tbuckley/cabot-search huggingface dataset:
Prospective Study of Urinary Prostaglandin E<sub>2</sub> Metabolite and Colorectal Cancer Risk
Authors: Qiuyin Cai, Yu-Tang Gao, Wong-Ho Chow, Xiao-Ou Shu, Gong Yang, Bu-Tian Ji, Wanqing Wen, Nathaniel Rothman, Hong-Lan Li, Jason D. Morrow, Wei Zheng
Journal: Journal of Clinical Oncology (2006)

Overexpression of cyclooxygenase-2 (COX-2) has been shown to play a major role in colorectal cancer pathogenesis. However, no human study has directly investigated whether biomarkers of COX-2 overexpression may predict colorectal cancer risk. We evaluated the association of urinary prostaglandin E2 metabolite (PGE-M) levels and colorectal cancer risk.A nested case-control study was conducted within the Shanghai Women's Health Study, in which 74,942 Chinese women ages 40 to 70 years were recruited from 1997 to 2000. Urinary PGE-M in 150 cohort members who developed colorectal cancer during the follow-up were compared with 150 matched controls.The baseline level of urinary PGE-M was more than 50% higher in cases than in controls. The relative risks (RRs) of developing colorectal cancer were elevated from 1.0 to 2.5 (95% CI, 1.1 to 5.8), 4.5 (95% CI, 1.9 to 10.9), and 5.6 (95% CI, 2.4 to 13.5) with increasing quartiles of urinary PGE-M levels (P for trend < .001). The positive association was observed for both colon cancer (RR = 4.9; 95% CI, 1.7 to 14.7 for the highest v lowest quartile; P for trend = .009) and rectal cancer (RR = 7.2; 95% CI, 1.7 to 30.7; P for trend = .048), and for colorectal cancer cases diagnosed in the first 30 months (RR = 7.6; 95% CI, 1.8 to 32.0; P for trend = .035) and subsequent months (RR = 4.4, 95% CI, 1.5 to 13.3; P for trend = .012) of follow-up.Given its strong association with colorectal cancer risk, urinary PGE-M may be a promising biomarker for risk assessment of this common malignancy.
A modest proposal for an outreach section in scientific publications
Authors: Chris Gunter, Anne Osterrieder
Journal: Genome biology (2012)

The idea for this column started with a tweet.

Both of us are active on Twitter, the social media website where users can share messages, or tweets, of 140 characters or less. While Twitter has swept around the world, a small but growing fraction of scientists are using it to establish collaborations or exchange information. More importantly, side effects of Twitter include a narrowing of the gaps between academic or industrial scientists, a burgeoning movement of science communicators, and a public very interested in science and technology.

As the saying goes: we're here to help.

We propose that scientific publications include a short section, akin to the acknowledgments at the end, which lists several outreach activities related to the paper. These could be new resources that the authors have created, or existing resources that are related to the paper's subject(s) - the goal is to reach out across that gap and help non-expert readers understand the work.

Yes, we know that writing a paper is hard enough. But if publishing scientists don't continue to help non-scientists (or even non-specialists in our areas) engage with our work, then disturbing trends will continue. Right now many of us bemoan the lack of science coverage in mainstream media - if we don't constantly work to translate our science, the coverage will continue to disappear. In addition, we will fail to give non-experts the tools and resources that will help them understand research and fact-check suspicious claims. Publishing scientists will also be increasingly unable to compete successfully against other demands for either governmental or philanthropic funds. Engagement even allows us to understand our own work better. If scientists can't summarize their work in a one-minute elevator pitch or in a phone call to their family, our experience suggests they'll have a harder time keeping pace with their peers. Increasing numbers of grant proposals require a section on education or outreach; our proposal could help you find the materials - or inspiration - you need for your next funding application.

