tbuckley/cabot-search huggingface dataset:
Functional variants of the macrophage migration inhibitory factor do not infer risk of cardiovascular disease in rheumatoid arthritis
Authors: T R D J Radstake, J Fransen, P L C M van Riel, E Toonen, M Coenen, R Donn
Journal: Annals of the Rheumatic Diseases (2007)

In the last decade it became apparent that patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) leading to an excess mortality of approximately 25%.1–3 Nowadays a substantial body of evidence indicates that atherosclerosis shares many features with inflammatory disease, such as RA, and that the involved inflammatory mediators are likely to be similar. More recently, evidence has emerged for the involvement of macrophage migration inhibitory factor (MIF) both in RA and atherosclerosis suggesting that MIF might form the link between RA and the increased incidence of CVD in this condition. Two known single nucleotide polymorphisms in the MIF gene have been …
Evidence that an angiotensin-converting enzyme inhibitor has a different effect on glomerular injury according to the different phase of the disease at which the treatment is started.
Authors: N Perico, S C Amuchastegui, V Colosio, G Sonzogni, T Bertani, G Remuzzi
Journal: Journal of the American Society of Nephrology (1994)

In rats with streptozotocin-induced diabetes, the effect of an angiotensin-converting enzyme (ACE) inhibitor on the evolution of glomerular injury according to the time at which the treatment is started with respect to the onset of the disease was studied. Three groups of animals were used, a control Group 1 and two groups of diabetic rats treated with insulin (Groups 2 and 3). The latter were monitored until urinary protein excretion reached 40 to 50 mg/24 h (on average, 23 wk after the induction of the diabetes). At this time, Group 2 continued to receive insulin alone, whereas Group 3 was also given the ACE inhibitor moexipril for 8 more wk. Untreated diabetic rats showed a moderate increase in systolic blood pressure that was normalized by moexipril administration. Urinary protein excretion progressively increased during the 8-wk follow-up in untreated diabetics that, at the end of the study, developed moderate glomerular sclerosis. Moexipril treatment lowered urinary protein excretion to a normal range and completely prevented glomerular injury. Three other groups of rats were similarly treated, except that moexipril treatment was started later on (when proteinuria reached 100 to 200 mg/24 h, on average, 32 wk after the induction of diabetes), and were monitored for another 8 wk. Untreated and treated diabetics had comparable blood glucose levels throughout. Systolic blood pressure, significantly increased in untreated diabetic rats, was effectively controlled by moexipril administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Strategy for encoding and comparison of gene expression signatures
Authors: Yajun Yi, Chun Li, Clay Miller, Alfred L George
Journal: Genome biology (2007)

EXALT (EXpression signature AnaLysis Tool) is a computational system enabling comparisons of microarray data across experimental platforms and different laboratories http://seq.mc.vanderbilt.edu/exalt/. An essential feature of EXALT is a database holding thousands of gene expression signatures extracted from the Gene Expression Omnibus, and encoded in a searchable format. This novel approach to performing global comparisons of shared microarray data may have enormous value when coupled directly with a shared data repository.
Research in progress: put the orphanage out of business: Table 1
Authors: Andrew Bush, Gisela Anthony, Angelo Barbato, Steve Cunningham, Annick Clement, R Epaud, Carlee Gilbert, Lutz Goldbeck, Kai Kronfeld, Andrew G Nicholson, Nicolaus Schwerk, Matthias Griese
Journal: Thorax (2013)

Paediatric interstitial lung disease (ILD) is rare and diverse, meaning no single centre will see sufficient children to perform the studies needed to make progress. This EU FP-7 grant will standardise the evaluation of these rare conditions by establishing pan-European multidisciplinary expert panels and establish consensus on treatment protocols and standard operating procedures across Europe. We will work with patient groups to determine optimal treatment end-points and biomarkers. A biobank will be established as a Europe-wide resource for mechanistic studies. Ultimately we aim to do the first randomised controlled trial of a pharmacological treatment in paediatric ILD.
Avian Influenza and Pandemics — Research Needs and Opportunities
Authors: Klaus Stöhr
Journal: New England Journal of Medicine (2005)

