tbuckley/cabot-search huggingface dataset:
Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-κB signaling
Authors: M Hahn, J-P Bürckert, C A Luttenberger, S Klebow, M Hess, M Al-Maarri, M Vogt, S Reißig, M Hallek, A Wienecke-Baldacchino, T Buch, C P Muller, C P Pallasch, F T Wunderlich, A Waisman, N Hövelmeyer
Journal: Leukemia (2017)
Evaluating the Cardiovascular Safety of Nonsteroidal Anti-Inflammatory Drugs
Authors: Elliott M. Antman
Journal: Circulation (2017)

Some drugs used to treat noncardiovascular conditions may adversely impact the cardiovascular status of individuals both with and without known cardiovascular disease. When the US Food and Drug Administration judges the potential cardiovascular safety signal to be of sufficient concern, it may require the pharmaceutical manufacturer of the drug in question to conduct a postmarketing (phase 4) randomized controlled trial (RCT). Although historically many phase 4 RCTs focused on efficacy (using a superiority design), contemporary phase 4 RCTs often are focused on safety and use a noninferiority design. The choices made by investigators during the planning stage of a postmarketing phase 4 RCT dedicated to the evaluation of cardiovascular safety can influence the ability to compare the standard and test agents. Multiple factors reflecting the conduct of a phase 4 RCT for a general medical condition may influence interpretation of a cardiovascular safety signal. The higher the rates of failure to adhere to the protocol and dropout from the study, the greater the risk of bias. Trials evaluating the cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs) when used for arthritis are difficult to conduct and even more challenging to interpret. Concerns include the comparison of drug regimens that do not provide comparable analgesic efficacy and problems with adherence to the protocol and retention in the study. On the basis of phase 4 RCTs of NSAIDs to date, it appears that a comparatively low dose of celecoxib administered to low-risk subjects is associated with approximately the same cardiovascular risk as NSAIDs with less cyclooxygenase-2 inhibitory activity, but at the cost of not controlling arthritic pain as effectively.
Incorporating catechol into electroactive polypyrrole nanowires on titanium to promote hydroxyapatite formation
Authors: Zhengao Wang, Jinquan Zeng, Guoxin Tan, Jingwen Liao, Lei Zhou, Junqi Chen, Peng Yu, Qiyou Wang, Chengyun Ning
Journal: Bioactive Materials (2017)

To improve the osteointegration property of biomedical titanium, nano-architectured electroactive coating was synthesized through the electrochemical polymerization of dopamine and pyrrole. The highly binding affinity of Ca2+ to the catechol moiety of doped dopamine enabled efficient interaction between polypyrrole/polydopamine nanowires and mineral ions. The results indicate that the PPy/PDA nanowires preserved its efficient electro-activity and accelerated the hydroxyapatite deposition in a simulated body fluid. The PPy/PDA nanowires coating could be applied to promote the osteointegration of titanium implant.
Progressive Decline in Late Mortality after Hematopoietic Cell Transplantation (HCT) over 40 Years - a Report from BMTSS
Authors: Liton F. Francisco, Saro Armenian, Mukta Arora, Yanjun Chen, Jessica Wu, James A. Watson, Lindsey Hageman, Emily C. Ness, Mariel Parman, Kevin D. Battles, Can-Lan Sun, Ravi Bhatia, Daniel J. Weisdorf, Stephen J. Forman, Smita Bhatia
Journal: Blood (2016)
Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia
Authors: M Mingay, A Chaturvedi, M Bilenky, Q Cao, L Jackson, T Hui, M Moksa, A Heravi-Moussavi, R K Humphries, M Heuser, M Hirst
Journal: Leukemia (2017)

