tbuckley/cabot-search huggingface dataset:
An Epidemic of Enterovirus 71 Infection in Taiwan
Authors: Monto Ho, Eng-Rin Chen, Kwo-Hsiung Hsu, Shiing-Jer Twu, Kow-Tong Chen, Su-Fen Tsai, Jen-Ren Wang, Shin-Ru Shih
Journal: New England Journal of Medicine (1999)

Enteroviruses can cause outbreaks of hand-foot-and-mouth disease (characterized by vesicular lesions on the hands, feet, and oral mucosa) or herpangina, usually without life-threatening manifestations. In 1998 an epidemic of enterovirus 71 infection caused hand-foot-and-mouth disease and herpangina in thousands of people in Taiwan, some of whom died.We assessed the epidemiologic aspects of this outbreak. Cases of hand-foot-and-mouth disease or herpangina in ambulatory patients were reported to the Taiwan Department of Health by a mean of 818 sentinel physicians. Severe cases in hospitalized patients were reported by 40 medical centers and regional hospitals. Viruses were isolated by 10 hospital laboratories and the department of health.The sentinel physicians reported 129,106 cases of hand-foot-and-mouth disease or herpangina in two waves of the epidemic, which probably represents less than 10 percent of the estimated total number of cases. There were 405 patients with severe disease, most of whom were five years old or younger; severe disease was seen in all regions of the island. Complications included encephalitis, aseptic meningitis, pulmonary edema or hemorrhage, acute flaccid paralysis, and myocarditis. Seventy-eight patients died, 71 of whom (91 percent) were five years of age or younger. Of the patients who died, 65 (83 percent) had pulmonary edema or pulmonary hemorrhage. Among patients from whom a virus was isolated, enterovirus 71 was present in 48.7 percent of outpatients with uncomplicated hand-foot-and-mouth disease or herpangina, 75 percent of hospitalized patients who survived, and 92 percent of patients who died.Although several enteroviruses were circulating in Taiwan during the 1998 epidemic, enterovirus 71 infection was associated with most of the serious clinical manifestations and with nearly all the deaths. Most of those who died were young, and the majority died of pulmonary edema and pulmonary hemorrhage.
SAT0291 Serum Osteopontin in GIANT Cell Arteritis: Abiomarker Associated with Systemic Inflammatory Response and Relapsing Course
Authors: S. Prieto-González, M. Corbera-Bellalta, E. Planas-Rigol, A. García-Martínez, M.A. Alba, I. Tavera-Bahillo, G. Espígol-Frigolé, G. Murgia, J. Hernández-Rodríguez, M.C. Cid
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteopontin (OPN) is a multifunctional glycoprotein with a relevant role in inflammatory scenarios, contributing to macrophage chemotaxis as well as Th1 and Th17 differentiation. Potential role of OPN in giant cell arteritis (GCA) pathogenesis has not been explored to date. <h3>Objectives</h3> The aim of our study was to determine OPN concentration in sera from GCA patients and its relationship with disease activity and persistence. <h3>Methods</h3> OPN levels in serum from 76 GCA patients at the time of diagnosis and from 25 healthy controls were measured by ELISA (R&amp;D Systems). A second measure was performed in 36 patients of the series in remission, after one year of GC treatment. Clinical manifestations and laboratory findings at diagnosis, and data about treatment requirements and relapses during follow-up were recorded. <h3>Results</h3> Serum OPN concentrations were significantly elevated in active patients (104,76±65,02) compared with healthy controls (41,29±22,67, p&lt;0,001) or patients in remission (48,78±23,97; p&lt;0,001). Patients with systemic symptoms presented OPN levels significantly higher at diagnosis (107,15±55,03 vs 64,13±37,35; p&lt;0,001). Circulating OPN showed a positive correlation with ERS, CRP (both r=0,35; p=0,006) and IL-6 (r=0,52; p&lt;0,001). Relapsing patients presented baseline OPN concentrations significantly higher than patients who achieved sustained remission (129,00±71,81 vs 81,62±42,15; p=0,02), and longer time to achieve a stable daily steroid dose &lt;10 mg and 5 mg (r=0,37, p=0,02 and r=0,45, p=0,03, respectively). Cumulated prednisone dosage at withdrawal correlated with baseline circulating OPN concentrations (r=0,40, p=0,01). <h3>Conclusions</h3> Increased serum OPN levels are found in active GCA patients at diagnosis and correlate with the intensity of the systemic inflammatory response and treatment requirements. OPN may have a relevant role as a proinflammatory biomarker and may be related to the persistence of inflammatory activity in GCA.Supported by SAF 11/30073. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5597
THU0163 Predictors of metabolic syndrome at enrolment into a multicentre international inception cohort of patients with SLE:
Authors: B. Parker, M.B. Urowitz, M. Lunt, I.N. Bruce
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The Metabolic Syndrome (MetS) is a clustering of metabolic abnormalities associated with an increased risk of developing diabetes and atherosclerosis, and may add to the increased cardiovascular risk seen in SLE. Inflammatory disease activity and therapeutic exposures, particularly to corticosteroids, may contribute to the development of MetS in SLE. <h3>Objectives</h3> We examined the impact of inflammation and corticosteroid exposure on the prevalence of MetS in a multicentre international inception cohort of patients with SLE. <h3>Methods</h3> The Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis (SLICC-RAS) inception cohort enrolled recently diagnosed (&lt;15 months) SLE patients from 30 centres across 11 countries since 2000. Baseline and annual assessments record clinical, laboratory and therapeutic data according to a standardized protocol. MetS was defined according to the 2009 Consensus Statement from the International Diabetes Federation. Multivariate logistic regression was used to examine the association between MetS and markers of inflammation, disease phenotype and corticosteroid exposure at the baseline enrolment visit into SLICC-RAS. <h3>Results</h3> Of the 1686 available patients at enrolment, 1494 (86.6%) had sufficient data to determine their MetS status. Mean (SD) age at enrolment was 35.2 (13.4) years, mean (SD) disease duration was 24.1 (18.0) weeks and 89.2% were female. The overall prevalence of MetS in this cohort was 16%. The prevalence was higher with increasing age, in those of Hispanic and Korean ethnicities compared to Caucasians (31.3% vs. 30.1% vs. 12.1%; p≤0.001), and in males compared to females (22.2% vs. 15.3%; p=0.03). Significant factors on univariate analysis, adjusted for age, race and sex, included: current corticosteroid use (OR 1.54 (1.04, 2.25)); current average prednisolone dose (mg) (OR 1.02 (1.01, 1.04)); cumulative prednisolone dose (g) (OR 1.05 (1.00, 1.09)); previous IV corticosteroid use (OR 3.22 (1.35, 7.68)); current anti-malarial use (OR 0.51 (0.38, 0.68)); current immunosuppressant use (or 2.21 (1.63, 3.00)); SLEDAI 2K (OR 1.05 (1.02, 1.07)); active renal disease (OR 2.87 (2.05, 4.02));and thrombocytopenia (OR 2.08 (1.02, 4.24)). The final model using multivariate analysis included age, Hispanic or Korean ethnicity, average steroid dose, active renal disease and immunosuppressive use (Table 1). <h3>Conclusions</h3> In this large multinational study of young, recently diagnosed SLE patients, MetS is associated with both severe inflammatory disease and exposure to higher doses of corticosteroids. The strong association of MetS with Korean and Hispanic ethnicities suggests that susceptibility to the adverse metabolic effects of both inflammation and corticosteroid exposure is also at least in part genetically determined. <h3>Disclosure of Interest</h3> None Declared
P64 Evaluation Of Saliva Biomarkers As Indicators Of Health Status And Exacerbations In Copd
Authors: N. Patel, P. Jones, V. Adamson, G. Thorpe, J. Belcher, M. Spiteri
Journal: Thorax (2014)