As the year 2004 progressed, so did conditions favoring the start of an influenza pandemic. The first warning came in January, when Thailand and Vietnam reported fatal human cases of avian influenza caused by the H5N1 strain of influenza A virus. That strain was already notorious for its pandemic potential, revealed during an outbreak in Hong Kong in 1997 and later in a smaller number of human cases in 2003.With the H5N1 strain now endemic in birds in large parts of Asia, the probability that this potential for a pandemic will be realized has increased. Recent laboratory and epidemiologic . . .
The global burden of rheumatoid arthritis: estimates from the Global Burden of Disease 2010 study
Authors: Marita Cross, Emma Smith, Damian Hoy, Loreto Carmona, Frederick Wolfe, Theo Vos, Benjamin Williams, Sherine Gabriel, Marissa Lassere, Nicole Johns, Rachelle Buchbinder, Anthony Woolf, Lyn March
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions. <h3>Methods</h3> The optimum case definition of RA for the study was the American College of Rheumatology 1987 criteria. A series of systematic reviews were conducted to gather age-sex-specific epidemiological data for RA prevalence, incidence and mortality. Cause-specific mortality data were also included. Data were entered into DisMod-MR, a tool to pool available data, making use of study-level covariates to adjust for country, region and super-region random effects to estimate prevalence for every country and over time. The epidemiological data, in addition to disability weights, were used to calculate years of life lived with disability (YLDs). YLDs were added to the years of life lost due to premature mortality to estimate the overall burden (disability-adjusted life years (DALYs)) for RA for the years 1990, 2005 and 2010. <h3>Results</h3> The global prevalence of RA was 0.24% (95% CI 0.23% to 0.25%), with no discernible change from 1990 to 2010. DALYs increased from 3.3 million (M) (95% CI 2.6 M to 4.1 M) in 1990 to 4.8 M (95% CI 3.7 M to 6.1 M) in 2010. This increase was due to a growth in population and increase in aging. Globally, of the 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency (measured in YLDs). <h3>Conclusions</h3> RA continues to cause modest global disability, with severe consequences in the individuals affected.
Effects of Oral Branched-Chain Amino Acid Granules on Event-Free Survival in Patients With Liver Cirrhosis
Authors: Yasutoshi Muto, Shunichi Sato, Akiharu Watanabe, Hisataka Moriwaki, Kazuyuki Suzuki, Akinobu Kato, Masahiko Kato, Teiji Nakamura, Kiyohiro Higuchi, Shuhei Nishiguchi, Hiromitsu Kumada
Journal: Clinical Gastroenterology and Hepatology (2005)
EMG-pattern of respiratory muscles during Muller manoeuvre: Effect of body posture
Authors: Marina Segizbaeva
Journal: European Respiratory Journal (2012)

The voluntary maximal inspiratory effort is the manoeuvre requiring activation, recruitment and coordination of different respiratory muscles. A study was undertaken to describe the pattern of recruitment of inspiratory muscles used in the generation of maximal inspiratory effort in different body postures. 10 young normal human participated in this study. Maximal inspiratory mouth pressure (MIP) during Muller manoeuvre was measured in the standing, sitting, right side lying (RSL), left side lying (LSL), supine and head-down-tilt (HDT -30°) posture. The level of electrical activity of the diaphragm (D), parasternal (PS), sternocleidomastoid (SM) and genioglossus (GG) was studied during Muller manoeuvre in each of body postures. MIP in the standing position was 105.3±12.0 in men and 59.9±10.1 cm H2O in women (control). Both in men and women MIP did not significantly differ from control in the sitting, supine, RSL and LSL. But MIP in HDT was lower by 23% and 27% compared with control in men and women respectively. Integrated EMG activity of D during Muller manoeuvre was near the control in sitting, supine, RSL, LSL and significantly greater in HDT compared with standing. On the contrary, the PS and SM showed the highest level of activation during Muller manoeuvre in standing position, but its activation was significantly lower in HDT (P
One million haemopoietic stem-cell transplants: a retrospective observational study
Authors: Alois Gratwohl, Marcelo C Pasquini, Mahmoud Aljurf, Yoshiko Atsuta, Helen Baldomero, Lydia Foeken, Michael Gratwohl, Luis Fernando Bouzas, Dennis Confer, Karl Frauendorfer, Eliane Gluckman, Hildegard Greinix, Mary Horowitz, Minako Iida, Jeff Lipton, Alejandro Madrigal, Mohamad Mohty, Luc Noel, Nicolas Novitzky, José Nunez, Machteld Oudshoorn, Jakob Passweg, Jon van Rood, Jeff Szer, Karl Blume, Frederic R Appelbaum, Yoshihisa Kodera, Dietger Niederwieser
Journal: The Lancet Haematology (2015)
CHRONIC TOTAL OCCLUSION: OPTICAL COHERENCE TOMOGRAPHY FINDINGS AT SIX MONTHS FOLLOWING TREATMENT WITH SIROLIMUS ELUTING STENTS
Authors: Haibo Jia, Ning Li, Xuedong Wang, Koji Kato, Taishi Yonetsu, Sining Hu, Jinwei Tian, Shaosong Zhang, Jingbo Hou, Bo Yu, Ik–Kyung Jang
Journal: Journal of the American College of Cardiology (2013)
Observations on Concealed Conduction in Atrial Fibrillation
Authors: E. NEIL MOORE
Journal: Circulation Research (1967)

