tbuckley/cabot-search huggingface dataset:
International gastroenterology research: subject areas, impact, and funding
Authors: G Lewison, J Grant, P Jansen
Journal: Gut (2001)

AIMS To examine the volume and potential impact of gastroenterology research outputs from 1985 to 1998 from 14 developed countries; the overlap with research in cancer, infectious diseases, and genetics; and the funding sources for this research. To determine if countries' research outputs correlated with their burden of corresponding diseases and inputs to their research. METHODS Selective retrieval of papers from the Science Citation Index and manual look up of a sample to determine funding sources. Classification of journals by four categories of research level (clinical/basic) and potential impact (low/high). RESULTS Gastroenterology represents about 8% of world biomedical research but over 11% in Italy, Japan, and Spain. Its potential impact is highest (but declining) for the USA. It has increased noticeably in most European countries, particularly in Finland. Gastroenterology research has become more clinical in Japan, Spain, Australia, and the Netherlands but more basic in Canada, Germany, Finland, Israel, and South Africa. Funding comes primarily from national governments, followed by national private non-profit sources and industry but little industrial funding occurs in some countries. There is a strong and positive correlation between reported deaths from gastrointestinal neoplasms and countries' outputs of research in gastrointestinal oncology. CONCLUSIONS Bibliometric analysis can reveal differences between countries in their research in a subject when a common methodology is applied to an international database. Variations in research methods in different countries can plausibly explain some of the variation in the potential impact of the work.
Cardiometabolic Risk of Second-Generation Antipsychotic Medications During First-Time Use in Children and Adolescents
Authors: Christoph U. Correll
Journal: JAMA (2009)

Cardiometabolic effects of second-generation antipsychotic medications are concerning but have not been sufficiently studied in pediatric and adolescent patients naive to antipsychotic medication.To study the association of second-generation antipsychotic medications with body composition and metabolic parameters in patients without prior antipsychotic medication exposure.Nonrandomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted between December 2001 and September 2007 at semi-urban, tertiary care, academic inpatient and outpatient clinics in Queens, New York, with a catchment area of 4.5-million individuals. Of 505 youth aged 4 to 19 years with 1 week or less of antipsychotic medication exposure, 338 were enrolled (66.9%). Of these patients, 272 had at least 1 postbaseline assessment (80.5%), and 205 patients [corrected] completed the study (60.7%). Patients had mood spectrum (n = 130; 47.8%), schizophrenia spectrum (n = 82; 30.1%), and disruptive or aggressive behavior spectrum (n = 60; 22.1%) disorders. Fifteen patients who refused participation or were nonadherent served as a comparison group.Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks.Weight gain and changes in lipid and metabolic parameters.After a median of 10.8 weeks (interquartile range, 10.5-11.2 weeks) of treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7 kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by 4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the minimal weight change of 0.2 kg (95% CI, -1.0 to 1.4 kg) in the untreated comparison group (n = 15). With olanzapine and quetiapine, respectively, mean levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to 24.3 mg/dL] P < .001 and 9.1 mg/dL [95% CI, 0.4 to 17.7 mg/dL] P = .046), triglycerides (24.3 mg/dL [95% CI, 9.8 to 38.9 mg/dL] P = .002 and 37.0 mg/dL [95% CI, 10.1 to 63.8 mg/dL] P = .01), non-high-density lipoprotein (HDL) cholesterol (16.8 mg/dL [95% CI, 9.3 to 24.3 mg/dL] P < .001 and 9.9 mg/dL [95% CI, 1.4 to 18.4 mg/dL] P = .03), and ratio of triglycerides to HDL cholesterol (0.6 [95% CI, 0.2 to 0.9] P = .002 and (1.2 [95% CI, 0.4 to 2.0] P = .004). With risperidone, triglycerides increased significantly (mean level, 9.7 mg/dL [95% CI, 0.5 to 19.0 mg/dL]; P = .04). Metabolic baseline-to-end-point changes were not significant with aripiprazole or in the untreated comparison group.First-time second-generation antipsychotic medication use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 antipsychotic medications.
Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling
Authors: Shu Zhu, Wen Pan, Peiqing Shi, Hanchao Gao, Fang Zhao, Xinyang Song, Yan Liu, Lihua Zhao, Xiaoxia Li, Yufang Shi, Youcun Qian
Journal: The Journal of Experimental Medicine (2010)

