tbuckley/cabot-search huggingface dataset:
dsRNA enhances eotaxin-3 production through interleukin-4 receptor upregulation in airway epithelial cells
Authors: K. Tsuji, S. Yamamoto, W. Ou, N. Nishi, I. Kobayashi, M. Zaitsu, E. Muro, Y. Sadakane, T. Ichimaru, Y. Hamasaki
Journal: European Respiratory Journal (2005)

The exacerbation of asthma during viral infections is mainly explained by neutrophils infiltrating into the airways. However, enhanced functions of eosinophils are also observed. The aim of this study was to reveal the mechanism of how eosinophils are activated during and after viral infection of the airways, using a model of viral infection. A synthetic double-stranded RNA, poly inosinic-cytidyric acid (poly(IC)), was transfected to a human airway epithelial cell line (BEAS-2B) and the primary bronchial epithelial cells, to mimic a viral infection. The production of chemokines from the cells was investigated. The transfection of poly(IC), alone, marginally affected the eotaxin-3 production of the cells. However, the transfection of poly(IC) prior to interleukin (IL)-4 stimulation enhanced eotaxin-3 production. Poly(IC) transfection increased mRNA and protein expressions of IL-4 receptor (R)α and IL-2Rγ, components of the IL-4R. In BEAS-2B cells, IL-4-mediated phosphorylation of signal transducer and activator of transcription six was enhanced in poly(IC) transfected cells. This was reversed by the addition of anti-IL-4Rα antibody, suggesting the role of an increased number of IL-4 receptors in enhanced IL-4-induced eotaxin-3 production. Poly(IC)-induced upregulation of IL-4Rα was inhibited by treatment with cycloheximide or dexamethasone. In conclusion, these results suggest that viral airway infection may enhance interleukin-4-induced eotaxin-3 production through upregulation of the interleukin-4 receptor in airway epithelial cells.
Venous Thromboembolism and Cancer
Authors: Gregory Piazza
Journal: Circulation (2013)

C ase Presentation 1: A 64-year-old man with prostate cancer who recently underwent radical retropubic prostatectomy presented to the emergency department with sudden-onset exertional dyspnea and chest heaviness.On physical examination, he was tachycardic with a heart rate of 110 beats per minute, normotensive with a blood pressure of 100/76 mm Hg, and hypoxemic with an oxygen saturation of 88% on room air.Left lower extremity edema and calf tenderness were noted.Contrast-enhanced chest computed tomography demonstrated bilateral segmental pulmonary embolism (PE) without right ventricular enlargement.A left lower extremity venous ultrasound documented left femoral, popliteal, and calf deep vein thrombosis.Case Presentation 2: A 70-year-old woman with renal cell carcinoma underwent resection of a solitary right upper lobe metastatic pulmonary nodule and was referred to the Vascular Medicine clinic after surveillance chest computed tomography performed 1-month postoperatively demonstrated a right lobar PE.She noted fatigue since her surgery but denied any dyspnea or chest discomfort.On physical examination, her heart rate was 82 beats per minute, blood pressure was 102/66 mm Hg, and oxygenation was 96% on room air.Cardiac and pulmonary examinations were unremarkable.
Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia
Authors: Martin Schrappe, Stephen P. Hunger, Ching-Hon Pui, Vaskar Saha, Paul S. Gaynon, André Baruchel, Valentino Conter, Jacques Otten, Akira Ohara, Anne Birgitta Versluys, Gabriele Escherich, Mats Heyman, Lewis B. Silverman, Keizo Horibe, Georg Mann, Bruce M. Camitta, Jochen Harbott, Hansjörg Riehm, Sue Richards, Meenakshi Devidas, Martin Zimmermann
Journal: New England Journal of Medicine (2012)

Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL).
Transcriptome analysis of functional differentiation between haploid and diploid cells of Emiliania huxleyi, a globally significant photosynthetic calcifying cell
Authors: Peter von Dassow, Hiroyuki Ogata, Ian Probert, Patrick Wincker, Corinne Da Silva, Stéphane Audic, Jean-Michel Claverie, Colomban de Vargas
Journal: Genome biology (2009)

