tbuckley/cabot-search huggingface dataset:
Abstract 895: Discriminant, identifiable plasma metabolites in pancreatic cancer-associated diabetes - candidate early-detection biomarkers
Authors: Shiro Urayama, Vladimir Tolstikov
Journal: Cancer Research (2014)

Abstract Background: Pancreatic cancer (PDAC) has been associated with development of glucose intolerance and dysregulation. Based on our previous report of strong potential for existence of metabolite biomarkers for PDAC detection, in this study, we have pursued initial characterization of plasma metabolites for discriminating PDAC cases among diabetic patients as a means to delineate further subset of patients who may benefit from screening protocol. Methods: IRB-approved prospectively collected database and corresponding plasma from UC Davis Pancreas Registry was searched for appropriate cases: PDAC patients with recent-onset diabetes (≤3yrs prior to the index PDAC diagnosis) (Grp 1) and non-PDAC patients with long history of diabetes mellitus (&amp;gt;3 yrs) (Grp 2). The plasma was processed and non-targeted GC/MS and targeted LC/MS were performed to assay for identifiable plasma metabolites. The data was processed and the peak intensity levels were normalized, scaled and identifiable metabolites were analyzed via metabolomics specific multivariate &amp; bootstrap methods as well as ROC evaluation (Metaboanalyst &amp; ROCCET) for visualization and biomarker development. Results: We have identified 36 patients in Grp 1 and 22 patients for Grp 2. The metabolite specific multivariate and ROC analyses revealed specific features such as elaidic acid, uric acid, 2,3-propanediol, arachidonic acid, docosahexanoic acid, 5-oxo-EET, lysine, LysoPC(18:2), 9(10)-EpOME, LysoPC(16:0), sphingosine-1-phosphate and others as strong discriminators for recent-onset diabetic patients with pancreatic cancer. Such set yielded AUC of 0.964 with 15 features [CI=0.876-1]. Conclusion: We have demonstrated that an identifiable set of plasma metabolite biomarkers exists for discriminating diabetic patients with developing pancreatic cancer. These features could be utilized in a larger set of new-onset diabetic population for further validation in near-future study. Citation Format: Shiro Urayama, Vladimir Tolstikov. Discriminant, identifiable plasma metabolites in pancreatic cancer-associated diabetes - candidate early-detection biomarkers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 895. doi:10.1158/1538-7445.AM2014-895
Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer
Authors: Hiroko Yamashita, Tatsuya Toyama, Maho Hamaguchi, Shunzo Kobayashi, Yoshitaka Fujii
Journal: Cancer Research (2006)

428   Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade ( P   P  = 0.02), and progesterone receptor (PR) ( P  = 0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival ( P  = 0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive had significantly better response to endocrine therapy ( P  = 0.04), and longer survival after relapse ( P  = 0.0003), that those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.
Driving Pressure as a Key Ventilation Variable
Authors: Eduardo L. V. Costa, Arthur S. Slutsky, Marcelo B. P. Amato
Journal: New England Journal of Medicine (2015)

n engl j med 372;21 nejm.org may 21, 2015 2071 interference with the dose of calcineurin inhibitors, a factor that might improve graft outcomes by lowering rejection rates. Currently, in South Africa, we are using raltegravir in salvage regimens only, but once these drugs become more affordable and available in South Africa, it will be interesting to see whether they are a good option for HIV-positive patients who receive a transplant. In our study, all the patients had completely mismatched human leukocyte antibodies with the donors, and the levels of panel reactive antibody ranged from 0 to 90%. We agree that this factor might be important in the high kidney-rejection rates among our patients. Elmi Muller, M.B., Ch.B., M.Med. Zunaid Barday, M.B., Ch.B. Delawir Kahn, M.B., Ch.B., Ch.M.
Does low prevalence of pig allergy among Danish farmers reflect flaws in the skin prick test
Authors: Vivi Schlünssen, Anne Puustinen, Grethe Elholm, Irmelin Lindström, Øyvind Omland, Torben Sigsgaard, Hille Suojalehto
Journal: European Respiratory Journal (2014)

