tbuckley/cabot-search huggingface dataset:
Phase I study of pazopanib in children with relapsed or refractory solid tumors (ADVL0815): A Children’s Oncology Group Phase I Consortium Trial.
Authors: J. L. Glade Bender, A. Lee, P. C. Adamson, A. M. Ingle, C. H. Ahern, B. Wu, S. Baruchel, P. J. Harris, M. M. Ames, B. Weigel, S. Blaney
Journal: Journal of Clinical Oncology (2011)

9501 Background: Pazopanib, an orally available potent and selective small molecule tyrosine kinase inhibitor, targets VEGFR 1-3, PDGFR α/β, and c-kit. A phase I trial to determine the toxicities, maximum tolerated dose (MTD), pharmacokinetics (PK) and pharmacodynamics of pazopanib in children with refractory solid tumors (including CNS) was performed. Methods: Oral pazopanib (tablet formulation) was administered once daily in 28 day cycles, for up to 24 cycles. Cohorts were enrolled at 4 dose levels (275 to 600 mg/m2) using the rolling-six design. Dose determination for subsequent cohorts was based on cycle 1 toxicity (CTC v3) in the prior cohort. Results: 27 subjects were enrolled; 25 were eligible and 23 were evaluable for dose-limiting toxicity (DLT) [13 male, median age 13 yrs (range, 4-21)]. Subjects received a median of 3 cycles (range 1-13). Observed cycle 1 DLTs included: Gr3 lipase elevation (n=1, 275 mg/m2), Gr3 proteinuria and Gr3 hypertension (n=1, 450 mg/m2), Gr3 amylase elevation (n=1, 600 mg/m2) and Gr3 hypertension (n=1, 600 mg/m2). Thus, the MTD was 450 mg/m2. Cycle 1 non-hematologic toxicities observed in >10% of patients included Gr2 hypertension (n=6), left ventricular dysfunction (n=1), fatigue (n=3), rash (n=2), hypothyroidism (n=1), diarrhea (n=1), nausea (n=1) vomiting (n=2), amylase (n=1), lipase (n=2), proteinuria (n=1), abdominal pain (n=2) and headache (n=5); and reversible Gr3 hypophosphatemia (n=1). Prolonged QTc was not observed. Later adverse events requiring treatment discontinuation included: intolerable Gr2 diarrhea; Gr3 myalgia associated with Gr3 microangiopathic hemolytic anemia; Gr3 hand foot syndrome; and recurrent Gr3 neutropenia (each, n=1). PK data will be presented. One subject with hepatoblastoma had a PR by cycle 6, but was removed for neutropenia after cycle 12 (now receiving via compassionate use), and 4 pts had SD > 6 cycles (3 remain on therapy). Plasma VEGF (p=0.006) and PlGF (p<0.001) increased, whereas endoglin (p=0.005) and soluble VEGFR2 (p<0.001) decreased from baseline to d15 (n=22). Conclusions: The MTD of pazopanib in children with solid tumors is 450 mg/m2with toxicities similar to other VEGF blocking agents.
Abstract P046: Hsp20 Promotes Cardiac Autophagy via Interaction with Beclin-1
Authors: Hongyan Zhu, Xiaohong Wang, Xiaowei Zhang, Evangelia G Kranias, Qiangrong Liang, Guo-Chang Fan
Journal: Circulation Research (2011)

