tbuckley/cabot-search huggingface dataset:
The effectiveness of once-daily dosing of inhaled flunisolide in maintaining asthma control☆, ☆☆, ★, ★★
Authors: R ZUWALLACK, J ROSEN, L COHEN, G RACHELEFSKY, H GONGJR, A GOLDSOBEL, M KALINER, M WHITE, E BRONSKY, P CHERVINSKY
Journal: Journal of Allergy and Clinical Immunology (1997)
Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity
Authors: Peng H. Tan, Helen E.J. Tyrrell, Liquan Gao, Danmei Xu, Jianchao Quan, Dipender Gill, Lena Rai, Yunchuan Ding, Gareth Plant, Yuan Chen, John Z. Xue, Ashok I. Handa, Michael J. Greenall, Kenneth Walsh, Shao-An Xue
Journal: Cancer Research (2014)

Immune escape is a fundamental trait of cancer. Dendritic cells (DC) that interact with T cells represent a crucial site for the development of tolerance to tumor antigens, but there remains incomplete knowledge about how DC-tolerizing signals evolve during tumorigenesis. In this study, we show that DCs isolated from patients with metastatic or locally advanced breast cancer express high levels of the adiponectin receptors AdipoR1 and AdipoR2, which are sufficient to blunt antitumor immunity. Mechanistic investigations of ligand-receptor interactions on DCs revealed novel signaling pathways for each receptor. AdipoR1 stimulated IL10 production by activating the AMPK and MAPKp38 pathways, whereas AdipoR2 modified inflammatory processes by activating the COX-2 and PPARγ pathways. Stimulation of these pathways was sufficient to block activation of NF-κB in DC, thereby attenuating their ability to stimulate antigen-specific T-cell responses. Together, our findings reveal novel insights into how DC-tolerizing signals evolve in cancer to promote immune escape. Furthermore, by defining a critical role for adiponectin signaling in this process, our work suggests new and broadly applicable strategies for immunometabolic therapy in patients with cancer.
How to increase the value of randomised trials in COPD research
Authors: M. A. Puhan, H. J. Schünemann
Journal: European Respiratory Journal (2009)

Methodological criteria that increase the validity of randomised trials are often not considered in respiratory research, even in large chronic obstructive pulmonary disease (COPD) trials. We describe four important aspects in the design, analysis and reporting of randomised trials, selected based on their relevance to current COPD research and based on our judgments of importance for researchers and users of the literature. First, to optimally control for confounding, where confounding refers to a factor that is associated with an exposure or intervention and influences the outcome, a clear definition of the main relationship between treatment and the primary outcome as well as identification of measurable confounders is required. In addition to randomisation per se as the key method to protect against confounding, restriction (excluding patients with specific characteristics that may introduce confounding), stratification (separate randomisation of patients with specific characteristics) and statistical adjustment are means to be considered to optimally control for confounding that simple randomisation may not achieve. Secondly, the selection of the primary outcome should be guided by the importance to patients. Secondary outcomes provide hypotheses about the effects observed for the primary outcome and can provide important data for systematic reviews and meta-analyses, but should be interpreted with caution in single trials. Thirdly, in study power calculations, not only the actual sample size, but the number of events, has a large influence on the power of the study and, often, unrealistic assumptions about event rates are made to increase the feasibility of trials. Finally, essential steps to transfer results from research to practice include complete reporting of trials and developing tools, such as decision aids, to support patients and physicians in their shared decision making.
Molecular Biology of Hereditary Diabetes Insipidus
Authors: T. Mary Fujiwara, Daniel G. Bichet
Journal: Journal of the American Society of Nephrology (2005)

The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A "pure" type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients.
Determinants of adherence in adults with cystic fibrosis
Authors: L J Kettler
Journal: Thorax (2002)

