tbuckley/cabot-search huggingface dataset:
Abstract 186: AMP-Activated Protein Kinase Mediates Cardioprotection in the Regenerative MRL Mouse Strain
Authors: Susan T Varghese, Jenan Holley-Cuthrell, Chad M Warren, Ann Kuenster, Ahlke Heydemann
Journal: Circulation Research (2012)

Introduction: The Murphy Roths Large (MRL/MpJ) mouse model is well-known for its healing and regenerative properties. The actual mechanisms promoting regeneration are still unknown. AMP activated protein kinase (AMPK) has been lauded for its role as a cardioprotective sensor of cellular metabolic stress, cell growth, and ATP depletion. Based on our preliminary data, we hypothesize that increased levels of AMPK in the MRL hearts is primarily responsible for its altered mitochondrial biogenesis and metabolism, reduced oxidative stress, and altered cardiac function in the MRL mice. Methods: Adult C57BL/6 (control) and MRL mice (n=5/group) were studied pre- and post-7 days of exercise, and post-exercise with 3 days injection of either 5-amino -imidazole carboxamide riboside (AICAR, AMPK stimulator, 250ug/g, IP), or Compound C (AMPK inhibitor, 20ug/g, IP). Results: Compared to control at baseline, the MRL hearts had higher AMPK protein levels (9 fold increase, p&lt;0.001), equivalent AMPK mRNA levels by qRT-PCR, and higher AMP to ATP ratios by HPLC (3 fold increase, p&gt;0.05, n.s.). The MRL hearts also had increased mitochondria by electron microscopy (by 65 ± 4.5%, p&lt;0.05), reduced HW to BW ratio (48% decrease, p&lt;0.001), reduced cellular and mitochondrial reactive oxygen species (by DHE and Mitosox stains respectively), and increased glycolysis (Glut-4 sarcolemmal translocation). Hypertrophic response to exercise was greater in the MRL mice (HW/BW increased by 40% vs. 2% in control, p&lt;0.001). Mimicking injury, Compound C reduced active phosphorylated AMPK protein levels in control (by 26%, p&lt;0.05), while increased it in MRL mice (by 30%, p&lt;0.05). AICAR injection significantly increased pAMPK protein in both strains (p=0.008). Baseline MRL mice echocardiographic analysis (vs. control) indicated higher systolic function, but increased diastolic E/A and E/E’ ratios (p&lt;0.05). In the MRL hearts, Compound C treatment reduced %EF and %FS, while AICAR reduced post-exercise hypertrophy (p=0.02). Conclusions: This study highlights the cardioprotective role AMPK plays in the MRL mice, through its modulation of mitochondrial function and reduction of oxidative stress. This can in turn be used to develop new therapeutic treatment for heart failure.
Expression of the transcription factor c-myb in atherosclerotic aortae of ApoE-/- mice.
Authors: Farrell K, C M Holt
Journal: Cardiovascular Research (2010)

Atherosclerosis involves the proliferation and death of vascular smooth muscle cells. C-Myb is a transcription factor that functions in cell cycle progression, proliferation and apoptosis of various cell types. Several studies have shown that c-Myb plays an important role following vascular injury;
Blunting of noradrenergic-stimulated growth hormone release in mania
Authors: T G Dinan, L N Yatham, V O'Keane, S Barry
Journal: American Journal of Psychiatry (1991)

Seven drug-free patients with bipolar affective disorder, currently in a manic phase, underwent desipramine-induced growth hormone (GH) stimulation, as did seven healthy age- and sex-matched subjects. There was significant blunting of GH release in the manic patients, suggesting a down-regulation of alpha 2-noradrenergic responses. Blunting of GH release was not related to severity of symptoms, duration of illness, or age. Similar blunting has previously been described in depressed patients.
<i>KIT</i> Exon 11 Codons 557–558 Deletion Mutation Promotes Liver Metastasis Through the CXCL12/CXCR4 Axis in Gastrointestinal Stromal Tumors
Authors: Hao-Chen Wang, Tzu-Ying Li, Ying-Jui Chao, Ya-Chin Hou, Yuan-Shuo Hsueh, Kai-Hsi Hsu, Yan-Shen Shan
Journal: Clinical Cancer Research (2016)