Background:  The measured prevalence of pig allergy among farmers is low. It has been suggested to reflect methodological flaws in allergological tests. This study aims to compare the pig dander (PD) skin prick test (SPT) performed with commercial extracts with results from western blot (WB) and specific IgE (sIgE) tests with in-house dander samples or commercial extracts.  Methods:  In 1992-94 and again in 2007-8 SPTs with PD extracts from ALK were performed for 1166 farmers. Only 5 (4 at baseline and one at follow-up) had a positive SPT. Blood samples from these 5 sensitized subjects and the 12 subjects with asthma and rhinitis related to working in a pig stable in 2007-8, and an additional 12 subjects having no respiratory symptoms related to work in pig stables were selected for further analysis.  The 29 blood samples collected in 2007-8 were tested with:  -Western blotting (WB) with Finnish in-house PD extract  -sIgE pig urine (ImmunoCAP e212  -sIgE PD (ImmunoCAP e83  -sIgE PD (ImmunoCAP based on in-house PD)  Results:  In the positive SPT group, 40% had a medium or strong reaction in WB. The same was true for 17% in the symptomatic group and 50% in the non-symptomatic group.  None in the positive SPT group had sIgE g 0.12 UA/l in any of the 4 sIgE tests. One from the symptomatic group had levels g 0.35 UA/l in the two PD tests, and one from the non-symptomatic group had levels g 0.35 UA/l in all three pig allergen tests.  Conclusion:  All tests confirmed a low prevalence of pig sensitization among Danish farmers. There was no clear consistency between sIgE tests and WB with PD. sIgE tests with in-house PD and commercial extracts had similar results, but more distinct in in-house PD based tests.
Abstract 14773: Ischemic Preconditioning Induces Rapid Changes In Oxidative Phosphorylation Proteins And Attenuates Protein Oxidation During Ischemia-reperfusion By Mechanisms Independent Of Cytosolic Signaling.
Authors: Estefania Nunez, Elisabet Miro-Casas, Pablo Martinez-Acedo, Celia Fernandez-Sanz, Pilar Caro, Andreu Porta, Antonio Rodriguez-Sinovas, Marisol Ruiz-Meana, Jesus Vazquez, David Garcia-Dorado
Journal: Circulation (2011)

Ischemic preconditioning (IP) cannot be applied to patients with unexpected ischemia, but understanding its mechanisms could lead to the development of new cardioprotective strategies. In this stud...
Folate and risk of cardiovascular disease
Authors: D. S Wald
Journal: BMJ (2003)

Editor—Hung et al conclude that their cohort study on serum folate and coronary heart disease provides evidence against the view that folic acid prevents coronary heart disease.1 We disagree and believe they have misinterpreted their results.

A meta-analysis of studies on homocysteine and cardiovascular disease, supported by others,2–4 together with randomised trial evidence on folic acid dose and serum homocysteine reduction, shows that the maximal homocysteine lowering effect of folic acid occurs at a dose of about 0.8 mg/day (which increases serum folate by 20 μg/l).5 This homocysteine reduction lowers the risk of coronary heart disease by about 16%. The difference in average serum folate between the highest and the lowest folate group in the cohort study of Hung et al was about 7 μg/l, since the median of the highest folate group was about 8 μg/l (the 93rd centile was stated as 9 μg/l, so the 85th centile must have been less than this) and the median in the lowest folate group was about 1 μg/l (stated as <3 μg/l).

Since a 20 mg/l higher serum folate is associated with a 16% higher risk of coronary heart disease the 7 μg/l difference will be associated with a 5% higher risk, a relative risk of 1.05 (1.167/20) consistent with the 1.10 (men) and 1.14 (women) in their study. These results weigh in favour, not against, the view that folic acid reduces the risk of coronary heart disease. The narrow range of serum folate values in their cohort study limits its ability to show a significant effect.

Table 4 in the paper confirms the link between low serum folate and increased risk of coronary heart disease. Hung et al present data from six other cohort studies. Each shows a higher risk of coronary heart disease in the lowest folate group compared with the highest. This observation alone is highly significant. The probability that all seven studies have estimates above 1.0 by chance alone is ()7 or 1 in 128, a P value of 0.008. Their negative conclusion is inappropriate.
The role of p21-activated kinase 3 (PAK3) in activating protein 1 (AP-1) induced oncogenesis
Authors: Nina Holderness, Howard Donninger, Michael J. Birrer, Virna Leaner
Journal: Clinical Cancer Research (2010)

