippe A/H7N7 aux Pays-Bas, une etude de cohorte retrospective a ete menee dans les familles des travailleurs de l’elevage infectes par le virus. Au total, 33 (58,9%) des 56 (parmi les 62) participants ayant accepte d’avoir un prelevement sanguin presentaient une serologie positive pour le virus H7. Les tests ont ete realises sur un seul prelevement obtenu au moins 3 semaines apres l’apparition des premiers symptomes chez le cas index. Sur les huit membres de ces familles (12.9%) ayant rapporte des symptomes (conjonctivite et/ou syndrome grippal), 4 (80%) des 5 ayant eu un prelevement sanguin etaient seropositifs. L’analyse univariee a permis de mettre en evidence, parmi les facteurs de risques significatifs d’une seropositivite, le fait d’avoir au moins deux toilettes, d’avoir un oiseau a domicile, et d’utiliser des mouchoirs en tissu. Il n’a pas ete possible d’obtenir un modele stable de regression binomiale pour etudier l’infection par A/H7N7. Des etudes de seroprevalence chez les personnes en contact avec des cas asymptomatiques positifs pour H7 devraient etre menees.
Triple Therapy for Atrial Fibrillation after PCI
Authors: Jonathan P. Piccini, W. Schuyler Jones
Journal: New England Journal of Medicine (2017)

The management of atrial fibrillation in patients who have undergone percutaneous coronary intervention (PCI) for the treatment of coronary-artery disease is a common and difficult challenge. In patients with atrial fibrillation, oral anticoagulation is administered to reduce the risk of stroke. In patients who have undergone PCI, dual antiplatelet therapy is administered to prevent major adverse cardiovascular events and stent thrombosis. The use of triple therapy is common in clinical practice; one in four older patients with atrial fibrillation who have had an acute myocardial infarction receives triple therapy.1 Although triple therapy may minimize the risk of stent thrombosis and . . .
Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer
Authors: Eric J. Chow, Yan Chen, Melissa M. Hudson, Elizabeth A.M. Feijen, Leontien C. Kremer, William L. Border, Daniel M. Green, Lillian R. Meacham, Daniel A. Mulrooney, Kirsten K. Ness, Kevin C. Oeffinger, Cécile M. Ronckers, Charles A. Sklar, Marilyn Stovall, Helena J. van der Pal, Irma W.E.M. van Dijk, Flora E. van Leeuwen, Rita E. Weathers, Leslie L. Robison, Gregory T. Armstrong, Yutaka Yasui
Journal: Journal of Clinical Oncology (2017)

Purpose We aimed to predict individual risk of ischemic heart disease and stroke in 5-year survivors of childhood cancer. Patients and Methods Participants in the Childhood Cancer Survivor Study (CCSS; n = 13,060) were observed through age 50 years for the development of ischemic heart disease and stroke. Siblings (n = 4,023) established the baseline population risk. Piecewise exponential models with backward selection estimated the relationships between potential predictors and each outcome. The St Jude Lifetime Cohort Study (n = 1,842) and the Emma Children’s Hospital cohort (n = 1,362) were used to validate the CCSS models. Results Ischemic heart disease and stroke occurred in 265 and 295 CCSS participants, respectively. Risk scores based on a standard prediction model that included sex, chemotherapy, and radiotherapy (cranial, neck, and chest) exposures achieved an area under the curve and concordance statistic of 0.70 and 0.70 for ischemic heart disease and 0.63 and 0.66 for stroke, respectively. Validation cohort area under the curve and concordance statistics ranged from 0.66 to 0.67 for ischemic heart disease and 0.68 to 0.72 for stroke. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups. The cumulative incidences at age 50 years among CCSS low-risk groups were &lt; 5%, compared with approximately 20% for high-risk groups ( P &lt; .001); cumulative incidence was only 1% for siblings ( P &lt; .001 v low-risk survivors). Conclusion Information available to clinicians soon after completion of childhood cancer therapy can predict individual risk for subsequent ischemic heart disease and stroke with reasonable accuracy and discrimination through age 50 years. These models provide a framework on which to base future screening strategies and interventions.
Photoactive Poly(3-hexylthiophene) Nanoweb for Optoelectrical Stimulation to Enhance Neurogenesis of Human Stem Cells
Authors: Kisuk Yang, Jin Young Oh, Jong Seung Lee, Yoonhee Jin, Gyeong-Eon Chang, Soo Sang Chae, Eunji Cheong, Hong Koo Baik, Seung-Woo Cho
Journal: Theranostics (2017)

Optoelectrical manipulation has recently gained attention for cellular engineering; however, few material platforms can be used to efficiently regulate stem cell behaviors via optoelectrical stimulation.In this study, we developed nanoweb substrates composed of photoactive polymer poly(3-hexylthiophene) (P3HT) to enhance the neurogenesis of human fetal neural stem cells (hfNSCs) through photo-induced electrical stimulation.Methods: The photoactive nanoweb substrates were fabricated by self-assembled one-dimensional (1D) P3HT nanostructures (nanofibrils and nanorods).The hfNSCs cultured on the P3HT nanoweb substrates were optically stimulated with a green light (539 nm) and then differentiation of hfNSCs on the substrates with light stimulation was examined.The utility of the nanoweb substrates for optogenetic application was tested with photo-responsive hfNSCs engineered by polymer nanoparticle-mediated transfection of an engineered chimeric opsin variant (C1V1)-encoding gene.Results: The nanoweb substrates provided not only topographical stimulation for activating focal adhesion signaling of hfNSCs, but also generated optoelectrical stimulation via photochemical and charge-transfer reactions upon exposure to 539 nm wavelength light, leading to significantly enhanced neuronal differentiation of hfNSCs.The optoelectrically stimulated hfNSCs exhibited mature neuronal phenotypes with highly extended neurite formation and functional neuron-like electrophysiological features of sodium currents and action potentials.Optoelectrical stimulation with 539 nm light simultaneously activated both C1V1-modified hfNSCs and nanoweb substrates, which upregulated the expression and activation of voltage-gated ion channels in hfNSCs and further increased the effect of photoactive substrates on neuronal differentiation of hfNSCs.Conclusion: The photoactive nanoweb substrates developed in this study may serve as platforms for producing stem cell therapeutics with enhanced neurogenesis and neuromodulation via optoelectrical control of stem cells.
Friday Music With Paul
Authors: Victoria M. Leavitt, Paul A. Tunick
Journal: JAMA Neurology (2017)