Hsp20 has been shown to prevent stress-triggered cardiac injury. However, it remains obscure whether Hsp20-elicited cardioprotection is associated with the activation of autophagy. We first assessed cardiac autophagy in a transgenic (TG) mouse model with 10-fold overexpression of Hsp20 by immunoblotting. Levels of two autophagy markers (LC3II and Beclin1) were increased by 1.6- and 2.2-fold, respectively, in Hsp20-hearts, compared to WTs. To examine whether Hsp20 activates autophagic flux in the heart, mice were i.p. injected with chloroquine (CQ, 50mg/kg), an inhibitor for autophagosome-lysosome fusion, for 4h. Cadaverine dye-binding analysis showed that autophagy levels were increased by 1.5-fold in CQ-treated Hsp20-hearts compared to saline controls. To examine whether increased autophagy levels contribute to Hsp20-induced cardioprotection, 3-methyladenine (3-MA, an inhibitor for autophgy) was i.p . injected into TG mice (30mg/kg). One hour later, hearts were subjected to global no-flow ischemia/reperfusion (I/R: 45min/1h), and showed that contractile function (+dP/dt) was recovered by 93α 5 % in saline-treated Hsp20-hearts, comparable to 74 α 6 % recovery in 3-MA-treated TGs (n=6, p&lt;0.05), indicating that the activation of autophagy by Hsp20 is beneficial for hearts upon I/R. To exclude in vivo compensatory effects, Hsp20 was delivered into isolated adult cardiomyocytes by adenoviral vector. Western-blotting analysis indicated that acute expression of Hsp20 increased the levels of LC3II and Beclin1 by ∼2-fold, compared to GFP control. Accordingly, overexpression of Hsp20 augmented myocyte survival upon addition of H 2 O 2 , as related to GFP-control. Furthermore, co-infection with AdBeclin1-siRNA attenuated the protective effects of Hsp20 in myocytes upon H 2 O 2 stress. Excitingly, Hsp20 was found to localize at the LC3-labeled autophagosome. Indeed, co-immunoprecipitation results showed an interaction of Hsp20 with Beclin-1 in the heart. Moreover, a competitive ELISA assay revealed that Hsp20 dose-dependently suppressed the interaction of Beclin1/Bcl-2, a known complex negatively regulating autophagy. In summary, Hsp20 activates cardiac autophagic flux via interaction with Beclin1, thereby confering cadioprotection.
Abstract 137: Ranolazine Increases Amplitude Spectrum Area During Untreated Ventricular Fibrillation and Cardiopulmonary Resuscitation
Authors: Francesca Fumagalli, Giuseppe Ristagno, Ilaria Russo, Lidia Staszewsky, Roberto Latini, Yongqin Li
Journal: Circulation (2013)

Background: Amplitude spectrum area (AMSA) has been demonstrated to be related to myocardial vitality during ventricular fibrillation (VF). Deregulation of intracellular Ca2+ homeostasis plays a cr...
Abstract 19201: Unseeded Engineered Valve Leaflets Retain Function and Remodel After Implant in Sheep Right Pulmonary Outflow Tract
Authors: Ahmed S Bayoumi, Antonio D'Amore, Elena Aikawa, Nicholas Amoroso, Sophie E New, Alexander Cubberley, Peter Chen, Kayle Shapero, Robert F Padera, Frederick J Schoen, William R Wagner, Michael S Sacks, John E Mayer
Journal: Circulation (2012)

Current materials for heart valve replacement and repair are limited by the inability to grow or remodel. Tissue engineered valves offer the potential to overcome these disadvantages by creating living structures, but is limited by the availability of biocompatible scaffold materials with desirable biomechanical properties. We assessed the in vivo performance of a novel scaffold poly(carbonate urethane) urea (PCUU), fabricated by electrospinning and implanted in the pulmonary outflow tract of sheep. PCUU was electrospun into elastomeric sheets of thickness ranging from 120-180 μm. Using cardiopulmonary bypass we replaced the native anterior pulmonary leaflet with an acellular PCUU leaflet. Valve function was evaluated by epicardial echocardiography at implant and explant at weeks 1 (n=3), 3 (n=3), 6 (n=3) and 16 (n=3). Histological, immunohistochemical, molecular imaging analyses and multi-photon imaging were performed on the explanted leaflets. Echocardiography demonstrated mobile functioning leaflets, with zero to mild pulmonary regurgitation. Molecular imaging showed increased levels of proteolytic activity and macrophage accumulation. Histology showed persistence of scaffold material up to 16 weeks with cellular infiltration throughout the leaflet. Picrosirius red revealed mature collagen deposition along the arterial surface of the construct at 6 and 16 weeks. These findings were corroborated by multi-photon analysis showing highly aligned collagen fibers across the leaflets. Both surfaces of the engineered leaflets were consistently covered with CD31 positive cells. The majority of cells expressed α-SMA and MMP2. CD45 positive cells, suggesting hematogenous origin, were found throughout the leaflet. These results suggest that: 1) PCUU can be a suitable polymer for valve bioengineering; 2) cell pre-seeding may not be required for tissue formation or remodeling for a functional engineered valve; 3) host cells seem to populate the leaflet either by migration from adjacent tissue or by attachment from circulating blood; 4) mature matrix orientation and increased proteolytic activity suggests active tissue remodeling. Longer term implants and the role of scaffold pre-seeding will require further study.
Moderators of Remission in Patients With Late-Life Depression
Authors: Warren D. Taylor
Journal: JAMA Psychiatry (2016)