<h3></h3> Saliva is increasingly promoted as a suitable alternative diagnostic bio-sample to blood, yet its role in respiratory disease is still to be elucidated. Salivary levels of C-Reactive Protein (CRP), Procalcitonin (PCT) and Neutrophil Elastase (NE) were assessed in patients with COPD to determine if saliva could provide an alternative diagnostic bio-sample to blood. As the clinical usefulness of biomarkers relies on correlation to patient events, we also explored the relationship between target saliva analyte levels and wellbeing scores on breathing and activities of daily living (ADL), recorded in a purposeful diary. The study included 139 subjects: 17 healthy non-smokers; 24 healthy smokers; 98 patients with COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I, 16; Stage II, 32; Stage III, 39; Stage IV, 11]. Participants were assessed over 3 visits, one week apart and involving patient completion of a self-assessment diary, spirometry and, saliva sampling. 22 randomly selected COPD subjects provided simultaneous blood samples. Each salivary biomarker could distinguish across the 3 health status groups; however when adjusted for confounding factors this significance only remained for salivary NE, which was increased in healthy smokers compared to healthy non-smokers (p &lt; 0.001) and stable COPD subjects (p &lt; 0.001). Patients with an acute exacerbation of COPD (n = 36) had a median increase in all 3 salivary biomarkers (p &lt; 0.001). CRP: median 5.74 ng/ml,[interquartile range 2.86–12.25], (95% Confidence Interval (CI): 3.72–11.47); PCT 0.38 ng/ml, [0.22–0.94], (95% CI: 0.31–0.54) and NE 539 ng/ml [112.25–1264], (95% CI: 169–982). Salivary CRP and PCT concentrations strongly correlated with their serum counterparts; salivary NE did not. Salivary CRP and PCT levels correlated with breathing scores (r = 0.14, p &lt; 0.02; r = 0.13, p &lt; 0.03 respectively) but not with activities of daily living. Salivary NE showed no relationship to wellbeing scores. Salivary CRP, PCT and NE provide clinically relevant information on disease status in COPD, and additionally NE on smoking status in healthy individuals. These results provide the conceptual basis for saliva to be used as a bio-sample in COPD monitoring.
Imaging diagnostic abilities for small pancreatic cancer
Authors: K Akio, H Maguchi, K Takahashi, M Osanai, K Nakahara, T Urata, S Matuzaki, H Iwano
Journal: Endoscopy (2006)

