tbuckley/cabot-search huggingface dataset:
Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years
Authors: G Fattovich, N Olivari, M Pasino, M D'Onofrio, E Martone, F Donato
Journal: Gut (2007)

<h3>Objective</h3> Ethnic differences in the prevalence of atrial fibrillation (AF) in heart failure (HF) remain unclear. We compared the prevalence and clinical correlates of AF among different ethnicities in an Asian-Pacific population with HF. <h3>Methods</h3> Patients with validated HF were prospectively studied across Singapore and New Zealand (NZ). <h3>Results</h3> Among 1746 patients with HF (62% Asian, 26% women, mean age 66 (SD 13) years, mean ejection fraction (EF) 37 (SD 16%), 39% had AF. The prevalence of AF was markedly lower in Singapore-Asians than NZ-Europeans (24% vs 63%; p&lt;0.001), even after adjusting for age, clinical and echocardiographic covariates, regardless of EF group (p<sub>interaction</sub> for EF=0.39). Patients with AF were older, had higher body mass index and were more likely to have a history of hypertension, stroke, peripheral vascular disease, renal disease, chronic respiratory disease and increased alcohol intake, but less likely to have diabetes. Clinical correlates were similar for Asians and NZ-Europeans, except diabetes: Asian diabetic patients with HF had less AF compared with Asian patients without diabetes (OR 0.66, 95% CI 0.50 to 0.88), whereas among NZ-Europeans there was no significant association between diabetes and AF (OR 1.22, 95% CI 0.85 to 1.75) (p<sub>interaction</sub> for ethnicity=0.01). AF was associated with a higher crude composite outcome of mortality and HF hospitalisations at 2 years (HR 1.19, 95% CI 1.02 to 1.38). <h3>Conclusion</h3> There is a strikingly lower prevalence of AF among Asian compared with NZ-European patients with HF. The underlying mechanisms for the lower prevalence of AF among Asians, particularly in the presence of diabetes, deserve further study. <h3>Trial registration number</h3> ACTRN12610000374066.
Molecular Mechanisms and Regulation of Opioid Receptor Signaling
Authors: Ping-Yee Law, Yung H. Wong, Horace H. Loh
Journal: The Annual Review of Pharmacology and Toxicology (2000)

Cloning of multiple opioid receptors has presented opportunities to investigate the mechanisms of multiple opioid receptor signaling and the regulation of these signals. The subsequent identification of receptor gene structures has also provided opportunities to study the regulation of receptor gene expression and to manipulate the concentration of the gene products in vivo. Thus, in the current review, we examine recent advances in the delineation basis for the multiple opioid receptor signaling, and their regulation at multiple levels. We discuss the use of receptor knockout animals to investigate the function and the pharmacology of these multiple opioid receptors. The reasons and basis for the multiple opioid receptor are addressed.
Renal CD133+/CD73+ Progenitors Produce Erythropoietin under Hypoxia and Prolyl Hydroxylase Inhibition
Authors: Benedetta Bussolati, Carola Lauritano, Aldo Moggio, Federica Collino, Massimiliano Mazzone, Giovanni Camussi
Journal: Journal of the American Society of Nephrology (2013)

