tbuckley/cabot-search huggingface dataset:
Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD
Authors: Antonino Di Stefano, Gaetano Caramori, Adam Barczyk, Chiara Vicari, Paola Brun, Andrea Zanini, Francesco Cappello, Elvira Garofano, Anna Padovani, Marco Contoli, Paolo Casolari, Andrew L Durham, Kian Fan Chung, Peter J Barnes, Alberto Papi, Ian Adcock, Bruno Balbi
Journal: Thorax (2014)

In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown.To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers.Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA.In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups.Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.
Predicting renal outcome in IgA nephropathy.
Authors: M G Radford, J V Donadio, E J Bergstralh, J P Grande
Journal: Journal of the American Society of Nephrology (1997)

Immunoglobulin A (IgA) nephropathy, the most common form of glomerulonephritis worldwide, is characterized by a heterogeneous clinical course. In this study, multivariate analysis was performed to identify histopathologic and clinical features that most accurately predict adverse outcome from a dataset of 148 individuals with IgA nephropathy who underwent renal biopsy at our institution between 1973 and 1995. A semiquantitative scoring system was developed for assessment of six glomerular, eight interstitial, and six vascular histopathologic features of IgA nephropathy. Glomerular and interstitial proliferative activity was evaluated by immunostaining archival biopsy specimens with Mib-1, an antibody directed against the Ki-67 antigen. Kaplan-Meier survival analysis was performed, with renal failure being defined as onset of dialysis or transplantation. A number of clinicopathologic factors were univariately associated with adverse outcome, including elevated serum creatinine levels; the presence of hypertension; proteinuria; component and total histopathologic scores; and positive glomerular or interstitial Mib-1 scores. The total glomerular score, consisting of the arithmetic sum of each of the six component scores, was the strongest histopathologic predictor of adverse outcome. Total interstitial and vascular scores also provided more prognostic information than did individual component scores. By multivariate analysis, high total glomerular scores, increased serum creatinine levels at diagnosis, and younger age were significant (P < 0.01) independent predictors of renal failure. Our studies provide a rational basis for the inclusion of composite histopathologic scores in clinical intervention studies of patients with IgA nephropathy and other glomerular disorders.
Tobacco use in pregnant women: analysis of data from Demographic and Health Surveys from 54 low-income and middle-income countries
Authors: Rishi Caleyachetty, Christopher A Tait, Andre P Kengne, Camila Corvalan, Ricardo Uauy, Justin B Echouffo-Tcheugui
Journal: The Lancet Global Health (2014)

Worldwide, use of tobacco is viewed as an important threat to the health of pregnant women and their children. However, the extent of tobacco use in pregnant women in low-income and middle-income countries (LMICs) remains unclear. We assessed the magnitude of tobacco use in pregnant women in LMICs.We used data from Demographic and Health Surveys (DHS) done in 54 LMICs between Jan 1, 2001, and Dec 1, 2012, comprising 58 922 pregnant women (aged 15-49 years), which were grouped by WHO region. Prevalence of current tobacco use (smoked and smokeless) was estimated for every country. Pooled estimates by regions and overall were obtained from random-effects meta-analysis.Pooled prevalence of any tobacco use in pregnant women in LMICs was 2·6% (95% CI 1·8-3·6); the lowest prevalence was in the African region (2·0%, 1·2-2·9) and the highest was in the Southeast Asian region (5·1%, 1·3-10·9). The pooled prevalence of current tobacco smoking in pregnant women ranged from 0·6% (0·3-0·8) in the African region to 3·5% (1·5-12·1) in the Western Pacific region. The pooled prevalence of current smokeless tobacco use in pregnant women was lowest in the European region (0·1%, 0·0-0·3) and highest in the Southeast Asian region (2·6%, 0·0-7·6).Overall, tobacco use in pregnant women in LMICs was low; however high prevalence estimates were noted in some LMICs. Prevention and management of tobacco use and exposure to second-hand smoke in pregnancy is crucial to protect maternal and child health in LMICs.None.
A2B Adenosine Receptor–Mediated Induction of IL-6 Promotes CKD
Authors: Yingbo Dai, Weiru Zhang, Jiaming Wen, Yujin Zhang, Rodney E. Kellems, Yang Xia
Journal: Journal of the American Society of Nephrology (2011)

