tbuckley/cabot-search huggingface dataset:
Testing the role of vitamin D in response to antitumour necrosis factor α therapy in a UK cohort: a Mendelian randomisation approach
Authors: Annie Yarwood, Sebastien Viatte, Darren Plant, Ann W Morgan, John Isaacs, Anthony G Wilson, Kimme Hyrich, Steve Eyre, Anne Barton
Journal: Annals of the Rheumatic Diseases (2013)

Approximately 30% of rheumatoid arthritis (RA) patients fail to respond to anti-tumour necrosis factor (anti-TNF) treatment;1 hence, the ability to predict which patients will respond to treatment would represent a major clinical advance. Vitamin D has been implicated in many autoimmune diseases including RA; in addition, vitamin D has been shown to induce TNFα production by some immune cells leading to the hypothesis that vitamin D levels may influence anti-TNF treatment response.2 ,3 Several studies have now confirmed the association of genetic variants within four vitamin D metabolism genes ( GC, DHCR7/NADSYN1, CYP2R1, CYP24A1 ) with circulating vitamin D levels in healthy controls.4 ,5 In addition, single nucleotide polymorphisms (SNPs) in these genes have also been associated with autoimmune diseases.6 The association of the same variants in the same genes that control circulating levels of vitamin D with response to anti-TNF treatment provides an unbiased test of the hypothesis that vitamin D levels are important in response to these therapies (Mendelian randomisation).7 We, therefore, investigated the effect of vitamin D on response to anti-TNF therapy, testing six SNPs previously associated with circulating levels of vitamin D4 ,5 for association with response to anti-TNF therapy in RA patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) cohort (table 1), which includes patients recruited across the UK.8 SNPs were selected to capture by linkage disequilibrium (LD) (r2>0.8) 94.26% of SNPs previously associated with vitamin D levels in two previous studies.4 ,5 Multivariate linear and logistic regression was used to assess the effects of each SNP on treatment response measured by absolute change in Disease Activity Score in 28 joints (DAS28) over 6 months9 (n=1396) or in poor (n=237) versus good (n=322) responders according to European League …
Review: Dabigatran increases MI and reduces mortality compared with warfarin, enoxaparin, or placebo
Authors: John Cairns
Journal: Annals of Internal Medicine (2012)

Source Citation Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med. 2012;172:397-40. 22231617
ACT-R: A higher-level account of processing capacity
Authors: John R. Anderson, Christian Lebiere, Marsha Lovett, Lynne Reder
Journal: Behavioral and Brain Sciences (1998)

We present an account of processing capacity in the ACT-R theory. At the symbolic level, the number of chunks in the current goal provides a measure of relational complexity. At the subsymbolic level, limits on spreading activation, measured by the attentional parameter W, provide a theory of processing capacity, which has been applied to performance, learning, and individual differences data.
Stitching and switching: the impact of discontinuous lung function reference equations: Figure 1–
Authors: Jane Kirkby, Paul Aurora, Helen Spencer, Stephanie Rees, Samantha Sonnappa, Janet Stocks
Journal: European Respiratory Journal (2012)

To the Editors:

In order to distinguish the effects of lung disease from those of normal growth and development, lung function is expressed in comparison with reference data, with forced expiratory volume in 1 s (FEV1) commonly being presented as % predicted. FEV1 % pred has been identified as being of prognostic value in cystic fibrosis (CF), such that an FEV1 of  20% from baseline determined by the average of two measurements made ≥3 weeks apart. Continuing to monitor FEV1 % pred after the development of BOS has also been shown to provide important insight into the patient’s prognosis and therapeutic options [2].