The genomes of myeloid malignancies are characterized by epigenomic abnormalities. Heterozygous, inactivating ten-eleven translocation 2 (TET2) mutations and neomorphic isocitrate dehydrogenase (IDH) mutations are recurrent and mutually exclusive in acute myeloid leukaemia genomes. Ascorbic acid (vitamin C) has been shown to stimulate the catalytic activity of TET2 in vitro and thus we sought to explore its effect in a leukaemic model expressing IDH1R132H. Vitamin C treatment induced an IDH1R132H-dependent reduction in cell proliferation and an increase in expression of genes involved in leukocyte differentiation. Vitamin C induced differentially methylated regions that displayed a significant overlap with enhancers implicated in myeloid differentiation and were enriched in sequence elements for the haematopoietic transcription factors CEBPβ, HIF1α, RUNX1 and PU.1. Chromatin immunoprecipitation sequencing of PU.1 and RUNX1 revealed a significant loss of PU.1 and increase of RUNX1-bound DNA elements accompanied by their demethylation following vitamin C treatment. In addition, vitamin C induced an increase in H3K27ac flanking sites bound by RUNX1. On the basis of these data we propose a model of vitamin C-induced epigenetic remodelling of transcription factor-binding sites driving differentiation in a leukaemic model.
Systolic Blood Pressure Reduction and Risk of Cardiovascular Disease and Mortality
Authors: Joshua D. Bundy, Changwei Li, Patrick Stuchlik, Xiaoqing Bu, Tanika N. Kelly, Katherine T. Mills, Hua He, Jing Chen, Paul K. Whelton, Jiang He
Journal: JAMA Cardiology (2017)

Clinical trials have documented that lowering blood pressure reduces cardiovascular disease and premature deaths. However, the optimal target for reduction of systolic blood pressure (SBP) is uncertain.To assess the association of mean achieved SBP levels with the risk of cardiovascular disease and all-cause mortality in adults with hypertension treated with antihypertensive therapy.MEDLINE and EMBASE were searched from inception to December 15, 2015, supplemented by manual searches of the bibliographies of retrieved articles.Studies included were clinical trials with random allocation to an antihypertensive medication, control, or treatment target. Studies had to have reported a difference in mean achieved SBP of 5 mm Hg or more between comparison groups.Data were extracted from each study independently and in duplicate by at least 2 investigators according to a standardized protocol. Network meta-analysis was used to obtain pooled randomized results comparing the association of each 5-mm Hg SBP category with clinical outcomes after adjusting for baseline risk.Cardiovascular disease and all-cause mortality.Forty-two trials, including 144 220 patients, met the eligibility criteria. In general, there were linear associations between mean achieved SBP and risk of cardiovascular disease and mortality, with the lowest risk at 120 to 124 mm Hg. Randomized groups with a mean achieved SBP of 120 to 124 mm Hg had a hazard ratio (HR) for major cardiovascular disease of 0.71 (95% CI, 0.60-0.83) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.58 (95% CI, 0.48-0.72) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.46 (95% CI, 0.34-0.63) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.36 (95% CI, 0.26-0.51) compared with those with a mean achieved SBP of 160 mm Hg or more. Likewise, randomized groups with a mean achieved SBP of 120 to 124 mm Hg had an HR for all-cause mortality of 0.73 (95% CI, 0.58-0.93) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.59 (95% CI, 0.45-0.77) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.51 (95% CI, 0.36-0.71) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.47 (95% CI, 0.32-0.67) compared with those with a mean achieved SBP of 160 mm Hg or more.This study suggests that reducing SBP to levels below currently recommended targets significantly reduces the risk of cardiovascular disease and all-cause mortality. These findings support more intensive control of SBP among adults with hypertension.
TMOD-08. INVESTIGATING PEDIATRIC GBM USING IN VIVO SOMATIC MOUSE MOSAICS WITH LOCUS-SPECIFIC, STABLY-INTEGRATED TRANSGENIC ELEMENTS
Authors: Gi Bum Kim, Marina Dutra-Clarke, Rachelle Levy, Hannah Park, Sara Sabet, Jessica Molina, Aslam Abbasi Akhtar, Moise Danielpour, Joshua Breunig
Journal: Neuro-Oncology (2017)