Chronic elevation of adenosine, which occurs in the setting of repeated or prolonged tissue injury, can exacerbate cellular dysfunction, suggesting that it may contribute to the pathogenesis of CKD. Here, mice with chronically elevated levels of adenosine, resulting from a deficiency in adenosine deaminase (ADA), developed renal dysfunction and fibrosis. Both the administration of polyethylene glycol-modified ADA to reduce adenosine levels and the inhibition of the A(2B) adenosine receptor (A(2B)R) attenuated renal fibrosis and dysfunction. Furthermore, activation of A(2B)R promoted renal fibrosis in both mice infused with angiotensin II (Ang II) and mice subjected to unilateral ureteral obstruction (UUO). These three mouse models shared a similar profile of profibrotic gene expression in kidney tissue, suggesting that they share similar signaling pathways that lead to renal fibrosis. Finally, both genetic and pharmacologic approaches showed that the inflammatory cytokine IL-6 mediates adenosine-induced renal fibrosis downstream of A(2B)R. Taken together, these data suggest that A(2B)R-mediated induction of IL-6 contributes to renal fibrogenesis and shows potential therapeutic targets for CKD.
Functional protein divergence in the evolution of Homo sapiens
Authors: Nuria Lopez-Bigas, Subhajyoti De, Sarah A Teichmann
Journal: Genome biology (2008)

Protein-coding regions in a genome evolve by sequence divergence and gene gain and loss, altering the gene content of the organism. However, it is not well understood how this has given rise to the enormous diversity of metazoa present today.To obtain a global view of human genomic evolution, we quantify the divergence of proteins by functional category at different evolutionary distances from human.This analysis highlights some general systems-level characteristics of human evolution: regulatory processes, such as signal transducers, transcription factors and receptors, have a high degree of plasticity, while core processes, such as metabolism, transport and protein synthesis, are largely conserved. Additionally, this study reveals a dynamic picture of selective forces at short, medium and long evolutionary timescales. Certain functional categories, such as 'development' and 'organogenesis', exhibit temporal patterns of sequence divergence in eukaryotes relative to human. This framework for a grammar of human evolution supports previously postulated theories of robustness and evolvability.
Functional defects of monocyte C3b receptor-mediated phagocytosis in rheumatoid arthritis (RA): evidence for an association with the appearance of a circulating population of non-specific esterase-negative mononuclear phagocytes.
Authors: N P Hurst, G Nuki, T Wallington
Journal: Annals of the Rheumatic Diseases (1983)

We have previously described a selective defect of monocyte C3b receptor-mediated phagocytosis in patients with rheumatoid cutaneous vasculitis. We have studied a further 15 rheumatoid arthritis patients with other associated diseases and complications and have identified 4 further patients with a similar defect. Serological and cytochemical studies suggest that the defect in phagocytosis is due to the appearance of increased numbers of large nonspecific esterase-negative mononuclear phagocytes with defective C3b receptor phagocytic function rather than to receptor blockade by immune complexes.
Three Daily Servings of Reduced-Fat Milk
Authors: David S. Ludwig, Walter C Willett
Journal: JAMA Pediatrics (2013)

In light of research linking sugar-sweetened beverage consumption to obesity, the US Department of Agriculture, the American Academy of Pediatrics, and other organizations have formulated recommendations on healthy beverages. These guidelines consistently recommend limiting consumption of all calorie-containing liquids, except reduced-fat milk, of which people in most age groups are encouraged to consume 3 cups daily. This article questions the scientific rationale for promoting reduced-fat milk consumption at these levels in children and adults and reconsiders the role of cow’s milk in human nutrition.
Comparison of Angioplasty With Infusion of Tirofiban or Abciximab and With Implantation of Sirolimus-Eluting or Uncoated Stents for Acute Myocardial Infarction&lt;subtitle&gt;The MULTISTRATEGY Randomized Trial&lt;/subtitle&gt;
Authors: Marco Valgimigli
Journal: JAMA (2008)