KIT mutations, the most prevalent genetic event in gastrointestinal stromal tumors (GIST), are associated with malignant features and poor prognosis. Aggressive GISTs possess a high propensity to spread to the liver. This study aimed to explore the role of KIT mutations in GIST liver metastasis.A total of 170 GISTs were used to determine the association between KIT mutations and liver metastasis. Immunohistochemistry was performed to assess the correlation of KIT mutations with CXCR4 and ETV1 expression. Genetic and pharmacologic methods were used to study the regulation of CXCR4 and ETV1 by KIT mutations.Codons 557 and 558 in KIT exon 11 were deletion hot spots in GISTs. KIT exon 11 deletions involving codons 557-558 were highly associated with liver metastasis. Overexpression of mutant KIT with exon 11 codons 557-558 deletion (KIT Δ557-558) increased GIST cell motility and liver metastasis. Mechanistically, overexpression of KIT Δ557-558 in GIST cells increased ETV1 and CXCR4 expression. CXCR4 knockdown counteracted KIT Δ557-558-mediated cell migration. Moreover, KIT Δ557-558-induced CXCR4 expression could be abolished by silencing ETV1. The chromatin immunoprecipitation assay showed that ETV1 directly bound to the CXCR4 promoter. After ERK inhibitor PD325901 treatment, the upregulation of ETV1 by KIT Δ557-558 was prevented. In addition, KIT exon 11 codons 557-558 deletion enhanced CXCL12-mediated GIST cell migration and invasion.KIT exon 11 557-558 deletion upregulates CXCR4 through increased binding of ETV1 to the CXCR4 promoter in GIST cells, which thus promotes liver metastasis. These findings highlighted the potential therapeutic targets for metastatic GISTs. Clin Cancer Res; 22(14); 3477-87. ©2016 AACR.
Moving Forwards by Blocking Back-Flow
Authors: Victoria R. Pell, Edward T. Chouchani, Michael P. Murphy, Paul S. Brookes, Thomas Krieg
Journal: Circulation Research (2016)

Mitochondrial reactive oxygen species production has emerged as an important pathological mechanism in myocardial ischemia/reperfusion injury. Attempts at targeting reactive oxygen species by scavenging using antioxidants have, however, been clinically disappointing. This review will provide an overview of the current understanding of mitochondrial reactive oxygen species in ischemia/reperfusion injury. We will outline novel therapeutic approaches designed to directly target the mitochondrial respiratory chain and prevent excessive reactive oxygen species production and its associated pathology. This approach could lead to more effective interventions in an area where there is an urgent need for new treatments.
Review of prescribed treatment for children with asthma
Authors: A M Ross, D M Fleming
Journal: BMJ (1995)

EDITOR,--Analysis of a computerised prescribing database showed that 9362 children were prescribed some form of preventive treatment for asthma. Of these, 1358 received sufficient repeat prescriptions to suggest that they were consistently receiving prophylactic treatment.1 Several weaknesses in this analysis limit the interpretation and conclusions reported.

Firstly, the author assumes that all children remained on the practice list for a whole year. Morton-Jones and Pringle estimated that …
Canadian Medical Association dismisses second journal editor in 10 years
Authors: Barbara Kermode-Scott
Journal: BMJ (2016)

The editor of Canada’s leading medical journal has left his post amid a “restructuring and modernisation plan.”

On 29 February the Canadian Medical Association’s president, Cindy Forbes, reported that John Fletcher, the editor in chief of CMAJ , the association’s journal, was “no longer with the organisation,” adding that the journal’s eight strong editorial oversight committee had also been “discontinued.”