Viral vectors and electroporation (EP)-mediated gene transfers are efficient means of inducing somatic mosaicism in mice, but they lack the exquisite control over transgene copy number, gene zygosity, and genomic-locus speci-ficity that genetically engineered mouse models (GEMMs) provide. Here, we develop and demonstrate a simple and generalizable in vivo method, mosaic analysis by dual recombinase-mediated cassette exchange (MADR). MADR allows for stable labeling of mutant cells express transgenic elements from a precisely-defined chromosomal locus. To test our method, we generated reporter-labeled lineages from stem and progenitor cells in a well-defined Rosa26mTmG mouse. We demonstrate the power and versatility of MADR by creating novel glioma models with mixed, reporter-defined zygosity or with "personalized," H3.3-containing driver mutation signatures from pediatric glioma-each manipulation altering the profile of resulting tumors. Thus, MADR provides a high-throughput genetic platform for the dissection of development and disease, and this rapid method can be applied to the thousands of existing gene-trap mice.
PDTM-14. THE DISTRIBUTION, CLEARANCE AND TOXICITY OF PANOBINOSTAT ADMINISTERED TO JUVENILE RAT AND PIG BRAINSTEM BY CONVECTION ENHANCED DELIVERY
Authors: Will Singleton, Alison Bienemann, Max Woolley, David Johnson, Owen Lewis, Marcella Wyatt, Steve Damment, Lisa Boulter, Clare Killick-Cole, Daniel Asby, Steven Gill
Journal: Neuro-Oncology (2017)

The pan-histone deacetylase inhibitor panobinostat has preclinical efficacy against DIPG and the oral formulation has entered a phase one clinical trial. However, panobinostat does not cross the blood brain barrier in humans. Convection enhanced delivery (CED) is a novel neurosurgical drug delivery technique that bypasses the blood brain barrier and is of considerable clinical interest in DIPG. We investigated the toxicity, distribution and clearance of a water-soluble formulation of panobinostat in small and large animal models of CED. 30 juvenile male Wistar rats received panobinostat administered to the pons by CED at increasing concentration and were compared to animals that received vehicle alone. Clinical observation continued for two weeks. Animals were sacrificed at 72 hours or two weeks following treatment and the brains were subjected to neuropathological analysis. A further 6 animals received panobinostat by CED to the striatum and were sacrificed zero, two or six hours after infusion, their brains explanted and snap-frozen. Brainstem drug concentration was determined by LC-MS/MS. Large animal toxicity was investigated using a clinically relevant MRI guided translational porcine model of CED using a drug delivery system designed for human use. 30 μM panobinostat was administered to the ventral pons of two juvenile Large White/Landrace-cross pigs and subject to clinical and neuropathological analysis compared to control after one or two weeks. Drug distribution was determined by LC-MS/MS in porcine white and gray matter immediately after CED. There were no clinical or neuropathological signs of toxicity up to an infused concentration of 30 μM in both small and large animal models. The half-life of panobinostat in rat brain after CED was 3 hours and the drug was observed to distribute in porcine white and gray matter with a volume infusion/distribution ratio of two and three respectively. CED of water-soluble panobinostat warrants investigation in children with DIPG.
Consciousness as Sequential Dynamics, Robustness, and Mental Disorders
Authors: Mikhail I. Rabinovich, Pablo Varona
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Selective Targeting Cyclin-Dependent Kinase-9 (CDK9) Downmodulates c-MYC and Induces Apoptosis in Diffuse Large B-Cell Lymphoma (DLBCL) Cells
Authors: Taylor Rowland, Cody Paiva, Joelle Rowley, Andy Chen, Lisa Drew, Peter Hurlin, Bill H. Chang, Alexey V Danilov
Journal: Blood (2016)
American College of Cardiology/American Heart Association Clinical Competence Statement on Invasive Electrophysiology Studies, Catheter Ablation, and Cardioversion
Authors: Cynthia M. Tracy, Masood Akhtar, John P. DiMarco, Douglas L. Packer, Howard H. Weitz, William L. Winters, James L. Achord, Alan W. Boone, John W. Hirshfeld, Beverly H. Lorell, George P. Rodgers, Cynthia M. Tracy, Howard H. Weitz
Journal: Circulation (2000)
Prothèse métallique auto-expansible couverte d’apposition pour sténose bénigne courte: une étude multicentrique
Journal: Endoscopy (2017)

