tbuckley/cabot-search huggingface dataset:
Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial
Authors: Giles J Peek, Miranda Mugford, Ravindranath Tiruvoipati, Andrew Wilson, Elizabeth Allen, Mariamma M Thalanany, Clare L Hibbert, Ann Truesdale, Felicity Clemens, Nicola Cooper, Richard K Firmin, Diana Elbourne
Journal: The Lancet (2009)
Human Vascular Smooth Muscle Cells Undergo Vesicle-Mediated Calcification in Response to Changes in Extracellular Calcium and Phosphate Concentrations
Authors: Joanne L Reynolds, Alexis J Joannides, Jeremy N Skepper, Rosamund McNair, Leon J Schurgers, Diane Proudfoot, Willi Jahnen-Dechent, Peter L Weissberg, Catherine M Shanahan
Journal: Journal of the American Society of Nephrology (2004)

Patients with ESRD have a high circulating calcium (Ca) x phosphate (P) product and develop extensive vascular calcification that may contribute to their high cardiovascular morbidity. However, the cellular mechanisms underlying vascular calcification in this context are poorly understood. In an in vitro model, elevated Ca or P induced human vascular smooth muscle cell (VSMC) calcification independently and synergistically, a process that was potently inhibited by serum. Calcification was initiated by release from living VSMC of membrane-bound matrix vesicles (MV) and also by apoptotic bodies from dying cells. Vesicles released by VSMC after prolonged exposure to Ca and P contained preformed basic calcium phosphate and calcified extensively. However, vesicles released in the presence of serum did not contain basic calcium phosphate, co-purified with the mineralization inhibitor fetuin-A and calcified minimally. Importantly, MV released under normal physiologic conditions did not calcify, and VSMC were also able to inhibit the spontaneous precipitation of Ca and P in solution. The potent mineralization inhibitor matrix Gla protein was found to be present in MV, and pretreatment of VSMC with warfarin markedly enhanced vesicle calcification. These data suggest that in the context of raised Ca and P, vascular calcification is a modifiable, cell-mediated process regulated by vesicle release. These vesicles contain mineralization inhibitors derived from VSMC and serum, and perturbation of the production or function of these inhibitors would lead to accelerated vascular calcification.
Oncogenesis Caused by Loss of the SNF5 Tumor Suppressor Is Dependent on Activity of BRG1, the ATPase of the SWI/SNF Chromatin Remodeling Complex
Authors: Xi Wang, Courtney G. Sansam, Christopher S. Thom, Daniel Metzger, Julia A. Evans, Phuong T.L. Nguyen, Charles W.M. Roberts
Journal: Cancer Research (2009)

Alterations in chromatin play an important role in oncogenic transformation, although the underlying mechanisms are often poorly understood. The SWI/SNF complex contributes to epigenetic regulation by using the energy of ATP hydrolysis to remodel chromatin and thus regulate transcription of target genes. SNF5, a core subunit of the SWI/SNF complex, is a potent tumor suppressor that is specifically inactivated in several types of human cancer. However, the mechanism by which SNF5 mutation leads to cancer and the role of SNF5 within the SWI/SNF complex remain largely unknown. It has been hypothesized that oncogenesis in the absence of SNF5 occurs due to a loss of function of the SWI/SNF complex. Here, we show, however, distinct effects for inactivation of Snf5 and the ATPase subunit Brg1 in primary cells. Further, using both human cell lines and mouse models, we show that cancer formation in the absence of SNF5 does not result from SWI/SNF inactivation but rather that oncogenesis is dependent on continued presence of BRG1. Collectively, our results show that cancer formation in the absence of SNF5 is dependent on the activity of the residual BRG1-containing SWI/SNF complex. These findings suggest that, much like the concept of oncogene addiction, targeted inhibition of SWI/SNF ATPase activity may be an effective therapeutic approach for aggressive SNF5-deficient human tumors.
Asthma exacerbations {middle dot} 1: Epidemiology
Authors: N W Johnston
Journal: Thorax (2006)