Forbes unveiled a new four person CMAJ taskforce, under the leadership of the association’s past president, Chris Simpson. The task force will consult association members, researchers, and academics to identify journal best practices and propose recommendations for a new mission statement, goals, and objectives for …
Mitochondrial DNA polymorphisms in the two subspecies of Drosophila sulfurigaster: relationship between geographic structure of population and nucleotide diversity.
Authors: K Tamura, T Aotsuka, O Kitagawa
Journal: Molecular Biology and Evolution (1991)

Recent empirical and theoretical studies on mitochondrial DNA (mtDNA) variation in higher animals have suggested that the extent of mtDNA polymorphism is largely affected by spatial population subdivision. To examine this we studied mtDNA polymorphism in two subspecies of Drosophila sulfurigaster: D. s. albostrigata and D. s. bilimbata. Drosophila sulfurigaster albostrigata is mainly distributed on the mainland of Southeast Asia. In contrast, D. s. bilimbata forms discontinuous populations on many islands scattered in the Pacific Ocean. Because of the difference in their distribution patterns, the two subspecies are thought to be different in the extent of spatial population subdivision. mtDNA was isolated from greater than 50 isofemale strains for each subspecies and were analyzed by eight restriction endonucleases. Nucleotide diversity within a population was higher in D. s. albostrigata than in D. s. bilimbata. However, haplotype diversity was 1.6 times greater in D. s. bilimbata (0.85) than in D. s. albostrigata (0.53). The large difference in overall heterogeneity was attributed to the difference in interpopulational nucleotide diversity. For the two subspecies the proportion of interpopulational gene diversity in a subdivided population was calculated to be 0.54 in D. s. bilimbata and 0.40 in D. s. albostrigata. These observations indicate that spatial population subdivision is a major factor in determining mtDNA polymorphism in these subspecies. The extent of mtDNA divergence between the subspecies was very high. The average nucleotide divergence between them was 7.6%, which is almost the interspecific level reported for other Drosophila species. The cause of the high degree of mtDNA divergence is discussed.
EDISON-WMW: Exact Dynamic Programing Solution of the Wilcoxon–Mann–Whitney Test
Authors: Alexander Marx, Christina Backes, Eckart Meese, Hans-Peter Lenhof, Andreas Keller
Journal: Genomics Proteomics & Bioinformatics (2016)

Abstract In many research disciplines, hypothesis tests are applied to evaluate whether findings are statistically significant or could be explained by chance. The Wilcoxon–Mann–Whitney (WMW) test is among the most popular hypothesis tests in medicine and life science to analyze if two groups of samples are equally distributed. This nonparametric statistical homogeneity test is commonly applied in molecular diagnosis. Generally, the solution of the WMW test takes a high combinatorial effort for large sample cohorts containing a significant number of ties. Hence, P value is frequently approximated by a normal distribution. We developed EDISON-WMW, a new approach to calculate the exact permutation of the two-tailed unpaired WMW test without any corrections required and allowing for ties. The method relies on dynamic programing to solve the combinatorial problem of the WMW test efficiently. Beyond a straightforward implementation of the algorithm, we presented different optimization strategies and developed a parallel solution. Using our program, the exact P value for large cohorts containing more than 1000 samples with ties can be calculated within minutes. We demonstrate the performance of this novel approach on randomly-generated data, benchmark it against 13 other commonly-applied approaches and moreover evaluate molecular biomarkers for lung carcinoma and chronic obstructive pulmonary disease (COPD). We found that approximated P values were generally higher than the exact solution provided by EDISON-WMW. Importantly, the algorithm can also be applied to high-throughput omics datasets, where hundreds or thousands of features are included. To provide easy access to the multi-threaded version of EDISON-WMW, a web-based solution of our algorithm is freely available at http://www.ccb.uni-saarland.de/software/wtest/.
Inhibition of Embryonic Cell Aggregation by Neoplastic Cells2
Authors: D. E. Maslow, E. Mayhew
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Inhibition of Embryonic Cell Aggregation by Neoplastic Cells Get access D. E. Maslow, D. E. Maslow Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Mayhew E. Mayhew Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 5, May 1975, Pages 1097–1102, https://doi.org/10.1093/jnci/54.5.1097 Published: 01 May 1975 Article history Received: 06 August 1974 Accepted: 14 January 1975 Published: 01 May 1975
Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy
Authors: Francesco Montorsi, Matthias Oelke, Carsten Henneges, Gerald Brock, Andrea Salonia, Gianluca d’Anzeo, Andrea Rossi, John P. Mulhall, Hartwig Büttner
Journal: European Urology (2016)
Methionine Regulation of &lt;italic&gt;N&lt;/italic&gt;-5-Methyltetrahydrofolate:Homocysteine Methyltransferase and Its Influence on the Growth and Protein Synthesis in Normal, Neoplastic, and Transformed Cells in Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J W Tautt, E L Anuszewska, J H Koziorowska
Journal: JNCI Journal of the National Cancer Institute (1982)