The identity of the peritubular population of cells with mesenchymal phenotype thought responsible for producing erythropoietin in humans remains unclear. Here, renal CD133(+)/CD73(+) progenitor cells, isolated from the human renal inner medulla and described as a population of mesenchymal progenitors, released erythropoietin under hypoxic conditions. CD133(-) cells did not synthesize erythropoietin, and CD133(+) progenitor cells stopped producing erythropoietin when they differentiated and acquired an epithelial phenotype. Inhibition of prolyl hydroxylases, using either dimethyloxalylglycine or a small hairpin RNA against prolyl hydroxylase-2, increased both hypoxia-inducible factor-2α (HIF-2α) expression and erythropoietin transcription. Moreover, under hypoxic conditions, inhibition of prolyl hydroxylase significantly increased erythropoietin release by CD133(+) progenitors. Finally, blockade of HIF-2α impaired erythropoietin synthesis by CD133(+) progenitors. Taken together, these results suggest that it is the renal CD133(+) progenitor cells that synthesize and release erythropoietin under hypoxia, via the prolyl hydroxylase-HIF-2α axis, in the human kidney. In addition, this study provides rationale for the therapeutic use of prolyl hydroxylase inhibitors in the setting of acute or chronic renal injury.
Preoperative dynamic contrast-enhanced MRI correlates with molecular markers of hypoxia and vascularity in specific areas of intratumoral microenvironment and is predictive of patient outcome
Authors: Randy L. Jensen, Michael L. Mumert, David L. Gillespie, Anita Y. Kinney, Matthias C. Schabel, Karen L. Salzman
Journal: Neuro-Oncology (2013)

Measures of tumor vascularity and hypoxia have been correlated with glioma grade and outcome. Dynamic contrast-enhanced (DCE) MRI can noninvasively map tumor blood flow, vascularity, and permeability. In this prospective observational cohort pilot study, preoperative imaging was correlated with molecular markers of hypoxia, vascularity, proliferation, and progression-free and overall patient survival. Pharmacokinetic modeling methods were used to generate maps of tumor blood flow, extraction fraction, permeability-surface area product, transfer constant, washout rate, interstitial volume, blood volume, capillary transit time, and capillary heterogeneity from preoperative DCE-MRI data in human glioma patients. Tissue was obtained from areas of peritumoral edema, active tumor, hypoxic penumbra, and necrotic core and evaluated for vascularity, proliferation, and expression of hypoxia-regulated molecules. DCE-MRI parameter values were correlated with hypoxia-regulated protein expression at tissue sample sites. Patient survival correlated with DCE parameters in 2 cases: capillary heterogeneity in active tumor and interstitial volume in areas of peritumoral edema. Statistically significant correlations were observed between several DCE parameters and tissue markers. In addition, MIB-1 index was predictive of overall survival (P = .044) and correlated with vascular endothelial growth factor expression in hypoxic penumbra (r = 0.7933, P = .0071) and peritumoral edema (r = 0.4546). Increased microvessel density correlated with worse patient outcome (P = .026). Our findings suggest that DCE-MRI may facilitate noninvasive preoperative predictions of areas of tumor with increased hypoxia and proliferation. Both imaging and hypoxia biomarkers are predictive of patient outcome. This has the potential to allow unprecedented prognostic decisions and to guide therapies to specific tumor areas.
Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study
Authors: Gregory Livshits, Maria Popham, Ida Malkin, Philip N Sambrook, Alex J MacGregor, Timothy Spector, Frances M K Williams
Journal: Annals of the Rheumatic Diseases (2011)

Objective Low back pain (LBP) is a common musculoskeletal disorder, but it is still unclear which individuals develop it. The authors examined the contribution of genetic factors, lumbar disc degeneration (LDD) and other risk factors in a female sample of the general population. Material and Methods A cross-sectional study was conducted among 2256 women (371 and 698 monozygotic and dizygotic twin pairs and 29 sibling pairs and 60 singletons) with a mean age of 50 years (18–84). A self-reported validated questionnaire was used to collect back pain data. Risk factors including body weight, smoking, occupation, physical exercise and MRI assessed LDD were measured. Data analysis included logistic regression and variance decomposition. Results The major factors associated with LBP included genetic background, with OR approximately 6 if the monozygotic co-twin had LBP, or 2.2 if she was a dizygotic co-twin. In addition, LDD and overweight were highly significantly (p&lt;0.001) associated with non-specific LBP. The single most important risk factor was the amount of LDD. After adjustment for other risk factors, the individuals who exhibited advanced LDD (90% vs 10%) had 3.2 higher odds of manifesting LBP. The data also showed a significant (p&lt;0.001) genetic correlation between the LBP and LDD measurements, suggesting that approximately 11–13% of the genetic effects are shared by LDD and LBP. Conclusions The main risk factors for reported episodes of severe and disabling LBP in UK women include the degree of LDD as assessed by MRI, being overweight and genetic heritability.
Importance of Baseline Distribution of Proteinuria in Renal Outcomes Trials: Lessons from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Study
Authors: Zhongxin Zhang, Shahnaz Shahinfar, William F. Keane, Denise Ramjit, Tania Z. Dickson, Gilbert W. Gleim, Carl Erik Mogensen, Dick de Zeeuw, Barry M. Brenner, Steven M. Snapinn
Journal: Journal of the American Society of Nephrology (2005)

