tbuckley/cabot-search huggingface dataset:
Integrated epigenomics identifies<i>BMP4</i>as a modulator of cisplatin sensitivity in gastric cancer
Authors: Tatiana Ivanova, Hermioni Zouridis, Yonghui Wu, Lai Ling Cheng, Iain Beehuat Tan, Veena Gopalakrishnan, Chia Huey Ooi, Julian Lee, Luo Qin, Jeanie Wu, Minghui Lee, Sun Young Rha, Dan Huang, Natalia Liem, Khay Guan Yeoh, Wei Peng Yong, Bin Tean Teh, Patrick Tan
Journal: Gut (2012)

<h3>Objective</h3> Cisplatin is a widely used gastric cancer (GC) chemotherapy; however, genetic factors regulating GC responses to cisplatin remain obscure. Identifying genes regulating cisplatin resistance could aid clinicians in tailoring treatments, by distinguishing cisplatin sensitive patients from those who might benefit from alternative platinum therapies, and highlight novel targeted strategies for overcoming cisplatin resistance. Here integrated epigenomics is applied to identify genes associated with GC cisplatin resistance. <h3>Design</h3> 20 GC cell lines were subjected to gene expression profiling, DNA methylation profiling and drug response assays. The molecular data were integrated to identify genes highly expressed and unmethylated specifically in cisplatin-resistant lines. Candidate genes were functionally tested by several <i>in vitro</i> and <i>in vivo</i> assays. Clinical impact of candidate genes was also assessed in a cohort of 197 GC patients. <h3>Results</h3> Epigenomic analysis identified bone morphogenetic protein 4 (<i>BMP4</i>) as an epigenetically regulated gene highly expressed in cisplatin-resistant lines. Functional assays confirmed that <i>BMP4</i> is necessary and sufficient for the expression of several prooncogenic traits, likely mediated through stimulation of the epithelial-mesenchymal transition. In primary tumours, <i>BMP4</i> promoter methylation levels were inversely correlated with <i>BMP4</i> expression, and patients with high <i>BMP4</i>-expressing tumours exhibited significantly worse prognosis. Therapeutically, targeted genetic inhibition of <i>BMP4</i> caused significant sensitisation of GC cells to cisplatin. Notably, <i>BMP4</i>-expressing GCs also did not exhibit cross resistance to oxaliplatin. <h3>Conclusions</h3> <i>BMP4</i> epigenetic and expression status may represent promising biomarkers for GC cisplatin resistance. Targeting <i>BMP4</i> may sensitise GC cells to cisplatin. Oxaliplatin, a clinically acceptable cisplatin alternative, may represent a potential therapeutic option for <i>BMP4</i>-positive GCs.
Direct-to-Consumer Advertising of Genetic Testing
Authors: Sarah E. Gollust, Sara Chandros Hull, Benjamin Wilfond
Journal: JAMA (2003)

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Insulin-stimulated release of d-chiro-inositol–containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome
Authors: Kai I. Cheang, Jean-Patrice Baillargeon, Paulina A. Essah, Richard E. Ostlund, Teimuraz Apridonize, Leila Islam, John E. Nestler
Journal: Metabolism (2008)
Is the blood B-cell subset profile diagnostic for Sjögren syndrome?
Authors: A Binard, L Le Pottier, V Devauchelle-Pensec, A Saraux, P Youinou, J-O Pers
Journal: Annals of the Rheumatic Diseases (2008)

Objective: To evaluate the relevance of the blood B-cell subset profile for the diagnosis of Sjögren syndrome. Methods: The distribution of mature blood B cells from Bm1 through Bm5 was determined in 161 patients, of whom 25 fulfilled the American–European Consensus Group criteria for primary SS (pSS), and 136 served as disease controls. Results: The percentage of Bm2 and Bm2′ cells was increased in the patients with pSS compared with 54 patients with rheumatoid arthritis (RA) and 18 with systemic lupus erythematosus (SLE) (p&lt;0.001 for the two comparisons). In contrast, those of early Bm5 (eBm5) and Bm5 were decreased in patients with pSS, compared with patients with RA and with SLE (p&lt;0.001 for the two comparisons). The receiver operating characteristic curves allowed for an optimising cut-off value of Bm2+Bm2′ cells at 71.1% for 88.0% sensitivity and 83.1% specificity, that of eBm5+Bm5 cells at ⩽13.5% for 84.0% sensitivity and 83.1% specificity, and, consequently, that of Bm2+Bm2′/eBm5+Bm5 at ⩾5 for 88.0% sensitivity and 84.6% specificity. Conclusion: Given its presentation as a signature for pSS, relative to RA and SLE, such a distribution of B-cell subsets might provide a useful diagnostic tool.
The Lausanne recommendations: a Dutch experience
Authors: B Bessem, F P Groot, W Nieuwland
Journal: British Journal of Sports Medicine (2009)