The mechanism of the ventricular dysrhythmia associated with atrial fibrillation in isolated rabbit heart was studied by recording electrograms from right atrium and ventricle simultaneously with transmembrane action potentials recorded from single fibers within the A-V node and right bundle branch. In most experiments, the variation in ventricular cycle length during experimentally initiated atrial fibrillation resulted from concealed conduction within the A-V node. The most frequently recorded ventricular interval during atrial fibrillation was found when a single response was concealed within the A-V node. In several experiments, as many as seven to nine consecutively concealed responses were recorded from the A-V node. When repetitive A-V nodal concealment occurred, the resulting ventricular cycle lengths were prolonged accordingly. In only a few experiments were conduction delay and block observed within the ventricular specialized conduction system (VSCS) during atrial fibrillation. Subsidiary pacemakers were never observed within the A-V node but were noted occasionally within the VSCS following epinephrine administration. Multiple A-V nodal concealments were usually associated with rapid atrial rates.
P96 Serum protein N-glycosylation as a biomarker of paediatric NAFLD
Authors: E. Fitzpatrick, B. Blomme, A. Quaglia, R. D. Bruyne, H. V. Vlierberghe, A. Dhawan
Journal: Gut (2011)

<h3>Introduction</h3> Serum protein N-glycosylation has previously been shown to distinguish adult patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH). The pattern of the disease in paediatric patients is distinct from adults. <h3>Aim</h3> The aim of this study was to characterise the glycomic profile of children with varying degrees of NAFLD to identify potential biomarker profiles of disease. <h3>Method</h3> Children with biopsy proven non-alcoholic fatty liver disease (n=51) were recruited from a tertiary paediatric hepatology unit. Liver biopsy was scored according to NAFLD activity score. Blood was taken on day of biopsy for analysis. Serum protein N-glycosylation patterns were assessed with DNA-sequencer assisted fluorophore-assisted capillary electrophoresis (DSA-FACE) and compared with histology. <h3>Results</h3> Median age at biopsy was 13.3 years (range 4.5–17.4). 31 were male. Median BMI z-score was 1.81. 23 children scored as simple steatosis/borderline NASH and 28 as true NASH. 18 children had no/minimal fibrosis (&lt; F2) and 33 had significant fibrosis (≥ F2). Similar to previous work in adult patients with NAFLD, peak 1 (NGA2F) was the most significantly raised N-glycan in paediatric NASH patients with peak 5 (NA2) demonstrating the greatest decrease. The logarithmically transformed ratio of peak 1 to peak 5 (Glycomarker) was −0.85 (SD 0.22) in simple steatosis/borderline NASH and −0.73 (SD 0.12) in NASH (p=0.02). The biomarker correlated well with the amount of lobular inflammation with a consistent increase with ascending grade of inflammation. There was also a trend towards significance in differentiating patients with significant fibrosis ≥ F2; −0.74 (SD 0.13) from patients with no/minimal fibrosis &lt; F2; −0.86 (SD 0.24), (p=0.06). Glyco-analysis of immunoglobulin G (IgG) confirmed the undergalactosylation status with a significant increase in peak 1 (NGA2F; p=0.024) and a significant decrease of peak 6 (NA2F; p=0.01) on IgG. In multivariate analysis of the Glycomarker, GGT, AST and INR, only the Glycomarker displayed a significant result for distinguishing simple steatosis from NASH (p=0.019). <h3>Conclusion</h3> In conclusion, the findings in this study are novel in that they represent the first Glycomic analysis of paediatric NAFLD. They validate findings in adults in that a Glycomarker can serve reliably as a biomarker of severity of disease in NAFLD. The same N-glycosylation alterations are observed in paediatric NASH patients when compared to an adult population and therefore the same biomarker can be used. B cells play a dominant role in the N-glycan alterations of NASH patients, both in an adult and paediatric population.
Expression of Epidermal Growth Factor Receptor (EGFR) and Activated EGFR Predict Poor Response to (Chemo)radiation and Survival in Cervical Cancer
Authors: Maartje G. Noordhuis, Jasper J.H. Eijsink, Klaske A. ten Hoor, Frank Roossink, Harry Hollema, Henriëtte J.G. Arts, Elisabeth Pras, John H. Maduro, Anna K.L. Reyners, Geertruida H. de Bock, G. Bea A. Wisman, Ed Schuuring, Ate G.J. van der Zee
Journal: Clinical Cancer Research (2009)

