tbuckley/cabot-search huggingface dataset:
Biomarkers of Rheumatoid Arthritis–Associated Interstitial Lung Disease
Authors: Juan Chen, Tracy J. Doyle, Yongliang Liu, Rohit Aggarwal, Xiaoping Wang, Yonghong Shi, Sheng Xiang Ge, Heqing Huang, Qingyan Lin, Wen Liu, Yongjin Cai, Diane Koontz, Carl R. Fuhrman, Maria F. Golzarri, Yushi Liu, Hiroto Hatabu, Mizuki Nishino, Tetsuro Araki, Paul F. Dellaripa, Chester V. Oddis, Ivan O. Rosas, Dana P. Ascherman
Journal: Arthritis & Rheumatology (2014)

Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication.Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA-no ILD, RA-mild ILD, or RA-advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest.MMP-7 and interferon-γ-inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA-no ILD, 41 RA-ILD, 42 RA-indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA-no ILD, 49 RA-ILD, 15 RA-indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses.Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.
Influenza A(H1N1)pdm09 antibodies after pandemic and trivalent seasonal influenza vaccination as well as natural infection in November 2010 in Hamburg, Germany
Authors: J P Cramer, T Mac, B Hogan, S Stauga, S Eberhardt, O Wichmann, T Mertens, G D Burchard
Journal: Eurosurveillance (2012)

The 2009 influenza pandemic has introduced the new re-assorted influenza A(H1N1)pdm09 virus which recirculated during the 2010/11 influenza season. Before that season, it was possible to acquire protective immunity either by pandemic or seasonal influenza vaccination against influenza A(H1N1)pdm09 or by natural infection. To obtain data on vaccination coverage and antibody levels in a reference population and to calculate whether or not the herd immunity threshold (HIT, calculated as 33% given an R 0 of 1.5) was reached at the beginning of the 2010/11 season we performed a seroprevalence study in November 2010 in Hamburg, Germany. Antibody titres were assessed applying a haemagglutination inhibition test. Vaccination coverage was very low: 14% for pandemic and 11% for seasonal 2010/11 vaccinations. Even in those with underlying risk factors, vaccination coverage was not much higher: 17% for both vaccines. Serological analysis revealed antibody titres of ≥1:10 in 135 of 352 (38%) and of ≥1:40 in 61 of 352 study participants (17%). Specific antibodies were measurable in 26% of those without history of vaccination or natural infection, indicating a high proportion of subclinical and mild influenza disease. Nevertheless, the HIT was not reached, leaving the majority of the population susceptible to influenza A(H1N1)pdm09 and its potential complications.
Abstract 16172: Predicting the Presence of a Mutation Resulting in Familial Hypercholesterolemia - Development of a Prediction Model in a Cohort of 64,000 Subjects
Authors: Joost Besseling, Johannes B Reitsma, Gerard K Hovingh, Barbara A Hutten
Journal: Circulation (2014)

Introduction: Familial hypercholesterolemia (FH) is a hereditary disease that warrants early diagnosis to prevent premature cardiovascular disease (CVD) by initiating therapy. A definitive diagnosis is made by demonstrating a causal mutation. This might not only increase therapy adherence, but is also an important requirement for cascade screening. However, DNA analysis is costly and careful selection of subjects is important. Unfortunately, the accuracy of current selection criteria is poor. Hypothesis: We set out to develop a model to predict the presence of an FH causing mutation in persons referred by general practitioners. Methods: All participants in the Dutch FH screening program from January 1994 till January 2014 were included. Cross-sectional data was available on medical history, lipid profile and DNA analysis. The primary outcome was the presence of a deleterious FH mutation. We developed a prediction model using multivariable logistic regression analysis. Results: Our study population consisted of 25,809 FH patients and 38,297 unaffected relatives. Our final model included age, gender, levels of LDL-cholesterol, HDL-cholesterol and triglycerides, history of CVD, use of statins and other lipid lowering therapy, smoking and alcohol. The performance was good: the area under the receiver operating characteristic curve (AUC) was 85.2% (95% CI: 84.9 - 85.5). The model was well calibrated with a slope of 1.02 (1 is optimal). Internal validation was excellent: the AUC was unaltered in 100 bootstrap samples. The performance of the model can be illustrated by selecting subjects with a predicted probability of 30% or lower. This would identify 87.0% of all unaffected subjects, and avoid testing in 46.1% of the population. Conclusions: We developed a model to predict the presence of a deleterious FH mutation in subjects referred by general practitioners. Our model showed good discrimination and calibration, with no signs of overfitting during internal validation. After external validation, we will develop an interactive web-based calculator or smart phone application that can be used to calculate the probability of the presence of an FH mutation in individual subjects and will facilitate the use of our prediction model in daily clinical practice.
Abstract 16992: The Impact of Pulmonary Insufficiency on Patients with Surgically Repaired Pulmonary Stenosis vs. Tetralogy of Fallot by Cardiac Magnetic Resonance
Authors: Michael R Joynt, Sunkyung Yu, Adam L Dorfman, Maryam Ghadimi Mahani, Prachi P Agarwal, Jimmy C Lu
Journal: Circulation (2014)