Cystic fibrosis (CF) is now as much a disease of adults as of children and adolescents. An important focus of recent research has been the impact of the complex, expensive, and time consuming routine of self-care and medical treatment that is required by adults with CF to maintain health. A growing concern for medical and allied health teams is the issue of patient adherence to prescribed health management plans. A summary of the particular medical and treatment context of CF is followed by a review of adherence measurement issues and the determinants of adherence to treatment regimens in people with CF, primarily adults. Evidence for factors which influence adherence decisions of people with CF is examined. The medical and psychological aspects of this complex problem have not been adequately addressed because of difficulties with definition and measurement. Only a small proportion of the variance in adherence has been accounted for in the literature. New measurement technologies and new theoretical directions offer promise for a better understanding of this complex and important issue and may result in more effective intervention strategies to improve adherence.
Relation between Q fever notifications and Coxiella burnetii infections during the 2009 outbreak in the Netherlands
Authors: W van der Hoek, B M Hogema, F Dijkstra, A Rietveld, C J Wijkmans, P M Schneeberger, H L Zaaijer
Journal: Eurosurveillance (2012)

Binary file ES_Abstracts_Final_ECDC.txt matches
Colorectal cancer: a model for epigenetic tumorigenesis
Authors: J J L Wong, N J Hawkins, R L Ward
Journal: Gut (2006)

Recent advances in basic and clinical science have driven epigenetics to the forefront of cancer research.Together with genetic changes, the disruption of epigenetic mechanisms is now established as a hallmark of human cancer.Colorectal cancer, long a classical model for the genetic basis of cancer, is now providing researchers with the opportunity to view epigenetic events in the context of human neoplasia.Knowledge of the heritable changes in gene expression that result from epigenetic events is of increasing relevance to clinical practice, particularly in terms of diagnostic and prognostic molecular markers, as well as novel therapeutic targets.
Change in diameter of coronary artery segments adjacent to stenosis after percutaneous transluminal coronary angioplasty: Failure of percent diameter stenosis measurement to reflect morphologic changes induced by balloon dilation
Authors: Kevin J. Beatt, Hans E. Luijten, Pim J. de Feyter, Marcel van den Brand, Johan H.C. Reiber, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (1988)
Direct binding of Nur77/NAK-1 to the plasminogen activator inhibitor 1 (PAI-1) promoter regulates TNFα-induced PAI-1 expression
Authors: Florian Gruber, Peter Hufnagl, Renate Hofer-Warbinek, Johannes A. Schmid, Johannes M. Breuss, Renate Huber-Beckmann, Markus Lucerna, Nikolina Papac, Hanna Harant, Ivan Lindley, Rainer de Martin, Bernd R. Binder
Journal: Blood (2003)
Doctors' emotional reactions to recent death of a patient: cross sectional study of hospital doctors
Authors: E. M Redinbaugh
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b>: To describe doctors9 emotional reactions to the recent death of an "average" patient and to explore the effects of level of training on doctors9 reactions. <b>Design</b>: Cross sectional study using quantitative and qualitative data. <b>Setting</b>: Two academic teaching hospitals in the United States. <b>Participants</b>: 188 doctors (attending physicians (equivalent to UK consultants), residents (equivalent to UK senior house officers), and interns (equivalent to UK junior house officers)) who cared for 68 patients who died in the hospital. <b>Main outcome measures</b>: Doctors9 experiences in providing care, their emotional reactions to the patient9s death, and their use of coping and social resources to manage their emotions. <b>Results</b>: Most doctors (139/188, 74%) reported satisfying experiences in caring for a dying patient. Doctors reported moderate levels of emotional impact (mean 4.7 (SD 2.4) on a 0-10 scale) from the death. Women and those doctors who had cared for the patient for a longer time experienced stronger emotional reactions. Level of training was not related to emotional reactions, but interns reported needing significantly more emotional support than attending physicians. Although most junior doctors discussed the patient9s death with an attending physician, less than a quarter of interns and residents found senior teaching staff (attending physicians) to be the most helpful source of support. <b>Conclusions</b>: Doctors who spend a longer time caring for their patients get to know them better but this also makes them more vulnerable to feelings of loss when these patients die. Medical teams may benefit from debriefing within the department to give junior doctors an opportunity to share emotional responses and reflect on the patient9s death.
MPs say more public education is needed before the drink drive limit can be reduced
Authors: A. O'Dowd
Journal: BMJ (2010)

Hopes from doctors’ leaders that the drink driving limit would be reduced soon to help prevent car crashes and save lives have been dashed by MPs.