Interleukin 17 (IL-17) plays critical roles in the pathogenesis of various autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE). How the signals triggered by this powerful inflammatory cytokine are controlled to avoid abnormal inflammatory responses is not well understood. In this study, we report that TRAF3 is a receptor proximal negative regulator of IL-17 receptor (IL-17R) signaling. TRAF3 greatly suppressed IL-17–induced NF-κB and mitogen-activated protein kinase activation and subsequent production of inflammatory cytokines and chemokines. Mechanistically, the binding of TRAF3 to IL-17R interfered with the formation of the receptor signaling activation complex IL-17R–Act1–TRAF6, resulting in suppression of downstream signaling. TRAF3 markedly inhibited IL-17–induced expression of inflammatory cytokine and chemokine genes in vivo and consequently delayed the onset and greatly reduced the incidence and severity of EAE. Thus, TRAF3 is a negative regulator of IL-17R proximal signaling.
A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus
Authors: E. Svenungsson, J. Gustafsson, D. Leonard, J. Sandling, I. Gunnarsson, G. Nordmark, A. Jonsen, A. A. Bengtsson, G. Sturfelt, S. Rantapaa-Dahlqvist, K. Elvin, U. Sundin, S. Garnier, J. F. Simard, S. Sigurdsson, L. Padyukov, A.-C. Syvanen, L. Ronnblom
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE. <h3>Methods</h3> Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped. <h3>Results</h3> The STAT4 risk allele was more frequent in patients with SLE with previous arterial events (combined OR (OR<sub>c</sub>)=1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The association was mainly attributable to an accumulation of the risk allele among patients with ICVD (OR<sub>c</sub>=2.3, CI 1.6 to 3.3). There was no association with IHD or VTE. The presence of two or more aPLs was associated with the risk allele (OR<sub>c</sub>=1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression analyses treatment for hypertension, at least one <i>STAT4</i> risk allele, older age, IgG anti-cardiolipin antibodies and longer SLE duration remained independently associated with previous ICVD (p≤0.02 for all). <h3>Conclusion</h3> Patients with SLE with the STAT4 risk allele had a strikingly increased risk of ICVD, comparable in magnitude to that of hypertension. The results imply that a genetic predisposition is an important and previously unrecognised risk factor for ICVD in SLE, and that aPLs may be one underlying mechanism.
Vinyl chloride: still a cause for concern.
Authors: J Kielhorn, C Melber, U Wahnschaffe, A Aitio, I Mangelsdorf
Journal: Environmental Health Perspectives (2000)

Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its production capacity has almost doubled over the last 20 years, currently 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroethylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide occupational exposure to VC still seems to be high in some countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure may also be high in others where VC is not regulated. By combining the most relevant epidemiologic studies from several countries, we observed a 5-fold excess of liver cancer, primarily because of a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellular carcinoma, and others suggest a possible risk of brain tumors among highly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra observed in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated with exposure to VC are clearly distinct from those observed in sporadic liver tumors or hepatic tumors that are associated with other exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC metabolites. Risk assessments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL.
Progressive Aortic Root Dilatation in Adults Late After Repair of Tetralogy of Fallot
Authors: Koichiro Niwa, Samuel C. Siu, Gary D. Webb, Michael A. Gatzoulis
Journal: Circulation (2002)

Aortic valve or aortic root (AoRo) replacement is occasionally required because of AoRo dilatation and aortic regurgitation (AR) in repaired tetralogy of Fallot (TOF). We evaluated AoRo size and possible factors associated with its dynamic nature in adults with repaired TOF.Of 216 patients with TOF repair who underwent echocardiography in 1997, we identified 32 patients (mean age, 36+/-8.0 years) with AoRo dilatation, defined as ratio of observed to expected AoRo size by standard nomogram >1.5 (group A), and 54 TOF controls, matched for age with AoRo ratio <1.5 (group B), who underwent at least 1 previous echocardiogram in the preceding 10 years. Mean indexed AoRo size (cm/m2) in 1997 was 2.5+/-0.5 in group A and 1.7+/-0.2 in group B (P<0.0001). AoRo rate of change (mm/year) from the first to 1997 study (mean interval, 5.2+/-3.8 years) was 1.7+/-3.8 in group A and 0.03+/-1.6 in group B (P=0.001). Patients from group A had a longer shunt-to-repair interval (P=0.048) with a higher prevalence of pulmonary atresia (P<0.0001), right aortic arch (P=0.03), moderate to severe AR (P=0.002), aortic valve replacement (P=0.02), larger cardiothoracic ratio (P=0.02), and increased left ventricular end-diastolic dimensions (P=0.002).A subset of adult TOF exhibits ongoing dilatation of AoRo late after repair. This dilatation relates to previous long-standing volume overload of AoRo and possibly to intrinsic properties of AoRo and may lead to AR. Meticulous follow-up of AoRo after TOF repair is recommended.
Effects of prior exercise on the performance of intense isometric exercise.
Authors: R J Maughan
Journal: British Journal of Sports Medicine (1988)