Background: Patients with repaired pulmonary stenosis (PS) and tetralogy of Fallot (TOF) both develop pulmonary insufficiency (PI) leading to right ventricular (RV) dilatation and dysfunction. Cardiac magnetic resonance (CMR) plays a key role in determining timing of pulmonary valve replacement (PVR) in TOF, but it is unclear whether these criteria can be extrapolated to patients with PS. We aimed to compare the differential effect of pulmonary insufficiency on RV volume and systolic and diastolic function in patients with surgically repaired PS and TOF. Methods: All patients with surgically repaired PS, undergoing CMR from 2007-2013, were matched 1:2 by age and pulmonary regurgitant fraction with TOF patients. Patients with prior PVR were excluded. Right and left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), and presence of end-diastolic forward flow in the pulmonary artery (EDFF) were compared. Using feature tracking software (Tomtec, Unterschleissheim, Germany), RV longitudinal s...
Weaning from inotropic support and concomitant beta‐blocker therapy in severely ill heart failure patients: take the time in order to improve prognosis
Authors: Alina A. Constantinescu, Kadir Caliskan, Olivier C. Manintveld, Ron van Domburg, Lucia Jewbali, Aggie H.M.M. Balk
Journal: European Journal of Heart Failure (2013)
The clinical significance of tumor necrosis factor-α plasma level in patients having chronic lymphocytic leukemia
Authors: Alessandra Ferrajoli, Michael J. Keating, Taghi Manshouri, Francis J. Giles, Amanda Dey, Zeev Estrov, Charles A. Koller, Razelle Kurzrock, Deborah A. Thomas, Stefan Faderl, Susan Lerner, Susan O'Brien, Maher Albitar
Journal: Blood (2002)
Genotype analysis in a patient with oculocutaneous albinism 1 minimal pigment type
Authors: M. Kono, T. Kondo, S. Ito, T. Suzuki, K. Wakamatsu, S. Ito, Y. Tomita
Journal: British Journal of Dermatology (2011)

Journal Article Genotype analysis in a patient with oculocutaneous albinism 1 minimal pigment type Get access M. Kono, M. Kono Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa‐ku, Nagoya 466‐8550, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Kondo, T. Kondo Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa‐ku, Nagoya 466‐8550, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Ito, S. Ito Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa‐ku, Nagoya 466‐8550, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Suzuki, T. Suzuki Department of Dermatology, Yamagata University School of Medicine, Yamagata, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Wakamatsu, K. Wakamatsu Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Japan E‐mail: miro@med.nagoya‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar S. Ito, S. Ito Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Japan E‐mail: miro@med.nagoya‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Tomita Y. Tomita Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa‐ku, Nagoya 466‐8550, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 4, 1 April 2012, Pages 896–898, https://doi.org/10.1111/j.1365-2133.2011.10690.x Published: 01 April 2012
Cardiovascular medication use after coronary bypass surgery in patients with renal dysfunction: A National Veterans Administration study
Authors: Eric M. Gibney, Adrianne W. Casebeer, Lynn M. Schooley, Francesca Cunningham, Frederick L. Grover, Missy R. Bell, Gerald O. Mcdonald, A. Laurie Shroyer, Chirag R. Parikh
Journal: Kidney International (2005)
Secretory IgA response in oral immunotherapy
Authors: E. Taudorf, C. Møller, M. W. Russell
Journal: Allergy (1994)