<h3>Context</h3>Abciximab infusion and uncoated-stent implantation is a complementary treatment strategy to reduce major adverse cardiac events in patients undergoing angioplasty for ST-segment elevation myocardial infarction (STEMI). It is uncertain whether there may be similar benefits in replacing abciximab with high-dose bolus tirofiban. Similarly, the use of drug-eluting stents in this patient population is currently discouraged because of conflicting results on efficacy reported in randomized trials and safety concerns reported by registries.<h3>Objective</h3>To evaluate the effect of high-dose bolus tirofiban and of sirolimus-eluting stents as compared with abciximab infusion and uncoated-stent implantation in patients with STEMI undergoing percutaneous coronary intervention.<h3>Design, Setting, and Patients</h3>An open-label, 2 × 2 factorial trial of 745 patients presenting with STEMI or new left bundle-branch block at 16 referral centers in Italy, Spain, and Argentina between October 2004 and April 2007.<h3>Interventions</h3>High-dose bolus tirofiban vs abciximab infusion and sirolimus-eluting stent vs uncoated stent implantation.<h3>Main Outcome Measures</h3>For drug comparison, at least 50% ST-segment elevation resolution at 90 minutes postintervention with a prespecified noninferiority margin of 9% difference (relative risk, 0.89); for stent comparison, the rate of major adverse cardiac events, defined as the composite of death from any cause, reinfarction, and clinically driven target-vessel revascularization within 8 months.<h3>Results</h3>ST-segment resolution occurred in 302 of 361 patients (83.6%) who had received abciximab infusion and 308 of 361 (85.3%) who had received tirofiban infusion (relative risk, 1.020; 97.5% confidence interval, 0.958-1.086; P &lt; .001 for noninferiority). Ischemic and hemorrhagic outcomes were similar in the tirofiban and abciximab groups. At 8 months, major adverse cardiac events occurred in 54 patients (14.5%) with uncoated stents and 29 (7.8%) with sirolimus stents (P = .004), predominantly reflecting a reduction of revascularization rates (10.2% vs 3.2%). The incidence of stent thrombosis was similar in the 2 stent groups.<h3>Conclusions</h3>In patients with STEMI undergoing percutaneous coronary intervention, compared with abciximab, tirofiban therapy was associated with noninferior resolution of ST-segment elevation at 90 minutes following coronary intervention, whereas sirolimus-eluting stent implantation was associated with a significantly lower risk of major adverse cardiac events than uncoated stents within 8 months after intervention.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00229515Published online March 30, 2008 (doi:10.1001/jama.299.15.joc80026).
The emergence of commercial genomics: analysis of the rise of a biotechnology subsector during the Human Genome Project, 1990 to 2004
Authors: Ilse R Wiechers, Noah C Perin, Robert Cook-Deegan
Journal: Genome Medicine (2013)

Development of the commercial genomics sector within the biotechnology industry relied heavily on the scientific commons, public funding, and technology transfer between academic and industrial research. This study tracks financial and intellectual property data on genomics firms from 1990 through 2004, thus following these firms as they emerged in the era of the Human Genome Project and through the 2000 to 2001 market bubble. A database was created based on an early survey of genomics firms, which was expanded using three web-based biotechnology services, scientific journals, and biotechnology trade and technical publications. Financial data for publicly traded firms was collected through the use of four databases specializing in firm financials. Patent searches were conducted using firm names in the US Patent and Trademark Office website search engine and the DNA Patent Database. A biotechnology subsector of genomics firms emerged in parallel to the publicly funded Human Genome Project. Trends among top firms show that hiring, capital improvement, and research and development expenditures continued to grow after a 2000 to 2001 bubble. The majority of firms are small businesses with great diversity in type of research and development, products, and services provided. Over half the public firms holding patents have the majority of their intellectual property portfolio in DNA-based patents. These data allow estimates of investment, research and development expenditures, and jobs that paralleled the rise of genomics as a sector within biotechnology between 1990 and 2004.
Updated consensus statement on biological agents, specifically tumour necrosis factor (TNF ) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases, 2005
Authors: D E Furst
Journal: Annals of the Rheumatic Diseases (2005)

s in previous years, the consensus group to consider the use of biological agents was constituted by rheumatologists from the Universities of Erlangen, Leiden, and Vienna in Europe in cooperation with other Universities in the USA, Canada, and Europe. Pharmaceutical industry support was obtained from a number of companies, but these institutions had no part in the decisions about the specific programme or about the academic participants at this conference.
Hepato-pulmonary syndrome: successful treatment by transjugular intrahepatic portosystemic stent-shunt (TIPS)
Authors: H.-P. Allgaier, K. Haag, A. Ochs, K.H. Hauenstein, M. Jeserich, T. Krause, C. Heilmann, W. Gerok, M. Rössle
Journal: Journal of Hepatology (1995)
Perflubron enhances mucin plug clearance in vitro in the presence of natural surfactant
Authors: Mustafa Al-Saiedy, Evan Nelson, Tamer El-Mays, Matthias Amrein, Francis Green
Journal: European Respiratory Journal (2013)

Introduction : Severe acute asthma is characterized by bronchoconstriction in combination with mucous plugs. These mucous plugs prevent effective delivery of aerosolized bronchodilators with potentially fatal consequences. Perflubron is a chemically stable and inert compound that has been used in many clinical applications, including bronchial lavage, liquid ventilation, with no significant toxicity. It is an excellent carrier of respiratory gases and may have mucolytic properties. We developed an in vitro model of airway mucous plug obstruction. We looked at the ability of perflubron to enhance clearance of a mucin plug with and without the addition of endogenous surfactant.

