tbuckley/cabot-search huggingface dataset:
Clinical associations of the metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort
Authors: Ben Parker, Murray B Urowitz, Dafna D Gladman, Mark Lunt, Sang-Cheol Bae, Jorge Sanchez-Guerrero, Juanita Romero-Diaz, Caroline Gordon, Daniel J Wallace, Ann E Clarke, Sasha Bernatsky, Ellen M Ginzler, David A Isenberg, Anisur Rahman, Joan T Merrill, Graciela S Alarcón, Barri J Fessler, Paul R Fortin, John G Hanly, Michelle Petri, Kristjan Steinsson, Mary-Anne Dooley, Susan Manzi, Munther A Khamashta, Rosalind Ramsey-Goldman, Asad A Zoma, Gunnar K Sturfelt, Ola Nived, Cynthia Aranow, Meggan Mackay, Manuel Ramos-Casals, Raymond F van Vollenhoven, Kenneth C Kalunian, Guillermo Ruiz-Irastorza, Sam Lim, Diane L Kamen, Christine A Peschken, Murat Inanc, Ian N Bruce
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The metabolic syndrome (MetS) may contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, lupus phenotype and therapy exposure with the presence of MetS. <h3>Methods</h3> The Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis inception cohort enrolled recently diagnosed (&lt;15 months) SLE patients from 30 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected according to a standardised protocol. MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Univariate and backward stepwise multivariate logistic regression were used to assess the relationship of individual variables with MetS. <h3>Results</h3> We studied 1686 patients, of whom 1494 (86.6%) had sufficient data to determine their MetS status. The mean (SD) age at enrolment and disease duration was 35.2 years (13.4) and 24.1 weeks (18.0), respectively. MetS was present at the enrolment visit in 239 (16%). In backward stepwise multivariable regression analysis, higher daily average prednisolone dose (mg) (OR 1.02, 95% CI 1.00 to 1.03), older age (years) (OR 1.04, 95% CI 1.03 to 1.06), Korean (OR 6.33, 95% CI 3.68 to 10.86) and Hispanic (OR 6.2, 95% CI 3.78 to 10.12) ethnicity, current renal disease (OR 1.79, 95% CI 1.14 to 2.80) and immunosuppressant use (OR 1.81, 95% CI 1.18 to 2.78) were associated with MetS. <h3>Conclusions</h3> Renal lupus, higher corticosteroid doses, Korean and Hispanic ethnicity are associated with MetS in SLE patients. Balancing disease control and minimising corticosteroid exposure should therefore be at the forefront of personalised treatment decisions in SLE patients.
Trends in the Use of Perioperative Chemotherapy for Localized and Locally Advanced Muscle-invasive Bladder Cancer: A Sign of Changing Tides
Authors: Zachary D. Reardon, Sanjay G. Patel, Harras B. Zaid, C.J. Stimson, Matthew J. Resnick, Kirk A. Keegan, Daniel A. Barocas, Sam S. Chang, Michael S. Cookson
Journal: European Urology (2014)
Why don't scientists have the same visa exemptions as footballers, ask Nobel winners
Authors: A. O'Dowd
Journal: BMJ (2010)

The government’s plan to cap immigration to the UK poses a serious threat to the country’s standing as a centre of scientific excellence, claim eight Nobel prize winning academics.

The group of research experts has spoken out collectively in opposition to the coalition government’s plans to restrict the number of migrants coming to the UK from outside the European Union.

In a letter to the Times (7 October), the laureates said, “The UK has long had a reputation as a global centre of research excellence.”

The world’s best scientists had long been …
Cooperative Interactions between Androgen Receptor (AR) and Heat-Shock Protein 27 Facilitate AR Transcriptional Activity
Authors: Amina Zoubeidi, Anousheh Zardan, Eliana Beraldi, Ladan Fazli, Richard Sowery, Paul Rennie, Colleen Nelson, Martin Gleave
Journal: Cancer Research (2007)