Asthma exacerbations may be triggered by a number of atmospheric and domiciliary environmental factors as well as by those encountered in schools and workplaces. The majority of exacerbations, particularly in children, coincide with respiratory viral infections, most commonly rhinovirus. As most respiratory viruses and many aeroallergens appear in seasonal patterns, asthma exacerbations, particularly those requiring emergency treatment, show analogous seasonal cycles which differ in form in children and adults. While similar in form between the sexes, they differ in amplitude, with boys having higher risks of exacerbation in childhood and women in adult life. Simultaneous exposure of asthmatics with respiratory viral infections to allergens or air pollutants may significantly increase the risks of exacerbation. Access to and compliance with inhaled corticosteroid treatment is an important predictor of the likelihood of asthma exacerbations occurring, including those that occur during respiratory viral infections. Epidemiologically, the degree of asthma control achieved by asthmatics is an important predictor of the likelihood of disease exacerbation including respiratory failure, death, and health service consumption.
Current concepts in the surgical management of chronic and recurrent acute sinusitis
Authors: D C Lanza, D W Kennedy
Journal: Journal of Allergy and Clinical Immunology (1992)

It was previously believed that sinusitis lasting longer than 3 months might lead to irreversible disease.Experience with functional endoscopic sinus surgery indicates that this is rarcl?; the case.Functional endoscopic sinus surgery describes an approach whereby target areas of' obstruction are cleared of disease, which allows for ventilation of secondarily involved sim4se.tand return of mucociliary function.Although endoscopic sinus surgery is one qf' the technique.vmost frequently used to manage chronic sinus disease, it is not a suitable surgical approach fin every otolaryngologist or all patient settings.Success with this endoscopic approach for chronic sinus disease is based primarily on rigorous perioperative medical care and postoperative surgical debridement.The greatest advancement that the nasal endoscope has brought to patient care is the ability to diagnose disease and follow objectively the effects of different treatment modalities.This advantage is recognized by allergists and used at several centers.(J AI.LI,KG~
Iontophoresis with alternating current and direct current offset (AC/DC iontophoresis): a new approach for the treatment of hyperhidrosis
Authors: S. REINAUER, A. NEUSSER, G. SCHAUF, E. HOLZLE
Journal: British Journal of Dermatology (1993)

Tap‐water iontophoresis (TWI) using direct current (DC) is the most effective therapy in palmoplantar hyperhidrosis. Side‐effects of this method are discomfort, with burning and tingling, and skin irritation, including erythema and vesicles. Incorrect use may induce iontophoretic burns at sites of minor skin injury. Elaborate safety measures are required to prevent electric shock. The aim of this study was to minimize side‐effects and to increase technical and safety standards of TWI, without loss of efficacy. In a controlled blind study, treatment of palmar hyperhidrosis by alternating current (AC) or by AC with DC‐offset (AC/DC) was compared with the conventional DC method. Palmar hyperhidrosis was completely controlled after an average of 11 treatments by either AC/DC iontophoresis or the conventional DC method. Virtually no effect was seen when AC without DC‐offset was used for TWI. There were no signs of cutaneous irritation, or subjective sensations of discomfort when AC with or without DC‐offset was employed. AC/DC iontophoresis should become the treatment of choice for palmoplantar hyperhidrosis. The mechanism of action is unknown. It is hypothesized that an interrupted stimulus‐secretion‐coupling leads to a functional disturbance of sweat secretion.
Diagnosis, prevention, and management of delirium: summary of NICE guidance
Authors: J. Young, L. Murthy, M. Westby, A. Akunne, R. O'Mahony
Journal: BMJ (2010)

Delirium is a complex clinical syndrome characterised by disturbed consciousness, cognitive function, or perception. Sometimes known as acute confusional state, delirium has an acute onset, a fluctuating course, and is associated with serious adverse outcomes such as death, dementia, and the need for long term care.1 Although common in general hospitals (affecting as many as about 30% of inpatients)1 and care homes, delirium is often poorly recognised1; however, it can be prevented in about one third of patients at risk.1 This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) guideline on how to recognise, prevent, and treat delirium.2 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the experience of the Guideline Development Group and their opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Assessment of risk factors [ Based on moderate and low quality evidence from prospective cohort studies ] ### Interventions to prevent delirium
Cancer Treatment Disparities in HIV-Infected Individuals in the United States
Authors: Gita Suneja, Meredith S. Shiels, Rory Angulo, Glenn E. Copeland, Lou Gonsalves, Anne M. Hakenewerth, Kathryn E. Macomber, Sharon K. Melville, Eric A. Engels
Journal: Journal of Clinical Oncology (2014)