Activation of the epidermal growth factor receptor (EGFR) signaling pathway has been reported to induce resistance to (chemo)radiation in cancers, such as head and neck cancer, whereas EGFR-targeted agents in combination with (chemo)radiation seem to improve treatment efficacy. The aim of this study was to determine the relation between proteins involved in the EGFR pathway and response to (chemo)radiation and survival in a large, well-documented series of cervical cancer patients.Pretreatment tissue samples of 375 consecutive International Federation of Gynecologists and Obstetricians stage Ib to IVa cervical cancer patients treated with (chemo)radiation between January 1980 and December 2006 were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. Protein expression of EGFR, phosphorylated EGFR (pEGFR), PTEN, phosphorylated AKT, and phosphorylated extracellular signal-regulated kinase (pERK) was assessed by immunohistochemistry on tissue microarrays.EGFR staining was present in 35.3%, pEGFR in 19.7%, PTEN in 34.1%, phosphorylated AKT in 4.1%, and pERK in 29.2% of tumors. pEGFR staining was related to PTEN (P = 0.001) and pERK staining (P = 0.004). EGFR staining was inversely related to PTEN (P = 0.011). In multivariate analysis, membranous staining of EGFR [hazard ratio (HR), 1.84; 95% confidence interval (95% CI), 1.20-2.82; P = 0.005] and cytoplasmic staining of pEGFR (HR, 1.71; 95% CI, 1.11-2.66; P = 0.016) were independent predictors of poor response to (chemo)radiation. Membranous EGFR staining also was an independent prognostic factor for poor disease-specific survival (HR, 1.54; 95% CI, 1.09-2.17; P = 0.014).EGFR and pEGFR immunostainings are frequently observed and independently associated with poor response to therapy and disease-specific survival in cervical cancer patients primarily treated by (chemo)radiation. Our data present the EGFR pathway as a promising therapeutic target in already ongoing clinical trials.
ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma
Authors: Pascale De Paepe, Mathijs Baens, Han van Krieken, Bruno Verhasselt, Michel Stul, Annet Simons, Bruce Poppe, Geneviève Laureys, Paul Brons, Peter Vandenberghe, Frank Speleman, Marleen Praet, Chris De Wolf-Peeters, Peter Marynen, Iwona Wlodarska
Journal: Blood (2003)
Long-term domiciliary oxygen therapy in cor pulmonale complicating chronic bronchitis and emphysema.
Authors: R J Leggett, N J Cooke, L Clancy, A G Leitch, B J Kirby, D C Flenley
Journal: Thorax (1976)