A rationale for oral immunotherapy (OIT) might be founded on two potential mechanisms: induction of a mucosal secretory IgA response, or induction of systemic hyporesponsiveness (oral tolerance). Previous studies have shown clinically that there is a beneficial effect of OIT in birch pollinosis, in both children and adults. During OIT, birch pollen antigens in enterocoated capsules were given to 20 adults (participating in a double‐blind, placebo‐controlled trial) and 10 children, all suffering from birch pollinosis. Saliva and tears (only adults) samples were collected before, during, and after OIT. Each sample was assayed for both IgA antibodies against birch pollen antigens and total IgA by enzyme‐linked immunosorbent assay. IgA antibody levels were also expressed in relation to total IgA concentrations, to correct for variations in secretion and flow rate between subjects and at different times. Changes in birch‐specific secretory IgA antibodies in saliva and tears could not explain the beneficial effect of OIT in birch pollinosis. Further studies in this field are warranted.
Porokeratotic eccrine ostial and dermal duct naevus with dermatomal trunk involvement: literature review and report on the efficacy of laser treatment
Authors: None Leung, None Tang, None Lam, None Fung, None LO
Journal: British Journal of Dermatology (1998)

Porokeratotic eccrine ostial and dermal duct naevus (PEODDN) is a rare, benign hamartomatous malformation involving the eccrine sweat duct. The existence of filiform keratinous plugs that represent cornoid lamellae overlying dilated infundibula of eccrine ducts is a distinctive feature and the presence of associated abnormal dermal ducts is frequent. We report a patient with PEODDN who exhibited lesions on the left side of her chest. Cases of PEODDN reported in the literature are reviewed. Our experience in treating this patient with ultrapulsed carbon dioxide laser is also presented.
Abstract 18538: The ATRIA Stroke Risk Score Predicts Ischemic Stroke Better than CHADS2 and CHA2DS2-VASc in a large Swedish Cohort of Patients with Atrial Fibrillation
Authors: Sara Aspberg, Yuchiao Chang, Daniel Singer
Journal: Circulation (2014)

Introduction: Atrial fibrillation (AF) is a major risk factor for acute ischemic stroke (AIS). Anticoagulation therapy (OAC) effectively prevents AIS, but increases bleeding risk. There is a need for better AIS risk prediction to optimize the anticoagulation decision in AF. The ATRIA stroke risk score (ATRIA) (table) was superior to CHADS2 and CHA2DS2-VASc in two large California community AF cohorts. We now report the performance of the 3 scores in a very large Swedish AF cohort. Methods: The cohort consisted of all Swedish patients hospitalized with a diagnosis of AF from July 1, 2005 to December 31, 2008. Predictor variables and the outcome, AIS, were obtained from inpatient ICD-10 codes. Warfarin use was determined from National Pharmacy Database. Risk scores were assessed via c-index (C) and net reclassification index (NRI). Results: The cohort included 158,370 AF patients off warfarin who contributed 340,332 person-years of follow-up, and 11,823 incident AIS, for an overall AIS rate of 3.47%/yr, higher than the 2%/yr seen in the California cohorts. Using the entire point score, ATRIA had a good C of 0.712 (0.708-0.716), significantly better than CHADS2, 0.694 (0.689-0.698), or CHA2DS2-VASc, 0.697 (0.693-0.702). Using published cut-points for Low/Moderate/High AIS risk, C deteriorated for all scores but ATRIA and CHADS2 were superior to CHA2DS2-VASc. NRI favored ATRIA; 0.16 (0.15-0.18) versus CHADS2; 0.22 (0.21-0.24) versus CHA2DS2-VASc. However, NRI decreased to near-zero when cut-points were altered to better fit the cohort’s stroke rates. Conclusion: Findings in this large Swedish AF cohort validate those in the California AF cohorts, with the ATRIA score predicting stroke risk better than CHADS2 or CHA2DS2-VASc. However, relative performance of the categorical scores varied by population stroke risk. Knowledge about this population risk may be needed to optimize cut-points on the multipoint scores to achieve better net clinical benefit from OAC.
Intramuscular Plasmid DNA Electrotransfer. Biodistribution, Degradation and Stability of the Transfectable Pool of Plasmid DNA
Authors: Michel-Francis Bureau, Naimi Sadoui, Johanne Seguin, Daniel Scherman
Journal: Molecular Therapy (2004)