Objective: This study presents the results of 28 months of preparticipation cardiovascular screening using the Lausanne recommendations, which include a personal and family history, physical examination and electrocardiogram (ECG). Design: From January 2006 to April 2008 the data of the Lausanne screenings carried out at the University Centre of Sports Medicine in Groningen were collected. Participants: 825 cardiovascular screenings were performed of which 397 were excluded. Exclusion criteria were age under 12 or over 35 years, multiple screenings (only the first was included) and known cardiovascular disease. Main outcome measures: Negative screening result, (false) positive screening result, medical consumption and number needed to screen. Results: A total of 371 (87%) athletes had a negative screening result. Fifty-five athletes (13%) underwent additional (stage 2) testing and seven (1.6%) further (stage 3) testing. Only 27 athletes (6.3%) were referred for additional testing based only on abnormalities of their ECG. Forty-seven athletes (11%) had a false-positive screening result. Ten athletes (2%) had a positive screening result and three (0.7%) were ultimately restricted from sports participation. Stage 2 medical consumption was 62%, 20% and 18% for one, two and three or more additional tests, respectively. Stage 3 medical consumption was 1.6%. The number of athletes needed to screen to find a single athlete with a potentially lethal cardiovascular disease was 143. Conclusion: This study found that when the Lausanne recommendations are implemented in The Netherlands, screening results resemble those found in previous studies. The number of athletes needed to screen to detect one athlete with a potentially lethal cardiovascular disease is also within an acceptable range.
Relations of Dietary Magnesium Intake to Biomarkers of Inflammation and Endothelial Dysfunction in an Ethnically Diverse Cohort of Postmenopausal Women
Authors: Sara A. Chacko, Yiqing Song, Lauren Nathan, Lesley Tinker, Ian H. de Boer, Fran Tylavsky, Robert Wallace, Simin Liu
Journal: Diabetes Care (2009)

OBJECTIVE Although magnesium may favorably affect metabolic outcomes, few studies have investigated the role of magnesium intake in systemic inflammation and endothelial dysfunction in humans. RESEARCH DESIGN AND METHODS Among 3,713 postmenopausal women aged 50–79 years in the Women's Health Initiative Observational Study and free of cardiovascular disease, cancer, and diabetes at baseline, we measured plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), turnor necrosis factor-α receptor 2 (TNF-α-R2), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin. Magnesium intake was assessed using a semiquantitative food frequency questionnaire. RESULTS After adjustment for age, ethnicity, clinical center, time of blood draw, smoking, alcohol, physical activity, energy intake, BMI, and diabetes status, magnesium intake was inversely associated with hs-CRP (P for linear trend = 0.003), IL-6 (P &amp;lt; 0.0001), TNF-α-R2 (P = 0.0006), and sVCAM-1 (P = 0.06). Similar findings remained after further adjustment for dietary fiber, fruit, vegetables, folate, and saturated and trans fat intake. Multivariable-adjusted geometric means across increasing quintiles of magnesium intake were 3.08, 2.63, 2.31, 2.53, and 2.16 mg/l for hs-CRP (P = 0.005); 2.91, 2.63, 2.45, 2.27, and 2.26 pg/ml for IL-6 (P = 0.0005); and 707, 681, 673, 671, and 656 ng/ml for sVCAM-1 (P = 0.04). An increase of 100 mg/day magnesium was inversely associated with hs-CRP (−0.23 mg/l ± 0.07; P = 0.002), IL-6 (−0.14 ± 0.05 pg/ml; P = 0.004), TNF-α-R2 (−0.04 ± 0.02 pg/ml; P = 0.06), and sVCAM-1 (−0.04 ± 0.02 ng/ml; P = 0.07). No significant ethnic differences were observed. CONCLUSIONS High magnesium intake is associated with lower concentrations of certain markers of systemic inflammation and endothelial dysfunction in postmenopausal women.
Relation between treatment benefit and underlying risk in meta-analysis
Authors: S. Senn
Journal: BMJ (1996)

