tbuckley/cabot-search huggingface dataset:
Requirement for p38 Mitogen-Activated Protein Kinase Activity in Neointima Formation After Vascular Injury
Authors: Brandon M. Proctor, Xiaohua Jin, Traian S. Lupu, Louis J. Muglia, Clay F. Semenkovich, Anthony J. Muslin
Journal: Circulation (2008)

Angioplasty and stent delivery are performed to treat atherosclerotic vascular disease but often cause deleterious neointimal lesion formation. Previously, growth factor receptor-bound protein 2 (Grb2), an intracellular linker protein, was shown to be essential for neointima formation and for p38 mitogen-activated protein kinase (MAPK) activation in vascular smooth muscle cells (SMCs). In this study, the role of vascular SMC p38alpha MAPK in neointimal development was examined.Compound transgenic mice were generated with doxycycline-inducible SMC-specific expression of dominant-negative p38alpha MAPK (DN-p38alpha). Doxycycline treatment resulted in the expression of DN-p38alpha mRNA and protein in transgenic arteries. Doxycycline-treated compound transgenic mice were resistant to neointima formation 21 days after carotid injury and showed reduced arterial p38 MAPK activation. To explore the mechanism by which p38alpha MAPK promotes neointima formation, an in vitro SMC culture system was used. Inhibition of p38alpha MAPK in cultured SMCs by treatment with SB202190 or small interfering RNA blocked platelet-derived growth factor-induced SMC proliferation, DNA replication, phosphorylation of the retinoblastoma protein, and induction of minichromosome maintenance protein 6.SMC p38alpha MAPK activation is required for neointima formation, perhaps because of its ability to promote retinoblastoma protein phosphorylation and minichromosome maintenance protein 6 expression.
Author Financial Conflicts of Interest, Industry Funding, and Clinical Practice Guidelines for Anticancer Drugs
Authors: Ariadna Tibau, Philippe L. Bedard, Amirrtha Srikanthan, Josee-Lyne Ethier, Francisco E. Vera-Badillo, Arnoud J. Templeton, Alberto Ocaña, Bostjan Seruga, Agustí Barnadas, Eitan Amir
Journal: Journal of Clinical Oncology (2014)

Purpose Clinical practice guidelines (CPGs) and consensus statements (CSs) are used to apply evidence-based medicine or expert recommendations to clinical practice. Here we explore author financial conflicts of interest (FCOIs), sources of guideline funding, and their relationship with endorsement of specific drugs. Methods An electronic search of MEDLINE was conducted to identify CPGs and CSs for common solid cancers published between January 2003 and October 2013. The search was restricted to articles evaluating systemic therapy. We extracted data on self-reported author FCOIs, funding sources, use of manuscript writers, and endorsement of specific drugs in the abstract of the article. Results Of 142 articles evaluated, 64% were CPGs, and 36% were CSs. The proportion of articles reporting FCOIs improved from 11% in 2003 to 93% in 2013 (P for trend &lt; .001). Only 45% of articles explicitly reported funding sources. Of these, 65% disclosed partial or full industry sponsorship. Use of manuscript writers was declared in 13%, but many articles did not explicitly report the role of authors in the writing of the manuscript. Endorsement of specific drugs was significantly associated with author FCOIs (odds ratio [OR], 7.29; P = .001), but not with industry funding (OR, 0.95; P = .37). Conclusion Reporting of FCOIs in CPGs and CSs has improved over time. Despite prevalent funding of guideline development by industry, such funding is not associated with endorsement of specific drugs. Author FCOIs are prevalent, and endorsement of a specific drug seems to be more common when authors have FCOIs with the pharmaceutical company marketing that drug.
The Impact of Toxins on the Developing Brain
Authors: Bruce P. Lanphear
Journal: Annual Review of Public Health (2015)

The impact of toxins on the developing brain is usually subtle for an individual child, but the damage can be substantial at the population level. Numerous challenges must be addressed to definitively test the impact of toxins on brain development in children: We must quantify exposure using a biologic marker or pollutant; account for an ever-expanding set of potential confounders; identify critical windows of vulnerability; and repeatedly examine the association of biologic markers of toxins with intellectual abilities, behaviors, and brain function in distinct cohorts. Despite these challenges, numerous toxins have been implicated in the development of intellectual deficits and mental disorders in children. Yet, too little has been done to protect children from these ubiquitous but insidious toxins. The objective of this review is to provide an overview on the population impact of toxins on the developing brain and describe implications for public health.
Early Events in Axon/Dendrite Polarization
Authors: Pei-lin Cheng, Mu-ming Poo
Journal: Annual Review of Neuroscience (2012)

Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure.
Phase 1 Study of ABT-751, a Novel Microtubule Inhibitor, in Patients with Refractory Hematologic Malignancies
Authors: Karen W.L. Yee, Anne Hagey, Srdan Verstovsek, Jorge Cortes, Guillermo Garcia-Manero, Susan M. O'Brien, Stefan Faderl, Deborah Thomas, William Wierda, Steven Kornblau, Alessandra Ferrajoli, Maher Albitar, Evelyn McKeegan, David R. Grimm, Toby Mueller, Rhonda R. Holley-Shanks, Leonardo Sahelijo, Gary B. Gordon, Hagop M. Kantarjian, Francis J. Giles
Journal: Clinical Cancer Research (2005)

Abstract Purpose: ABT-751 is an oral antimitotic agent that binds to the colchicine site on β-tubulin. A phase 1 study was conducted to determine the maximum tolerated dose and toxicities of ABT-751 in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias. Study Design: Thirty-two patients were treated: nine with 100 (n = 3), 125 (n = 3), or 150 mg/m2 (n = 3) of ABT-751 given orally once daily for 7 days every 3 weeks and 23 with 75 (n = 3), 100 (n = 3), 125 (n = 5), 150 (n = 5), 175 (n = 3), or 200 mg/m2 (n = 4) of ABT-751 given orally once daily for 21 days every 4 weeks. Consenting patients had pharmacogenetic sampling and enumeration of circulating endothelial cells (CEC). Results: Dose-limiting toxicity consisted of ileus in one patient at 200 mg/m2, with a subsequent patient developing grade 2 constipation at the same dose level. One patient with relapsed acute myelogenous leukemia achieved a complete remission that was sustained for 2 months. Four other patients had transient hematologic improvements, consisting of a decrease in peripheral blood blasts and improvements in platelet counts. CEC number was reduced in three patients with a concomitant reduction in peripheral blasts. A previously undescribed nonsynonymous single nucleotide polymorphism, encoding Ala185Thr, was identified in exon 4 of the β-tubulin gene, TUBB, in three other patients. The recommended phase 2 dose in hematologic malignancies is 175 mg/m2 daily orally for 21 days every 4 weeks. Conclusion: Further assessment of ABT-751, especially in combination with other agents, in patients with acute leukemias is warranted.
Habits, Rituals, and the Evaluative Brain
Authors: Ann M. Graybiel
Journal: Annual Review of Neuroscience (2008)