Background and Aim: Pancreatic cancer is a disease of poor prognosis, compared with other cancers of the digestive system, and it is often too difficult to resect when advanced tumor is detected. Even though imaging diagnostic modalities are advanced today. However it is still hard to get a pancreatic cancer image of small tumor diameter, and how to detect small resectable pancreatic cancer is an important point. In this study, we examined imaging diagnostic abilities of US, CT and EUS for small pancreatic cancer.
P4-18-04: Hypofractionated Radiotherapy for Breast Ductal Carcinoma In Situ.
Authors: L Hathout, B Fortin, H Vulpe, T Hijal, H Bahig, P Dubé, M Yassa
Journal: Cancer Research (2011)

Abstract Background Conventional radiotherapy at a dose of 50 Gy in 25 fractions after breast conservative surgery is the standard treatment for ductal carcinoma in situ of the breast (DCIS). Hypofractionation is an interesting alternative for the treatment of breast cancer, providing a less intense treatment scheme for the patient. While the hypofractionated regimen of 42.5 Gy in 16 fractions has been shown to be equivalent to 50 Gy in 25 in infiltrating ductal carcinoma, few studies and no prospective study have reported results using hypofractionation in DCIS. Materials and Methods: In this multicenter collaborative effort, we retrospectively reviewed the records of women with a diagnosis of DCIS at two Canadian institutions, treated with conservative surgery followed by hypofractionated radiotherapy (42.5 Gy in 16 fractions) to the whole breast. Tumor, patient and treatment factors were collected. Local control was evaluated using the Kaplan Meier method. Curves were compared using log rank. Results: Between 2003 to 2008, 292 patients with DCIS underwent conservative surgery followed by hypofractionated radiation in 16 fractions for a total dose of 42.5 Gy. Treatment delivery was similar at both institutions. Mean age at diagnosis was 59 years, with 70 % of women being postmenopausal. Nuclear grade was 1–2 in 65 % of patients while 28 % had grade 3 tumors. Complete surgical excision with negative margins was achieved in 92 % of patients. Radiotherapy boost was given to 92 patients (31.5 %) at the discretion of the radiation oncologist. After a mean follow up of 3.35 years (range 1–8 years), 10 patients (3.4 %) had ipsilateral local relapse resulting in a disease-free survival (DFS) of 96 % at 4 years. The histology at recurrence was DCIS for 8 patients; infiltrative disease for one patient and one patient had an unknown histology at recurrence. Age was statistically associated with local relapse (DFS 89 % for patients under 50 years old vs 97 % for those older than 50, p=0.027). Grade was also a significant prognostic factor (DFS 98% for grade 1–2 vs 91 % for grade 3, p = 0.015). Finally, administration of boost did not have an impact on local control (DFS boost 98 % vs 95 % for no boost, p=0.44). Discussion: Hypofractionated radiotherapy (42.5 Gy in 16 fractions) provides excellent local control for patients with DCIS undergoing breast conservative surgery. This regimen is more convenient to both patient and physician since it is less time consuming. Further work needs to be done to determine if this regimen is as effective as conventional radiotherapy in younger women (age less than 50) and those with grade 3 tumors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-18-04.
PTU-044 Tertiary Centre Experience Of 360 Degree Side-viewing Video Capsule Endoscopy
Authors: R Goel, DM Borrow, KV Patel, I Nasr, M Ward, S Ray, PM Irving, JD Sanderson, SH Anderson
Journal: Gut (2014)