A key issue in the analysis of outcome trials is the adjustment for baseline covariates that influence the primary outcome. Imbalance of an important covariate between treatment groups at baseline is of considerable concern if one treatment group is favored over another with respect to the hypothesis testing outcome. With the use of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study database as an example, the influence of baseline proteinuria on the primary composite endpoint, ESRD, and ESRD or death after adjusting for baseline proteinuria as a continuous covariate was examined. Increasing baseline proteinuria was associated with increased risk for renal events, confirming that proteinuria is an important covariate for renal outcomes. When the randomization was stratified according proteinuria <2000 mg/g or >/=2000 mg/g, within the higher proteinuria stratum (>/=2000 mg/g), patients in the losartan group had a higher baseline mean proteinuria value. When the imbalance was adjusted, an increase in the magnitude and the significance of the risk reduction with losartan for each outcome was observed. No apparent interaction between treatment effect and baseline proteinuria was found, and there was no heterogeneity in the treatment response in patients with different baseline proteinuria levels. After proteinuria was adjusted as a continuous variable, greater treatment effects were observed in the RENAAL study. This effect was due solely to the imbalance in baseline proteinuria. Considering the importance of proteinuria as a risk factor, adjustment for baseline proteinuria as a continuous covariate should be prespecified in the design and analysis of clinical trials involving renal outcomes, even when patients are stratified on the basis of level of proteinuria.
Disruption of methylarginine metabolism impairs vascular homeostasis
Authors: James Leiper, Manasi Nandi, Belen Torondel, Judith Murray-Rust, Mohammed Malaki, Bernard O'Hara, Sharon Rossiter, Shelagh Anthony, Melanie Madhani, David Selwood, Caroline Smith, Beata Wojciak-Stothard, Alain Rudiger, Ray Stidwill, Neil Q McDonald, Patrick Vallance
Journal: Nature Medicine (2007)
Migraine aura as artistic inspiration.
Authors: G. N. Fuller, M. V. Gale
Journal: BMJ (1988)

de Chirico was a central figure in twentieth r century art.In Paris before the first world war he knew Picasso and the cubists and was a friend of their i main advocate Guillaume Apollinaire, who dubbed de Chirico's independent style "metaphysical, art."During and after the war the work of the "Metafisica" group gathered around him was important to painting not only in Italy but also in Germany and France.-DeChirico's early works were especially influential on the.surrealists in Paris after the war.In-'de-' Chirco's paintings and drawings there are several unusual "x'd recurrent features that have, not previously been explained.This paper postulates an illness as a basis for these details. Motion sickness and headachesDe Chirico suffered from several complaints, which he recorded in his memoirs.'As a young man his journey from Greece to Italy had to be broken because ofsevere motion sickness.He described,several attacks of abdominal pain associated with anorexia.These episodes, described in some detail in his memoirs, led him to seek medical help several times; no diagnosis, however, was recorded.The pains seemed to last quite.a short time, between 12 hours and three days, and were reported to be relieved by sleep and followed by full recovery.He is also reported to have suffered from attacks of vomiting, on one occasion before the opening of an exhibition.In his memoirs he recalled two episodes of headache as a young man.These were described as "terrible" and "exiremely painful."The triad of motion sickness, abdomial pain, and, vomiting suggest the "periodic" syndrome.This is also- known as abdominal migraine and is ften found im migraineurs.Lanzi found that between 30% and 40% of 16-18 year old patients who had migraine had cyclical abdominal pain and recurrent vomiting.2De FIG 2-An enty in the national migraine art competition .
Choline PET and PET/CT in Primary Diagnosis and Staging of Prostate Cancer
Authors: S. Schwarzenböck, M. Souvatzoglou, B. J. Krause
Journal: Theranostics (2012)