Abstract Activating protein 1 (AP-1) is a fundamental transcription factor that plays a role in cell proliferation, differentiation and apoptosis. Little is known about the role of the diverse downstream targets of the active AP-1 complex, a dimer comprising of the Jun, Fos or ATF bZIP-domain proteins. Deregulation of AP-1 has been linked to many cancers, with its over-expression leading to the transformation of normal cells. Previous studies utilizing a doxycycline-inducible cJun/AP-1 construct identified PAK3, a serine/threonine kinase signal transduction molecule, as a potential AP-1-target involved in the AP-1 characteristic transformation. PAK3 has been implicated in a variety of pathological disorders and over-expression of other PAK-family members has been linked to certain cancers. This project aims to investigate the role of PAK3 in cJun/AP-1 induced oncogenesis. Quantitative RT-PCR and Western Blot Analysis showed elevated PAK3 expression at both the mRNA and protein level in cJun-overexpressing cells. PAK3 expression levels were also elevated in transformed human and cancer cell lines compared to normal cells. Analysis of the PAK3 promoter using promoter luciferase assays identified a putative AP-1 binding site, at position +52 to +60, which may be responsible for the increased PAK3 promoter activity in response to cJun/AP-1 over-expression. siRNA inhibition of the PAK3 protein showed the regression of the morphological phenotype and migratory potential associated with cJun-transformed cells. However PAK3 inhibition showed no significant effect on the proliferative response of cJun-transformed cells. This study suggests a potential regulation of cJun/AP-1 on PAK3 as well as a role for PAK3 in AP-1 induced transformation; specifically that associated with cell morphology and migration.
Abstract 12935: Therapeutic Silencing of Leukocyte Adhesion Molecules in Atherosclerosis and Acute Myocardial Infarction
Authors: Hendrik B Sager, Partha Dutta, James Dahlmann, Anna Borodovsky, Kevin Fitzgerald, Timo Heidt, Gabriel Courties, Gregory Wojtkiewicz, Yoshiko Guiles, Omar Khan, Robert Langer, Filip Swirski, Ralph Weissleder, Daniel Anderson, Matthias Nahrendorf
Journal: Circulation (2014)

INTRODUCTION/HYPOTHESIS: Leukocytes are a major component of atherosclerotic plaques, drive plaque progression and are continuously recruited from the blood. The leukocyte adhesion molecules VCAM-1, ICAM-1/2 and E-/P-Selectin are expressed on plaque endothelial cells and are the key players in this recruitment process. We here present a novel therapeutic approach that targets leukocyte recruitment to plaques. METHODS: We tested a nanoparticle system that effectively delivered short interfering RNAs targeting VCAM-1, ICAM-1/2 and E-/P-Selectin simultaneously (siCAM5) to endothelial cells of atherosclerosis prone ApoE-/- mice and C57BL/6J mice after myocardial infarction (permanent coronary ligation) and assessed leukocyte recruitment/content and plaque phenotype by flow cytometry, histology, qPCR and fluorescence molecular tomography/computed tomography imaging. RESULTS: Efficient degradation of VCAM-1, ICAM-1/2 and E-/P-Selectin on endothelial cells attenuated neutrophil and monocyte numbers in infarcts and atherosclerotic plaques (neutrophil numbers, siControl 10,974±1,250 vs. siCAM5 6,963±1,077, p&lt;0.05; Ly6Chigh monocyte numbers, siControl 6,044±1,212 vs. siCAM5 3,770±293, p&lt;0.05), reduced levels of pro-inflammatory cytokines in plaques, decreased protease activity in plaques (protease activity in pmol, siControl 49.4±2.8 vs. siCAM5 35.9±3.0, p&lt;0.01), and resulted in a less inflammatory plaque phenotype (necrotic core mm2/aortic root, siControl 0.09±0.01 vs. siCAM5 0.05±0.01, p&lt;0.05; fibrous cap μm/aortic root, siControl 36.7±9.5 vs. siCAM5 63.1±5.4, p&lt;0.05) and lower numbers of plaque macrophages (siControl 30,313±4,414 vs. siCAM5 17,198±2,070, p&lt;0.01). CONCLUSIONS: Taken together, the described approach can successfully suppress leukocyte recruitment to atherosclerotic plaques and infarcted hearts. It may allow aggressive medical interventions in patients with inflammatory atherosclerosis.
Current system has lost touch with reality of patient care
Authors: Andrew N Bamji
Journal: BMJ (2008)