Abstract Androgen receptor (AR) transactivation is known to enhance prostate cancer cell survival. However, the precise effectors by which the prosurvival effects of androgen and AR drive prostate cancer progression are poorly defined. Here, we identify a novel feed-forward loop involving cooperative interactions between ligand-activated AR and heat-shock protein 27 (Hsp27) phospho-activation that enhance AR stability, shuttling, and transcriptional activity, thereby increasing prostate cancer cell survival. Androgen-bound AR induces rapid Hsp27 phosphorylation on Ser78 and Ser82 residues in an AR- and p38 kinase–dependent manner. After this androgen-induced, non-nuclear phospho-activation, Hsp27 displaces Hsp90 from a complex with AR to chaperone AR into the nucleus and interact with its response elements to enhance its genomic activity. Inhibition of Hsp27 phosphorylation, or knockdown using the antisense drug OGX-427, shifted the association of AR with Hsp90 to MDM2, increased proteasome-mediated AR degradation, decreased AR transcriptional activity, and increased prostate cancer LNCaP cell apoptotic rates. OGX-427 treatment of mice bearing LNCaP xenografts transfected with an androgen-regulated, probasin-luciferase reporter construct resulted in decreased bioluminescence and serum PSA levels as pharmacodynamic readouts of AR activity, as well as AR, Hsp27, and Hsp90 protein levels in LNCaP tumor tissue. These data identify novel nongenomic mechanisms involving androgen, AR, and Hsp27 activation that cooperatively interact to regulate the genomic activity of AR and justify further investigation of Hsp27 knockdown as an AR disrupting therapeutic strategy in prostate cancer. [Cancer Res 2007;67(21):10455–65]
The Impact of Founder Events on Chromosomal Variability in Multiply Mating Species
Authors: J. E. Pool, R. Nielsen
Journal: Molecular Biology and Evolution (2008)

In species with heterogametic males, the relative levels of X chromosome versus autosome diversity hold key information about the evolutionary forces at work in a population. It has been shown that population size changes alter the ratio of X linked to autosomal (X/A) variation, with population size reductions and recent bottlenecks leading to decreased X/A diversity ratios. Here we use theory and simulation to investigate a separate demographic effect-that of founder events involving multiply mated females-and find that it leads to much stronger reductions in X/A diversity ratios than are produced by simple population size changes. Investigating the potential of this process to account for sharply reduced X-linked diversity in European Drosophila melanogaster, we find that this model yields predictions that are compatible with the empirical data.
Volume of services delivered by NHS will shrink, warns think tank
Authors: A. O'Dowd
Journal: BMJ (2010)

Services that the NHS will be able to provide over the next few years may shrink without a firm grip on pay and price inflation, reports an expert think tank.

In its analysis of October’s spending review and the government’s health white paper the Nuffield Trust has warned that the NHS will be forced to become smarter at controlling costs.

The trust said the NHS was facing an “unprecedented challenge” in that it was being expected to deliver far reaching reforms to patient care at the same time as increasing demand and what was effectively a real terms reduction in its funding over the next four …
A LATENT VIRUS IN NORMAL MICE CAPABLE OF PRODUCING PNEUMONIA IN ITS NATURAL HOST
Authors: Frank L. Horsfall, Richard G. Hahn
Journal: The Journal of Experimental Medicine (1940)

1. A virus capable of producing fatal pneumonia in mice has been isolated repeatedly from the lungs of certain apparently healthy mice. Not all mice carry the virus. It was obtained only from mice supplied by three breeders although mice from eight different sources were studied. 2. The virus was avirulent as it occurred in normal mouse lungs and became virulent only after serial mouse lung passage. It was strictly pneumotropic for mice and produced pneumonia when given intranasally but showed no evidence of infection when given by other routes. The virus was non-infectious for ferrets and did not become pathogenic for this species after numerous serial passages. It was also non-pathogenic for rabbits, guinea pigs, rhesus monkeys, voles, deer mice, skunks, wood-chucks, opossums, and Syrian hamsters. 3. All strains of the virus which have been tested have been immunologically identical, as indicated both by cross immunity and cross neutralization tests in mice. 4. The virus was antigenic both in mice and in rabbits and was readily differentiated from viruses of human influenza and of swine influenza by means of either cross immunity or cross neutralization tests. 5. The virus was also neutralized by about 30 per cent of normal human sera tested. 6. The virus was extremely labile, and suspensions prepared in saline or broth became inactivated within a few hours at room temperature. The addition of normal horse serum to the virus suspensions, however, exerted a definite stabilizing effect. 7. Ultrafiltration results indicated that the virus particles have a diameter of about 100 to 150 millimicrons. 8. Evidence is presented which indicates that this virus is different from other viruses which various investigators have found in normal mouse lungs.
Oral Acyclovir Suppression and Neurodevelopment after Neonatal Herpes
Authors: David W. Kimberlin, Richard J. Whitley, Wen Wan, Dwight A. Powell, Gregory Storch, Amina Ahmed, April Palmer, Pablo J. Sánchez, Richard F. Jacobs, John S. Bradley, Joan L. Robinson, Mark Shelton, Penelope H. Dennehy, Charles Leach, Mobeen Rathore, Nazha Abughali, Peter Wright, Lisa M. Frenkel, Rebecca C. Brady, Russell Van Dyke, Leonard B. Weiner, Judith Guzman-Cottrill, Carol A. McCarthy, Jill Griffin, Penelope Jester, Misty Parker, Fred D. Lakeman, Huichien Kuo, Choo Hyung Lee, Gretchen A. Cloud
Journal: New England Journal of Medicine (2011)

Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease.We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy.A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09).Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).
Apples to Origins: Identifying Brain Tumor Stem Cell Genes by Comparing Transcriptomes of Normal and Cancer Stem Cells
Authors: Matthew Wortham, Hai Yan
Journal: Cancer Discovery (2012)

The mechanisms whereby medulloblastoma stem cells coordinate tumor propagation are poorly understood. Using microarray analysis, Corno and colleagues draw parallels and distinctions between medulloblastoma stem cells from the Ptch+/− mouse and normal neural stem cells, identifying Ebf3 as a cancer stem cell–specific transcript critical for tumor growth. Cancer Discov; 2(6); 492–4. ©2012 AACR.Commentary on Corno et al., p. 554.
Abdominal Aortic Aneurysms, Increasing Infrarenal Aortic Diameter, and Risk of Total Mortality and Incident Cardiovascular Disease Events
Authors: Matthew S. Freiberg, Alice M. Arnold, Anne B. Newman, Matthew S. Edwards, Kevin L. Kraemer, Lewis H. Kuller
Journal: Circulation (2008)

Background— Long-term data describing small abdominal aortic aneurysms (AAAs) and increasing infrarenal aortic diameters and their relationship to future surgical repair, total mortality, and incident cardiovascular disease (CVD) events, particularly among women, are sparse. Methods and Results— In 1992 to 1993, 4734 Cardiovascular Health Study participants ≥65 years old had an abdominal aortic ultrasound evaluation. Of those screened, 416 had an AAA (infrarenal aortic diameter ≥3.0 cm or an infrarenal/suprarenal ratio ≥1.2). By 2002, there were 56 surgical AAA repairs and 10 AAA-related deaths. A single ultrasound screening demonstrated that aneurysm dilation ≥3 cm identified 68% of all AAA repairs over the next 10 years and 6 of the 10 AAA-related deaths in 4% of the total population and that a ≥2.5-cm dilation identified 91% of all AAA repairs and 9 of the 10 deaths in 10% of the total population. With adjusted Cox proportional hazard models, AAAs were associated with a higher risk of total mortality (hazard ratio 1.44, 95% confidence interval 1.25 to 1.66) and incident CVD events (hazard ratio 1.52, 95% confidence interval 1.25 to 1.85). Compared with diameters &lt;2.0 cm, infrarenal aortic diameters 2.0 to &lt;3.0 cm were associated with increased risk of incident CVD events in women and total mortality in men. Conclusions— This study suggests that a 1-time screening of the abdominal aorta can acceptably identify individuals with a clinically significant AAA. Infrarenal aortic diameters &gt;2.0 cm are associated with a significantly increased risk of future CVD events and total mortality.
Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial
Authors: Iain B McInnes, Joachim Sieper, Jürgen Braun, Paul Emery, Désirée van der Heijde, John D Isaacs, Georg Dahmen, Jürgen Wollenhaupt, Hendrik Schulze-Koops, Joseph Kogan, Shenglin Ma, Martin M Schumacher, Arthur P Bertolino, Wolfgang Hueber, Paul P Tak
Journal: Annals of the Rheumatic Diseases (2013)

To evaluate the efficacy and safety of secukinumab, a fully human, anti-interleukin (IL)-17A monoclonal antibody, in patients with psoriatic arthritis (PsA).42 patients with active PsA fulfilling ClASsification for Psoriatic ARthritis (CASPAR) criteria were randomly assigned (2:1) to receive two intravenous secukinumab doses (10 mg/kg; n=28) or placebo (n=14) 3 weeks apart. The primary endpoint was the proportion of American College of Rheumatology (ACR) 20 responses at week 6 for secukinumab versus placebo (one-sided p<0.1).Primary endpoint: ACR20 responses at week 6 were 39% (9/23) for secukinumab versus 23% (3/13) for placebo (p=0.27). ACR20 responses were greater with secukinumab versus placebo at week 12 (39% (9/23) vs 15% (2/13), p=0.13) and week 24 (43% (10/23) vs 18% (2/11), p= 0.14). At week 6, 'good' European League Against Rheumatism response was seen in 21.7% (5/23) secukinumab versus 9.1% (1/11) placebo patients. Compared with placebo at week 6, significant reductions were observed among secukinumab recipients for C reactive protein (p=0.039), erythrocyte sedimentation rate (p=0.038), Health Assessment Questionnaire Disability Index (p=0.002) and Short Form Health Survey (SF-36; p=0.030) scores. The overall adverse event (AE) frequency was comparable between secukinumab (26 (93%)) and placebo (11 (79%)) recipients. Six serious AEs (SAEs) were reported in four secukinumab patients and one SAE in one placebo patient.Although the primary endpoint was not met, clinical responses, acute-phase reactant and quality of life improvements were greater with secukinumab versus placebo, suggesting some clinical benefit. Secukinumab exhibited satisfactory safety. Larger clinical trials of secukinumab in PsA are warranted.
Oncologist Burnout: Causes, Consequences, and Responses
Authors: Tait Shanafelt, Lotte Dyrbye
Journal: Journal of Clinical Oncology (2012)