Under normal circumstances we would leave it to Purves to decide when and how to publish the results of the evaluation.In the light of the intense interest in the project among doctors and industry, however, we took the rather unusual step of inviting Purves to prepare an interim report that we could put in the public domain.2The interim report is just that: an appreciation of work in progress, not a definitive statement of results.The conclusions in the report ("our very tentative assessment ...") are guarded, and the strongest claims are made not for the Prodigy system itself but for only the general concept of patient specific decision support.Those who wish to see formal tests of statisti- cal significance will have to wait patiently, as we are doing, for the final report.In the meantime, we continue to have every confidence in the integrity, statistical or otherwise, of Purves and his team.
Concurrent Suppression of Integrin α5, Radixin, and RhoA Phenocopies the Effects of miR-31 on Metastasis
Authors: Scott Valastyan, Amelia Chang, Nathan Benaich, Ferenc Reinhardt, Robert A. Weinberg
Journal: Cancer Research (2010)

miR-31 inhibits breast cancer metastasis via the pleiotropic suppression of a cohort of prometastatic target genes that include integrin alpha(5) (ITGA5), radixin (RDX), and RhoA. We previously showed that the concomitant overexpression of ITGA5, RDX, and RhoA was capable of overriding the antimetastatic effects of ectopically expressed miR-31 in vivo. However, these prior studies failed to investigate whether the combined suppression of the endogenous mRNAs encoding these three proteins recapitulated the in vivo consequences of miR-31 expression on metastasis. We show here that short hairpin RNA-mediated concurrent downregulation of ITGA5, RDX, and RhoA is sufficient to phenocopy the full spectrum of described influences of miR-31 on metastasis in vivo, including the effects of this microRNA (miRNA) on local invasion, early post-intravasation events, and metastatic colonization. These findings provide mechanistic insights into the metastatic process and have implications about the importance of pleiotropy for the biological actions of miRNAs.
Margaret McCartney: Fat doctors are patients too
Authors: M. McCartney
Journal: BMJ (2014)

The new Belgian health minister, Maggie De Block, is a former GP.She also reportedly weighs 20 stone (127 kg), prompting critics to claim that she is unsuitable to manage a portfolio that includes reducing obesity.Recently, England's chief medical officer, Sally Davies, said that she was "perpetually surprised" at how many NHS staff were overweight."How are they to have the impact on patients
Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease.
Authors: D Rachmilewitz, J S Stamler, D Bachwich, F Karmeli, Z Ackerman, D K Podolsky
Journal: Gut (1995)