<h3>Introduction</h3> Since it’s development in 1999, video capsule endoscopy (VCE) has become the investigation of choice for examining the small bowel. Recently, a novel panoramic 360 degree side-viewing VCE (Capsovision, Medical Innovations, USA) was launched. It differs from previous capsules in that no data recorder or sensors are required. The images are stored on the capsule itself, which when passed, must be retrieved and sent to the endoscopy reader for analysis. We report our initial experience of this novel VCE. <h3>Methods</h3> We retrospectively analysed the first 51 side-viewing VCE over a 6-month period at our institution. All patients had a clear liquid diet as preparation the day before. <h3>Results</h3> 51 patients (26 males) underwent examination with the side-viewing VCE. 39 (76.4%) examinations were completed and 12 were incomplete. This included 4 which were lost due to being flushed away. Over the same time period, forward-viewing VCE complete results were available in 83.2% patients. 1 of the incomplete examinations was due to a NSAID-induced stricture, subsequently diagnosed with a forward-viewing VCE. 31 patients had good bowel preparation, 11 satisfactory preparation and 6 were reported as having poor bowel preparation. The duodenal ampulla was reliably identified in 3/47 (6.4%) examinations. Pathology was identified in 11/47 (23.4%) examinations. <h3>Conclusion</h3> Side-viewing VCE was well tolerated and completed examination results were available for 76.4% of patients examined. Our findings did not correlate with previous reported results (71%) regarding the identification rate of the duodenal papilla as a small bowel landmark with side-viewing VCE. Advantages of the side-viewing VCE are not needing the patient to wear a recorder, with the data being stored in the capsule itself. This enables multiple patients to be examined on the same day and the number of examinations is not limited by available data recorders. Patients can also take the capsule home and take the capsule at any time which can be useful in the investigation of obscure GI bleeding. Side-viewing VCE is comparable to forward viewing VCE with respect to cost and accuracy. <h3>Disclosure of Interest</h3> None Declared.
SC-33 * POLYCOMB GROUP PROTEIN Bmi1 CONTROLS NEURAL STEM AND PROGENITOR CELL MAINTENANCE AND GLIOBLASTOMA TUMOUR DEVELOPMENT
Authors: P. Vora, C. Venugopal, M. Qazi, S. Mahendram, N. McFarlane, S. Singh
Journal: Neuro-Oncology (2014)

Bmi1, a polycomb group protein is required for self-renewal of neural stem and progenitor cells (NSPCs). Elevated Bmi1 expression is observed in most brain tumours, including glioblastoma (GBM). GBM, one of the most aggressive and heterogeneous tumours is known to possess a subpopulation of brain tumour initiating cells (BTICs) that have acquired stem cell properties and are exclusively capable of driving tumour formation in a human-mouse xenograft model. These observations raise the question of whether over-expressing Bmi1 is sufficient to promote self-renewal or tumorigenesis by NSPCs and whether loss of Bmi1 in GBM BTICs affects the progression of brain tumours. Using lentiviral constructs, we studied the gain of Bmi1 in human NSPCs and observed increased self-renewal and proliferative capacity of these cells. Subsequently, OEBmi1 NSPCs were injected in NOD-SCID mouse brains to assess their tumorigenic ability. Furthermore, knockdown of Bmi1 was performed in human GBM BTICs, which resulted in inhibition of clonogenic potential in vitro as well as decreased tumour cell mass in vivo. Lastly, to determine the comprehensive Bmi1 transcriptional network in human NSPCs and GBM BTICs, we applied ChIP-seq strategy to discover if Bmi1 binds to the promoter region of genes critical for neural lineage commitment and if these genes are involved in brain tumour formation. Together with RNA-seq data from human NSPCs and GBM BTICs sorted for stem cell marker CD133, this data will generate a comprehensive genome-wide Bmi1 binding profile and identify critical downstream Bmi1 targets & signaling pathways important for brain tumour maintenance.
Abstract 4798: Pilot study of plasma biomarker candidates for pancreatic cancer detection - a targeted proteomics approach
Authors: Sheng Pan, Ru Chen, Randall Brand, Sarah Hawley, Yasuko Tamura, Philip Gafken, Brian Milless, David Goodlett, John Rush, Teresa Brentnall
Journal: Cancer Research (2012)