PET and PET/CT using [(11)C]- and [(18)F]-labelled choline derivates is increasingly being used for imaging of primary and recurrent prostate cancer. While PET and PET/CT with [(11)C]- and [(18)F]-labelled choline derivates in patients suffering from biochemical recurrence of prostate cancer has been examined in many studies that demonstrate an increasing importance, its role in the primary staging of prostate cancer is still a matter of debate.Morphological and functional imaging techniques such as CT, MRI and TRUS have demonstrated only limited accuracy for the diagnosis of primary prostate cancer. Molecular imaging with PET and PET/CT could potentially increase accuracy to localize primary prostate cancer. A considerable number of studies have examined the value of PET/CT with [(11)C]- and [(18)F]- labelled choline derivates for the diagnosis of primary prostate cancer with mixed results. Primary prostate cancer can only be detected with moderate sensitivity using [(11)C]- and [(18)F]choline PET and PET/CT. The detection rate depends on the tumour configuration. Detection is also limited by a considerable number of microcarcinomas that cannot be detected due to partial volume effects. Therefore small and in part rind-like tumours can often not be visualized. Furthermore, the differentiation between benign changes like prostatitis, high-grade intraepithelial neoplasia (HGPIN) or prostatic hyperplasia is not always possible. Therefore, at the present time, the routine use of PET/CT with [(11)C]- and [(18)F]-labelled choline derivates cannot be recommended as a first-line screening procedure for primary prostate cancer in men at risk. A potential application of choline PET and PET/CT may be to increase the detection rate of clinically suspected prostate cancer with multiple negative prostate biopsies, for example in preparation of a focused re-biopsy and may play a role in patient stratification with respect to primary surgery and radiation therapy in the future.
Paroxysmal nocturnal hemoglobinuria type III. Lack of an erythrocyte membrane protein restricting the lysis by C5b-9.
Authors: G M Hänsch, S Schönermark, D Roelcke
Journal: Journal of Clinical Investigation (1987)

The complement-mediated lysis is inefficient when complement and target cells are homologous with regard to the species. In erythrocytes from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH), the species restriction is lost: PNH-erythrocytes (PNH-E) are susceptible to lysis by human complement. In human erythrocytes (huE) the species restriction is ascribed to an integral membrane protein, designated C8-binding protein (C8bp). In the present study, we tested membranes of PNH-E type III for the presence of C8bp. A protein with C8-binding capacity could not be detected. C8bp, which was isolated from the membrane of huE, inhibited the lysis of PNH-E by C5b-9 as well as the C9 polymerization. Thus, addition of C8bp restored the species restriction in PNH-E. In conclusion, we propose that lack of C8bp might represent the defect in PNH-E type III membranes, which is responsible for their enhanced lytic susceptibility towards lysis by the late complement components.
Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study
Authors: Matthew J. Ellis, Antonio Llombart-Cussac, David Feltl, John A. Dewar, Marek Jasiówka, Nicola Hewson, Yuri Rukazenkov, John F.R. Robertson
Journal: Journal of Clinical Oncology (2015)

