tbuckley/cabot-search huggingface dataset:
Glucocorticoid signaling synchronizes the liver circadian transcriptome
Authors: Akhilesh B. Reddy, Elizabeth S. Maywood, Natasha A. Karp, Verdun M. King, Yusuke Inoue, Frank J. Gonzalez, Kathryn S. Lilley, Charalambos P. Kyriacou, Michael H. Hastings
Journal: Hepatology (2007)

Circadian control of physiology is mediated by local, tissue-based clocks, synchronized to each other and to solar time by signals from the suprachiasmatic nuclei (SCN), the master oscillator in the hypothalamus. These local clocks coordinate the transcription of key pathways to establish tissue-specific daily metabolic programs. How local transcriptomes are synchronized across the organism and their relative contribution to circadian output remain unclear. In the present study we showed that glucocorticoids alone are able to synchronize expression of about 60% of the circadian transcriptome. We propose that synchronization occurs directly by the action of glucocorticoids on a diverse range of downstream targets and indirectly by regulating the core clock genes mPer1, Bmal1, mCry1, and Dbp. We have identified the pivotal liver transcription factor, HNF4alpha, as a mediator of circadian and glucocorticoid-regulated transcription, showing that it is a key conduit for downstream targeting.We have demonstrated that by orchestrating transcriptional cascades, glucocorticoids are able to direct synchronization of a diverse range of functionally important circadian genes.
Tropical spastic paraparesis associated with human T lymphotropic virus type I in an east African naturalised in Sweden.
Authors: B Ryberg, J Blomberg, P J Klasse
Journal: BMJ (1987)

Our findings are in direct contrast with those of Dundee et al.2A much larger study, of more than 200 subjects, would be required to rule out even a minor antiemetic effect of acupuncture (that is, a 10% difference between the groups).We chose, however, to limit our study to 46 subjects, as our results suggested that acupuncture at the P6 locus, in the way that we used it, is unlikely to be a clinically useful prophylactic for postoperative nausea and vomiting.
Genetic testing for familial Alzheimer's must be debated
Authors: J. M Garcia
Journal: BMJ (2002)

EDITOR—Rigg's news item about genetic testing for familial Alzheimer's disease in a Spanish hospital highlights the need to extend the current debate in the Spanish press to the scientific community.1 In spite of its high genetic penetrance, environmental factors can also determine the phenotypic presentation of familial Alzheimer's disease.2 Since the disease is currently incurable and no interventions have been proved to either prevent or delay the onset of the disease, considerations of the quality of life of future patients are paramount.

People who have …
Chronic fenoterol exposure increases in vivo and in vitro airway responses in guinea pigs.
Authors: Z L Wang, A M Bramley, A McNamara, P D Paré, T R Bai
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

We tested the hypothesis that the regular inhalation of a beta 2-adrenergic receptor (beta 2AR) agonist increases airway responsiveness in guinea pigs. A potent beta 2AR agonist, fenoterol hydrobromide, in sublaryngeal doses equivalent to maximal doses used in the treatment of asthma on a weight basis (5.28 micrograms/kg), was administered by nebulizer three times a day for 6 weeks to normal adolescent guinea pigs (FEN, n = 10) and to ovalbuminsensitized guinea pigs challenged twice weekly with ovalbumin (OA + FEN, n = 20), although not in the 12 h prior to or 4 h after antigen challenge. Controls included saline-treated normal animals (CON, n = 10) and ovalbumin-sensitized animals treated with repeated antigen challenge and saline (OA, n = 20). At 72 h after the last administration of saline, fenoterol, and ovalbumin, the dose-response relationship between pulmonary resistance (RL) and nebulized acetylcholine (ACh) was measured. RLmax increased 2-fold and the ACh concentration causing a 10-fold increase in RL (PC10) decreased 4-fold in the FEN, OA, and OA + FEN groups as compared to the CON group. In the FEN, OA, and OA + FEN groups, in vitro tracheal smooth-muscle contractile responses to maximal concentrations of acetylcholine increased 2-fold, and this increase was not due to increased smooth-muscle mass. There was no evidence for beta 2AR desensitization as judged by in vitro tracheal smooth-muscle relaxant responses to fenoterol. These results suggest that chronic beta 2AR stimulation increases airway smooth-muscle contractility and in vivo airways responsiveness to a degree similar to that induced by chronic antigen exposure. A similar effect in human asthmatics may explain the adverse effects observed during prolonged treatment with these drugs.
Preferential Attack on Cancer by Selected SH Inhibitors
Authors: Frances E. Knock
Journal: JAMA (1970)