MPs on the parliamentary transport committee have published a report that says the government should aim for an “effectively zero” limit of 20 mg alcohol per 100 ml of blood in place of the current drink drive limit of 80 mg per 100 ml.

This, however, is a long term aim, says the report which calls for police to be given stronger enforcement powers and for ministers to retain the current 12 month mandatory disqualification minimum penalty.

The committee’s inquiry followed the publication of an independent …
Homocysteine Impairs the Nitric Oxide Synthase Pathway
Authors: Markus C. Stühlinger, Philip S. Tsao, Jeng-Horng Her, Masumi Kimoto, Robert F. Balint, John P. Cooke
Journal: Circulation (2001)

Background Hyperhomocysteinemia is a putative risk factor for cardiovascular disease, which also impairs endothelium-dependent vasodilatation. A number of other risk factors for cardiovascular disease may exert their adverse vascular effects in part by elevating plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. Accordingly, we determined if homocysteine could increase ADMA levels. Methods and Results When endothelial or nonvascular cells were exposed to DL-homocysteine or to its precursor L-methionine, ADMA concentration in the cell culture medium increased in a dose- and time-dependent fashion. This effect was associated with the reduced activity of dimethylarginine dimethylaminohydrolase (DDAH), the enzyme that degrades ADMA. Furthermore, homocysteine-induced accumulation of ADMA was associated with reduced nitric oxide synthesis by endothelial cells and segments of pig aorta. The antioxidant pyrrollidine dithiocarbamate preserved DDAH activity and reduced ADMA accumulation. Moreover, homocysteine dose-dependently reduced the activity of recombinant human DDAH in a cell free system, an effect that was due to a direct interaction between homocysteine and DDAH. Conclusion Homocysteine post-translationally inhibits DDAH enzyme activity, causing ADMA to accumulate and inhibit nitric oxide synthesis. This may explain the known effect of homocysteine to impair endothelium-mediated nitric oxide–dependent vasodilatation.
Evaluation of the appropriateness of composite disease activity measures for assessment of psoriatic arthritis
Authors: Valerie P Nell-Duxneuner, Tanja A Stamm, Klaus P Machold, Stephan Pflugbeil, Daniel Aletaha, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2009)

Specific composite indices assessing disease activity in psoriatic arthritis (PsA) have not yet been sufficiently validated. The objective of this study was to identify instruments best reflecting disease activity in PsA.Measures for inclusion in clinical trials, as recommended by the OMERACT-7/8 PsA workshops, were assessed. A principal component analysis (PCA) was performed with cross-sectional data of 105 patients with PsA to identify a minimal set of important dimensions for a disease activity assessment tool for PsA. This was compared with components contained in existing composite indices.The PCA revealed four principal components best reflecting disease activity. The first contained patient global and pain assessment; the second contained 66/68 swollen and tender joint counts as main variables; C-reactive protein (CRP) best loaded to the third component; and the fourth was loaded by skin assessment but did not reach significance. When comparing the three significant principal components with items of established composite measures, they were best covered by the Disease Activity Index for Reactive Arthritis (DAREA) which comprises patient pain and global assessments, 66/68 joint counts and CRP.Among the currently available indices used in arthritic conditions, the DAREA best reflects the domains found to be important in PsA.
Using Qualitative Evidence in Decision Making for Health and Social Interventions: An Approach to Assess Confidence in Findings from Qualitative Evidence Syntheses (GRADE-CERQual)
Authors: Simon Lewin, Claire Glenton, Heather Munthe-Kaas, Benedicte Carlsen, Christopher J. Colvin, Metin Gülmezoglu, Jane Noyes, Andrew Booth, Ruth Garside, Arash Rashidian
Journal: PLoS Medicine (2015)