Given that FEV1 % pred plays such a key role in the clinical management of a child with CF or any child who has undergone lung transplantation, it is imperative to ensure that it is measured and interpreted accurately. Although guidelines for standardised measurement of spirometry have been developed for both adults [3] and children [4], the decision on which spirometry reference equation to use, amongst the plethora available [5], varies widely. This situation is further complicated by …
The Postpericardiotomy Syndrome
Authors: Lewis M. Drusin, Mary Allen Engle, Jack W. C. Hagstrom, Melvin S. Schwartz
Journal: New England Journal of Medicine (1965)

THE postpericardiotomy syndrome as described by Ito et al.1,2 is a febrile illness with pericardial and sometimes pleuropulmonary reaction that follows extensive pericardiotomy. This clinical entity had originally been called postcommissurotomy syndrome because it was seen in some patients after mitral valvulotomy; it was thought to represent reactivation of rheumatic fever. Ito and her associates,1,2 however, pointed out that patients with no evidence of rheumatic heart disease had the identical postoperative reaction and that the common factor in both groups of patients was pericardiotomy with or without cardiotomy. A similar illness, the postmyocardial-infarction syndrome, was described by Dressier . . .
Harnessing the immune system to treat cancer
Authors: Nina Bhardwaj
Journal: Journal of Clinical Investigation (2007)

A major challenge for the immune system is to recognize and eliminate cells undergoing carcinogenesis. Immune defense against tumors is complex. It can be mediated early by the innate immune system (i.e., phagocytes, NK cells, NKT cells, cytokines, and complement proteins) and later by the adaptive immune system (i.e., B cells and T cells). The eight articles in this Review series on tumor immunology discuss the mechanisms underlying immune surveillance of tumors, the regulation of carcinogenesis by immune inflammatory mediators, current approaches to controlling tumor growth through immunotherapy, and novel targets of immunotherapy.
Debating the Risks of Drug-Eluting Stents
Authors: Miriam Shuchman
Journal: New England Journal of Medicine (2007)

Last September, a firestorm was ignited over drug-eluting stents when data were released showing an increase in the risk of late stent thrombosis. In response, the Food and Drug Administration (FDA) held an open meeting of its Circulatory System Devices Panel on December 7 and 8, 2006.1 The advisory group of about 20 academics and clinicians was sharply divided on the ramifications of the findings: a thoracic surgeon, on one side, argued that the new data necessitate a black-box warning; an interventional cardiologist, on the other side, said these data would barely change his practice. In part, the frequent disagreements . . .
The relationship between tumour NF-kB expression, hormone status, and clinicopathological factors in primary invasive breast cancer.
Authors: CL Tannahill, C Obondo, AM Al-Murri, JD Doughty, A Lannigan, CR Wilson, DC McMillan, J Edwards
Journal: Cancer Research (2009)

Abstract Abstract #4038 Breast cancer is one of the most common and lethal malignancies in the UK. Conventionally, prognosis is based on hormone status, tumour size, grade and lymph node involvement. Recently it has been proposed that Nuclear Factor Kappa B (NF-kB) is associated with breast cancer development and progression (1). The aim of the present study was to examine the relationship between NF-kB, hormone status and clinicopathological factors in primary invasive breast cancer.&amp;#x2028; Immunohistochemistry was performed on 168 breast tumour sections, with full clinicopathological characteristics. Antibodies were directed against total NF-kB and NF-kB phosphorylated at serine 536 (phospho NF-kB). Two observers independently scored expression using the weighted histoscore technique and grouped tumours as having high or low expression according to the median value.&amp;#x2028; Cytoplasmic and nuclear NF-kB expression, either total or phosphorylated did not correlate with grade, size or lymph node involvement. However, nuclear phospho NF-kB expression was inversely associated with Ki67 proliferation index (p&amp;lt;0.05). In addition an association between total nuclear NF-kB (p&amp;lt;0.050) and total cytoplasmic NF-kB (p&amp;lt;0.05) was observed with oestrogen (ER) and progesterone receptor (PR) status, total NF-kB expression was higher in ER and PR positive tumours (n=53) compared with ER negative and PR negative tumours (n=34). This association was also observed for nuclear phospho NF-kB (p&amp;lt;0.001) but not cytoplasmic phospho NF-kB (p=0.292). In addition, ER positive and PR negative tumours (n=78) had reduced nuclear phospho NF-kB (p&amp;lt;0.001) and cytoplasmic phospho NF-kB (p&amp;lt;0.001) expression when compared with ER positive and PR positive tumours (n=53).&amp;#x2028; These results suggest that reduced tumour expression of phospho NF-kb is associated with increased cell proliferation and PR negativity but not ER negativity in primary invasive breast cancer. The impact of such differential tumour expression of phospho NF-kB on outcome in breast cancer remains to be determined.&amp;#x2028; 1. Cao Y, Karin M. NF-kappaB in mammary gland development and breast cancer.J Mammary Gland Biol Neoplasia. 2003;8:215-23. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4038.
Cardiomyogenic induction of human mesenchymal stem cells by altered Rho family GTPase expression on dendrimer-immobilized surface with d-glucose display
Authors: Mee-Hae Kim, Masahiro Kino-oka, Nao Maruyama, Atsuhiro Saito, Yoshiki Sawa, Masahito Taya
Journal: Biomaterials (2010)
Kinship terminology: polysemy or categorization?
Authors: Lotte Hogeweg, Géraldine Legendre, Paul Smolensky
Journal: Behavioral and Brain Sciences (2010)

