tbuckley/cabot-search huggingface dataset:
Differential DNA methylation and expression of inflammatory and zinc transporter genes defines subgroups of osteoarthritic hip patients
Authors: Michael D Rushton, David A Young, John Loughlin, Louise N Reynard
Journal: Annals of the Rheumatic Diseases (2015)

We have previously shown that the cartilage DNA methylome delineates two clusters of osteoarthritic (OA) hip patients, characterised by differential methylation of inflammatory genes, while others have demonstrated a link between zinc homeostasis and inflammation in OA. We aimed to investigate these effects at the methylation and gene expression level.We used our previously generated methylation data while quantitative PCR was used to measure gene expression using RNA from the hip cartilage of members of both clusters and from control individuals without hip OA.One of the OA clusters is characterised by the promoter hypomethylation and increased expression of inflammation-associated genes including IL1A and TNF. Furthermore, we show that the increase in expression of these genes is accompanied by increased expression of several zinc transporter genes. In addition, the zinc responsive transcription factor MTF1 is also upregulated, which is accompanied by an increase in the expression of its targets the metalloproteinases MMP13 and ADAMTS5.We have identified a subgroup of OA hip patients that are epigenetically and transcriptiomically characterised by a cartilage inflammatory phenotype with concurrent differential regulation of zinc regulators. The identification of subgroups enhances stratified phenotyping of OA patients and has important implications for future therapeutic applications.
The Incidence of Bradyarrhythmias and Clinical Bradyarrhythmic Events in Patients With Acute Coronary Syndromes Treated With Ticagrelor or Clopidogrel in the PLATO (Platelet Inhibition and Patient Outcomes) Trial
Authors: Benjamin M. Scirica, Christopher P. Cannon, Håkan Emanuelsson, Eric L. Michelson, Robert A. Harrington, Steen Husted, Stefan James, Hugo Katus, Prem Pais, Dimitar Raev, Jindrich Spinar, Ph. Gabriel Steg, Robert F. Storey, Lars Wallentin
Journal: Journal of the American College of Cardiology (2011)
Relevance of L-selectin Shedding for Leukocyte Rolling In Vivo
Authors: Ali Hafezi-Moghadam, Klaus Ley
Journal: The Journal of Experimental Medicine (1999)

The velocity of rolling leukocytes is thought to be determined by the expression of adhesion molecules and the prevailing wall shear stress. Here, we investigate whether rapid cleavage of L-selectin may be an additional physiologic regulatory parameter of leukocyte rolling. A unique protease in the membrane of leukocytes cleaves L-selectin after activation, resulting in L-selectin shedding. The hydroxamic acid–based metalloprotease inhibitor KD-IX-73-4 completely prevented L-selectin shedding in vitro and significantly decreased the rolling velocity of leukocytes in untreated wild-type C57BL/6 mice from 55 to 35 μm/s in vivo. When E-selectin was expressed on the endothelium (tumor necrosis factor [TNF]-α treatment 2.5–3 h before the experiment), rolling velocity was 4 μm/s and did not change after the application of KD-IX-73-4. However, KD-IX-73-4 decreased mean rolling velocity by 29% from 23 to 16 μm/s in E-selectin–deficient mice treated with TNF-α. The reduction of velocity caused by KD-IX-73-4 was immediate (&amp;lt;5 s) after injection of KD-IX-73-4 as shown by a novel method using a local catheter. These results establish a role for L-selectin shedding in regulating leukocyte rolling velocity in vivo.
A ROLE OF POLYMORPHONUCLEAR LEUKOCYTES AND COMPLEMENT IN NEPHROTOXIC NEPHRITIS
Authors: Charles G. Cochrane, Emil R. Unanue, Frank J. Dixon
Journal: The Journal of Experimental Medicine (1965)