Ham’s dissection of the problems of NHS commissioning is welcome to me as it shows I am not the lone voice crying in the wilderness that I feared I was.1 2

The current system of commissioning has lost touch with the reality of patient care. Commissioners have become obsessed with saving money and have started playing games to achieve this. Secondary care services are (largely) paid for through the payment by results (PbR) tariff, but increasingly we are seeing attempts …
Programme for preventing perinatal hepatitis B infection through screening of pregnant women and immunisation of infants of infected mothers in the Netherlands, 1989-92
Authors: P M Grosheide, J M Klokman-Houweling, M A E C.-v. Spaendonck
Journal: BMJ (1995)

To launch a programme for the prevention of perinatal infection with hepatitis B in the Netherlands.Routine antenatal screening and intervention programme.Community antenatal programme, the Netherlands.Infants of mothers who were carriers of hepatitis B detected by routine screening.Infants of infected mothers received hepatitis B immunoglobulin at birth and four doses of hepatitis B vaccine in conjunction with routine immunisation at 3, 4, 5, and 11 months of age.Results of screening and immunisation from 1989-92.The coverage of screening increased from 46% in 1989 to 84% in 1992. Hepatitis B surface antigen was detected in 2145 women (0.44%). The coverage of postnatal immunoprophylaxis in 1645 neonates born to mothers who were carriers of hepatitis B was 85% (1391); in 3% (42) there was a delay in administration of immunoglobulin of over 24 hours. In 1991, 96% (537), 95% (532), 94% (525), and 87% (489) of the infants received the first, second, third, and fourth dose of vaccine, respectively. There was considerable variation in the timing of vaccination; 17% (258) of the infants received their first dose more than two weeks late. Of the 59% (583) of infants who received the fourth dose more than two weeks beyond target age, 14% (141) also received their first dose too late.A prevention programme for perinatal hepatitis B in an area of low prevalence, when incorporated into existing health care, is feasible and achieves satisfactory coverage rates. Intensive follow up is needed to improve adherence to the immunisation schedule.
Abstract 17824: Nocturnal Intermittent Hypoxia is Associated With Reduced Left Atrial Appendage Function in Atrial Fibrillation
Authors: Takehiro Kimura, Takashi Kohno, Shin Kashimura, Yoshinori Katsumata, Takahiko Nishiyama, Nobuhiro Nishiyama, Yoko Tanimoto, Yoshiyasu Aizawa, Keiichi Fukuda, Seiji Takatsuki
Journal: Circulation (2014)

Background: Sleep-disordered breathing (SDB) is closely related to stroke and atrial fibrillation (AF), however the mechanism of these associations is not well established. We assessed the hypothesis that SDB could be associated with reduced left atrial appendage (LAA) function as well as spontaneous echo contrast development in patients with AF.

Methods and Results: Consecutive 134 AF patients (age, 59.6 ± 9.4 years; body mass index [BMI], 24.8 ± 3.2; CHADS2 score, 0.7 ± 0.9; CHA2DS2-VASc score, 1.2 ± 1.1, paroxysmal AF, n = 83) who were candidates for catheter ablation were evaluated. We used a nocturnal pulse oximetry as a non-invasive screening method for nocturnal intermittent hypoxia, a surrogate marker of SDB. Nocturnal intermittent hypoxia was evaluated using 3% oxygen desaturation index (3% ODI) which was the number of oxygen desaturation measurement ≤ 3% per hour, and we divided the patients into nocturnal intermittent hypoxia group (3% ODI>15; n =32) and control group (3% ODI<15; n =102). Nocturnal intermittent hypoxia group had significantly higher weight, BMI, CHADS2 and CHA2DS2-VASc scores, serum HbA1c and plasma BNP level, and left atrial size (all p<0.05). The prevalence of hypertension, vascular disease, and sick sinus syndrome was also higher in nocturnal intermittent hypoxia group (all p<0.05). Among paroxysmal AF patients, the incidence of nocturnal AF attacks was not different between two groups. Transesophageal echocardiography (TEE) data showed that nocturnal intermittent hypoxia was associated with a higher grade of spontaneous echo contrast and lower LAA flow velocity (all p<0.05). The multiple regression analysis adjusted by the type of AF (odds ratio [OR] = -0.313; p=0.002; 95% confidence interval [CI], -19.816 to -4.590), CHA2DS2-VASc score (p=0.423), BMI (p=0.553), plasma BNP level (p=0.209), left atrial size (p=0.159), and rhythm during TEE (p=0.510) revealed that 3% ODI was the independent risk factor for the LAA flow velocity (OR = -0.184; p=0.047; 95% CI, -0.818 to -0.006).