Ten patients with cor pulmonale complicating severe chronic bronchitis and emphysema have been treated with 2 litres/min of oxygen for prolonged periods in the day, at home, over 12 to 62 months. Two patients died after 12 and 36 months of treatment. Pulmonary arterial pressure was reduced in seven patients, and red cell mass in eight, when the oxygen was given for over 15 hours in the day. Hospital inpatient treatment was greatly reduced following the start of long-term oxygen treatment in all patients. This treatment is expensive, and a controlled trial is necessary to establish its definitive place and cost-effectiveness, but the results of such a current Medical Research Council trial will not be available for a further two years.
Is liver fibrosis reversible?
Authors: R C BENYON
Journal: Gut (2000)

Liver fibrosis and cirrhosis result from the majority of chronic liver insults and represent a common and difficult clinical challenge of worldwide importance. At present, the only curative treatment for end stage cirrhosis is transplantation, but even in the developed world, the number of donor organs available and the clinical condition of the potential recipient limit the applicability of this technique. The alternative clinical course is one familiar to gastroenterologists—that of a progressive damage limitation exercise in which the complications of fibrosis and cirrhosis are treated with greater or lesser success. The development of fibrosis, and particularly cirrhosis, is associated with a significant morbidity and mortality. Thus, there is a considerable imperative to develop antifibrotic strategies that are applicable to liver fibrosis. Such an approach is attractive precisely because it is aimed at the final common pathological pathway of chronic liver disease, regardless of aetiology. However, because fibrotic liver disease may not present clinically until an advanced or cirrhotic stage, the possibility of reversing the fibrosis is an essential issue for developing therapeutic approaches.

Liver fibrosis represents the wound healing response of the liver, as such it demonstrates generic aspects that characterise tissue healing elsewhere in the body — a wound healing response that is dynamic and has the potential to resolve without persistent scarring. This may seem at odds with the clinical impression that advanced fibrosis and cirrhosis are at best irreversible and at worst progressive. However, recent developments in our understanding of the process of hepatic fibrogenesis confirm that the process is dynamic with respect to both cell and extracellular matrix (ECM) turnover and suggest that a capacity for recovery from advanced cirrhosis and fibrosis is possible. Moreover, with the advent of effective antiviral therapies, biopsy documented examples of improvements in fibrosis and in some examples resolution, including …
IL-6 Haplotypes, Inflammation, and Risk for Cardiovascular Disease in a Multiethnic Dialysis Cohort
Authors: Yongmei Liu, Yvette Berthier-Schaad, Margaret D Fallin, Nancy E Fink, Russell P Tracy, Michael J Klag, Michael W Smith, Josef Coresh
Journal: Journal of the American Society of Nephrology (2006)

It is unknown whether IL-6, a central regulator of inflammation, is a cause of or just a marker of atherosclerosis. Studies of genetic susceptibility to inflammation, however, avoid the potential for reverse causality. Variation in IL6 gene was studied as a predictor of cardiovascular disease (CVD) risk in a cohort of 775 incident dialysis patients, in whom IL-6 levels are elevated. On the basis of published resequencing data on the IL6 gene, a phylogenetic tree with three main branches (clades 1 to 3) was constructed. Two "clade tag" polymorphisms, -174G/C and 1888G/T, and two missense variants, Pro32Ser and Asp162Val, were genotyped. Circulating IL-6 and albumin were measured a median of 5 mo after the start of dialysis. CVD events were ascertained from medical records. During a median follow-up of 2.5 yr, 294 CVD events occurred. The two coding variants, Pro32Ser (present only in black patients, 10% Ser allele) and Asp162Val (present only in white patients, 1% Val), were associated with lower levels of IL-6 and higher levels of albumin. The common variant in the promoter region, -174G/C, was strongly associated with higher CVD risk and weakly with IL-6 levels. Clade 3 (-174C carriers in the absence of 162 Val allele) was associated with higher IL-6 levels (P=0.03) and higher CVD risk (hazard ratio 1.44, P=0.006) after adjustment for covariates. The IL6 gene has functional variants that affect inflammation and risk for CVD among dialysis patients, supporting a causal role for IL6 in CVD.
High Schools Find Later Start Time Helps Students’ Health and Performance
Authors: Lynne Lamberg
Journal: JAMA (2009)

High school will start at 8:15 AM this September in Duxbury, Mass, a Boston suburb, instead of at 7:30 AM, as it did last year. School officials hope the 45-minute delay will allow the 1000 students in grades 9 through 12 to sleep longer and arrive at school more alert and ready to learn.