Methods : Mucin (M3895) was reconstituted with PBS to a concentration of 150 mg/mL. The mucin was placed between two 2.5% agarose gel plugs and inserted into a siliconized 100 µl capillary tube. The tube was exposed to a respiratory ventilator with a stroke volume of 0.5 mL of air at a rate of 20 strokes/min. The apparatus was connected to 10 cm water column to maintain constant peak pressure. Perflubron and bovine lipid extract surfactant (BLES) were added to the capillary tubes separately and together and their effect on mucin movement rates (mm/sec) analyzed

Results :

![Figure][1] 



Conclusion : This study demonstrates that mucin clearance was significantly (P<0.001) increased when treated with PFOB in the presence of surfactant.

 [1]: pending:yes
DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis
Authors: Bettina Lorenz-Depiereux, Murat Bastepe, Anna Benet-Pagès, Mustapha Amyere, Janine Wagenstaller, Ursula Müller-Barth, Klaus Badenhoop, Stephanie M Kaiser, Roger S Rittmaster, Alan H Shlossberg, José L Olivares, César Loris, Feliciano J Ramos, Francis Glorieux, Miikka Vikkula, Harald Jüppner, Tim M Strom
Journal: Nature Genetics (2006)
Primary Care Physicians' Views of Routine Follow-Up Care of Cancer Survivors
Authors: M. Elisabeth Del Giudice, Eva Grunfeld, Bart J. Harvey, Eugenia Piliotis, Sunil Verma
Journal: Journal of Clinical Oncology (2009)

Routine follow-up of adult cancer survivors is an important clinical and health service issue. Because of a lack of evidence supporting advantages of long-term follow-up care in oncology clinics, there is increasing interest for the locus of this care to be provided by primary care physicians (PCPs). However, current Canadian PCP views on this issue have been largely unknown.A mail survey of a random sample of PCPs across Canada, stratified by region and proximity to urban centers, was conducted. Views on routine follow-up of adult cancer survivors and modalities to facilitate PCPs in providing this care were determined.A total of 330 PCPs responded (adjusted response rate, 51.7%). After completion of active treatment, PCPs were willing to assume exclusive responsibility for routine follow-up care after 2.4 +/- 2.3 years had elapsed for prostate cancer, 2.6 +/- 2.6 years for colorectal cancer, 2.8 +/- 2.5 years for breast cancer, and 3.2 +/- 2.7 years for lymphoma. PCPs already providing this care were willing to provide exclusive care sooner. The most useful modalities PCPs felt would assist them in assuming exclusive responsibility for follow-up cancer care were (1) a patient-specific letter from the specialist, (2) printed guidelines, (3) expedited routes of rereferral, and (4) expedited access to investigations for suspected recurrence.With appropriate information and support in place, PCPs reported being willing to assume exclusive responsibility for the follow-up care of adult cancer survivors. Insights gained from this survey may ultimately help guide strategies in providing optimal care to these patients.
Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial
Authors: Konstantinos K. Tsilidis, Despoina Capothanassi, Naomi E. Allen, Evangelos C. Rizos, David S. Lopez, Karin van Veldhoven, Carlotta Sacerdote, Deborah Ashby, Paolo Vineis, Ioanna Tzoulaki, John P.A. Ioannidis
Journal: Diabetes Care (2014)

OBJECTIVE Meta-analyses of epidemiologic studies have suggested that metformin may reduce cancer incidence, but randomized controlled trials did not support this hypothesis. RESEARCH DESIGN AND METHODS A retrospective cohort study, Clinical Practice Research Datalink, was designed to investigate the association between use of metformin compared with other antidiabetes medications and cancer risk by emulating an intention-to-treat analysis as in a trial. A total of 95,820 participants with type 2 diabetes who started taking metformin and other oral antidiabetes medications within 12 months of their diagnosis (initiators) were followed up for first incident cancer diagnosis without regard to any subsequent changes in pharmacotherapy. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% CI. RESULTS A total of 51,484 individuals (54%) were metformin initiators and 18,264 (19%) were sulfonylurea initiators, and 3,805 first incident cancers were diagnosed during a median follow-up time of 5.1 years. Compared with initiators of sulfonylurea, initiators of metformin had a similar incidence of total cancer (HR 0.96; 95% CI 0.89–1.04) and colorectal (HR 0.92; 95% CI 0.76–1.13), prostate (HR 1.02; 95% CI 0.83–1.25), lung (HR 0.85; 95% CI 0.68–1.07), or postmenopausal breast (HR 1.03; 95% CI 0.82–1.31) cancer or any other cancer. CONCLUSIONS In this large study, individuals with diabetes who used metformin had a similar risk of developing cancer compared with those who used sulfonylureas.