Finding material for this section will not be as difficult as you might think: many scientists may not be aware that the past few years have seen an explosion in high-quality, multimedia resources in science communication. Consider the 2012 Flame Challenge, hosted by the Center for Science Communication in NY, USA and the actor Alan Alda. Participants were challenged to explain with scientific accuracy, but speaking to an 11-year-old, what exactly a flame is. Entries included written text, videos, graphics and animations (viewable at http://flamechallenge.org/). The winning entry is definitely worth a watch and ends with a rocking chorus of pyrolysis - chemiluminescence - oxidation - incandescence in front of both molecular-block diagrams of the process and a guitar-playing Lucifer. Not exactly a paper in a high-profile journal, but scientifically accurate and more likely to be retained in the mind of an 11-year-old.
Detection of Luse bodies, spiralled collagen, dysplastic collagen, and intracellular collagen in rheumatoid connective tissues: an electron microscopic study.
Authors: M F Neurath
Journal: Annals of the Rheumatic Diseases (1993)

BACKGROUND--Rheumatoid arthritis is a chronic inflammatory disease leading to alterations of the extracellular matrix in tendons, ligaments, and cartilage. The structural changes of the collagenous systems in rheumatoid connective tissues are largely unknown, however. METHODS--Thirty four samples of menisci, 36 cruciate ligaments, and four tendons were taken during joint surgery in patients with rheumatoid arthritis. Eighteen menisci, 35 ligaments, and 30 tendons obtained at necropsy served as a control group. The extracellular matrix in the two groups was analysed by the combined use of transmission and scanning electron microscopy, immunohistochemistry with monoclonal antibodies recognising collagen types IV and VI, and ultramorphometry. RESULTS--Normal tendons and ligaments predominantly showed a unidirectional fibril arrangement. Whereas type IV collagen showed a positive staining pattern along all basement membranes, type VI collagen formed fine, filaments aligned in parallel. In patients with rheumatoid arthritis a significant reduction of the mean diameter of the collagen fibrils was found owing to the presence of thin collagenous fibrils 20-60 nm in diameter. Most of these fibrils showed considerable changes in their arrangement with irregular courses (so-called interfibrillar dysplastic collagen). Up to 410 nm thick frayed fibrils with irregular outlines (spiralled collagen) and intracellular collagen forms were found in rheumatoid tissues. In addition, atypical thick collagenous structures with 41 nm periodicity (Luse bodies) were detected in the matrix. The upregulation of type IV collagen in rheumatoid arthritis was associated with an increase in the vascular density. The expression of type VI collagen was upregulated in fibrotic zones. CONCLUSIONS--The dramatic ultrastructural collagen changes lead to a structural and functional insufficiency of the extracellular matrix in rheumatoid connective tissues. The results suggest that collagen alterations may contribute to the development of tendon and ligament ruptures in rheumatoid arthritis.
p53 Codon 72 Polymorphism Predicts the Pathologic Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer
Authors: Ye Xu, Lihua Yao, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Benyao Lin, Youyong Lu, Yuntao Xie
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recent studies have highlighted that the p53 codon 72 polymorphism plays a crucial role in modulating wild-type p53 apoptotic capacity, and as such may influence the response to chemotherapy. Thus, the purpose of this study was to investigate whether the p53 codon 72 polymorphism might influence pathologic response to neoadjuvant chemotherapy in primary breast cancer. Experimental Design: One hundred and ten operable breast cancer patients received anthracycline-based neoadjuvant chemotherapy and p53 codon 72 polymorphism status was analyzed by PCR-RFLP. Results: The distribution of initial clinical stage, tumor size, estrogen receptor or progesterone receptor status, menopausal status, or erbB2 expression was not significantly different among the polymorphic variants. However, we found that only 13% (3 of 23) of patients with the Pro/Pro variant had a good pathologic response, defined as a complete pathologic response or minimal residual disease. In comparison, 40% (22 of 55) or 37.5% (12 of 32) of patients with the Pro/Arg or Arg/Arg variant had a good pathologic response (P = 0.019). Moreover, patients with the Pro/Pro variant were more likely to have a positive axillary lymph node status than those with the Pro/Arg or Arg/Arg variant (P = 0.007). Furthermore, in multivariate analysis, p53 codon 72 polymorphism was found to be a strong predictor of pathologic response (odds ratio 6.7, 95% confidence interval, 1.4-31.2; P = 0.016). Conclusion: Our study indicates that breast cancer patients with the Pro/Pro variant may be less sensitive to anthracycline-based treatment than those with the Pro/Arg or Arg/Arg variant and suggests that analysis of p53 codon 72 polymorphism may provide a simple predictive marker for selecting the right breast cancer patients to anthracycline-based neoadjuvant chemotherapy in clinical setting.
The Presence of Specific IgG Antibodies to Type II Collagen and Proteoglycans Associated With Specific IgG and IgE to TDI in Firemen with High Exposure Level to Isocyanates in Fire Accidents
Authors: J. Muino, M. Romero, M. Ferrero, D. Lerda
Journal: Journal of Allergy and Clinical Immunology (2011)
Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke
Authors: Joseph P. Broderick, Yuko Y. Palesch, Andrew M. Demchuk, Sharon D. Yeatts, Pooja Khatri, Michael D. Hill, Edward C. Jauch, Tudor G. Jovin, Bernard Yan, Frank L. Silver, Rüdiger von Kummer, Carlos A. Molina, Bart M. Demaerschalk, Ronald Budzik, Wayne M. Clark, Osama O. Zaidat, Tim W. Malisch, Mayank Goyal, Wouter J. Schonewille, Mikael Mazighi, Stefan T. Engelter, Craig Anderson, Judith Spilker, Janice Carrozzella, Karla J. Ryckborst, L. Scott Janis, Renée H. Martin, Lydia D. Foster, Thomas A. Tomsick
Journal: New England Journal of Medicine (2013)

Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain.
Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes
Authors: Angela Montecalvo, Adriana T. Larregina, William J. Shufesky, Donna Beer Stolz, Mara L. G. Sullivan, Jenny M. Karlsson, Catherine J. Baty, Gregory A. Gibson, Geza Erdos, Zhiliang Wang, Jadranka Milosevic, Olga A. Tkacheva, Sherrie J. Divito, Rick Jordan, James Lyons-Weiler, Simon C. Watkins, Adrian E. Morelli
Journal: Blood (2011)
High glucose promotes intracellular lipid accumulation in vascular smooth muscle cells by impairing cholesterol influx and efflux balance
Authors: Jia-hong Xue, Zuyi Yuan, Yue Wu, Yan Liu, Yan Zhao, Wei-ping Zhang, Yu-ling Tian, Wei-min Liu, Yu Liu, Chiharu Kishimoto
Journal: Cardiovascular Research (2009)

High glucose promotes macrophage-derived foam cell formation involved in increased influx or reduced efflux of lipids. The aim of this study is to investigate the influence of hyperglycaemia on foam cell transformation of vascular smooth muscle cells (VSMCs) and possible mechanisms contributing to these effects.The results showed that high glucose increased the expression of CD36, a regulator of lipid influx, and suppressed the expression and activity of the adenosine triphosphate-binding cassette (ABC) transporter ABCG1, a regulator of cholesterol efflux to high-density lipoprotein, in a dose- and time-dependent manner. However, cholesterol efflux to lipid-free apoAI was not impaired. VSMCs exposed to high glucose readily developed into lipid-loaded cells, as demonstrated by Oil Red O staining and cholesterol content analysis. In addition, high glucose-induced down-regulation of ABCG1 was reversed by nuclear factor-kappaB (NF-kappaB) inhibitors BAY 11-7085 and tosyl-phenylalanine chloromethyl ketone and by the antioxidant N-acetyl-L-cysteine (NAC). This reversal was accompanied by reduced cellular lipid content. Also, NAC and NF-kappaB inhibitors can effectively block the high glucose-induced activity of NF-kappaB binding to DNA and/or peroxide production.These results suggested that hyperglycaemia-induced foam cell formation in VSMCs was related to the imbalanced lipid flux by increasing CD36-mediated modified low-density lipoprotein uptake and reducing ABCG1-regulated cellular cholesterol efflux. Moreover, this effect was associated with increased oxidative stress and activated NF-kappaB pathway signalling.
Increased lipoprotein(a) concentrations in chronic renal failure.
Authors: S M Haffner, K K Gruber, G Aldrete, P A Morales, M P Stern, K R Tuttle
Journal: Journal of the American Society of Nephrology (1992)