Scientists in many different fields have been attracted to the study of habits because of the power habits have over behavior and because they invoke a dichotomy between the conscious, voluntary control over behavior, considered the essence of higher-order deliberative behavioral control, and lower-order behavioral control that is scarcely available to consciousness. A broad spectrum of behavioral routines and rituals can become habitual and stereotyped through learning. Others have a strong innate basis. Repetitive behaviors can also appear as cardinal symptoms in a broad range of neurological and neuropsychiatric illness and in addictive states. This review suggests that many of these behaviors could emerge as a result of experience-dependent plasticity in basal ganglia–based circuits that can influence not only overt behaviors but also cognitive activity. Culturally based rituals may reflect privileged interactions between the basal ganglia and cortically based circuits that influence social, emotional, and action functions of the brain.
Bespoke smoking cessation for people with severe mental ill health (SCIMITAR): a pilot randomised controlled trial
Authors: Simon Gilbody, Emily Peckham, Mei-See Man, Natasha Mitchell, Jinshuo Li, Taeko Becque, Catherine Hewitt, Sarah Knowles, Tim Bradshaw, Claire Planner, Steve Parrott, Susan Michie, Charles Shepherd
Journal: The Lancet Psychiatry (2015)
Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom?
Authors: Jan J. Cornelissen, Wim L. J. van Putten, Leo F. Verdonck, Matthias Theobald, Emanuel Jacky, Simon M. G. Daenen, Marinus van Marwijk Kooy, Pierre Wijermans, Harry Schouten, Peter C. Huijgens, Hans van der Lelie, Martin Fey, Augustin Ferrant, Johan Maertens, Alois Gratwohl, Bob Lowenberg
Journal: Blood (2007)
Lateral and Medial Hypofrontality in First-Episode Schizophrenia: Functional Activity in a Medication-Naive State and Effects of Short-Term Atypical Antipsychotic Treatment
Authors: Beth E. Snitz, Angus MacDonald, Jonathan D. Cohen, Raymond Y. Cho, Theresa Becker, Cameron S. Carter
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The dorsolateral prefrontal cortex and the anterior cingulate cortex are critical components of the brain circuitry underlying executive control. The objective of this study was to investigate control-related dorsolateral prefrontal cortex functioning and conflict-related anterior cingulate cortex functioning in a group of never medicated first-episode schizophrenia patients to determine whether both regions show dysfunction at illness onset. A second objective was to assess short-term effects of atypical antipsychotic medication on dorsolateral prefrontal cortex and anterior cingulate cortex functioning. METHOD: First-episode schizophrenia patients (N=23) and healthy comparison subjects (N=24) underwent event-related fMRI and performed a cognitive task designed to functionally dissociate the two regions. Four weeks after initiation of pharmacotherapy for patients, a subset of 11 patients and 16 comparison subjects underwent a repeat assessment. RESULTS: At baseline, patients exhibited hypoactivation in the dorsolateral prefrontal cortex and anterior cingulate cortex. After 4 weeks of antipsychotic treatment, the patients demonstrated improved functioning in the anterior cingulate cortex but not in the dorsolateral prefrontal cortex. CONCLUSIONS: These findings confirm the presence of dorsolateral prefrontal cortex dysfunction early in the course of schizophrenia and suggest that anterior cingulate cortex functioning may be altered at illness onset as well. Results also suggest that anterior cingulate cortex functioning may be especially sensitive to remedial antipsychotic treatment effects. These findings are consistent with an emerging literature documenting short-term benefits of atypical antipsychotic medication for the neural circuitry underlying cognitive deficits in schizophrenia.
Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4.
Authors: J W Yoon, T Onodera, A L Notkins
Journal: The Journal of Experimental Medicine (1978)

Coxsackie virus B4 that had been passaged in cultures enriched for pancreatic beta cells produced a diabetes-like syndrome when inoculated into SJL/J mice. The infection resulted in insulitis and destruction of beta cells. Viral antigens were found in beta cells by staining with fluorescein-labeled antibody to Coxsackie virus B4. The destruction of beta cells led to a decrease in the immunoreactive insulin content of the pancreas and hypoinsulinemia. The reduction in immunoreactive insulin correlated inversely with the elevation of glucose in the blood and over 80% of the animals were found to be hyperglycemic within 14 days after infection. The percentage of animals with hyperglycemia decreased with time and at the end of 60 days, less than 5% of the animals were still hyperglycemic. However, many of the normoglycemic mice were found to be metabolically abnormal when evaluated by glucose tolerance tests. Studies on the susceptibility of the host showed that only certain inbred strains of mice became diabetic when infected with Coxsackie virus B4. It is concluded that both the passage history of the virus and the strain of the host influence the development of diabetes.
Magnetic-resonance imaging for kinetic analysis of permeability changes during focused ultrasound-induced blood–brain barrier opening and brain drug delivery
Authors: Wen-Yen Chai, Po-Chun Chu, Meng-Yen Tsai, Yu- Chun Lin, Jiun-Jie Wang, Kuo-Chen Wei, Yau-Yau Wai, Hao-Li Liu
Journal: Journal of Controlled Release (2014)
Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein
Authors: L Senolt
Journal: Annals of the Rheumatic Diseases (2005)

Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders-for example, rheumatoid arthritis.To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)-a marker of articular cartilage destruction.Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA.Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease.Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker.
A role for Dicer in immune regulation
Authors: Bradley S. Cobb, Arnulf Hertweck, James Smith, Eric O'Connor, Daniel Graf, Terence Cook, Stephen T. Smale, Shimon Sakaguchi, Frederick J. Livesey, Amanda G. Fisher, Matthias Merkenschlager
Journal: The Journal of Experimental Medicine (2006)