Abstract Background Eukaryotes are classified as either haplontic, diplontic, or haplo-diplontic, depending on which ploidy levels undergo mitotic cell division in the life cycle. Emiliania huxleyi is one of the most abundant phytoplankton species in the ocean, playing an important role in global carbon fluxes, and represents haptophytes, an enigmatic group of unicellular organisms that diverged early in eukaryotic evolution. This species is haplo-diplontic. Little is known about the haploid cells, but they have been hypothesized to allow persistence of the species between the yearly blooms of diploid cells. We sequenced over 38,000 expressed sequence tags from haploid and diploid E. huxleyi normalized cDNA libraries to identify genes involved in important processes specific to each life phase (2N calcification or 1N motility), and to better understand the haploid phase of this prominent haplo-diplontic organism. Results The haploid and diploid transcriptomes showed a dramatic differentiation, with approximately 20% greater transcriptome richness in diploid cells than in haploid cells and only ≤ 50% of transcripts estimated to be common between the two phases. The major functional category of transcripts differentiating haploids included signal transduction and motility genes. Diploid-specific transcripts included Ca 2+ , H + , and HCO 3 - pumps. Potential factors differentiating the transcriptomes included haploid-specific Myb transcription factor homologs and an unusual diploid-specific histone H4 homolog. Conclusions This study permitted the identification of genes likely involved in diploid-specific biomineralization, haploid-specific motility, and transcriptional control. Greater transcriptome richness in diploid cells suggests they may be more versatile for exploiting a diversity of rich environments whereas haploid cells are intrinsically more streamlined.
Getting quality data back to frontline providers.
Authors: Anne Barry-Weers, Carol Huibregtse, Sue Ihde, Marija Bjegovich-Weidman, James L. Weese
Journal: Journal of Clinical Oncology (2014)

196 Background: Oncology quality performance metrics may be improved by establishing a coordinated process for getting data back to providers. However, establishing ownership of quality metric data can be a challenge, especially in a large, integrated health system. Methods: Aurora Cancer Care’s team developed quality charters and a coordinated process for its 15-hospital, integrated health system that outlines a course of action for metric selection, data distribution, peer review and development of process improvement plans. A weighted tool was developed and implemented to prioritize measure selection. The weighted tool described and scored each quality measure against its performance improvement opportunity, ease in data collection, national benchmarks, regulatory and reimbursement impact, value to the patient and consideration of the resources required to implement change. The final score was used to prioritize and select measures. The System Multidisciplinary Disease-Specific Quality Subcommittees established quality measures. Abstraction began, outliers were reviewed and results were disseminated to the System Cancer Leadership Council as well as the 15 hospitals via the Regional Cancer Quality Subcommittees (RCQS). The RCQS chairs and quality directors meet quarterly with the system quality liaison to ensure the communication of data back to the front-line providers. Results: We found a rise in the percentages of invasive rectal cancers diagnosed with endorectal ultrasound or magnetic resonance imaging (no stage IV) (2012: 76%, 2013: 84%) and treated with total mesorectal excision (no stage IV) (2012: 72%, 2013: 87%). In addition, increases in the examination of at least 12 regional lymph nodes for invasive colorectal cancer (2012: 93%, 2013: 98%; p&lt;0.05) and partial, rather than total, nephrectomy for renal cancer patients with T1a tumors (2012: 71%, 2013: 95%; p&lt;0.05) were statistically significant. Conclusions: Though our coordinated process to get quality data back to providers continues to evolve, our front-line providers have shown greater enthusiasm for the data, engaged in behavior modification and become more accountable with process improvement plans that are integral to establishing the best patient outcomes.
Early Detection and Treatment of Type 2 Diabetes Reduce Cardiovascular Morbidity and Mortality: A Simulation of the Results of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Europe)
Authors: William H. Herman, Wen Ye, Simon J. Griffin, Rebecca K. Simmons, Melanie J. Davies, Kamlesh Khunti, Guy E.H.M. Rutten, Annelli Sandbaek, Torsten Lauritzen, Knut Borch-Johnsen, Morton B. Brown, Nicholas J. Wareham
Journal: Diabetes Care (2015)