Le traitement endoscopique des sténoses bénignes est un problème difficile et courant. La technique de référence est la dilatation itérative, mais les résultats sont décevants dans certaines indications. C’est pourquoi plusieurs essais de traitement par stents entièrement couverts extirpables (FCSEMS) ont vu le jour, eux aussi avec des résultats rédhibitoires dû à un fort taux de migration. D’autre part un nouveau type de stent d’apposition est commercialisé pour les drainages de pseudokystes et d’abcès: les prothèses dites d’apposition “Lumen-apposing covered expandable metal stents (LAMS)”.
Stratification of Allogeneic Hematopoietic Cell Transplant By Risk of Developing Veno-Occlusive Disease: A Model for Assigning a Risk Score
Authors: Christopher Strouse, Ying Zhang, Mei-Jie Zhang, Alyssa DiGilio, Marcelo C. Pasquini, Mary M. Horowitz, Stephanie J. Lee, Muthalagu Ramanathan, Wichai Chinratanalab, Alison W Loren, Linda J. Burns, Andrew Artz, Kathleen F. Villa, Wael Saber
Journal: Blood (2016)
Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017
Authors: Wenfei Zhu, Jianfang Zhou, Zi Li, Lei Yang, Xiyan Li, Weijuan Huang, Sumei Zou, Wenbing Chen, Hejiang Wei, Jing Tang, Liqi Liu, Jie Dong, Dayan Wang, Yuelong Shu
Journal: Eurosurveillance (2017)

With no or low virulence in poultry, avian influenza A(H7N9) virus has caused severe infections in humans. In the current fifth epidemic wave, a highly pathogenic avian influenza (HPAI) H7N9 virus emerged. The insertion of four amino acids (KRTA) at the haemagglutinin (HA) cleavage site enabled trypsin-independent infectivity of this virus. Although maintaining dual receptor-binding preference, its HA antigenicity was distinct from low-pathogenic avian influenza A(H7N9). The neuraminidase substitution R292K conferred a multidrug resistance phenotype.
SOX11 promotes tumor protective microenvironment interactions through CXCR4 and FAK regulation in mantle cell lymphoma
Authors: Patricia Balsas, Jara Palomero, Álvaro Eguileor, Marta Leonor Rodríguez, Maria Carmela Vegliante, Ester Planas-Rigol, Marta Sureda-Gómez, Maria C. Cid, Elias Campo, Virginia Amador
Journal: Blood (2017)
MEDU-37. CHOLESTEROL BIOSYNTHESIS REPRESENTS A NOVEL THERAPEUTIC TARGET FOR THE SONIC HEDGEHOG TYPE OF MEDULLOBLASTOMA
Authors: Renata Gordon, Zeng-Jie Yang
Journal: Neuro-Oncology (2017)

Aberrant activation of Sonic hedgehog (Shh) signaling leads to formation of numerous malignancies, including the most common pediatric brain tumor - medulloblastoma (MB). Despite recent advances in MB treatment, a significant proportion of patients still succumb to this disease. MB survivors often suffer from severe, long-lasting effects of therapy, including cognitive and endocrine disorders, as well as increased incidence of secondary tumors. Therefore, targeted therapies for MB treatment are urgently needed. Proposed strategies are aimed at blockade of Shh signaling through inhibition of its effector transmembrane protein, Smoothened (Smo). This approach is problematic as the high doses required for tumor regression are toxic and cause developmental disorders and drug resistance. Cholesterol plays a pivotal role in Shh signaling. We observed an enhanced expression pattern of cholesterol synthesis genes in Shh-driven MB. Here, we demonstrate that tumor cell-derived cholesterol is required for Shh-driven MB tumorigenesis in vivo. Additionally, ablation of Shh signaling by cholesterol depletion, both genetically and via cholesterol synthesis inhibitors, results in dramatic inhibition of tumor cell proliferation and allograft growth. Because cholesterol and traditional Smo antagonists interact with distinct sites on the Smo protein, we proposed that altering both mechanisms of Shh pathway activation could synergize to result in further tumor reduction. Excitingly, we found that combination therapy with cholesterol inhibitor simvastatin and a low dose of Smo antagonist vismodegib in an allograft model of MB results in a synergistic effect, decreasing MB tumor burden. This strategy offers a promising new avenue of therapy for this population of pediatric patients and offers further implications for other Shh-dependent malignancies.
Toward true integration
Authors: Joana Rosselló, Otávio Mattos, Wolfram Hinzen
Journal: Behavioral and Brain Sciences (2017)