<h3>To the Editor.—</h3> In sensitivity tests on hundreds of human cancers, selected sulfhydryl (SH) inhibitors have shown greater effect against tumors than against normal tissues. Clinically, SH inhibitors have caused the regression of a variety of human carcinomas, sarcomas, and lymphomas without injury to wound healing and with minimal injury to hematologic status and even improvement in some patients. The drug regimens are started within 24 to 48 hours of major cancer surgery, such as palliative bowel resection or pelvic exenteration. In two series totalling over 100 patients, the majority of patients whose tumors could be measured objectively received objective benefit from chemotherapy with the SH inhibitor oxophenarsine plus adjuncts, alone or in combination with other anticancer drugs which were picked in accord with sensitivity tests on each patient's own cancer.<sup>1</sup> From the work of Di Paolo<sup>2</sup>and Kondo<sup>3</sup>the sensitivity tests are now known to be
The Impact of National Press Coverage on Early Phase Clinical Trial Recruitment and Enrollment.
Authors: N. Bates, D. Higgins, J. Childs, M. Boettcher, L. Salazar, M. Disis
Journal: Cancer Research (2009)

Abstract The American Society of Clinical Oncologists reports that only 5% of cancer patients ultimately enroll in a clinical trial. According to the National Cancer Institute, one key barrier to participation is a lack of knowledge about clinical trials, both on behalf of oncologists and the patients themselves. Unfortunately, many investigator-initiated and academic clinical trials simply do not have budgets that permit implementation of large-scale recruitment efforts. Recent experience by our group demonstrates that press coverage by national media is a particularly effective tool for generating public interest in clinical research, as well as increasing trial enrollment.In the third quarter of 2008, our academic translational research group was featured on a national news program. In the week following the broadcast, our group's website, which had been listed in the broadcast and accompanying web story, received an unprecedented number of hits. Not only did the broadcast generate interest in our group's research; more specifically, it translated to substantial increases in potential clinical trial candidates, and subsequently, increased trial enrollment. In the month following the broadcast, our group received 125 new clinical trial inquiries as a result of the feature. That number represented a seven-fold increase in new inquiries during the same period in 2007. Of those 125 contacts, more than half of patients were potentially eligible for one of our clinical trials based on an initial screening. From November 2008 to the present, nearly one-third of all clinical trial enrollments can be attributed to the news story. Enrollment to the vaccine trial specifically described in the news feature increased four fold in comparison to the same 6-month period in 2008-2009, with half of all new enrollments attributable to the news feature. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6078.
Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain
Authors: Niroshana Anandasabapathy, Gabriel D. Victora, Matthew Meredith, Rachel Feder, Baojun Dong, Courtney Kluger, Kaihui Yao, Michael L. Dustin, Michel C. Nussenzweig, Ralph M. Steinman, Kang Liu
Journal: The Journal of Experimental Medicine (2011)

Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5–7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia.
‘Gamification’: Influencing health behaviours with games
Authors: Dominic King, Felix Greaves, Christopher Exeter, Ara Darzi
Journal: Journal of the Royal Society of Medicine (2013)

Every month at Google Campus in London, dozens of software developers, clinicians, behavioural scientists and investors get together to discuss new strategies to influence health behaviours. The collective aim of these networking events is to develop digital ‘games with purpose’ that can improve health by integrating software design and game mechanics with public health theory and behavioural insights. Gamification is a purposely-broad umbrella term used to encompass the process of using ‘gaming’ elements to motivate and engage people in non-game contexts.1 Enhanced opportunities now exist to deliver behaviour change interventions through game platforms on new smartphone devices.

Defying traditional stereotypes, people across demographic boundaries now play video games on a wide range of digital devices.2 Whilst such games continue to be primarily used for entertainment purposes, there is increasing interest in their potential to influence positive changes in health behaviours.3 This has been encouraged by the finding that rather than spending hours being sedentary and chasing intangible outcomes, players of active video games (e.g. Nintendo Wii Fit) are motivated to exert themselves to achieve activity goals through game mechanics.4,5

Whilst still in its infancy, we predict that gamification will become an increasingly familiar concept in healthcare as a consequence of two trends. The first builds on the consumer's appetite for new smartphone devices that provide games designers with a wider audience to target and more attractive tools to use in designing interactive health interventions. The second factor is the enthusiasm and willingness of developers to incorporate the latest behavioural insights into electronic interventions.
Oesophageal chest pain
Authors: H A. Davies, A M Dart, J Rhodes, A H Henderson
Journal: Gut (1984)