The influence of a regimen designed to lower the muscle glycogen content on the capacity to perform a single brief isometric contraction has been studied. Eight male subjects performed a single exhausting isometric contraction of the knee extensor muscles at a tension corresponding to 60% of maximum voluntary contraction (MVC). This was followed by prolonged cycling exercise at a work rate equivalent to approximately 75% of maximum oxygen uptake in order to reduce the muscle glycogen content. A diet low in carbohydrate was consumed for the remainder of this day in order to retard the resynthesis of muscle glycogen. The isometric contraction at 60% of MVC was repeated on the following day. Endurance time on the first day was 53.8 +/- 8.4 s (mean +/- SD); this was reduced (45.8 +/- 12.1 s; p less than 0.02) on the second day. From previously published data on rates of muscle glycogen utilisation during isometric exercise, it seems probable that insufficient glycogen is available in the muscle under the low carbohydrate condition to enable maximum performance to be achieved.
Telaprevir for Previously Treated Chronic HCV Infection
Authors: John G. McHutchison, Michael P. Manns, Andrew J. Muir, Norah A. Terrault, Ira M. Jacobson, Nezam H. Afdhal, E. Jenny Heathcote, Stefan Zeuzem, Hendrik W. Reesink, Jyotsna Garg, Mohammad Bsharat, Shelley George, Robert S. Kauffman, Nathalie Adda, Adrian M. Di Bisceglie
Journal: New England Journal of Medicine (2010)

Patients with genotype 1 hepatitis C virus (HCV) who do not have a sustained response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment.We randomly assigned patients with HCV genotype 1 who had not had a sustained virologic response after peginterferon alfa-ribavirin therapy to one of four treatment groups: 115 patients to the T12PR24 group, receiving telaprevir (1125-mg loading dose, then 750 mg every 8 hours) for 12 weeks and peginterferon alfa-2a (180 microg per week) and ribavirin (1000 or 1200 mg per day, according to body weight) for 24 weeks; 113 patients to the T24PR48 group, receiving telaprevir for 24 weeks and peginterferon alfa-2a and ribavirin for 48 weeks (at the same doses as in the T12PR24 group); 111 patients to the T24P24 group, receiving telaprevir and peginterferon alfa-2a for 24 weeks (at the same doses as in the T12PR24 group); and 114 patients to the PR48 (or control) group, receiving peginterferon alfa-2a and ribavirin for 48 weeks (at the same doses as in the T12PR24 group). The primary end point was sustained virologic response (undetectable HCV RNA levels 24 weeks after the last dose of study drugs).The rates of sustained virologic response in the three telaprevir groups--51% in the T12PR24 group, 53% in the T24PR48 group, and 24% in the T24P24 group--were significantly higher than the rate in the control group (14%; P<0.001, P<0.001, and P=0.02, respectively). Response rates were higher among patients who had previously had relapses than among nonresponders. One of the most common adverse events in the telaprevir groups was rash (overall, occurring in 51% of patients, with severe rash in 5%). Discontinuation of study drugs because of adverse events was more frequent in the telaprevir groups than in the control group (15% vs. 4%).In HCV-infected patients in whom initial peginterferon alfa and ribavirin treatment failed, retreatment with telaprevir in combination with peginterferon alfa-2a and ribavirin was more effective than retreatment with peginterferon alfa-2a and ribavirin alone. (ClinicalTrials.gov number, NCT00420784.)
The status of indoor air pollution.
Authors: N A Esmen
Journal: Environmental Health Perspectives (1985)

Indoor air pollution, specifically restricted in its meaning to chemicals in home indoor air environment, presents a new and probably an important challenge to the researchers of the air pollution field. The general overview of this topic suggests that the voluminous data generated in the past ten or so years have only defined the rudiments of the problem, and significant areas of research still exist. Among the important areas where information is lacking, the exposures to contaminants generated by the use of consumer products and through hobbies and crafts represent perhaps the most urgent need for substantial research.
Rise in Insulin Resistance Is Associated With Escalated Telomere Attrition
Authors: Jeffrey P. Gardner, Shengxu Li, Sathanur R. Srinivasan, Wei Chen, Masayuki Kimura, Xiaobin Lu, Gerald S. Berenson, Abraham Aviv
Journal: Circulation (2005)