Micro RNAs (miRNAs) regulate gene expression at the posttranscriptional level. Here we show that regulatory T (T reg) cells have a miRNA profile distinct from conventional CD4 T cells. A partial T reg cell–like miRNA profile is conferred by the enforced expression of Foxp3 and, surprisingly, by the activation of conventional CD4 T cells. Depleting miRNAs by eliminating Dicer, the RNAse III enzyme that generates functional miRNAs, reduces T reg cell numbers and results in immune pathology. Dicer facilitates, in a cell-autonomous fashion, the development of T reg cells in the thymus and the efficient induction of Foxp3 by transforming growth factor β. These results suggest that T reg cell development involves Dicer-generated RNAs.
Qualitative study of patients' perceptions of doctors' advice to quit smoking: implications for opportunistic health promotion
Authors: C. C Butler, R. Pill, N. C H Stott
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives:</b> To determine the effectiveness and acceptability of general practitioners9opportunistic antismoking interventions by examining detailed accounts of smokers9 experiences of these. <b>Design:</b> Qualitative semistructured interview study. <b>Setting:</b> South Wales. <b>Subjects:</b> 42 participants in the Welsh smoking intervention study were asked about initial smoking, attempts to quit, thoughts about future smoking, past experiences with the health services, and the most appropriate way for health services to help them and other smokers. <b>Results:</b> Main emerging themes were that subjects already made their own evaluations about smoking, did not believe doctors9 words could influence their smoking, believed that quitting was down to the individual, and felt that doctors who took the opportunity to talk about smoking should focus on the individual patient. Smokers anticipated that they would be given antismoking advice by doctors when attending for health care; they reacted by shrugging this off, feeling guilty, or becoming annoyed. These reactions affected the help seeking behaviour of some respondents. Smokers were categorised as “contrary,” “matter of fact,” and “self blaming,” depending on their reported reaction to antismoking advice. <b>Conclusions:</b> Doctor-patient relationships can be damaged if doctors routinely advise all smokers to quit. Where doctors intervene, a patient centred approach—one that considers how individual patients view themselves as smokers and how they are likely to react to different styles of intervention is the most—acceptable. <h3>Key messages</h3> Many patients who smoke are sceptical about the power of doctors9 words to influence smoking since most know about the dangers, make their own evaluations, and feel that quitting is down to the individual Opportunistic antismoking interventions should be sympathetic, not preaching, and centred on the patient as an individual Repeated ritualistic intervention on the part of doctors may deter patients from seeking medical help when they need it Smokers can be categorised as “contrary,” “matter of fact,” or “self blaming” in their reaction to antismoking advice Doctors can tailor their approach according to the type of patient
Pulmonary Vascular Hemodynamic Response to Exercise in Cardiopulmonary Diseases
Authors: Gregory D. Lewis, Eduardo Bossone, Robert Naeije, Ekkehard Grünig, Rajeev Saggar, Patrizio Lancellotti, Stefano Ghio, Janos Varga, Sanjay Rajagopalan, Ronald Oudiz, Melvyn Rubenfire
Journal: Circulation (2013)
Therapeutic Hypothermia and Targeted Temperature Management After Cardiac Arrest—Reply
Authors: Neal E. Little, Eva L. Feldman
Journal: JAMA Neurology (2014)

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Antioxidant therapy in idiopathic pulmonary fibrosis: hope is kindled
Authors: A. U. Wells
Journal: European Respiratory Journal (2006)

Respiratory Society classification of the idiopathic interstitial pneumonias [1] has redefined entities previously grouped as ''idiopathic pulmonary fibrosis'' (IPF), but carrying a much better prognosis than that disorder.As a result, the core entity of IPF is now diagnosed with greater precision than ever before.The outcome has worsened correspondingly, with an average survival of ,3 yrs from the onset of dyspnoea.Until recently, therapeutic nihilism in IPF has prevailed.Treatment recommendations have come and gone, high-dose corticosteroid therapy has had its day [2], and ''standard therapy'' has essentially failed.DEMEDTS et al. [3] recently reported outcome data that ought to encourage the optimists amongst us.For the first time, a widely available and inexpensive agent has effected a real difference in the rate of disease progression in a large cohort of patients.The methodology was straightforward.All patients remained on low-dose prednisolone and azathioprine throughout.The studied intervention consisted of the addition of Nacetylcysteine (NAC) at a dose of 600 mg t.i.d., controlled against placebo.There were differences in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DL,CO) at 12 months in favour of active treatment.With placebo, FVC and DL,CO fell 6 and 8% of predicted, respectively, but only 1.5 and 3% with active therapy.In other words, the rapidity of disease progression was curtailed by ,70% when antioxidant therapy was added to ''best current treatment''.