In acute nephrotoxic nephritis, polymorphonuclear leukocytes (polymorphs) accumulated in large numbers in the glomeruli in the first 12 hours. The endothelial cells were dislodged by the polymorphs which then came to lie immediately adjacent to the glomerular basement membranes. Ultrastructural changes in neither polymorphs nor basement membranes were observed. Depletion of polymorphs in both rats and rabbits prevented the development of proteinuria. This occurred when doses of nephrotoxic globulin were employed that produced proteinurias of as much as 1800 mg/kg/24 hours in intact rabbits, or enough to yield near maximal immediate proteinuria in intact rats. In addition, measurable glomerular damage was frequently averted until the onset of the secondary stage of NTN. Controls indicated that the polymorph depleted animals exhibited minimal non-specific changes in the blood, that the ability of their vascular beds to react to stimuli was not affected, and that deposition of nephrotoxic antibody and C' in the glomeruli was not inhibited. Elimination of polymorphs from the circulation was only partially effective in preventing glomerular damage when large doses of nephrotoxic globulin were used. This indicated that under these circumstances, a polymorph independent glomerular injury may also take place in first stage nephrotoxic nephritis. An indirect role of C', i.e., the accumulation of polymorphs, in bringing about glomerular injury in first stage nephrotoxic nephritis was apparent. When rabbit nephrotoxic globulin was injected into rats depleted of C', or when duck nephrotoxic globulin that fixed C' poorly was injected into normal rats, C' failed to bind with the antibody along glomerular basement membranes and polymorphs did not accumulate.
Use of Radioactive Iodine for Thyroid Cancer
Authors: Megan R. Haymart
Journal: JAMA (2011)

<h3>Context</h3>Substantial uncertainty persists about the indications for radioactive iodine for thyroid cancer. Use of radioactive iodine over time and the correlates of its use remain unknown.<h3>Objective</h3>To determine practice patterns, the degree to which hospitals vary in their use of radioactive iodine, and factors that contribute to this variation.<h3>Design, Setting, and Patients</h3>Time trend analysis of radioactive iodine use in a cohort of 189 219 patients with well-differentiated thyroid cancer treated at 981 hospitals associated with the US National Cancer Database between 1990 and 2008. We used multilevel analysis to assess the correlates of patient and hospital characteristics on radioactive iodine use in the cohort treated from 2004 to 2008.<h3>Main Outcome Measure</h3>Use of radioactive iodine after total thyroidectomy.<h3>Results</h3>Between 1990 and 2008, across all tumor sizes, there was a significant increase in the proportion of patients with well-differentiated thyroid cancer receiving radioactive iodine (1373/3397 [40.4%] vs 11 539/20 620 [56.0%]; P &lt; .001). Multivariable analysis of patients treated from 2004 to 2008 found that there was a statistical difference in radioactive iodine use between American Joint Committee on Cancer stages I and IV (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.31-0.37) but not between stages II/III and IV (for stage II vs stage IV, OR, 0.97; 95% CI, 0.88-1.07 and for stage III vs stage IV, OR, 1.06; 95% CI, 0.95-1.17). In addition to patient and tumor characteristics, hospital volume was associated with radioactive iodine use. Wide variation in radioactive iodine use existed, and only 21.1% of this variation was accounted for by patient and tumor characteristics. Hospital type and case volume accounted for 17.1% of the variation. After adjusting for available patient, tumor, and hospital characteristics, 29.1% of the variance was attributable to unexplained hospital characteristics.<h3>Conclusion</h3>Among patients treated for well-differentiated thyroid cancer at hospitals in the National Cancer Database, there was an increase in the proportion receiving radioactive iodine between 1990 and 2008; much of the variation in use was associated with hospital characteristics.
Sarcoplasmic Reticulum Calcium Content Fluctuation Is the Key to Cardiac Alternans
Authors: Mary E. Díaz, Stephen C. O’Neill, David A. Eisner
Journal: Circulation Research (2004)