Purpose To compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer. Patients and Methods The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor–positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring. Results In total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed. Conclusion There are several limitations of this OS analysis, including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed, and that not all patients participated in additional OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast Cancer) trial (ClinicalTrials.gov identifier: NCT01602380).
Ebola Virus Disease in the Democratic Republic of Congo
Authors: Gaël D. Maganga, Jimmy Kapetshi, Nicolas Berthet, Benoît Kebela Ilunga, Felix Kabange, Placide Mbala Kingebeni, Vital Mondonge, Jean-Jacques T. Muyembe, Eric Bertherat, Sylvie Briand, Joseph Cabore, Alain Epelboin, Gary Kobinger, Licé González-Angulo, Jean-Claude Manuguerra, Jean-Marie Okwo-Bele, Christopher Dye, D. Phil, Eric M. Leroy, Abstr Act
Journal: New England Journal of Medicine (2014)

The seventh reported outbreak of Ebola virus disease (EVD) in the equatorial African country of the Democratic Republic of Congo (DRC) began on July 26, 2014, as another large EVD epidemic continued to spread in West Africa. Simultaneous reports of EVD in equatorial and West Africa raised the question of whether the two outbreaks were linked.We obtained data from patients in the DRC, using the standard World Health Organization clinical-investigation form for viral hemorrhagic fevers. Patients were classified as having suspected, probable, or confirmed EVD or a non-EVD illness. Blood samples were obtained for polymerase-chain-reaction-based diagnosis, viral isolation, sequencing, and phylogenetic analysis.The outbreak began in Inkanamongo village in the vicinity of Boende town in Équateur province and has been confined to that province. A total of 69 suspected, probable, or confirmed cases were reported between July 26 and October 7, 2014, including 8 cases among health care workers, with 49 deaths. As of October 7, there have been approximately six generations of cases of EVD since the outbreak began. The reported weekly case incidence peaked in the weeks of August 17 and 24 and has since fallen sharply. Genome sequencing revealed Ebola virus (EBOV, Zaire species) as the cause of this outbreak. A coding-complete genome sequence of EBOV that was isolated during this outbreak showed 99.2% identity with the most closely related variant from the 1995 outbreak in Kikwit in the DRC and 96.8% identity to EBOV variants that are currently circulating in West Africa.The current EVD outbreak in the DRC has clinical and epidemiologic characteristics that are similar to those of previous EVD outbreaks in equatorial Africa. The causal agent is a local EBOV variant, and this outbreak has a zoonotic origin different from that in the 2014 epidemic in West Africa. (Funded by the Centre International de Recherches Médicales de Franceville and others.).
Sedentary behaviour and diet across the lifespan: an updated systematic review
Authors: Matthew Hobbs, Natalie Pearson, Perry J Foster, Stuart J H Biddle
Journal: British Journal of Sports Medicine (2014)

Background Sedentary behaviour and its association with dietary intake in young people and adults are important topics and were systematically reviewed in 2011. There is a need to update this evidence given the changing nature of sedentary behaviour and continued interest in this field. This review aims to assist researchers in better interpreting the diversity of findings concerning sedentary behaviour and weight status. Objective To provide an update of the associations between sedentary behaviour and dietary intake across the lifespan. Methods Electronic databases searched were MEDLINE, PsychInfo, Cochrane Library, Web of Science and Science Direct for publications between January 2010 and October 2013, thus updating a previous review. Included were observational studies assessing an association between at least one sedentary behaviour and at least one aspect of dietary intake in preschool children (&lt;5 years), school-aged children (6–11 years), adolescents (12–18 years) and adults (&gt;18 years). Results 27 papers met inclusion criteria (preschool k=3, school-aged children k=9, adolescents k=15, adults k=3). For all three groups of young people, trends were evident for higher levels of sedentary behaviour, especially TV viewing, to be associated with a less healthful diet, such as less fruit and vegetable and greater consumption of energy-dense snacks and sugar sweetened beverages. Data for the three studies with adults were less conclusive. Conclusions Sedentary behaviour continues to be associated with unhealthy diet in young people in mostly cross-sectional studies. More studies utilising a prospective design are needed to corroborate findings and more studies are needed with adults.