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
Life History Traits, Protein Evolution, and the Nearly Neutral Theory in Amniotes
Authors: Emeric Figuet, Benoît Nabholz, Manon Bonneau, Eduard Mas Carrio, Krystyna Nadachowska-Brzyska, Hans Ellegren, Nicolas Galtier
Journal: Molecular Biology and Evolution (2016)

The nearly neutral theory of molecular evolution predicts that small populations should accumulate deleterious mutations at a faster rate than large populations. The analysis of nonsynonymous (dN) versus synonymous (dS) substitution rates in birds versus mammals, however, has provided contradictory results, questioning the generality of the nearly neutral theory. Here we analyzed the impact of life history traits, taken as proxies of the effective population size, on molecular evolutionary and population genetic processes in amniotes, including the so far neglected reptiles. We report a strong effect of species body mass, longevity, and age of sexual maturity on genome-wide patterns of polymorphism and divergence across the major groups of amniotes, in agreement with the nearly neutral theory. Our results indicate that the rate of protein evolution in amniotes is determined in the first place by the efficiency of purifying selection against deleterious mutations—and this is true of both radical and conservative amino acid changes. Interestingly, the among-species distribution of dN/dS in birds did not follow this general trend: dN/dS was not higher in large, long-lived than in small, short-lived species of birds. We show that this unexpected pattern is not due to a more narrow range of life history traits, a lack of correlation between traits and Ne, or a peculiar distribution of fitness effects of mutations in birds. Our analysis therefore highlights the bird dN/dS ratio as a molecular evolutionary paradox and a challenge for future research.
Health Information Exchange—Obvious Choice or Pipe Dream?
Authors: Anish P. Mahajan
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
Overwhelming majority of junior doctors vote for strike action
Authors: A. Rimmer
Journal: BMJ (2015)

An overwhelming majority of junior doctors who were balloted on taking strike action over changes to their contract in England have voted in favour.

The BMA said that of the 37 155 junior doctor members in England it balloted on industrial action, 28 305 responded, a 76% response rate. In total there are 54 074 junior doctors in England.

Of those balloted, 99% voted in favour of taking industrial action short of strike, and 98% voted in favour of strike action.

The BMA previously announced that the first day of industrial action would be on Tuesday 1 December.1 Junior doctors taking action on that day would …
Disabling Palpitations in an Adolescent
Authors: Mohamed ElMaghawry, Josep Brugada, Magdi Yacoub
Journal: JAMA Cardiology (2016)