Background— Insulin resistance predisposes to cardiovascular disease and shortens human lifespan. We therefore tested the hypothesis that a rise in insulin resistance in concert with gain in body mass is associated with accelerated white blood cell telomere attrition. Methods and Results— We measured white blood cell telomere dynamics and age-related changes in insulin resistance and body mass index in young adults of the Bogalusa Heart Study. Over 10.1 to 12.8 years, the relative changes in telomere length were correlated with the homeostasis model assessment of insulin resistance ( r =−0.531, P &lt;0.001) and changes in the body mass index ( r =−0.423, P &lt;0.001). Conclusions— These findings provide the first tangible nexus of telomere biology with insulin resistance and adiposity in humans.
Endocrine Fibroblast Growth Factor FGF19 Promotes Prostate Cancer Progression
Authors: Shu Feng, Olga Dakhova, Chad J. Creighton, Michael Ittmann
Journal: Cancer Research (2013)

Abstract Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that fibroblast growth factor (FGF) receptors are important in prostate cancer initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21, and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require α-Klotho (KL) and/or β-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as coreceptors along with classic FGF receptors (FGFR) to mediate potent biologic activity. Here we show that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion, and colony formation of prostate cancer cells at low ligand concentrations. FGF19 silencing in prostate cancer cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in prostate cancer cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biologic effects in prostate cancer. Our findings support the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlight FGF19 as a relevant endocrine FGF in this setting. Cancer Res; 73(8); 2551–62. ©2013 AACR.
Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study
Authors: Ping Qin, Huilan Xu, Thomas Munk Laursen, Mogens Vestergaard, Preben Bo Mortensen
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To investigate whether age at onset of epilepsy, type of epilepsy, family history of psychosis, or family history of epilepsy affect the risk of schizophrenia or schizophrenia-like psychosis among patients with epilepsy. <b>Design</b> Comparison of population based data. <b>Setting</b> Danish longitudinal registers. <b>Subjects</b> The cohort comprised 2.27 million people. <b>Main outcome measures</b> Epilepsy, psychosis, personal birth data. <b>Results</b> We found an increased risk of schizophrenia (relative risk 2.48, 95% confidence interval 2.20 to 2.80) and schizophrenia-like psychosis (2.93, 2.69 to 3.20) in people with a history of epilepsy. The effect of epilepsy was the same in men and in women and increased with age. Family history of psychosis and a family history of epilepsy were significant risk factors for schizophrenia and schizophrenia-like psychosis, and the effect of epilepsy, both in cases and families, was greater among people with no family history of psychosis. In addition, the increased risk for schizophrenia or schizophrenia-like psychosis did not differ by type of epilepsy but increased with increasing number of admissions to hospital and, particularly, was significantly greater for people first admitted for epilepsy at later ages. <b>Conclusions</b> There is a strong association between epilepsy and schizophrenia or schizophrenia-like psychosis. The two conditions may share common genetic or environmental causes.
A case of necrotizing fasciitis due to Streptococcus pnewnoniae
Authors: S. H. CHOUDHRI, R. BROWNSTONE, F. HASHEM, C. M. MAGRO, A. N. CROWSON
Journal: British Journal of Dermatology (2006)

We report a patient suffering from necrotizing fasclitis. The principal pathogen was Streptococcus pneumoniae. As far as we are aware, this is the first reported case of necrotizing fasciitis (NF) attributable to this organism. We discuss the pathogenesis of NF, and review the literature relating to this disorder.
Pilot study of the epidemiology of sports injuries and exercise-related morbidity.
Authors: J P Nicholl, P Coleman, B T Williams
Journal: British Journal of Sports Medicine (1991)

In the pilot phase of a national study of the incidence of exercise-related morbidity (ERM), funded by the Sports Council, a questionnaire about recent participation in 'active sports and other recreational activities involving vigorous physical exercise' and associated injuries or illnesses was sent to a sample of 6744 people aged 16 to 65 years in two areas. Interviews with 101 respondents were held to validate the questions. Return rates of 73 and 81% from the two areas were achieved and results from the interviews indicated that sports and injuries were being reported sufficiently accurately on the postal questionnaires to yield reliable information. Of the 4961 usable returns, a total of 1249 respondents (25%) reported taking part in some activity in the 4 weeks before completing the questionnaire, and 137 (3%) reported 158 injury incidents. Nearly half (76, 48%) of these incidents resulted in some restriction in activity, and 21 resulted in some restriction in activity, and 21 resulted in a visit to a hospital casualty department. It is estimated that nationally 1-1.5 million episodes of ERM result annually in attendance at a hospital casualty department, and 4-5 million episodes of ERM result in some, usually temporary, incapacity.