Abstract With the advances in genomics and proteomics, the number of biomarker candidates associated with pancreatic cancer has increased explosively in recent years. Many putative biomarkers have been discovered in pancreatic tumor tissue and pancreatic juice; such targets will need to be rigorously verified in plasma or serum for blood-based biomarker development. Currently, validation of putative biomarkers in blood largely relies on antibody creation for ELISA assays, and has been the bottleneck for biomarker development. Analytical techniques to robustly measure these proteins in plasma, which is arguably the most complex biological matrix with protein abundance exceeding 10 orders of magnitude, has been a challenge. In this study, we applied a mass spectrometry-based targeted proteomics platform to directly detect candidate biomarker proteins in plasma to evaluate their clinical utility for pancreatic cancer diagnosis. The characterization of these protein candidates used a clinically well-characterized cohort that included plasma samples from patients with pancreatic cancer, chronic pancreatitis and healthy age-matched controls. Based on the receiver operating characteristic (ROC) analysis, two of the five candidate proteins tested, demonstrated an Area Under Curve (AUC) value greater than 0.89 in the detection of pancreatic cancer from healthy controls and chronic pancreatitis controls. We further demonstrated that a composite biomarker by combining two complementary independent biomarkers improves the sensitivity for pancreatic cancer detection at 95% specificity. Based on this evidence, these biomarker candidates merit further validation in larger patient and control cohorts for their potential utility in clinical application. In addition, we provide an analysis of the reproducibility, accuracy, and robustness of the mass spectrometry-based targeted proteomics platform. This information addresses important technical issues that could aid in the adoption of the targeted proteomics platform for practical clinical utility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4798. doi:1538-7445.AM2012-4798
Abstract 3706: Novel analogs of dietary thymoquinone with superior bioavailability and anti-tumor activity against GI cancers
Authors: Asfar S. Azmi, Subhash Padhye, Sanjeev Banerjee, Amro Aboukameel, Fazlul H. Sarkar, Ramzi M. Mohammad
Journal: Cancer Research (2011)

Abstract Alterations in multiple signaling pathways are a hallmark of most epithelial cancers, including pancreatic (PC) and colon cancers (CC). In principle, agents such as dietary bioactive compounds that affect multiple pathways should exhibit superior effectiveness due to their pleiotrophic actions compared to single pathway targeted therapies. Earlier we had shown that thymoquinone (TQ), a bioactive agent derived from edible black seed plant Nigella Sativa exerts anticancer activity against PC and CC alone or can enhance the effects of chemotherapeutics through mechanisms involving down-regulation of multiple pathways [such as NF-kB, cell cycle, inflammation, anti-apoptosis and angiogenic signaling (Cancer Research 69(13) 2009)]. However, due to poor bioavailability the anti-tumor effects of TQ that are observed at pharmacological high doses (&amp;gt;25 µM in vitro that translates to ∼7.4 g/kg in humans) cannot be considered clinically relevant. To address this problem we have developed a series of potent TQ analogs and among them two (TQ-THB and TQ-TFB patent pending) were found to have greater potency (growth inhibition and apoptosis) than parent TQ (IC50s 5 and 7µM respectively). TQ-THB and TQ-TFB not only show superior in vitro activity against PC, they also demonstrate greater anti-tumor activity in a highly metastatic BxPC-3 pancreatic xenograft model. The analogs are well tolerated and can be given i.v. Most interestingly, these analogs synergize with gemcitabine and FOLFOX that are the standard care for pancreatic and colon cancer respectively. The synergy was found both in cell culture and animal tumor models. Molecular Docking studies revealed that both TQ-THB and TQ-TFB binds very strongly to Cox-2 and NF-kB. This suggests that the analogs work by inhibiting the tumor survival and angiogenic pathways. Based on our novel findings we believe that these dietary analogs hold promise as anticancer agents that warrant further clinical development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3706. doi:10.1158/1538-7445.AM2011-3706
Mortality over a Period of 10 Years in Patients with Peripheral Arterial Disease
Authors: Michael H. Criqui, Robert D. Langer, Arnost Fronek, Heather S. Feigelson, Melville R. Klauber, Theresa J. McCann, Deirdre Browner
Journal: New England Journal of Medicine (1992)

Previous investigators have observed a doubling of the mortality rate among patients with intermittent claudication, and we have reported a fourfold increase in the overall mortality rate among subjects with large-vessel peripheral arterial disease, as diagnosed by noninvasive testing. In this study, we investigated the association of large-vessel peripheral arterial disease with rates of mortality from all cardiovascular diseases and from coronary heart disease.