In the present work, we used plasmid DNA radiolabelled with 3H by methylation (10) to study radiolabelled plasmid DNA biodistribution and degradation in the muscle at different times after injection, with or without electrotransfer using previously defined conditions. Radiolabelled plasmid progressively left the muscle and was degraded as soon as 5 minutes after plasmid injection, with or without electrotransfer. Autoradiography showed that the major part of injected radioactivity was detected in the interfibrilar space of a large proportion of the muscle. Large zones of accumulation of radioactivity which seems to be into some fibres (more than 20 μm) were identified as soon as 5 minutes after electrotransfer. Such structures were never observed on slices of non-electrotransfered muscles. However, these structures were not frequent and probably lesional. The surprising fact is that despite the amount of intact plasmid having been greatly reduced between 5 minutes and 3 hours after injection, the level of transfection remains unchanged whether electric pulses were delivered 20 sec, 1 hour, 2 hours or 3 hours after injection. Such a behavior was similarly observed when injecting 0.3, 3 or 30 μg of plasmid DNA. Moreover, the transfection level was correlated to the amount of plasmid DNA injected. These results suggest that as soon as it is injected, plasmid DNA is proportionally partitioned between at least two compartments. While a major part of plasmid DNA is rapidly cleared and degraded, the electrotransferable pool of plasmid DNA represents a very small part of the amount injected and belongs to another compartment where it is protected from endogenous DNAses.
Abstract 18460: Asymmetric Septal Hypertrophy as a Prognostic Indicator During Progression of Aortic Valve Stenosis
Authors: Eigir Einarsen, Dana Cramariuc, Mai Tone Lonnebakken, Kurt Boman, Christa Gohlke-Bärwolf, John B Chambers, Eva Gerdts
Journal: Circulation (2014)

Objective: Asymmetric septal hypertrophy (ASH) in patients with severe aortic stenosis (AS) has been associated with increased perioperative morbidity and mortality in smaller studies with severe aortic stenosis (AS). This association has not been tested in a large, longitudinal study. Methods: Clinical, echocardiographic and outcome data from 1730 patients with asymptomatic AS, participated in the Simvastatin Ezetimibe in Aortic Stenosis study (SEAS), a randomized placebo controlled study evaluating the effect of lipid lowering medications on progression of AS, were used. ASH was considered present if interventricular septal/posterior wall thickness ratio exceeded 1.5. The association of ASH with rate of major cardiovascular (CV) events was tested in time-dependent cox-regression analysis. Results: During a median of 4.3 years follow-up, ASH developed in 17.0 % of patients, and was associated with higher left ventricular mass (LVM) and body mass index (BMI) compared to non-ASH patients (all p&lt;0.05). In time-varying Cox regression analysis, ASH predicted a 50% greater incidence of ischemic CV events (ICE), a 63% greater incidence in the need for coronary artery bypass grafting (CABG) at the time of aortic valve replacement, and a 2-fold higher incidence of hospitalization for heart failure due to progression of AS (CHFAS) independent of important confounders (all p&lt;0.05) (Table). Conclusions: Development of ASH during progression of AS was a strong predictor of major CV events in patients participating in the SEAS-study. Table: Results are presented as Hazard ratio (95% Confidence Interval).
Abstract 14486: Adrenomedullin-RAMP2 System Regulates Vascular Endothelial Integrity
Authors: Teruhide Koyama, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Takuma Arai, Takahiro Yoshizawa, Lei Yang, Ryuichi Uetake, Akihiro Yamauchi, Megumu Tanaka, Takayuki Shindo
Journal: Circulation (2011)

Adrenomedullin (AM) is a peptide involved in both the pathogenesis of cardiovascular diseases and circulatory homeostasis. AM knockout mice (AM-/-) are lethal with edema and hemorrhage at mid-gesta...
Abstract 15289: Urine Sample-derived Human Induced Pluripotent Stem Cells as a Model to Study PCSK9-mediated Autosomal Dominant Hypercholesterolemia
Authors: Karim Si-Tayeb, Salam Idriss, Benoite Champon, Amandine Caillaud, Matthieu Pichelin, Lucie Arnaud, Bertrand Cariou
Journal: Circulation (2014)