<h3>Objective</h3> Patients with liver cirrhosis suffer from increased susceptibility to life-threatening bacterial infections that cause substantial morbidity. <h3>Methods</h3> Experimental liver fibrosis in mice induced by bile duct ligation or CCl<sub>4</sub> application was used to characterise the mechanisms determining failure of innate immunity to control bacterial infections. <h3>Results</h3> In murine liver fibrosis, translocation of gut microbiota induced tonic type I interferon (IFN) expression in the liver. Such tonic IFN expression conditioned liver myeloid cells to produce high concentrations of IFN upon intracellular infection with <i>Listeria</i> that activate cytosolic pattern recognition receptors. Such IFN-receptor signalling caused myeloid cell interleukin (IL)-10 production that corrupted antibacterial immunity, leading to loss of infection-control and to infection-associated mortality. In patients with liver cirrhosis, we also found a prominent liver IFN signature and myeloid cells showed increased IL-10 production after bacterial infection. Thus, myeloid cells are both source and target of IFN-induced and IL-10-mediated immune dysfunction. Antibody-mediated blockade of IFN-receptor or IL-10-receptor signalling reconstituted antibacterial immunity and prevented infection-associated mortality in mice with liver fibrosis. <h3>Conclusions</h3> In severe liver fibrosis and cirrhosis, failure to control bacterial infection is caused by augmented IFN and IL-10 expression that incapacitates antibacterial immunity of myeloid cells. Targeted interference with the immune regulatory host factors IL-10 and IFN reconstitutes antibacterial immunity and may be used as therapeutic strategy to control bacterial infections in patients with liver cirrhosis.
Reducing Black Neonatal Mortality
Authors: Nancy J. Binkin
Journal: JAMA (1985)

To study some of the factors contributing to the higher rate of black neonatal mortality in the United States, we used matched cohort records for California between 1980 and 1981 and for Georgia between 1979 and 1981. We found that at any combination of birth weight and gestational age, black neonates weighing less than 3,000 g had lower mortality rates than whites, but this survival advantage was outweighed by considerably higher rates of low birth weight among blacks. At 3,000 g or more, whites had the survival advantage; even at optimal survival weight, the black mortality rate was nearly twice that for whites. If a reduction in the black mortality rate is to occur, improvements are needed both in the black birth-weight distribution and in birth-weight-specific mortality rates, particularly in the normal birth-weight ranges. (<i>JAMA</i>1985;253:372-375)
Reply to the Letter to the Editor from Arai et al.
Authors: Emily Abdoler, David Wendler
Journal: Clinical Cancer Research (2009)

In Response: We agree that payment to phase 0 oncology trial participants must be carefully considered. However, to the extent that healthy volunteers are paid to participate in research that does not offer the prospect of direct benefit, the same modest incentives should be considered for cancer patients who are enrolled in nonbeneficial studies. Research in the developing world raises additional concerns; yet, insofar as people in developing countries receive fair benefits, including, possibly, compensation for participating in research, phase 0 oncology trial participants in these regions should not be overlooked. Paying patients is a potential strategy for combating the therapeutic misconception in nonbeneficial research, and one of the key arguments against paying subjects, their receipt of medical treatment, is not applicable in the context of phase 0 trials (1).Arai and colleagues rightly point out that the population likely recruited to participate in phase 0 trials, terminally ill cancer patients, will not benefit directly from the research. Extending post-trial access to drugs that prove successful in phase III trials to patients who were enrolled in earlier-phase research is certainly worth evaluating; nevertheless, it may not be the best strategy to maximize benefits to participants. Many drugs fail before reaching even late-phase trials, and the late-stage cancer patients who participate in phase 0 trials may not survive to see successful drugs reach efficacy studies. One important policy to implement is to ensure that participants are not excluded from trials that may benefit them merely because of their previous participation in phase 0 studies (2, 3).No potential conflicts of interest were disclosed.We are grateful to Arai and colleagues for their comments.
Author's reply to Scott and colleagues and Gough and Foo
Authors: D. Spence
Journal: BMJ (2011)