To estimate the benefits of screening and early treatment of type 2 diabetes compared with no screening and late treatment using a simulation model with data from the ADDITION-Europe study.We used the Michigan Model, a validated computer simulation model, and data from the ADDITION-Europe study to estimate the absolute risk of cardiovascular outcomes and the relative risk reduction associated with screening and intensive treatment, screening and routine treatment, and no screening with a 3- or 6-year delay in the diagnosis and routine treatment of diabetes and cardiovascular risk factors.When the computer simulation model was programmed with the baseline demographic and clinical characteristics of the ADDITION-Europe population, it accurately predicted the empiric results of the trial. The simulated absolute risk reduction and relative risk reduction were substantially greater at 5 years with screening, early diagnosis, and routine treatment compared with scenarios in which there was a 3-year (3.3% absolute risk reduction [ARR], 29% relative risk reduction [RRR]) or a 6-year (4.9% ARR, 38% RRR) delay in diagnosis and routine treatment of diabetes and cardiovascular risk factors.Major benefits are likely to accrue from the early diagnosis and treatment of glycemia and cardiovascular risk factors in type 2 diabetes. The intensity of glucose, blood pressure, and cholesterol treatment after diagnosis is less important than the time of its initiation. Screening for type 2 diabetes to reduce the lead time between diabetes onset and clinical diagnosis and to allow for prompt multifactorial treatment is warranted.
The Stem Cell Movement
Authors: Nicola Smart, Paul R. Riley
Journal: Circulation Research (2008)

Stem or progenitor cell-based strategies to combat ischemic heart disease and myocardial infarction, whether autologous transplantation or stimulation of resident populations, not only require detailed insight into transdifferentiation potential and functional coupling, but the efficacy of this approach is underpinned by the need to induce appropriate migration and homing to the site of injury. This review focuses on existing insights into the trafficking of stem cells in the context of cardiac regenerative therapy, with particular focus on the wide variety of potential sources of cells, critical factors that may regulate their migration, and how extrapolating from embryonic stem/progenitor cell behavior during cardiogenesis may reveal pathways implicit in the adult heart postinjury.
Sleep Duration as a Risk Factor for the Development of Type 2 Diabetes
Authors: H. Klar Yaggi, Andre B. Araujo, John B. McKinlay
Journal: Diabetes Care (2006)

OBJECTIVE—Short-term partial sleep restriction results in glucose intolerance and insulin resistance. The purpose of this study was to assess the long-term relationship between sleep duration and the incidence of clinical diabetes. RESEARCH DESIGN AND METHODS—A cohort of men from the Massachusetts Male Aging Study without diabetes at baseline (1987–1989) were followed until 2004 for the development of diabetes. Average number of hours of sleep per night was grouped into the following categories: ≤5, 6, 7, 8, and &amp;gt;8 h. Incidence rates and relative risks (RRs) were calculated for the development of diabetes in each sleep duration category. Those reporting 7 h of sleep per night served as the reference group. Multivariate analysis was performed using Poisson regression. RESULTS—Men reporting short sleep duration (≤5 and 6 h of sleep per night) were twice as likely to develop diabetes, and men reporting long sleep duration (&amp;gt;8 h of sleep per night) were more than three times as likely to develop diabetes over the period of follow-up. Elevated risks remained essentially unchanged after adjustment for age, hypertension, smoking status, self-rated health status, education, and waist circumference (RR 1.95 [95% CI 0.95–4.01] for ≤5 h and 3.12 [1.53–6.37] for &amp;gt;8 h). RRs were altered considerably for the two extreme sleep groups when adjusted for testosterone (1.51 [0.71–3.19] for ≤5 h and 2.81 [1.34–5.90] for &amp;gt;8 h), suggesting that the effects of sleep on diabetes could be mediated via changes in endogenous testosterone levels. CONCLUSIONS—Short and long sleep durations increase the risk of developing diabetes, independent of confounding factors. Sleep duration may represent a novel risk factor for diabetes.
A high-throughput approach to identify genomic variants of bacterial metabolite producers at the single-cell level
Authors: Stephan Binder, Georg Schendzielorz, Norma Stäbler, Karin Krumbach, Kristina Hoffmann, Michael Bott, Lothar Eggeling
Journal: Genome biology (2012)

Abstract We present a novel method for visualizing intracellular metabolite concentrations within single cells of Escherichia coli and Corynebacterium glutamicum that expedites the screening process of producers. It is based on transcription factors and we used it to isolate new L-lysine producing mutants of C. glutamicum from a large library of mutagenized cells using fluorescence-activated cell sorting (FACS). This high-throughput method fills the gap between existing high-throughput methods for mutant generation and genome analysis. The technology has diverse applications in the analysis of producer populations and screening of mutant libraries that carry mutations in plasmids or genomes.
Ouabain Protects against Shiga Toxin–Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL
Authors: Ievgeniia Burlaka, Xiao Li Liu, Johan Rebetz, Ida Arvidsson, Liping Yang, Hjalmar Brismar, Diana Karpman, Anita Aperia
Journal: Journal of the American Society of Nephrology (2013)