Subjects with chronic renal failure have a greatly increased risk of coronary heart disease and dyslipidemia. Relatively few studies have examined the relationship of chronic renal failure to lipoprotein (Lp)(a) concentrations, an important risk factor for coronary heart disease. Diabetic subjects have been reported to have both increased Lp(a) concentrations and an increased risk of renal failure, thereby possibly confounding the Lp(a)-renal failure association. The association between Lp(a) and chronic renal failure in 359 control subjects and 111 subjects with renal failure was examined. Lp(a) (in milligrams per deciliter) was elevated in subjects with chronic renal failure, regardless of ethnicity (Mexican Americans, 19.8 +/- 2.7 versus 14.1 +/- 1.3; P = 0.03; non-Hispanic white patients, 24.9 +/- 3.0 versus 16.3 +/- 1.2; P = 0.006;). These differences persisted after adjustment for diabetes and ethnicity (P < 0.001). The type of treatment for chronic renal failure (diet, hemodialysis, or peritoneal dialysis) did not have an effect on Lp(a) concentrations. Lp(a) levels were not correlated with the level of creatinine in subjects with chronic renal failure. Thus, the elevation of Lp(a) levels in renal failure must occur early in renal failure, or alternatively, elevated Lp(a) levels may promote progression to chronic renal failure. These results indicate that Lp(a) concentrations are increased in chronic renal failure and may increase the risk for coronary heart disease in these subjects.
Patient Self-Reports of Symptoms and Clinician Ratings as Predictors of Overall Cancer Survival
Authors: Chantal Quinten, John Maringwa, Carolyn C. Gotay, Francesca Martinelli, Corneel Coens, Bryce B. Reeve, Henning Flechtner, Eva Greimel, Madeleine King, David Osoba, Charles Cleeland, Jolie Ringash, Joseph Schmucker-Von Koch, Martin J. B. Taphoorn, Joachim Weis, Andrew Bottomley
Journal: JNCI Journal of the National Cancer Institute (2011)

The National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) reporting system is widely used by clinicians to measure patient symptoms in clinical trials. The European Organization for Research and Treatment of Cancer's Quality of Life core questionnaire (EORTC QLQ-C30) enables cancer patients to rate their symptoms related to their quality of life. We examined the extent to which patient and clinician symptom scoring and their agreement could contribute to the estimation of overall survival among cancer patients. We analyzed baseline data regarding six cancer symptoms (pain, fatigue, vomiting, nausea, diarrhea, and constipation) from a total of 2279 cancer patients from 14 closed EORTC randomized controlled trials. In each trial that was selected for retrospective pooled analysis, both clinician and patient symptom scoring were reported simultaneously at study entry. We assessed the extent of agreement between clinician vs patient symptom scoring using the Spearman and kappa correlation statistics. After adjusting for age, sex, performance status, cancer severity, and cancer site, we used Harrell concordance index (C-index) to compare the potential for clinician-reported and/or patient-reported symptom scores to improve the accuracy of Cox models to predict overall survival. All P values are from two-sided tests. Patient-reported scores for some symptoms, particularly fatigue, did differ from clinician-reported scores. For each of the six symptoms that we assessed at baseline, both clinician and patient scorings contributed independently and positively to the predictive accuracy of survival prognostication. Cox models of overall survival that considered both patient and clinician scores gained more predictive accuracy than models that considered clinician scores alone for each of four symptoms: fatigue (C-index = .67 with both patient and clinician data vs C-index = .63 with clinician data only; P <.001), vomiting (C-index = .64 vs .62; P = .01), nausea (C-index = .65 vs .62; P < .001), and constipation (C-index = .62 vs .61; P = .01). Patients provide a subjective measure of symptom severity that complements clinician scoring in predicting overall survival.
A family based study shows no association between rheumatoid arthritis and the PADI4 gene in a white French population
Authors: L Caponi
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Autoantibodies to citrullinated proteins (ACPA) are considered a specific marker for rheumatoid arthritis. Peptidylarginine deiminase (PAD) is the enzyme that converts arginyl into citrullyl residues; different isoforms of the enzyme are expressed in mammals. It has been suggested that the <i>PADI4</i> gene may contribute to genetic susceptibility to rheumatoid arthritis, but conflicting results have been obtained in different populations. <b>Objective:</b> To test the hypothesis that the <i>PADI4</i> gene may confer susceptibility to rheumatoid arthritis in a white French population, using powerful and highly reliable family based association tests. <b>Methods:</b> DNA samples were analysed from 100 families where one member was affected by rheumatoid arthritis and both parents were available for sampling. Five single nucleotide polymorphisms, located within the <i>PADI4</i> gene and in its close proximity, were genotyped by restriction fragment length polymorphism, and haplotypes were constructed. The analysis involved use of the transmission disequilibrium test and genotype relative risk. ACPA were detected by ELISA on cyclic citrullinated peptides and on human deiminated fibrinogen. <b>Results:</b> No single SNP or haplotype was associated with the disease, or was preferentially transmitted. No association was found when patients were partitioned according to ACPA positivity. <b>Conclusions:</b> No <i>PADI4</i> haplotype is associated with rheumatoid arthritis in a white French population. The role of genes encoding the other PAD isoforms, or modulating tissue expression or enzyme activity, remains to be elucidated.
Visceral Fat Area and Markers of Insulin Resistance in Relation to Colorectal Neoplasia
Authors: Shuichiro Yamamoto, Toru Nakagawa, Yumi Matsushita, Suzushi Kusano, Takeshi Hayashi, Masataka Irokawa, Takatoshi Aoki, Yukunori Korogi, Tetsuya Mizoue
Journal: Diabetes Care (2009)