HIV-infected individuals with cancer have worse survival rates compared with their HIV-uninfected counterparts. One explanation may be differing cancer treatment; however, few studies have examined this.We used HIV and cancer registry data from Connecticut, Michigan, and Texas to study adults diagnosed with non-Hodgkin's lymphoma, Hodgkin's lymphoma, or cervical, lung, anal, prostate, colorectal, or breast cancers from 1996 to 2010. We used logistic regression to examine associations between HIV status and cancer treatment, adjusted for cancer stage and demographic covariates. For a subset of local-stage cancers, we used logistic regression to assess the relationship between HIV status and standard treatment modality. We identified predictors of cancer treatment among individuals with both HIV and cancer.We evaluated 3,045 HIV-infected patients with cancer and 1,087,648 patients with cancer without HIV infection. A significantly higher proportion of HIV-infected individuals did not receive cancer treatment for diffuse large B-cell lymphoma (DLBCL; adjusted odds ratio [aOR], 1.67; 95% CI, 1.41 to 1.99), lung cancer (aOR, 2.18; 95% CI, 1.80 to 2.64), Hodgkin's lymphoma (aOR, 1.77; 95% CI, 1.33 to 2.37), prostate cancer (aOR, 1.79; 95% CI, 1.31 to 2.46), and colorectal cancer (aOR, 2.27; 95% CI, 1.38 to 3.72). HIV infection was associated with a lack of standard treatment modality for local-stage DLBCL (aOR, 2.02; 95% CI, 1.50 to 2.72), non-small-cell lung cancer (aOR, 2.43; 95% CI, 1.46 to 4.03), and colon cancer (aOR, 4.77; 95% CI, 1.76 to 12.96). Among HIV-infected individuals, factors independently associated with lack of cancer treatment included low CD4 count, male sex with injection drug use as mode of HIV exposure, age 45 to 64 years, black race, and distant or unknown cancer stage.HIV-infected individuals are less likely to receive treatment for some cancers than uninfected people, which may affect survival rates.
Benefit of Maintenance Therapy with Trabectedin (T) Beyond the 6 First Cycles: Results of a Prospective Randomized Phase Ii Trial Comparing Interruption Vs. Continuation of T in Patients (Pts) with Advanced Soft Tissue Sarcoma (Asts): an Update
Authors: A. Le Cesne, J. Blay, T. Ryckewaert, C. Chevreau, F. Bertucci, C. Delcambre, E. Saada, S. Piperno-Neumann, J. Bay, O. Mir, J. Domont, I.L. Ray-Coquard, T. Valentin, E. Tresch, S. Clisant, N. Isambert, A. Italiano, S. Clisant, N. Badri, N. Penel
Journal: Annals of Oncology (2014)
Mitochondrial Cholesterol Contributes to Chemotherapy Resistance in Hepatocellular Carcinoma
Authors: Joan Montero, Albert Morales, Laura Llacuna, Josep M. Lluis, Oihana Terrones, Gorka Basañez, Bruno Antonsson, Jesús Prieto, Carmen García-Ruiz, Anna Colell, José C. Fernández-Checa
Journal: Cancer Research (2008)

Abstract Cholesterol metabolism is deregulated in carcinogenesis, and cancer cells exhibit enhanced mitochondrial cholesterol content whose role in cell death susceptibility and cancer therapy has not been investigated. Here, we describe that mitochondria from rat or human hepatocellular carcinoma (HC) cells (HCC) or primary tumors from patients with HC exhibit increased mitochondrial cholesterol levels. HCC sensitivity to chemotherapy acting via mitochondria is enhanced upon cholesterol depletion by inhibition of hydroxymethylglutaryl-CoA reductase or squalene synthase (SS), which catalyzes the first committed step in cholesterol biosynthesis. HCC transfection with siRNA targeting the steroidogenic acute regulatory protein StAR, a mitochondrial cholesterol–transporting polypeptide which is overexpressed in HCC compared with rat and human liver, sensitized HCC to chemotherapy. Isolated mitochondria from HCC with increased cholesterol levels were resistant to mitochondrial membrane permeabilization and release of cytochrome c or Smac/DIABLO in response to various stimuli including active Bax. Similar behavior was observed in cholesterol-enriched mitochondria or liposomes and reversed by restoring mitochondrial membrane order or cholesterol extraction. Moreover, atorvastatin or the SS inhibitor YM-53601 potentiated doxorubicin-mediated HCC growth arrest and cell death in vivo. Thus, mitochondrial cholesterol contributes to chemotherapy resistance by increasing membrane order, emerging as a novel therapeutic niche in cancer therapy. [Cancer Res 2008;68(13):5246–56]
Contractile Proteins in Cell Structure and Function
Authors: T P Stossel
Journal: Annual Review of Medicine (1978)