The aim of this work was to investigate whether beat-to-beat alternation in the amplitude of the systolic Ca(2+) transient (Ca(2+) alternans) is due to changes of sarcoplasmic reticulum (SR) Ca(2+) content, and if so, whether the alternans arises due to a change in the gain of the feedback controlling SR Ca(2+) content. We found that, in rat ventricular myocytes, stimulating with small (20 mV) depolarizing pulses produced alternans of the amplitude of the Ca(2+) transient. Confocal measurements showed that the larger transients resulted from propagation of Ca(2+) waves. SR Ca(2+) content (measured from caffeine-evoked membrane currents) alternated in phase with the alternans of Ca(2+) transient amplitude. After a large transient, if SR Ca(2+) content was elevated by brief exposure of the cell to a Na(+)-free solution, then the alternans was interrupted and the next transient was also large. This shows that changes of SR Ca(2+) content are sufficient to produce alternans. The dependence of Ca(2+) transient amplitude on SR content was steeper under alternating than under control conditions. During alternation, the Ca(2+) efflux from the cell was also a steeper function of SR Ca(2+) content than under control. We attribute these steeper relationships to the fact that the larger responses in alternans depend on wave propagation and that wave propagation is a steep function of SR Ca(2+) content. In conclusion, alternans of systolic Ca(2+) appears to depend on alternation of SR Ca(2+) content. This, in turn results from the steep dependence on SR Ca(2+) content of Ca(2+) release and therefore Ca(2+) efflux from the cell as a consequence of wave propagation.
Infection Control Assessment of Ambulatory Surgical Centers
Authors: Melissa K. Schaefer
Journal: JAMA (2010)

cades, health care delivery in the United States has shifted toward the outpatient setting; ambulatory surgery in particular has been an area of immense growth.Ambulatory surgical centers (ASCs) are defined by the Centers for Medicare & Medicaid Services (CMS) as facilities that operate exclusively to provide surgical services to patients who do not require hospitalization or stays in a surgical facility longer than 24 hours. 1 Between 2001 and 2008 there was a greater than 50% increase in the number of Medicare-certified ASCs in the United States; currently more than 5000 ASCs participate in the Medicare program. 2,3In 2007, these facilities performed more than 6 million procedures with services extending beyond what is traditionally considered surgery to include endoscopy, pain injections, and dental procedures among others. 2][6][7][8][9][10][11] The recent outbreak of hepatitis C virus infections and large-scale patient notification resulting from unsafe injection practices at
Calreticulin expression in neuroblastoma—a novel independent prognostic factor
Authors: W.M. Hsu, F.J. Hsieh, Y.M. Jeng, M.L. Kuo, C.N. Chen, D.M. Lai, L.J. Hsieh, B.T. Wang, P.N. Tsao, H. Lee, M.T. Lin, H.S. Lai, W.J. Chen
Journal: Annals of Oncology (2005)

BackgroundCalreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB.Patients and methodsSixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings.ResultsAmong 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (≤1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan–Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions.ConclusionsCRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.
Are we really moralizing creatures through and through?
Authors: Stephen Stich, Tomasz Wysocki
Journal: Behavioral and Brain Sciences (2010)