Normal human embryonic fibroblasts (CLV-58) and normal embryonic rat fibroblasts (REF) revealed equal growth in media containing 0.2 mM DL-homocysteine thiolactone (HOM) or in methionine (METH) enriched with 1.5 microM cyanocobalamin and 0.1 mM folic acid, whereas L 5178Y lymphoblasts and transformed rat fibroblasts (REF-S) showed more or less acute need for exogenous METH. In normal cells general protein synthesis remained unimpaired during 24 hours after substitution of METH by HOM. In L 5178Y and REF-S cells, however, protein synthesis was significantly inhibited. Measurements of N-5-methyltetrahydrofolate:homocysteine methyltransferase revealed a two- to threefold increase of enzyme activity in normal cells grown on HOM and in L 5178Y and REF-S cells grown on HOM with added METH. HeLa cells showed variability in growth pattern, in general protein synthesis response, and in inducibility of methyltransferase upon substitution of METH by HOM.
Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians
Authors: Amir Qaseem, Michael J. Barry, Devan Kansagara
Journal: Annals of Internal Medicine (2016)

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness of treatment with second-generation antidepressants versus nonpharmacologic treatments for major depressive disorder in adults. Methods: This guideline is based on a systematic review of published, English-language, randomized, controlled trials from 1990 through September 2015 identified using several databases and through hand searches of references of relevant studies. Interventions evaluated include psychotherapies, complementary and alternative medicines (including acupuncture, ω-3 fatty acids, S-adenosyl-l-methionine, St. John's wort [Hypericum perforatum]), exercise, and second-generation antidepressants. Evaluated outcomes included response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with major depressive disorder. This guideline grades the evidence and recommendations using ACP's clinical practice guidelines grading system. Recommendation: ACP recommends that clinicians select between either cognitive behavioral therapy or second-generation antidepressants to treat patients with major depressive disorder after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient (Grade: strong recommendation, moderate-quality evidence).
Pretransplant thymic function predicts acute rejection in antithymocyte globulin–treated renal transplant recipients
Authors: Jamal Bamoulid, Cécile Courivaud, Thomas Crepin, Clémence Carron, Emilie Gaiffe, Caroline Roubiou, Caroline Laheurte, Bruno Moulin, Luc Frimat, Philippe Rieu, Christiane Mousson, Antoine Durrbach, Anne-Elisabeth Heng, Jean-Michel Rebibou, Philippe Saas, Didier Ducloux
Journal: Kidney International (2016)

Lack of clear identification of patients at high risk of acute rejection hampers the ability to individualize immunosuppressive therapy. Here we studied whether thymic function may predict acute rejection in antithymocyte globulin (ATG)-treated renal transplant recipients in 482 patients prospectively studied during the first year post-transplant of which 86 patients experienced acute rejection. Only CD45RA(+)CD31(+)CD4(+) T cell (recent thymic emigrant [RTE]) frequency (RTE%) was marginally associated with acute rejection in the whole population. This T-cell subset accounts for 26% of CD4(+) T cells. Pretransplant RTE% was significantly associated with acute rejection in ATG-treated patients (hazard ratio, 1.04; 95% confidence interval, 1.01-1.08) for each increased percent in RTE/CD4(+) T cells), but not in anti-CD25 monoclonal (αCD25 mAb)-treated patients. Acute rejection was significantly more frequent in ATG-treated patients with high pretransplant RTE% (31.2% vs. 16.4%) or absolute number of RTE/mm(3) (31.7 vs. 16.1). This difference was not found in αCD25 monclonal antibody-treated patients. Highest values of both RTE% (>31%, hazard ratio, 2.50; 95% confidence interval, 1.09-5.74) and RTE/mm(3) (>200/mm(3), hazard ratio, 3.71; 95% confidence interval, 1.59-8.70) were predictive of acute rejection in ATG-treated patients but not in patients having received αCD25 monoclonal antibody). Results were confirmed in a retrospective cohort using T-cell receptor excision circle levels as a marker of thymic function. Thus, pretransplant thymic function predicts acute rejection in ATG-treated patients.
Difference in reaction time between subjects with schizotypal and borderline personality disorders
Authors: K Chapin, L Wightman, H Lycaki, N Josef, G Rosenbaum
Journal: American Journal of Psychiatry (1987)