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Abstract 11395: Enhanced External Counter Pulsation Improves Lipid Abnormalities in Patients With Chronic Ischemic Heart Disease
Authors: Sanjay Mittal, Vivek Jain, Manish Bansal, Jyotsana Kapoor, Ravi R Kasliwal, Naresh Trehan
Journal: Circulation (2016)

Introduction: Enhanced external counter pulsation (EECP) is effective in improving anginal symptoms in patients with ischemic heart disease (IHD); however its effect on the lipid profile has not yet been reported. Hypothesis: Exercise like peripheral muscle training effect of EECP could improve lipid profile. Methods: Two hundred and twenty nine consecutive patients, age 61.2+/-9.5 years, 207 (90.3%) males, left ventricular ejection fraction 35.5+/-11.7%, referred for EECP therapy between 2013 and 2016 were included in the study. All patients had symptomatic IHD and were on anti-ischemic and statin therapy. Patients were subjected to 35 EECP sessions of one hour each. All patients were subjected to a thorough clinical evaluation and a 12 hour fasting lipid profile estimation at the baseline and after completion of 35 sessions of EECP therapy. Concomitant medical therapy, including statins, remained unaltered during the course of EECP. Results: Significant improvement was noted in functional class, 6 minute hall walk test and activity scale after EECP therapy. Lipid abnormalities were common in these patients at baseline with 104 (45.4%) subjects having low density lipoprotein cholesterol (LDLC) &gt; 70 mg/dl, 128 (55.8%) having high density lipoprotein cholesterol (HDLC) &lt;35mg/dl and 79 (34.5%) having triglycerides &gt;140mg/dl. EECP resulted in significant improvement in lipid parameters in these patients- LDLC decreased by 18.5% (from 95.1+/-26.7 to 77.5+/-24.3 mg/dl, P value &lt;0.0001), triglycerides decreased by 18.9% (from 198.3+/-76.4 to 160.8+/-56.6 mg/dl, , P value &lt;0.0001) and HDLC increased by 14.2% (from 28.1+/-5.2 to 32.1+/-9.1 mg/dl, P value &lt;0.0001). The subgroups with worse baseline lipid levels showed larger improvement- patients having baseline LDLC &gt;100mg/dl showed 29.6% reduction in LDLC and those with HDLC &lt;25mg/dl showed 41.3% increase in HDLC after EECP therapy. Conclusions: Patients with IHD having abnormal baseline lipid levels despite statin therapy show significant improvement in LDLC, triglyceride and HDLC levels after EECP therapy. This improvement is likely to be due to the exercise like peripheral muscle training effect of EECP and needs further evaluation.
MicroRNA‐21 and Dicer are dispensable for hepatic stellate cell activation and the development of liver fibrosis
Authors: Jorge Matias Caviglia, Jun Yan, Myoung‐Kuk Jang, Geum‐Youn Gwak, Silvia Affo, Lexing Yu, Peter Olinga, Richard A. Friedman, Xin Chen, Robert F. Schwabe
Journal: Hepatology (2017)

Fibrosis and cancer represent two major complications of chronic liver disease. MicroRNAs have been implicated in the development of fibrosis and cancer, thus constituting potential therapeutic targets. Here, we investigated the role of microRNA‐21 (miR‐21), a microRNA that has been implicated in the development of fibrosis in multiple organs and has also been suggested to act as an “oncomir.” Accordingly, miR‐21 was the microRNA that showed the strongest up‐regulation in activated hepatic stellate cells (HSCs) in multiple models of fibrogenesis, with an 8‐fold to 24‐fold induction compared to quiescent HSCs. However, miR‐21 antisense inhibition did not suppress the activation of murine or human HSCs in culture or in liver slices. Moreover, genetic deletion of miR‐21 in two independently generated knockout mice or miR‐21 antisense inhibition did not alter HSC activation or liver fibrosis in models of toxic and biliary liver injury. Despite a strong up‐regulation of miR‐21 in injury‐associated hepatocellular carcinoma and in cholangiocarcinoma, miR‐21 deletion or antisense inhibition did not reduce the development of liver tumors. As inhibition of the most up‐regulated microRNA did not affect HSC activation, liver fibrosis, or fibrosis‐associated liver cancer, we additionally tested the role of microRNAs in HSCs by HSC‐specific Dicer deletion. Although Dicer deletion decreased microRNA expression in HSCs and altered the expression of select genes, it only exerted negligible effects on HSC activation and liver fibrosis. Conclusion : Genetic and pharmacologic manipulation of miR‐21 does not inhibit the development of liver fibrosis and liver cancer. Moreover, suppression of microRNA synthesis does not significantly affect HSC phenotype and activation. (H epatology 2018;67:2414‐2429).