No one disputes the importance of early treatment of rheumatoid arthritis.1 2 The central theme is whether the disease is over-diagnosed and over-treated. The epidemiological data are limited, but rates halved from 1955 to the late 1980s.3 Since then it has inexplicably increased but only in women.3 The terrible complications of rheumatoid …
Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia
Authors: Rainer Claus, David M. Lucas, Amy S. Ruppert, Katie E. Williams, Daniel Weng, Kara Patterson, Manuela Zucknick, Christopher C. Oakes, Laura Z. Rassenti, Andrew W. Greaves, Susan Geyer, William G. Wierda, Jennifer R. Brown, John G. Gribben, Jacqueline C. Barrientos, Kanti R. Rai, Neil E. Kay, Thomas J. Kipps, Peter Shields, Weiqiang Zhao, Michael R. Grever, Christoph Plass, John C. Byrd
Journal: Blood (2014)
Racial and Ethnic Differences in the Treatment of Acute Myocardial Infarction
Authors: Mauricio G. Cohen, Gregg C. Fonarow, Eric D. Peterson, Mauro Moscucci, David Dai, Adrian F. Hernandez, Robert O. Bonow, Sidney C. Smith
Journal: Circulation (2010)

Racial/ethnic differences in cardiovascular care have been well documented. We sought to determine whether racial/ethnic differences in evidence-based acute myocardial infarction care persist among hospitals participating in a national quality improvement program.
NHS review. Internal markets for surgical services: opportunity for trade in orthopaedics.
Authors: R. J. Fordham, R. J. Newman
Journal: BMJ (1989)

The white paper Working for Patients represents the cumulative achievement ofthe most radical free market proposals for the NHS since the government came into office in 1979.2 Change has occurred in a step wise fashion through several measures designed to alter the cultural norms of the health service. Increased local accountability, quicker decision making,3 the identification of key decision makers,4 contracting out of nonclinical services, cost improvement schemes and efficiency through the resource management initiative have all played a part in preparing the NHS for these latest reforms. The government has stopped short, however, of full privatisation in the face of continued overwhelming public and professional support for a tax based, zero priced health care system.5 The NHS review has instead introduced several free market principles, such as greater consumer sovereignty and increased competition among producers, while remaining within a state run framework. Greater choice and diversity of services in primary and secondary care are to be encouraged, with value for money and efficient use of resources being the ultimate goals.
Summary of other responses
Authors: Sharon Davies
Journal: BMJ (2007)

Westaby et al make a good case for not publishing unreliable outcome data based on hospital episode statistics (HES),1 but they miss what ought to be two important issues, says Stephen Black, a management consultant in London.

The first concerns how statistical information is presented. “Standard practice gives information to the public and to experts in a form almost guaranteed to mislead. This leads to the erroneous conclusion that members of the public can't …
Elevated circulating soluble CD30 levels in patients with polymyositis/dermatomyositis
Authors: N. Yazawa, H. Ihn, K. Yamane, M. Kubo, M. Fujimoto, K. Kikuchi, Y. Soma, K. Tamaki
Journal: British Journal of Dermatology (2001)

Journal Article Elevated circulating soluble CD30 levels in patients with polymyositis/dermatomyositis Get access N. Yazawa, N. Yazawa Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, JapanE‐mail: YAZAWA‐DER@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Ihn, H. Ihn Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, JapanE‐mail: YAZAWA‐DER@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Yamane, K. Yamane Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, JapanE‐mail: YAZAWA‐DER@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar M. Kubo, M. Kubo Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, JapanE‐mail: YAZAWA‐DER@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar M. Fujimoto, M. Fujimoto Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, JapanE‐mail: YAZAWA‐DER@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Kikuchi, K. Kikuchi Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, JapanE‐mail: YAZAWA‐DER@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Soma, Y. Soma Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, JapanE‐mail: YAZAWA‐DER@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Tamaki K. Tamaki Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, JapanE‐mail: YAZAWA‐DER@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 145, Issue 4, 1 October 2001, Pages 676–678, https://doi.org/10.1046/j.1365-2133.2001.04417.x Published: 01 October 2001
An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice
Authors: Morag A Lewis, Elizabeth Quint, Anne M Glazier, Helmut Fuchs, Martin Hrabé De Angelis, Cordelia Langford, Stijn van Dongen, Cei Abreu-Goodger, Matias Piipari, Nick Redshaw, Tamas Dalmay, Miguel Angel Moreno-Pelayo, Anton J Enright, Karen P Steel
Journal: Nature Genetics (2009)
Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome
Authors: Huai-Chia Chuang, Jong-Ding Lay, Wen-Chuan Hsieh, Hui-Ching Wang, Yao Chang, Shuang-En Chuang, Ih-Jen Su
Journal: Blood (2005)