Recent studies have suggested that nitric oxide (NO.), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase activity was determined in ulcerative colitis and Crohn9s disease. Colonic biopsy specimens were obtained from inflammatory bowel disease patients and from normal controls. Mucosal explants were cultured in vitro for 24 hours and NOx generation was determined. Nitric oxide synthase activity was monitored by the conversion of [3H]-L-arginine to citrulline. Median NOx generation by inflamed colonic mucosa of patients with active ulcerative colitis and Crohn9s colitis was 4.2- and 8.1-fold respectively higher than that by normal human colonic mucosa. In ulcerative colitis and Crohn9s colitis nitric oxide synthase activity was 10.0- and 3.8-fold respectively higher than in normal subjects. Colonic NOx generation is significantly decreased by methylprednisolone and ketotifen. The decrease in NOx generation by cultured colonic mucosa induced by methylprednisolone suggests that NO synthase activity is induced during the culture and the steroid effect may contribute to its therapeutic effect. Enhanced colonic NOx generation by stimulated nitric oxide synthase activity in ulcerative colitis and Crohn9s disease may contribute to tissue injury.
Antiinflammatory Effects of the Phosphodiesterase-4 Inhibitor Cilomilast (Ariflo) in Chronic Obstructive Pulmonary Disease
Authors: Elizabeth Gamble, Diana C. Grootendorst, Christopher E. Brightling, Susannah Troy, Yusheng Qiu, Jie Zhu, Debbie Parker, Dean Matin, Swati Majumdar, Antonio M. Vignola, Claus Kroegel, Ferran Morell, Trevor T. Hansel, Stephen I. Rennard, Christopher Compton, Ohad Amit, Tri Tat, Jeffrey Edelson, Ian D. Pavord, Klaus F. Rabe, Neil C. Barnes, Peter K. Jeffery
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function in chronic obstructive pulmonary disease (COPD). We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast, 15 mg two times a day, or placebo for 12 weeks. Induced sputum differential cell counts were obtained at baseline and at five further visits. Interleukin-8 and neutrophil elastase were measured in sputum supernatant. Bronchial biopsies obtained at baseline and at Week 10 were immunostained and counted for neutrophils, CD8+ and CD4+ T-lymphocyte subsets, and CD68+ macrophages. Cells expressing the genes for interleukin-8 and tumor necrosis factor-alpha were identified by in situ hybridization and quantified. Compared with placebo, analysis of variance (ANOVA) of the change from baseline showed that cilomilast did not alter any sputum endpoint or FEV1. However, bronchial biopsies demonstrated that cilomilast treatment was associated with reductions in CD8+ (p = 0.001; ANOVA) and CD68+ cells (p < 0.05; ANOVA). In addition, by Poisson analysis, comparison of cell counts analyzed as a ratio of active to placebo demonstrated reductions of CD8+ (48% p < 0.01) and CD68+ (47% p = 0.001) cells. This is the first demonstration of reduction by any agent of airway tissue inflammatory cells characteristic of COPD. Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease.
Regions, networks: Interpreting functional neuroimaging data
Authors: Barry Horwitz
Journal: Behavioral and Brain Sciences (1995)

Abstract The subtraction and covariance paradigms are two analytic techniques used with functional neuroimaging data. The first assumes that a brain region participating in a task should show altered neural activity (relative to a control task). The second assumes that tasks are mediated by networks of interacting regions. Images of mind attempts to link results from the subtraction paradigm with a network interpretation that could have been more explicitly done using the covariance paradigm.
Low Value of [<sup>18</sup>F]-Fluoro-2-Deoxy-<scp>d</scp>-Glucose Positron Emission Tomography in Primary Staging of Early-Stage Cervical Cancer Before Radical Hysterectomy
Authors: Hung-Hsueh Chou, Ting-Chang Chang, Tzu-Chen Yen, Koon-Kwan Ng, Swei Hsueh, Shih-Ya Ma, Chee-Jen Chang, Huei-Jean Huang, Angel Chao, Tzu-I Wu, Shih-Ming Jung, Yen-Ching Wu, Cheng-Tao Lin, Kuan-Gen Huang, Chyong-Huey Lai
Journal: Journal of Clinical Oncology (2005)

The role of positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) in early-stage cervical cancer is unclear. We aimed to investigate the clinical benefit of FDG-PET in primary staging before radical hysterectomy and pelvic lymphadenectomy (RH-PLND).Patients with untreated stage IA2 to IIA adenocarcinoma (AD) or adenosquamous carcinoma (ASC) or nonbulky (< or = 4 cm) squamous cell carcinoma cervical cancer with magnetic resonance imaging (MRI) -defined negative nodal metastasis were enrolled onto a prospective study with a two-stage design. All patients had a preoperative dual-phase FDG-PET, technetium-99m-sulfur colloid lymphoscintigraphy, and intraoperative sentinel lymph node (LN) detection at RH-PLND. The gold standard of LN metastasis is histologic. A sample size of 120 patients was calculated to fit study aims (diagnostic efficacy of PET and sentinel LN sampling). An interim analysis was performed when 60 patients were accrued, which led to the current report.There were 36 SCCs, 20 ADs, and four ASCs. Of the 60 patients, 10 (16.7%) had pelvic LN metastases, and one (1.7%) had para-aortic LN (PALN) metastasis histologically. FDG-PET detected the single PALN metastasis (one of one patient) but detected only one (10%) of the 10 pelvic LN metastases. The PET false-negative pelvic LN micrometastases measured a median of 4.0 x 3.0 mm (range, 0.5 x 0.5 to 7 x 6 mm). The second stage of this trial will be continued without PET.This study shows that dual-phase FDG-PET has little value in primary, nonbulky, stage IA2 to IIA and MRI-defined, LN-negative cervical cancer.
Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle-cell lymphoma: a matched pair analysis
Authors: J. Mangel, H.A. Leitch, J.M. Connors, R. Buckstein, K. Imrie, D. Spaner, M. Crump, N. Pennell, A. Boudreau, N.L. Berinstein
Journal: Annals of Oncology (2004)