A teenage girl presented with recurrent episodes of palpitations for 6 consecutive years.The resting 12-lead electrocardiogram showed sinus rhythm with no preexcitation or repolarization abnormalities.There were incessant multiple runs of nonsustained ventricular tachycardia with right bundle branch block morphologic features.QRS complexes were negative in the rest of the precordial leads (V2-V6) and in leads I and avL, but positive in III, avR, and avF, suggesting a left (lateral) ventricular apical origin (Figure 1).The echocardiogram showed no structural abnormalities.The patient was prescribed sotalol but her symptoms did not improve.Invasive electrophysiological mapping of the left ventricle endocardium demonstrated that the ventricular tachycardia probably originated from the epicardial surface of left ventricular apex. Quiz at jamacardiology.comFigure 1.Twelve-lead surface electrocardiogram during tachycardia.QRS complexes are positive in V1, negative in the rest of the precordial leads (V2-V6), and negative in leads I and avL but positive in III, avR, and avF.WHAT WOULD YOU DO NEXT? A. Map and ablate the epicardium B. Add a second antiarrhythmic drug and reassess the need for epicardial intervention after 3 to 6 months C. Implant a cardioverter defibrillator D. Perform cardiac magnetic resonance imaging to define pathologic substrate
Delays experienced by doctors suspended by GMC
Authors: S. Cox, D Irvine
Journal: BMJ (1999)

Low dose aspirin for preventing and treating pre-eclampsia Author of editorial did not criticise studies' methodologyEditor-In her editorial discussing the value or otherwise of aspirin for preventing and treating pre-eclampsia Duley wonders why the small trials have such different results from the large trials. 1 We suggest the following answer.Evidence based medicine means integrating individual skill with the best available evidence from systematic research.Duley's conclusions, based on several multicentre studies, seem to rely on the conclusions of these studies without her making criticisms of the methodology used.Firstly, the timing of the start of treatment with low dose aspirin is important.The studies consistently fail to show the percentage of women who were < 16 weeks pregnant, the crucial time when maximum trophoblastic invasion is taking place (table ).This issue was raised by de Swiet in Bower's news article 2 and by Beaufilis et al. 3 Secondly, the dose of aspirin used in the later large trials is low.A meta-analysis by Leitich et al (not quoted in the editorial) shows that aspirin was more effective at higher doses (100-150 mg/day) than at lower doses (50-80 mg/day). 4It seems that these large studies have looked at the wrong dose of aspirin used at the wrong time of pregnancy.The editorial's conclusions are based on trials with flawed methodology.The question of whether aspirin given in early pregnancy in an appropriate dose is effective in preventing pre-eclampsia remains unanswered.
Case Report : Metronidazole-induced encephalopathy in a patient with Liver cirrhosis
Authors: Hyeong Cheol Cheong, Taek Geun Jeong, Young Bum Cho, Bong Joon Yang, Tae Hyeon Kim, Haak Cheoul Kim, Eun Young Cho
Journal: Clinical and Molecular Hepatology (2011)

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.
Abstract 14633: Elevated microRNA-155 Promotes Foam Cell Formation by Targeting HBP1 in Atherogenesis
Authors: Fu-Ju Tian, Qing Jing
Journal: Circulation (2013)

Aims: MicroRNAs (miRNAs) play key roles in inflammatory responses of macrophages. However, the function of miRNAs in macrophage-derived foam cell formation is unclear. Here, we investigated the rol...
Step-up fecal microbiota transplantation (FMT) strategy
Authors: Bota Cui, Pan Li, Lijuan Xu, Zhaoyuan Peng, Jie Xiang, Zhi He, Ting Zhang, Guozhong Ji, Yongzhan Nie, Kaichun Wu, Daiming Fan, Faming Zhang
Journal: Gut Microbes (2016)

Gut dysbiosis is a characteristic of inflammatory bowel disease (IBD) and is believed to play a role in the pathogenesis of IBD. Fecal microbiota transplantation (FMT) is an effective strategy to restore intestinal microbial diversity and has been reported to have a potential therapeutic value in IBD. Our recent study reported a holistic integrative therapy called “step-up FMT strategy,” which was beneficial in treating steroid-dependent IBD patients. This strategy consists of scheduled FMTs combined with steroids, anti-TNF-α antibody treatment or enteral nutrition. Herein, we will elaborate the strategy thoroughly, introducing the concept, potential indication, methodology, and safety of “step-up FMT strategy” in detail.
MET mutations are associated with aggressive and radioresistant brain metastatic non-small-cell lung cancer: Table 1.
Authors: Giulia Maria Stella, Rebecca Senetta, Simona Inghilleri, Ludovica Verdun di Cantogno, Cristina Mantovani, Davide Piloni, Luigia Scudeller, Federica Meloni, Mauro Papotti, Umberto Ricardi, Paola Cassoni
Journal: Neuro-Oncology (2016)
P274 Moving from rescue to prevention: real world evidence of reduction in IV antibiotic requirement following improvement in adherence to maintenance nebulised treatment in an adult cystic fibrosis centre: Abstract P274 Table 1
Authors: ZH Hoo, R Curley, C Carolan, C Hinchliffe, M Hutchings, MJ Campbell, MJ Wildman
Journal: Thorax (2015)