Although the practice of oncology can be extremely rewarding, it is also one of the most demanding and stressful areas of medicine. Oncologists are faced with life and death decisions on a daily basis, administer incredibly toxic therapies with narrow therapeutic windows, must keep up with the rapid pace of scientific and treatment advances, and continually walk a fine line between providing palliation and administering treatments that lead to excess toxicity. Personal distress precipitated by such work-related stress may manifest in a variety of ways including depression, anxiety, fatigue, and low mental quality of life. Burnout also seems to be one of the most common manifestations of distress among physicians, with studies suggesting a prevalence of 35% among medical oncologists, 38% among radiation oncologists, and 28% to 36% among surgical oncologists. Substantial evidence suggests that burnout can impact quality of care in a variety of ways and has potentially profound personal implications for physicians including suicidal ideation. In this review, we examine the causes, consequences, and personal ramifications of oncologist burnout and explore the steps oncologists can take to promote personal well-being and professional satisfaction.
Hepatitis C Virus Infection and Coinfection With Human Immunodeficiency Virus
Authors: Colleen Hadigan, Shyamasundaran Kottilil
Journal: JAMA (2011)

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) both emerged in the second half of the 20th century, and chronic infection with these agents is among the greatest challenges facing health care in the United States and worldwide. Despite tremendous advances in treatment and management of HIV and HCV, individuals with HIV/HCV coinfection experience a more complicated disease course and treatment. Recognition of the important role that host factors, such as IL28B genotype, have in response to HCV therapy and the emergence of new effective therapies for HCV are actively reshaping the standard of care. These advances may translate into more effective treatment and management of patients with chronic HCV and HIV coinfection in the years ahead.
Revised International Prognostic Scoring System (IPSS) Predicts Survival and Leukemic Evolution of Myelodysplastic Syndromes Significantly Better Than IPSS and WHO Prognostic Scoring System: Validation by the Gruppo Romano Mielodisplasie Italian Regional Database
Authors: Maria Teresa Voso, Susanna Fenu, Roberto Latagliata, Francesco Buccisano, Alfonso Piciocchi, Maria Antonietta Aloe-Spiriti, Massimo Breccia, Marianna Criscuolo, Alessandro Andriani, Stefano Mancini, Pasquale Niscola, Virginia Naso, Carolina Nobile, Anna Lina Piccioni, Mariella D'Andrea, Ada D'Addosio, Giuseppe Leone, Adriano Venditti
Journal: Journal of Clinical Oncology (2013)

The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by a heterogeneous clinical behavior.We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data.We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis.Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.
Global initiative for chronic obstructive lung diseases (GOLD): time to act
Authors: R. Pauwels
Journal: European Respiratory Journal (2001)

What is global initiative for chronic obstructive lung diseases?In January 1997, chronic obstructive pulmonary disease (COPD) experts from several countries met in Brussels, Belgium to explore the development of a Global Initiative for Chronic Obstructive Lung Disease (GOLD).Representatives of the National Heart, Lung and Blood Institute, USA (NHLBI) and of the World Health Organization (WHO) attended.Participants agreed that the project was timely and important, and recommended the establishment of a panel with expertize on a wide variety of COPDrelated topics to prepare an evidence-based document on diagnosis, management, and prevention of COPD as a tool for GOLD.From 1998-2000, the panel members met several times to prepare the document (see further).In 2001, the GOLD initiative was firmly launched in collaboration with NHLBI and WHO.The project was, and continues to be, supported by unrestricted educational grants from a multitude of pharmaceutical companies.The goals of GOLD are to increase awareness of COPD and decrease morbidity and mortality from this disease.GOLD aims to improve prevention and management of COPD through a concerted worldwide effort of people involved in all facets of healthcare and healthcare policy, and to encourage a renewed research interest in this extremely prevalent disease.