Simon Lewin and colleagues present a methodology for increasing transparency and confidence in qualitative research synthesis.
Soft Tissue Sarcoma and Military Service in Vietnam: A Case-Control Study
Authors: H Kang, F M Enzinger, P Breslin, M Feil, Y Lee, B Shepard, F Enziger
Journal: JNCI Journal of the National Cancer Institute (1987)

A case-control study was conducted in men who were of draftable age during the Vietnam conflict to examine the association of soft tissue sarcomas (STSs) with military service in Vietnam as well as other host and environmental risk factors. A total of 217 STS cases selected from the Armed Forces Institute of Pathology were compared to 599 controls for Vietnam service, occupational and nonoccupational exposure to various chemicals, occupational history, medical history, and life-style (smoking, alcohol, coffee, etc.). Military service information was verified by a review of the patient's military personnel records. Other information was ascertained from a telephone interview with either subjects or their next of kin. Cases and controls were stratified on the basis of the hospital type (civilian, Veterans Administration, and military); the Mantel-Haenszel estimate of the odds ratio (OR), adjusted for the effects of the stratification variable, was calculated. Vietnam veterans in general did not have an increased risk of STS when compared to those men who had never been in Vietnam (OR, 0.85; 95% confidence interval, 0.54-1.36). Subgroups of Vietnam veterans who had higher estimated opportunities for Agent Orange exposure seemed to be at greater risk of STSs when their counterparts in Vietnam were taken as a reference group. However, this risk was not statistically significant.
Genetics of toll like receptor 9 in ANCA associated vasculitides
Authors: C A Husmann, J U Holle, F Moosig, S Mueller, B Wilde, J W Cohen Tervaert, L Harper, G Assmann, W L Gross, J T Epplen, S Wieczorek
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To investigate the contribution of genetic polymorphisms of toll like receptor (TLR) 9 and related genes on the susceptibility and clinical manifestation of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV). <h3>Methods</h3> Four single nucleotide polymorphisms (SNPs) in <i>TLR9</i> were genotyped in 863 German AAV cases and 1344 healthy controls. Significant results were replicated in a cohort of 426 Dutch and British AAV cases. 11 polymorphisms in TLR9 related genes were studied concomitantly. <h3>Results</h3> A strong association of TLR9 genotypes and haplotypes with granulomatosis with polyangiitis was observed as well as a contrariwise association with microscopic polyangiitis. The association was confirmed when cases were compared according to ANCA status rather than to clinical entity. This was partly replicated in the second cohort leading to a striking overall difference in TLR9 allele/haplotype frequencies between proteinase 3 (PR3) ANCA+ and myeloperoxidase (MPO) ANCA+ cases (p=0.00000398, pc=0.000016, OR 1.68 (95% CI 1.35 to 2.1) for rs352140; p=0.000011, pc=0.000044, OR 1.64 (95% CI 1.31 to 2.04) for a 3-SNP haplotype). No significant association or epistatic effect was detected for TLR9 related genes: interleukin 6, interleukin 23 receptor, myeloid differentiation primary response 88, TNF receptor-associated factor 6, interleukin-1 receptor-associated kinase 4, discs large homolog 5 and nucleotide-binding oligomerisation domain containing 2. <h3>Conclusions</h3> We provide further evidence that PR3-ANCA+ AAV differs genetically from MPO-ANCA+ AAV. TLR9 signalling may be involved in disease pathology, favouring models of infectious agents triggering AAV development.
GPs will have to perform well to earn a "quality premium" in shake up of commissioning
Authors: A. O'Dowd
Journal: BMJ (2010)

A part of GPs’ income will in future be allocated only to those doctors who are part of a successful commissioning group, under government plans to shake up the NHS.