Hemolytic uremic syndrome, a life-threatening disease often accompanied by acute renal failure, usually occurs after gastrointestinal infection with Shiga toxin 2 (Stx2)-producing Escherichia coli. Stx2 binds to the glycosphingolipid globotriaosylceramide receptor, expressed by renal epithelial cells, and triggers apoptosis by activating the apoptotic factor Bax. Signaling via the ouabain/Na,K-ATPase/IP3R/NF-κB pathway increases expression of Bcl-xL, an inhibitor of Bax, suggesting that ouabain might protect renal cells from Stx2-triggered apoptosis. Here, exposing rat proximal tubular cells to Stx2 in vitro resulted in massive apoptosis, upregulation of the apoptotic factor Bax, increased cleaved caspase-3, and downregulation of the survival factor Bcl-xL; co-incubation with ouabain prevented all of these effects. Ouabain activated the NF-κB antiapoptotic subunit p65, and the inhibition of p65 DNA binding abolished the antiapoptotic effect of ouabain in Stx2-exposed tubular cells. Furthermore, in vivo, administration of ouabain reversed the imbalance between Bax and Bcl-xL in Stx2-treated mice. Taken together, these results suggest that ouabain can protect the kidney from the apoptotic effects of Stx2.
Influence of Cooling the Heart on Reactive Hyperemia of the Coronary Bed in the Heart-Lung Preparation
Authors: HENRY S. BADEER
Journal: Circulation Research (1965)

Left coronary artery inflow was recorded in the dog heart-lung preparation by means of a Gregg cannula and a Shipley-Wilson recording rotameter. Reactive hyperemia (RH) was induced by 10-second occlusions. The excess blood flow after release was quantified by planimetry and related to the "blood flow debt" incurred during the period of occlusion. In the normothermic heart, the excess coronary flow was 431% of the flow debt. At heart temperatures of 30 and 25.6° C, it dropped to 228% and 143% respectively. There was shortening of the duration of reactive hyperemia and reduction of peak flow at lower temperatures. These results were discussed in the light of chemical theories of the mechanism of reactive hyperemia and the effect of hypothermia thereon.
Brodalumab and ixekizumab, anti-interleukin-17-receptor antibodies for psoriasis: a critical appraisal
Authors: Ph. I. Spuls, L. Hooft
Journal: British Journal of Dermatology (2012)

Journal Article Brodalumab and ixekizumab, anti‐interleukin‐17‐receptor antibodies for psoriasis: a critical appraisal ORIGINAL ARTICLE: Papp KA, Leonardi C, Menter A et al. Brodalumab, an anti‐interleukin‐17‐receptor antibody for psoriasis. N Engl J Med 2012; 366: 1181–9.ORIGINAL ARTICLE: Leonardi C, Matheson R, Zachariae C, et al. Anti‐interleukin‐17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med 2012; 366: 1190–9. Get access Ph. I. Spuls, Ph. I. Spuls Department of Dermatology, University of Amsterdam, PO Box 22700, 1100 DD Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar L. Hooft L. Hooft Dutch Cochrane Centre, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DD Amsterdam, The Netherlands E‐mail: ph.i.spuls@amc.uva.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 4, 1 October 2012, Pages 710–713, https://doi.org/10.1111/bjd.12025 Published: 01 October 2012
Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease
Authors: Walid Beghdadi, Adeline Porcherie, Bradley S. Schneider, David Dubayle, Roger Peronet, Michel Huerre, Takeshi Watanabe, Hiroshi Ohtsu, Jacques Louis, Salaheddine Mécheri
Journal: The Journal of Experimental Medicine (2008)