Abstract Knobe contends that in making judgments about a wide range of matters, moral considerations and scientific considerations are “jumbled together” and thus that “we are moralizing creatures through and through.” We argue that his own account of the mechanism underlying these judgments does not support this radical conclusion.
Factors that predict in‐hospital mortality in eosinophilic granulomatosis with polyangiitis
Authors: W. Hasegawa, Y. Yamauchi, H. Yasunaga, M. Sunohara, T. Jo, H. Matsui, K. Fushimi, K. Takami, T. Nagase
Journal: Allergy (2015)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis associated with asthma, eosinophilia, and necrotizing vasculitis. EGPA is potentially life-threatening and often involves peripheral neuropathies, peptic ulcers, cerebral vessel disease, and cardiovascular disease. However, there is limited understanding of the prognostics factors for patients with EGPA. We investigated the clinical features and factors affecting patients' in-hospital mortality, using a national inpatient database in Japan.We retrospectively collected data of EGPA patients who required hospitalization between July 2010 and March 2013, using the Diagnosis Procedure Combination database. We evaluated EGPA patients' characteristics and performed multivariate logistic regression analyses to assess the factors associated with in-hospital mortality.A total of 2195 EGPA patients were identified. The mean age was 61.9 years, 42.1% (924/2195) were male, and 41.6% (914/2195) had emergent admission. In-hospital deaths occurred in 97/2195 patients (4.4%). Higher in-hospital mortality was associated with age older than 65 years, disturbance of consciousness on admission, unscheduled admission, respiratory disease, cardio-cerebrovascular disease, renal disease, sepsis, and malignant disease on admission. Lower mortality was associated with female gender and peripheral neuropathies.Our study revealed the clinical features of EGPA patients who required hospitalization and the factors associated with their mortality. These results may be useful for physicians when assessing disease severity or treatments for hospitalized EGPA patients.
Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis
Authors: Daniel Picard, Suzanne Miller, Cynthia E Hawkins, Eric Bouffet, Hazel A Rogers, Tiffany SY Chan, Seung-Ki Kim, Young-Shin Ra, Jason Fangusaro, Andrey Korshunov, Helen Toledano, Hideo Nakamura, James T Hayden, Jennifer Chan, Lucie Lafay-Cousin, Pingzhao Hu, Xing Fan, Karin M Muraszko, Scott L Pomeroy, Ching C Lau, Ho-Keung Ng, Chris Jones, Timothy Van Meter, Steven C Clifford, Charles Eberhart, Amar Gajjar, Stefan M Pfister, Richard G Grundy, Annie Huang
Journal: The Lancet Oncology (2012)
Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.
Authors: K L Lim, A C Jones, N S Brown, R J Powell
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To investigate urine neopterin as a parameter of disease activity in an unselected group of patients with systemic lupus erythematosus (SLE) and to study the relation between urine neopterin and certain patterns of organ disease and differing drug regimens in the treatment of SLE. METHODS--Neopterin was determined by high performance liquid chromatography in 115 early morning urine samples from 68 patients with SLE. Serum soluble interleukin 2 receptor (sIL-2R) and antibodies to double stranded DNA (dsDNA) were determined by enzyme linked immunosorbent assay (ELISA), and the erythrocyte sedimentation rate (ESR), plasma C3, C4, and C3 degradation products (C3dg) were measured in corresponding blood samples. Disease activity was scored using the British Isles Lupus Assessment Group (BILAG) index. RESULTS--Urine neopterin was significantly increased in patients with active and inactive SLE compared with the control group and was significantly higher in patients with active than in those with inactive SLE. Urine neopterin did not distinguish between subsets of patients with SLE with particular patterns of organ disease, as defined by the BILAG index, nor was its level primarily influenced by differing drug regimens. Levels of serum sIL-2R, antibodies to dsDNA, the ESR, and plasma C3, C4, and C3dg were also significantly different between the patients with active and inactive SLE. Unlike urine neopterin there was considerable overlap in the values of these parameters between the two activity groups. Highly significant correlations found between urine neopterin and serum sIL-2R, ESR, and plasma C3, C4, and C3dg suggest the close association of neopterin with clinical activity in SLE. Multivariate logistic regression analysis showed that urine neopterin > 300 mumol/mol creatinine was a highly significant predictor of disease activity with an odds ratio of 3.51. CONCLUSIONS--Determination of urine neopterin, a non-invasive, relatively simple and inexpensive measurement, appears to be the best parameter for assessing and monitoring disease activity and treatment in patients with SLE.
Generation of Effector Memory T Cell–Based Mucosal and Systemic Immunity with Pulmonary Nanoparticle Vaccination
Authors: Adrienne V. Li, James J. Moon, Wuhbet Abraham, Heikyung Suh, Jamal Elkhader, Michael A. Seidman, Minmin Yen, Eung-Jun Im, Maria H. Foley, Dan H. Barouch, Darrell J. Irvine
Journal: Science Translational Medicine (2013)

A lipid nanocapsule vaccine promotes cross-presentation of antigen with enhanced draining lymph node delivery to elicit an effector memory CD8 + T cell response.
Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis
Authors: N. Haase, A. Perner, L. I. Hennings, M. Siegemund, B. Lauridsen, M. Wetterslev, J. Wetterslev
Journal: BMJ (2013)

To assess the effects of fluid therapy with hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin on mortality, kidney injury, bleeding, and serious adverse events in patients with sepsis.
Long-term Nicotine Replacement Therapy
Authors: Robert A. Schnoll, Patricia M. Goelz, Anna Veluz-Wilkins, Sonja Blazekovic, Lindsay Powers, Frank T. Leone, Peter Gariti, E. Paul Wileyto, Brian Hitsman
Journal: JAMA Internal Medicine (2015)