Abstract The target article offers an analysis of the categorization of kin types and empirical evidence that cross-cultural universals may be amenable to OT explanation. Since the analysis concerns the structuring of conceptual categories rather than the use of words, it differs from previous OT analyses in lexical semantics in what is considered to be the input and output of optimization.
RESISTANT HYPERTENSION IS ASSOCIATED WITH AN INCREASED RISK FOR INCIDENT HEART FAILURE IN THE ARIC STUDY
Authors: Orly Vardeny, Pardeep Jhund, Deepak Gupta, Susan Cheng, Flavio Fuchs, Brian Claggett, Josef Coresh, Kunihiro Matsushita, Jacqueline Wright, Scott Solomon
Journal: Journal of the American College of Cardiology (2014)
Thromboembolism in a Child
Authors: Kasem Sangbhundu
Journal: JAMA (1971)

<h3>To the Editor.—</h3> An 18-month-old boy was admitted to Harlem Hospital Center in New York city with extensive burns of the mouth and pharynx one-half hour after ingestion of a concentrated lye solution. <i>Initial treatment</i>consisted of orally given vinegar and milk and intravenous infusions including penicillin and dexamethasone. Respiratory distress secondary to laryngeal edema necessitated tracheostomy 11 hours after admission. At this time esophagoscopy revealed severe burns of the esophagus. On the fifth hospital day, a gastrostomy, through which he was subsequently fed, was performed. Dexamethasone, 2 mg every six hours, was given intramuscularly for the first eight days and subsequently 2 mg every eight hours. He did well, was active, and had normal vital signs until the 21st hospital day when he suddenly became blue, gasped a few times, and died. Autopsy revealed a blood clot extending from the pulmonary valve occluding the main pulmonary artery and both
Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action, by V. Di Marzo, D. Melck, T. Bisogno and L. De Petrocellis, Vol. 21, pp. 521–528.
Authors: V. Di Marzo, D. Melck, T. Bisogno, L. De Petrocellis
Journal: Trends in Neurosciences (1999)
The benefit and cost of prostate cancer early detection. The Investigators of the American Cancer Society-National Prostate Cancer Detection Project
Authors: P. J. Littrup, A. C. Goodman, C. J. Mettlin
Journal: CA A Cancer Journal for Clinicians (1993)