From the inoculation of Plasmodium sporozoites via Anopheles mosquito bites to the development of blood-stage parasites, a hallmark of the host response is an inflammatory reaction characterized by elevated histamine levels in the serum and tissues. Given the proinflammatory and immunosuppressive activities associated with histamine, we postulated that this vasoactive amine participates in malaria pathogenesis. Combined genetic and pharmacologic approaches demonstrated that histamine binding to H1R and H2R but not H3R and H4R increases the susceptibility of mice to infection with Plasmodium. To further understand the role of histamine in malaria pathogenesis, we used histidine decarboxylase–deficient (HDC−/−) mice, which are free of histamine. HDC−/− mice were highly resistant to severe malaria whether infected by mosquito bites or via injection of infected erythrocytes. HDC−/− mice displayed resistance to two lethal strains: Plasmodium berghei (Pb) ANKA, which triggers cerebral malaria (CM), and Pb NK65, which causes death without neurological symptoms. The resistance of HDC−/− mice to CM was associated with preserved blood–brain barrier integrity, the absence of infected erythrocyte aggregation in the brain vessels, and a lack of sequestration of CD4 and CD8 T cells. We demonstrate that histamine-mediated signaling contributes to malaria pathogenesis. Understanding the basis for these biological effects of histamine during infection may lead to novel therapeutic strategies to alleviate the severity of malaria.
Loss of BAP1 function leads to EZH2-dependent transformation
Authors: Lindsay M LaFave, Wendy Béguelin, Richard Koche, Matt Teater, Barbara Spitzer, Alan Chramiec, Efthymia Papalexi, Matthew D Keller, Todd Hricik, Katerina Konstantinoff, Jean-Baptiste Micol, Benjamin Durham, Sarah K Knutson, John E Campbell, Gil Blum, Xinxu Shi, Emma H Doud, Andrei V Krivtsov, Young Rock Chung, Inna Khodos, Elisa de Stanchina, Ouathek Ouerfelli, Prasad S Adusumilli, Paul M Thomas, Neil L Kelleher, Minkui Luo, Heike Keilhack, Omar Abdel-Wahab, Ari Melnick, Scott A Armstrong, Ross L Levine
Journal: Nature Medicine (2015)
ACL injuries -- problem solved?
Authors: Roald Bahr
Journal: British Journal of Sports Medicine (2009)

To the novice reader, it must seem like sports medicine journals provide inordinate attention to the middle and anterior third of the tibia plateau and the ligament attaching there: the anterior cruciate ligament. This issue of the BJSM is no exception, with as many as five papers on the ACL; but why all the fuss? Aren’t there excellent programmes to prevent ACL injuries?

It is true that last year three large-scale studies reported that serious knee injuries can be prevented. In the BMJ , Pasanen and colleagues1 showed that their neuromuscular training programme is effective in preventing non-contact leg injuries in elite female floorball players and Soligard and colleagues2 showed that a structured warm-up programme — The 11+ — can prevent lower extremity injuries in young female football players. In addition, Gilchrist et al 3 showed that a similar programme, also focusing on neuromuscular control, reduced the risk of ACL injuries in collegiate female soccer players. So, isn’t the problem solved?

Not according to Quatman and Hewett,4 who in their linked paper discuss the controversy regarding the main mechanism of injury …
Eprodisate for the Treatment of Renal Disease in AA Amyloidosis
Authors: Laura M. Dember, Philip N. Hawkins, Bouke P.C. Hazenberg, Peter D. Gorevic, Giampaolo Merlini, Irena Butrimiene, Avi Livneh, Olga Lesnyak, Xavier Puéchal, Helen J. Lachmann, Laura Obici, Robert Balshaw, Denis Garceau, Wendy Hauck, Martha Skinner
Journal: New England Journal of Medicine (2007)

Amyloid A (AA) amyloidosis is a complication of chronic inflammatory conditions that develops when proteolytic fragments of serum amyloid A protein (SAA) are deposited in tissues as amyloid fibrils. Amyloid deposition in the kidney causes progressive deterioration in renal function. Eprodisate is a member of a new class of compounds designed to interfere with interactions between amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization of amyloid fibrils and deposition of the fibrils in tissues.We performed a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of eprodisate in patients with AA amyloidosis and kidney involvement. We randomly assigned 183 patients from 27 centers to receive eprodisate or placebo for 24 months. The primary composite end point was an assessment of renal function or death. Disease was classified as worsened if any one of the following occurred: doubling of the serum creatinine level, reduction in creatinine clearance by 50% or more, progression to end-stage renal disease, or death.At 24 months, disease was worsened in 24 of 89 patients who received eprodisate (27%) and 38 of 94 patients given placebo (40%, P=0.06); the hazard ratio for worsening disease with eprodisate treatment was 0.58 (95% confidence interval, 0.37 to 0.93; P=0.02). The mean rates of decline in creatinine clearance were 10.9 and 15.6 ml per minute per 1.73 m(2) of body-surface area per year in the eprodisate and the placebo groups, respectively (P=0.02). The drug had no significant effect on progression to end-stage renal disease (hazard ratio, 0.54; P=0.20) or risk of death (hazard ratio, 0.95; P=0.94). The incidence of adverse events was similar in the two groups.Eprodisate slows the decline of renal function in AA amyloidosis. (ClinicalTrials.gov number, NCT00035334.)