The fact that doctors will have to perform well as commissioners to earn so called “quality premiums” was revealed by the Department of Health for England on 22 July in a consultation document that put more flesh on the bones of the recent white paper ( BMJ 2010;341:c3796, 14 Jul, doi:10.1136/bmj.c3796).

The consultation document, Liberating the NHS: Commissioning for Patients , gives details of how the new system will work when control of most of the NHS’s budget passes to GP commissioning groups called consortiums while primary care trusts and strategic health authorities are phased out by 2013.

A part of a general practice’s …
Personalized Medicine: What Exactly Is It and Can We Truly Measure It?
Authors: Catherine M. Kelly, Kathleen I. Pritchard
Journal: Journal of Clinical Oncology (2012)

For years, oncologists have agonized over the appropriate treatment of patients with estrogen receptor–positive, human epidermal growth factor receptor 2–negative, lymph node–negative breast cancer. Consultations involve weighing the risk of recurrence against estimated harms and benefits of treatment as perceived by both physician and patient. Gene expression profiling (GEP), using multivariate models to predict an individual’s risk of recurrence, has found a niche within this molecularly distinct breast cancer subgroup. In the article that accompanies this editorial, Hassett et al 1 studied temporal trends in the use of GEP, identified predictors of GEP, and examined the influence of GEP on chemotherapy use across low–, intermediate–, and high– clinical risk groups as defined by the National Comprehensive Cancer Network (NCCN) clinical practice guidelines. Two tests were commercially available during the study period (Oncotype DX [Genomic Health, Redwood City, CA] and MammaPrint [Agendia, Irvine, CA]); however, the study involved Oncotype DX because it was the most widely used GEP in this patient cohort. This study 1 was conducted using the NCCN breast cancer out
Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment
Authors: Ronald C. Petersen, Ronald G. Thomas, Michael Grundman, David Bennett, Rachelle Doody, Steven Ferris, Douglas Galasko, Shelia Jin, Jeffrey Kaye, Allan Levey, Eric Pfeiffer, Mary Sano, Christopher H. van Dyck, Leon J. Thal
Journal: New England Journal of Medicine (2005)

Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease.
The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia
Authors: Karen A. Fagan, Brian W. Fouty, Robert C. Tyler, Kenneth G. Morris, Lisa K. Hepler, Koichi Sato, Timothy D. LeCras, Steven H. Abman, Howard D. Weinberger, Paul L. Huang, Ivan F. McMurtry, David M. Rodman
Journal: Journal of Clinical Investigation (1999)

Acute hypoxic vasoconstriction and development of hypoxic pulmonary hypertension (PHTN) are unique properties of the pulmonary circulation. The pulmonary endothelium produces vasoactive factors, including nitric oxide (NO), that modify these phenomena. We tested the hypothesis that NO produced by endothelial nitric oxide synthase (eNOS) modulates pulmonary vascular responses to hypoxia using mice with targeted disruption of the eNOS gene (eNOS–/–). Marked PHTN was found in eNOS–/– mice raised in mild hypoxia when compared with either controls or eNOS–/– mice raised in conditions simulating sea level. We found an approximate twofold increase in partially and fully muscularized distal pulmonary arteries in eNOS–/– mice compared with controls. Consistent with vasoconstriction being the primary mechanism of PHTN, however, acute inhalation of 25 ppm NO resulted in normalization of RV pressure in eNOS–/– mice. In addition to studies of eNOS–/– mice, the dose–effect of eNOS was tested using heterozygous eNOS+/– mice. Although the lungs of eNOS+/– mice had 50% of normal eNOS protein, the response to hypoxia was indistinguishable from that of eNOS–/– mice. We conclude that eNOS-derived NO is an important modulator of the pulmonary vascular response to chronic hypoxia and that more than 50% of eNOS expression is required to maintain normal pulmonary vascular tone.