The US Food and Drug Administration adopted labeling for nicotine patches to allow use beyond the standard 8 weeks. This decision was based in part on data showing increased efficacy for 24 weeks of treatment. Few studies have examined whether the use of nicotine patches beyond 24 weeks provides additional therapeutic benefit.To compare 8 (standard), 24 (extended), and 52 (maintenance) weeks of nicotine patch treatment for promoting tobacco abstinence.We recruited 525 treatment-seeking smokers for a randomized clinical trial conducted from June 22, 2009, through April 15, 2014, through 2 universities.Smokers received 12 smoking cessation behavioral counseling sessions and were randomized to 8, 24, or 52 weeks of nicotine patch treatment.The primary outcome was 7-day point prevalence abstinence, confirmed with breath levels of carbon monoxide at 6 and 12 months (intention to treat).At 24 weeks, 21.7% of participants in the standard treatment arm were abstinent, compared with 27.2% of participants in the extended and maintenance treatment arms (χ(2)(1) = 1.98; P = .17). In a multivariate model controlled for covariates, participants in the extended and maintenance treatment arms reported significantly greater abstinence rates at 24 weeks compared with participants in the standard treatment arm (odds ratio [OR], 1.70 [95% CI, 1.03-2.81]; P = .04), had a longer duration of abstinence until relapse (β = 21.30 [95% CI, 10.30-32.25]; P < .001), reported smoking fewer cigarettes per day if not abstinent (mean [SD], 5.8 [5.3] vs 6.4 [5.1] cigarettes per day; β = 0.43 [95% CI, 0.06-0.82]; P = .02), and reported more abstinent days (mean [SD], 80.5 [38.1] vs 68.2 [43.7] days; OR, 1.55 [95% CI, 1.06-2.26]; P = .02). At 52 weeks, participants in the maintenance treatment arm did not report significantly greater abstinence rates compared with participants in the standard and extended treatment arms (20.3% vs 23.8%; OR, 1.17 [95% CI, 0.69-1.98]; P = .57). Similarly, we found no difference in week 52 abstinence rates between participants in the extended and standard treatment arms (26.0% vs 21.7%; OR, 1.33 [95% CI, 0.72-2.45]; P = .36). Treatment duration was not associated with any adverse effects or adherence to the counseling regimen, but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the standard and extended treatment arms (mean [SD], 3.94 [2.5], 4.61 [2.0], and 4.7 [2.4] patches/wk, respectively; F2,522 = 6.03; P = .003).The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers.clinicaltrials.gov Identifier: NCT01047527.
Early assessment of exercise induced skeletal muscle injury using plasma fatty acid binding protein.
Authors: S Sorichter, J Mair, A Koller, M M Pelsers, B Puschendorf, J F Glatz
Journal: British Journal of Sports Medicine (1998)

To test whether fatty acid binding protein (FABP) is a useful plasma marker for the early detection of exercise induced skeletal muscle injury in healthy subjects.Plasma concentrations of FABP and myoglobin (Mb) were measured in six healthy physical education teacher trainees after 20 minutes of downhill running (16% incline; mean lactate 4 mmol/l; 70% (VO2MAX). Creatine kinase (CK) was measured for comparison.Significant increases were found in plasma FABP (mean peak level 50 micrograms/l), Mb (823 micrograms/l), and CK (491 U/l). Mb and FABP concentrations were already significantly elevated (p < 0.05) at 30 minutes, but CK not until two hours after exercise. Whereas Mb and FABP decreased to normal levels within 24 hours, CK activity remained elevated until 48 hours. The Mb to FABP ratio in plasma after exercise induced muscle injury was 15.0 (1.3) (mean (SEM)) (range 7.4-31.1), which is within the range of ratios calculated for skeletal muscle tissue contents of Mb and FABP, but different from the reported plasma ratio after myocardial injury (4-6).After eccentric exercise induced muscle injury, plasma FABP and Mb increase and decrease more rapidly than CK, indicating that both FABP and Mb are more useful than CK for the early detection of such injuries and the monitoring of injury during repeated exercise bouts. In addition, the Mb to FABP ratio in the plasma identifies the type of muscle injured.