Although abdominal obesity and related metabolic abnormalities are hypothesized to promote colorectal carcinogenesis, direct confirmation of this effect is required. Here, we examined the relation of early-stage colorectal neoplasia to visceral fat area and markers of insulin resistance.Subjects were participants in a comprehensive health screening conducted at the Hitachi Health Care Center, Ibaraki, Japan. During a 3-year period (2004-2007), a total of 108 patients with early-stage colorectal neoplasia, including 22 with early cancer, were identified among individuals who received both colorectal cancer screening and abdominal computed tomography scanning. Three control subjects matched to each case subject were randomly selected from those whose screening results were negative. Conditional logistic regression analysis was used to examine the association of measures of obesity and markers of insulin resistance with colorectal neoplasia, with adjustment for smoking and alcohol drinking.Visceral fat area, but not subcutaneous fat area, was significantly positively associated with colorectal cancer, with odds ratios (95% CI) for the lowest to highest tertile of visceral fat area of 1 (reference), 2.17 (0.45-10.46), and 5.92 (1.22-28.65), respectively (P(trend) = 0.02). Markers of insulin resistance, particularly fasting glucose, were also positively associated with colorectal cancer risk. In contrast, no associations were observed for colorectal adenomas.These results suggest that visceral adipose tissue accumulation and insulin resistance may promote the development of early-stage cancer but not adenoma in the colorectum.
Optimal search strategies for retrieving scientifically strong studies of diagnosis from Medline: analytical survey
Authors: R Brian Haynes, Nancy L Wilczynski
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To develop optimal search strategies in Medline for retrieving sound clinical studies on the diagnosis of health disorders. <b>Design</b> Analytical survey. <b>Setting</b> Medline, 2000. <b>Participants</b> 170 journals for 2000 of which 161 were indexed in Medline. <b>Main outcome measures</b> The sensitivity, specificity, precision ("positive predictive value"), and accuracy of 4862 unique terms in 17 287 combinations were determined by comparison with a hand search of all articles (the "gold standard") in 161 journals published during 2000 (49 028 articles). <b>Results</b> Only 147 (18.9%) of 778 articles about diagnostic tests met basic criteria for scientific merit. Combinations of search terms reached peak sensitivities of 98.6% at a specificity of 74.3%. Compared with best single terms, best multiple terms increased sensitivity forsound studies by 6.8% (absolute increase), while also increasing specificity (absolute increase 6.0%) when sensitivity was maximised. When terms were combined to maximise specificity, the singleterm, specificity.tw. (98.4%), outperformed combinations of terms. The strategies newly reported in this paper outperformed other validated search strategies except for one strategy that had slightly higher sensitivity (99.3% <i>v</i> 98.6%) but lower specificity (54.7% <i>v</i> 74.3%). <b>Conclusion</b> New empirical search strategies in Medline can optimise retrieval of articles reporting high quality clinical studies of diagnosis.