<h3>Background</h3> Adherence to preventative nebulised therapy is associated with better health and lower costs for rescue treatment. However, adherence with nebulised treatment is generally poor and there is currently no systematic adherence intervention for people with CF. The Sheffield Adult CF centre has embarked on various pilot projects in this area, culminating in an NIHR programme grant awarded in 2014 to develop such a systematic adherence intervention. We hypothesised that the pilot projects would have improved the adherence levels and health outcomes among people with CF receiving care at the CF centre. <h3>Objectives</h3> To determine overall change in nebuliser adherence and health outcomes among the cohort of people with CF in Sheffield from 2013 to 2014. <h3>Methods</h3> Demographic data, spirometry, BMI, annual total intravenous antibiotics days and prescription details were obtained by reviewing patient notes. Adherence was measured with I-neb nebuliser and calculated as a percentage of the agreed regimen between clinicians and people with CF. People on ivacaftor or with previous lung transplantation were excluded from this analysis. <h3>Results</h3> 15 people were excluded from the analysis for both years. The cohort increased from n = 166 in 2013 to n = 170 in 2014, with a similar increase in the number of people with I-neb data for ≥3 months (n = 83 in 2013, n = 85 in 2014). Median nebuliser adherence improved from 40.5% in 2013 to 49.5% in 2014. The median FEV1 remained stable at 79% while BMI improved slightly from 22.0 in 2013 to 22.7 in 2014. The total IV days reduced by 657 from 3970 in 2013 to 3313 in 2014; a potential saving of around £156,000. <h3>Conclusion</h3> Although adherence remains a challenging issue, these data suggest the potential of benefits of improved adherence. More work will be needed to examine the adherence data in more detail and to collect further longitudinal data to determine if there is a clear trend of improvement.
Bacterial species involved in the conversion of dietary flavonoids in the human gut
Authors: Annett Braune, Michael Blaut
Journal: Gut Microbes (2016)

The gut microbiota plays a crucial role in the conversion of dietary flavonoids and thereby affects their health-promoting effects in the human host. The identification of the bacteria involved in intestinal flavonoid conversion has gained increasing interest. This review summarizes available information on the so far identified human intestinal flavonoid-converting bacterial species and strains as well as their enzymes catalyzing the underlying reactions. The majority of described species involved in flavonoid transformation are capable of carrying out the O-deglycosylation of flavonoids. Other bacteria cleave the less common flavonoid-C-glucosides and/or further degrade the aglycones of flavonols, flavanonols, flavones, flavanones, dihydrochalcones, isoflavones and monomeric flavan-3-ols. To increase the currently limited knowledge in this field, identification of flavonoid-converting bacteria should be continued using culture-dependent screening or isolation procedures and molecular approaches based on sequence information of the involved enzymes.
Corrigendum to ‘The use of granulocyte-colony stimulating factor induced mobilization for isolation of dental pulp stem cells with high regenerative potential’ [Biomaterials 34/36 (2013) 9036–9047]
Authors: Masashi Murakami, Hiroshi Horibe, Koichiro Iohara, Yuki Hayashi, Yohei Osako, Yoshifumi Takei, Kazuhiko Nakata, Noboru Motoyama, Kenichi Kurita, Misako Nakashima
Journal: Biomaterials (2016)