Conclusions: Nocturnal intermittent hypoxia was highly prevalent among AF patients and was an independent determinant for reduced LAA flow velocity, suggesting that SDB might be associated with cardiogenic stroke through reduced LAA function.
Eradication of Dysplastic Barrett’s Oesophagus Using Photodynamic Therapy: Long-Term Follow-Up
Authors: R Ackroyd, C J Kelty, N J Brown, T J Stephenson, C J Stoddard, M W R Reed
Journal: Endoscopy (2003)

Barrett's oesophagus is a major risk factor for oesophageal adenocarcinoma, a condition which is rapidly increasing in incidence. Photodynamic therapy (PDT) is a developing treatment in which tissue damage is caused by the action of light on a previously administered photosensitizing agent. We present the results of long-term follow-up of its efficacy in patients with dysplastic Barrett's oesophagus.A total of 40 patients with low-grade dysplasia in Barrett's oesophagus were treated with oral 5-aminolaevulinic acid (ALA) at a dose of 30 mg/kg, followed by laser endoscopy 4 hours later. Patients were treated between December 1995 and December 1998, and all were followed up regularly with endoscopy and biopsies in our surveillance programme.Among the patients, 35 (88%) showed a macroscopic reduction in the area of the columnar epithelium, and in all 40 patients dysplasia was found to be eradicated at 1 month. The effect has been maintained for a median follow-up of 53 months (range 18-68 months), although one patient developed a late carcinoma in an untreated area of Barrett's oesophagus 3 years after the intervention.Safe and effective ablation of low-grade dysplastic Barrett's oesophagus can be achieved with the use of ALA-induced PDT, and the effects are maintained in the long term.
Abstract 16698: Comparison of Hospital Length of Stay Between Hospitalized Non-Valvular Atrial Fibrillation Patients Treated With Either Apixaban or Warfarin
Authors: Amanda Farr, Yonghua Jing, Stephen Johnston, Jeffrey Trocio, Shalabh Singhal, John Graham
Journal: Circulation (2014)

Hospital length of stay (LOS) is an important cost driver for hospitals and payers alike. Hospitalized non-valvular atrial fibrillation (NVAF) patients treated with apixaban may have shorter LOS than those treated with warfarin because of the absence of need for INR monitoring in apixaban. Thus, this study compared LOS between hospitalized NVAF patients treated with either apixaban or warfarin. This was a retrospective, observational cohort study based on a large U.S. database including diagnosis, procedure, and drug administration information from over 600 acute-care hospitals. Patients selected for study were aged ≥18 years and had a hospitalization record with an ICD-9-CM diagnosis code for atrial fibrillation (AF) in any position from Jan-1-2013 to Feb-28-2014 (index hospitalization). Patients with diagnoses indicative of rheumatic mitral valvular heart disease or a valve replacement procedure during index hospitalization were excluded. Patients were required to have been treated with either apixaban or warfarin, and not treated with rivaroxaban or dabigatran, during index hospitalization. Apixaban patients were propensity score (PS) matched to warfarin patients at a 1:1 ratio, using patient demographic/clinical and hospital characteristics. Study outcome was LOS, calculated as discharge date minus admission date; a sensitivity analysis calculated LOS as discharge date minus first anticoagulant administration date. Subanalyses were conducted among patients with a primary diagnosis of AF. The study included 832 apixaban patients matched to 832 warfarin patients. Patients had a mean age of 74 years and 46% were female. Mean [standard deviation (SD)] and median LOS was significantly (P&lt;0.001) shorter in apixaban patients (4.5 [4.2] and 3 days) than in warfarin patients (5.4 [5.0] and 4); results were consistent in sensitivity analyses of LOS after first anticoagulant administration date (2.8 [3.5] and 2 days for apixaban vs. 3.9 [3.9] and 3 for warfarin, P&lt;0.001). Subanalyses yielded very similar results. Among NVAF patients, apixaban treatment was associated with shorter hospital LOS when compared with warfarin treatment. These findings may have important clinical and economic implications for hospitals, payers, and patients.