Abstract Whether in sign or speech, language is more integrative than the target article suggests. A more integrative view embraces not only sign/speech and co-sign/speech gesture, but also indicative gestures irrespective of modality, and locations along with movements in the signed modality, as suggested by both linguistic acquisition and pathologies. An extended integrative view also proves advantageous in terms of conceptual coherence.
Suppressing mosaicism by Au nanowire injector-driven direct delivery of plasmids into mouse embryos
Authors: Kkotchorong Park, Keun Cheon Kim, Hyoban Lee, Yoori Sung, Mijeong Kang, Yun Mi Lee, Ji Yeon Ahn, Jeong Mook Lim, Taejoon Kang, Bongsoo Kim, Eun Ju Lee
Journal: Biomaterials (2017)
Physiologically Based Pharmacokinetic and Pharmacodynamic Analysis Enabled by Microfluidically Linked Organs-on-Chips
Authors: Rachelle Prantil-Baun, Richard Novak, Debarun Das, Mahadevabharath R. Somayaji, Andrzej Przekwas, Donald E. Ingber
Journal: The Annual Review of Pharmacology and Toxicology (2018)

Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches are beginning to be integrated into drug development and approval processes because they enable key pharmacokinetic (PK) parameters to be predicted from in vitro data. However, these approaches are hampered by many limitations, including an inability to incorporate organ-specific differentials in drug clearance, distribution, and absorption that result from differences in cell uptake, transport, and metabolism. Moreover, such approaches are generally unable to provide insight into pharmacodynamic (PD) parameters. Recent development of microfluidic Organ-on-a-Chip (Organ Chip) cell culture devices that recapitulate tissue-tissue interfaces, vascular perfusion, and organ-level functionality offer the ability to overcome these limitations when multiple Organ Chips are linked via their endothelium-lined vascular channels. Here, we discuss successes and challenges in the use of existing culture models and vascularized Organ Chips for PBPK and PD modeling of human drug responses, as well as in vitro to in vivo extrapolation (IVIVE) of these results, and how these approaches might advance drug development and regulatory review processes in the future.
The metabolic regulator mTORC1 controls terminal myeloid differentiation
Authors: Pui Y. Lee, David B. Sykes, Sarah Ameri, Demetrios Kalaitzidis, Julia F. Charles, Nathan Nelson-Maney, Kevin Wei, Pierre Cunin, Allyn Morris, Astrid E. Cardona, David E. Root, David T. Scadden, Peter A. Nigrovic
Journal: Science Immunology (2017)

The mTORC1-S6K1 pathway controls terminal differentiation of myeloid progenitors through regulation of Myc.
Cell of Origin By Immunohistochemistry Is Not Prognostic of Overall Survival in HIV Associated DLBCL- Analysis of Clinical Pathological Markers in HIV DLBCL
Authors: Amara Gayathri Nandikolla, Yanhua Wang, Urvi A Shah, Olga Derman, Noah Kornblum, Ioannis Mantzaris, Aditi Shastri, Khan Hina, Kim Nina, Mike Grant, Ira Braunschweig, B. Hilda Ye, Amit Verma, Murali Janakiram
Journal: Blood (2016)
&lt;xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en"&gt;Travel-associated gonorrhoea in four Nordic countries, 2008&amp;#160;to&amp;#160;2013&lt;/xhtml:span&gt;
Authors: Julien Beauté, Susan Cowan, Eija Hiltunen-Back, Hilde Kløvstad, Inga Velicko, Gianfranco Spiteri
Journal: Eurosurveillance (2017)

Travel may be associated with a higher risk of gonorrhoea and infection by antibiotic-resistant strains. The objective of this study was to estimate the risk for gonorrhoea among travellers from four Nordic European countries using surveillance data and to identify at-risk travellers to help target interventions. We retrieved gonorrhoea surveillance data from Denmark, Finland, Norway and Sweden and tourism denominator data from the Statistical Office of the European Union. A travel-associated case of gonorrhoea was defined as one for which the reported country of infection differed from the reporting country. During 2008−2013, the four countries reported 3,224 travel-associated gonorrhoea cases, of which 53% were among individuals below 35 years of age. The overall risk associated with travel abroad was 2.4 cases per million nights abroad. The highest risk was observed with travel to Asia (9.4). Cases more likely to be reported as travel-associated were: males, heterosexuals of both sexes, people older than 65 years, and foreign-born individuals. More effective interventions targeting young adults and other at-risk groups are needed. The use of travel-planning websites and social media should be explored further.