Background:The outcome of 20 patients with newly diagnosed mantle-cell lymphoma (MCL) treated on a prospective trial of autologous stem-cell transplantation (ASCT) and rituximab immunotherapy was compared with the outcome of 40 matched historical control patients treated with standard combination chemotherapy.Patients and methods:Control patients with MCL were identified from a lymphoma database, and pairs were matched with patients receiving ASCT–rituximab for stage of disease, gender and age (±5 years). Only patients treated with an anthracycline- or cyclophosphamide–fludarabine-based regimen were included.Results:Seventeen of 20 patients who received ASCT–rituximab remain alive in remission at a median of 30 months from diagnosis; one patient relapsed 2 years post-ASCT, and two died at 7 and 11 months post-ASCT without evidence of lymphoma. Of 40 patients treated with conventional chemotherapy, with a median follow-up of 80 months, 33 have relapsed or progressed and 29 have died. Overall (OS) and progression-free (PFS) survival were superior in patients treated with ASCT–rituximab compared with those treated with conventional chemotherapy (PFS at 3 years, 89% versus 29%, P <0.00001; OS at 3 years, 88% versus 65%, P = 0.052).Conclusions:This matched-pair analysis suggests that patients with advanced-stage MCL treated with ASCT–rituximab had statistically significantly better PFS and a trend toward better OS than patients treated with conventional chemotherapy. Longer follow-up will determine response duration and the true impact of this treatment strategy on PFS and OS.
Acromiohumeral distance measurement in rotator cuff tendinopathy: is there a reliable, clinically applicable method? A systematic review
Authors: Karen M McCreesh, James M Crotty, Jeremy S Lewis
Journal: British Journal of Sports Medicine (2013)

Abstract Background Narrowing of the subacromial space has been noted as a common feature of rotator cuff (RC) tendinopathy. It has been implicated in the development of symptoms and forms the basis for some surgical and rehabilitation approaches. Various radiological methods have been used to measure the subacromial space, which is represented by a two-dimensional measurement of acromiohumeral distance (AHD). A reliable method of measurement could be used to assess the impact of rehabilitation or surgical interventions for RC tendinopathy; however, there are no published reviews assessing the reliability of AHD measurement. Objectives The aim of this review was to systematically assess the evidence for the intrarater and inter-rater reliability of radiological methods of measuring AHD, in order to identify the most reliable method for use in RC tendinopathy. Study appraisal and synthesis An electronic literature search was carried out and studies describing the reliability of any radiological method of measuring AHD in either healthy or RC tendinopathy groups were included. Eighteen studies met the inclusion criteria and were appraised by two reviewers using the Quality Appraisal for reliability Studies checklist. Results Eight studies were deemed to be of high methodological quality. Study weaknesses included lack of tester blinding, inadequate description of tester experience, lack of inclusion of symptomatic populations, poor reporting of statistical methods and unclear diagnosis. There was strong evidence for the reliability of ultrasound for measuring AHD, with moderate evidence for MRI and CT measures and conflicting evidence for radiographic methods. Overall, there was lack of research in RC tendinopathy populations, with only six studies including participants with shoulder pain. Conclusions The results support the reliability of ultrasound and CT or MRI for the measurement of AHD; however, more studies in symptomatic populations are required. The reliability of AHD measurement using radiographs has not been supported by the studies reviewed.