Patients with schizophrenic spectrum disorders and affective disorders were compared on a reaction time procedure. The nonhospitalized schizotypal subjects performed similarly to the schizophrenic patients on the crossover measure. Mean reaction time discriminated between hospitalized and nonhospitalized patients rather than between types of pathology.
Epithelial Cell Cultures From Normal and Cancerous Human Tissues2
Authors: R. B. Owens, H. S. Smith, W. A. Nelson-Rees, E. L. Springer
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Epithelial Cell Cultures From Normal and Cancerous Human Tissues Get access R. B. Owens, R. B. Owens Search for other works by this author on: Oxford Academic PubMed Google Scholar H. S. Smith, H. S. Smith Search for other works by this author on: Oxford Academic PubMed Google Scholar W. A. Nelson-Rees, W. A. Nelson-Rees Search for other works by this author on: Oxford Academic PubMed Google Scholar E. L. Springer E. L. Springer Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 4, April 1976, Pages 843–849, https://doi.org/10.1093/jnci/56.4.843 Published: 01 April 1976 Article history Received: 24 October 1975 Accepted: 03 November 1975 Published: 01 April 1976
Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial
Authors: Elvira O G van Vliet, Tobias A J Nijman, Ewoud Schuit, Karst Y Heida, Brent C Opmeer, Marjolein Kok, Wilfried Gyselaers, Martina M Porath, Mallory Woiski, Caroline J Bax, Kitty W M Bloemenkamp, Hubertina C J Scheepers, Yves Jacquemyn, Erik van Beek, Johannes J Duvekot, Maureen T M Franssen, Dimitri N Papatsonis, Joke H Kok, Joris A M van der Post, Arie Franx, Ben W Mol, Martijn A Oudijk
Journal: The Lancet (2016)
Pilot educational interventions
Authors: Roger A Fisken
Journal: BMJ (2008)

tackling alcohol misuse Needs in adolescentsParker et al's review of alcohol misuse did not deal with the problems and needs of adolescent drinkers, who often present to emergency departments when drunk. 1 Alcohol misuse is common in this age group and its incidence is rising, at great cost to individuals, families, and wider society.It is significantly associated with risk of suicide, violence, and accidents-the most common causes of death for young people. 2 It is also an important marker of serious social problems, which should be explored with all those who present to health services. 3 Despite this, emergency department doctors often don't screen for alcohol misuse in young people and are poor at recognising it without formalised screening tools.AUDIT and its derivatives can be used in adolescents, although lower cut-off scores than for adults are probably wise.Just asking, "How often do you get drunk?"identifies young people at risk of traumatic injury through drinking, 4 and the Paddington alcohol test identifies "binge" drinkers. 5 Testing blood alcohol levels at presentation is no substitute for formally investigating drinking habits and risk behaviour because young people are drunk at lower blood alcohol concentrations than adults and binge drinking is intermittent.Although it has been reported that young people are more prone than adults to hypoglycaemia when drunk, this is rare.Other pathologies must be considered in intoxicated adolescents with hypoglycaemia, including infection or additional toxic and metabolic insults.
Multi-stage inhibition in breast cancer metastasis by orally active triple conjugate, LHTD4 (low molecular weight heparin-taurocholate-tetrameric deoxycholate)
Authors: Farzana Alam, Taslim A. Al-Hilal, Jooho Park, Jeong Uk Choi, Foyez Mahmud, Jee-Heon Jeong, In-San Kim, Sang Yoon Kim, Seung Rim Hwang, Youngro Byun
Journal: Biomaterials (2016)