Introduction:  Human induced pluripotent stem cells (hiPSC) are becoming a relevant model for the study of liver metabolic diseases once differentiated into hepatocyte-like cells (HLC), and it has been shown that they can faithfully recapitulate autosomal dominant hypercholesterolemia (ADH). PCSK9 is a critical modulator of cholesterol homeostasis, and quickly became a hot target for ADH pharmacological treatment strategies. However, current cellular models to further decipher the role of PCSK9 in ADH are limited, especially to study the PCSK9 gain of function mutation S127R, which seems to interfere with LDL cholesterol homeostasis intracellularly by still unknown mechanisms.   Hypothesis:  Human iPS cells will provide an appropriate tool to model PCSK9-mediated ADH and screen molecules with pharmacological properties.   Methods:  We used urine samples as a source of somatic cells in order to obtain hiPSC upon episomal vectors-mediated reprogramming (UhiPSC). After characterization and validation, UhiPS control or carrying the S127R mutation were differentiated into HLC.   Results:  Compared to control cells, HLC-S127R secreted less PCSK9 in the media (-38.5 ± 47.2%; p=0.08), and had a 3.5 fold (±0.17; p   Conclusions:  Our study demonstrates that not only patient’s urine samples provide an attractive source of somatic cells for reprogramming and hepatocyte differentiation but also a powerful tool to further study PCSK9 functions and test new therapeutic approaches.
OC-066 A preliminary study of neurostimulation based interventions in the treatment of chronic dysphagia post-stroke
Authors: E Michou, S Mistry, S Jefferson, S Singh, S Hamdy
Journal: Gut (2010)

<h3>Introduction</h3> Oropharyngeal dysphagia after stroke has an incidence up to 45% and when chronic, leads to increased risk of institutionalisation and death in the long term. Pharyngeal electrical stimulation (PES),1 repetitive transcranial magnetic stimulation (rTMS)2 and paired associative stimulation (PAS)3 are three neurostimulation techniques developed to increase cortical excitability of pharyngeal motor cortex, with therapeutic potential. However the effects of these techniques on chronic but stable swallowing problems in stroke patients remain unknown. We therefore investigated the effects of these interventions in stroke patients with dysphagia persisting for &gt;6 weeks. <h3>Methods</h3> In 12 dysphagic stroke patients (69±9 years (mean±SD), 79±25 weeks post-stroke (mean±SD), 6 left, 5 right hemispheric, 1 undetermined) pharyngeal electromyographic responses were recorded using an intraluminal catheter after the application of single TMS pulses over pharyngeal motor cortex, in order to measure cortico-bulbar excitability before, immediately and 30 minutes after real and sham applications of either: a) PES (10 mins of 5 Hz), b) rTMS (250 repeated TMS pulses at 5 Hz), or c) PAS (10 mins of repeated pairs of pharyngeal and TMS pulse every 20 s). In nine subjects, swallowing performance and safety (aspiration-penetration scores, APs) were assessed with videofluoroscopy before and after both real and sham neurostimulation techniques. <h3>Results</h3> Compared to sham, the application of all neurostimulation interventions showed a significant increase in cortical excitability in the unaffected hemisphere by 54%±17% (mean±SEM) immediately post (repeated measures ANOVA p&lt;0.001, Time*Intervention p=0.005), not observed in the affected hemisphere (p=0.12). In addition, after active neurostimulation, APs were reduced by −14%±6% (mean±SEM) compared to sham (Wilcoxon9s test, p=0.05). Moreover, the delay between the oral and pharyngeal phases of swallowing, important for swallowing safety, was shortened by −56%±13% (mean±SEM) after real neurostimulation (Wilcoxon9s test, p=0.01) compared to sham. There was no consistent difference in cortical or swallowing response between the interventions. <h3>Conclusion</h3> These preliminary results show that neurostimulation interventions have beneficial neurophysiological and behavioural effects in chronic stroke patients with dysphagia, increasing cortical excitability and improving swallowing safety. These findings provide support for neurostimulation being a useful adjunct in swallowing rehabilitation, even in chronic neurologic illness, and lay the foundation for further clinical trials of these forms of intervention.