Cost-effectiveness calculations of prostate cancer early detection have not been possible due to the lack of any data demonstrating reduction in mortality from any test or procedure. Prior analyses focused only on cost assessments without consideration of any possible benefits. We used current data from three consecutive years of the American Cancer Society-National Prostate Cancer Detection Project to assess different economic perspectives of test performance, marginal costs, and benefit-cost analysis. The marginal cost, or cost per cancer, of digital rectal examination (DRE) markedly increased by the third year relative to several proposed prostate-specific antigen (PSA) scenarios. Sensitivity analysis for average cost showed that at 4 ng/ml, pricing PSA below $30 would be the most potent factor in potentially lowering costs. Analysis of receiver operator characteristic curves suggested that optimal performance for PSA may be at 3 ng/ml when combined with DRE or between 2 to 3 ng/ml when used alone. Benefit-cost calculations demonstrated that DRE when performed by highly skilled examiners had the lowest cost. However, DRE became one of the most costly detection scenarios when a minor decrease in performance was assumed. Sensitivity analysis demonstrated that the three most determinant parameters of net benefit, in decreasing order, are: specificity, benefits from earlier therapy, and prevalence. If a slightly more specific PSA assay is developed, the higher prevalence of clinically detectable prostate cancer could also make screening less costly than breast cancer screening. Under the assumptions of these analyses, the combination of PSA and DRE appears to represent an ethical and economical detection choice for individual patients in consultation with their physicians. Additional research is needed to quantify the significance of differences between different screening strategies.
Phase II Trial of MEK Inhibitor Selumetinib (AZD6244, ARRY-142886) in Patients with BRAFV600E/K-Mutated Melanoma
Authors: Federica Catalanotti, David B. Solit, Melissa P. Pulitzer, Michael F. Berger, Sasinya N. Scott, Tunc Iyriboz, Mario E. Lacouture, Katherine S. Panageas, Jedd D. Wolchok, Richard D. Carvajal, Gary K. Schwartz, Neal Rosen, Paul B. Chapman
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Test the hypothesis that in BRAF-mutated melanomas, clinical responses to selumetinib, a MEK inhibitor, will be restricted to tumors in which the PI3K/AKT pathway is not activated. Experimental Design: We conducted a phase II trial in patients with melanoma whose tumors harbored a BRAF mutation. Patients were stratified by phosphorylated-AKT (pAKT) expression (high vs. low) and treated with selumetinib 75 mg per os twice daily. Pretreatment tumors were also analyzed for genetic changes in 230 genes of interest using an exon-capture approach. Results: The high pAKT cohort was closed after no responses were seen in the first 10 patients. The incidence of low pAKT melanoma tumors was low (∼25% of melanomas tested) and this cohort was eventually closed because of poor accrual. However, among the five patients with melanoma accrued in the low pAKT cohort, there was one partial response (PR). Two other patients had near PRs before undergoing surgical resection of residual disease (one patient) or discontinuation of treatment due to toxicity (one patient). Among the two nonresponding, low pAKT patients with melanoma, co-mutations in MAP2K1, NF1, and/or EGFR were detected. Conclusions: Tumor regression was seen in three of five patients with BRAF-mutated, low pAKT melanomas; no responses were seen in the high pAKT cohort. These results provide rationale for co-targeting MEK and PI3K/AKT in patients with BRAF mutant melanoma whose tumors express high pAKT. However, the complexity of genetic changes in melanoma indicates that additional genetic information will be needed for optimal selection of patients likely to respond to MEK inhibitors. Clin Cancer Res; 19(8); 2257–64. ©2013 AACR.
SKIN TESTING WITH COSMETICS
Authors: Norman R. Goldsmith
Journal: JAMA (1952)

<h3>To the Editor:—</h3> Our attention was called to the fallacy of the preliminary tests patients make on themselves, supposedly to assure their safety from irritation of certain substances, often cosmetics and especially hair dyes. Recently, we have seen cases of severe dermatitis of the face, neck, and ears among women who first proudly, and then with disillusionment, stated, "I did the test just as the manufacturer told me to, and now look at me!" This is the fallacy. Apparently, neither patients nor some manufacturers realize that a test done on the normal body will be negative, but that after exposure there is a period during which sensitization develops, and the same test performed a week or so later may prove quite positive. Thus, a woman will apply a hair dye convincingly ballyhooed and obtain no reaction from her first test; then, when she uses the product two or three weeks
Rho-kinase inhibition prevents the progression of diabetic nephropathy by downregulating hypoxia-inducible factor 1α
Authors: Keiichiro Matoba, Daiji Kawanami, Rina Okada, Masami Tsukamoto, Jun Kinoshita, Tomoko Ito, Sho Ishizawa, Yasushi Kanazawa, Tamotsu Yokota, Noriyuki Murai, Senya Matsufuji, Junko Takahashi-Fujigasaki, Kazunori Utsunomiya
Journal: Kidney International (2013)
Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications
Authors: Rong-Ze Yang, Mi-Jeong Lee, Hong Hu, Toni I Pollin, Alice S Ryan, Barbara J Nicklas, Soren Snitker, Richard B Horenstein, Kristen Hull, Nelson H Goldberg, Andrew P Goldberg, Alan R Shuldiner, Susan K Fried, Da-Wei Gong
Journal: PLoS Medicine (2006)

Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood.Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006), as well as in those treated with rosiglitazone (p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%.A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance with weight loss and rosiglitazone therapy may in part be mediated by decreases in adipocyte A-SAA production.
Expert panel will assess cost effectiveness of health checks
Authors: M. Gould
Journal: BMJ (2013)

An expert panel is to be established to review the effectiveness and value for money of NHS Health Checks, the £300m (€350m; $470m) a year screening programme for 40 to 74 year olds designed to identify and tackle early indicators of heart disease, stroke, and diabetes.

The announcement by Public Health England comes after repeated calls for the programme to be scrapped because evidence indicated that the checks were a waste of time and money. In a letter to the Times on Tuesday,1 Lasse Krogsboll and colleagues from the Nordic Cochrane Centre in Copenhagen said that their review published in the BMJ in October last year of 14 trials with a total of over 182 000 participants “could not find any beneficial effects of health checks, whereas they likely lead to unnecessary diagnoses and treatments.”2

They wrote, “Screening healthy people for disease or risk factors is justified only if there is …
The diagnosis of asthma using a self‐questionnaire in those suffering from allergic rhinitis: a pharmaco‐epidemiological survey in everyday practice in France
Authors: P. Demoly, M.‐C. Bozonnat, P. Dacosta, J.‐P. Daures
Journal: Allergy (2006)

All recent guidelines recommend a search for asthma utilizing both specific interrogation and pulmonary function tests in patients suffering from allergic rhinitis. Although the mandatory place of spirometry has not been confirmed, a self-questionnaire containing nine specific questions on asthma symptoms in different daily life situations was found to be capable of discriminating asthmatics from nonasthmatics in a rhinitic population.We addressed the questions of prevalence of asthma using a validated self-questionnaire and what might be the risk factors of being asthmatic according to that specific self-questionnaire.Between April 2003 and September 2004, nearly 12,000 rhinitis patients were enrolled by more than 2300 physicians (78% general practitioners, 22% ear nose and throat specialists). Patients were consulting for an exacerbation of chronic rhinitis and did not have a previous diagnosis of asthma. Both doctors and patients filled out a specific questionnaire on rhinitis and asthma.Almost 30% of the patients had at least three positive answers to the self-questionnaire and could possibly be considered as asthmatics. We found five independent clinical risk factors for having >or=3 positive answers to the self-questionnaire. Severity of rhinitis (moderate-severe vs mild, OR=1.84; 95% CI=1.68-2.00), diagnosis of allergy (yes vs no) (OR=1.86; 95% CI=1.68-2.00), body mass index (<or=18.5 vs >30) (OR=0.51; 95% CI=0.39-0.66), type of rhinitis (persistent vs intermittent) (OR=1.25; 95% CI=1.15-1.37), and patient age (<or=25 vs >47) (OR=0.73; 95% CI=0.65-0.80).Asthma symptoms are frequent in rhinitics without a prior history of asthma. Several variables were shown to be predictive of asthma in these patients.
Screening for scoliosis: the problem of arm length.
Authors: A J Stirling, R M Smith, R A Dickson
Journal: BMJ (1986)

Les tests en position penchee en avant font partie du depistage de la scoliose chez l'enfant et de la surveillance de l'evolution. Les mesures faites au moyen du «scoliometre» gagnent en precision si on tient compte de la difference de longueur des bras, frequente dans la scoliose idiopathique. Les mesures sont faites avec differentes positions des bras
HIV prevalence in China: integration of surveillance data and a systematic review
Authors: Lei Zhang, Eric P F Chow, Jun Jing, Xun Zhuang, Xiaoshan Li, Meiqi He, Huamin Sun, Xiaoyan Li, Marelize Gorgens, David Wilson, Lan Wang, Wei Guo, Dongming Li, Yan Cui, Lu Wang, Ning Wang, Zunyou Wu, David P Wilson
Journal: The Lancet Infectious Diseases (2013)