1. The cytoplasm of cells is a colloidal network of contractile proteins. Actin filaments are the major components of this network. Other contractile proteins interact with these filaments to create structural rigidity and movement. 2. The structure and function of contractile proteins is striated muscles is well characterized and thus provides a good example for extrapolitation to an analysis of contractile-protein structure and function of nonmuscle cells. However, the interaction of contractile proteins of various cells may be unique. 3. The study of contractile proteins in cells other than muscle has distinct difficulties: (a) The proteins are present in much lower concentration than in muscle, and only a few cell types are obtainable for study in quantities comparable to muscle. (b) Proteolysis and other detriments may be more severe in nonmuscle cells. (c) The organization of contractile proteins is difficult to define in nonmuscle cells. (d) The effort is diffuse; investigations examine a wide variety of different, or less commonly the same, cells. Reflecting these difficulties, a catalogue of putative nonmuscle cell fucntions related to contractile proteins reveals no one system to be definitively worked out. Nevertheless, the ubiquity of contractile proteins and the obvious importance of their intractions presages increasing relevancy for physiology and medicine.
Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus
Authors: Anna Kanerva, Petri Nokisalmi, Iulia Diaconu, Anniina Koski, Vincenzo Cerullo, Ilkka Liikanen, Siri Tähtinen, Minna Oksanen, Raita Heiskanen, Saila Pesonen, Timo Joensuu, Tuomo Alanko, Kaarina Partanen, Leena Laasonen, Kalevi Kairemo, Sari Pesonen, Lotta Kangasniemi, Akseli Hemminki
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Multiple injections of oncolytic adenovirus could enhance immunologic response. In the first part of this article, the focus was on immunologic aspects. Sixty patients previously naïve to oncolytic virus and who had white blood cells available were treated. Thirty-nine of 60 were assessed after a single virus administration, whereas 21 of 60 received a “serial treatment” consisting of three injections within 10 weeks. In the second part, we focused on 115 patients treated with a granulocyte macrophage colony-stimulating factor (GM–CSF)–coding capsid chimeric adenovirus, CGTG-102. Results: Following serial treatment, both increase and decrease in antitumor T cells in blood were seen more frequently, findings which are compatible with induction of T-cell immunity and trafficking of T cells to tumors, respectively. Safety was good in both groups. In 115 patients treated with CGTG-102 (Ad5/3-D24-GMCSF), median overall survival was 111 days following single and 277 days after serial treatment in nonrandomized comparison. Switching the virus capsid for avoiding neutralizing antibodies in a serial treatment featuring three different viruses did not impact safety or efficacy. A correlation between antiviral and antitumor T cells was seen (P = 0.001), suggesting that viral oncolysis can result in epitope spreading and breaking of tumor-associated immunologic tolerance. Alternatively, some patients may be more susceptible to induction of T-cell immunity and/or trafficking. Conclusions: These results provide the first human data linking antiviral immunity with antitumor immunity, implying that oncolytic viruses could have an important role in cancer immunotherapy. Clin Cancer Res; 19(10); 2734–44. ©2013 AACR.
Macronutrient intake and malabsorption in HIV infection: a comparison with other malabsorptive states
Authors: F Carbonnel, L Beaugerie, A Abou Rached, H D’Almagne, W Rozenbaum, Y Le Quintrec, J P Gendre, J Cosnes
Journal: Gut (1997)

Background —Wasting is a major complication of HIV infection. The role of malabsorption in wasting is controversial. Aims —To assess oral intake and malabsorption in a cohort of weight losing HIV infected patients, with or without chronic diarrhoea. Methods —A prospective study using a predefined protocol for HIV infected patients was performed in a gastroenterology and nutrition unit in a university hospital. A retrospective comparison was made with HIV negative patients with malabsorption due either to small bowel disease or resection. Body weight and height, serum albumin, oral intake of macronutrients, faecal weight, and faecal fat were measured. Results —Seventy nine weight losing HIV infected patients were studied. Among the 66 patients with more than 5% lipid malabsorption, wasting was significantly greater in patients with cryptosporidiosis (n=22) than in patients with microsporidiosis (n=18) who exhibited significantly more wasting than patients with no identified enteropathogen (n=26) (body mass index 16.8 (14.0–20.7), 18.9 (16.5–21.3), 19.7 (15.9–23), respectively). When controlling for the level of lipid malabsorption, HIV infected patients had a significantly lower energy intake than HIV negative patients with chronic malabsorption. In HIV infected patients, but not in other categories of malabsorbers, body mass index correlated significantly with energy intake ( r =0.33, 95% confidence intervals 0.12 to 0.51). Conclusion— In weight losing HIV infected patients, reduced energy intake is superimposed on malabsorption and significantly contributes to wasting.
Adherence to HAART (Highly Active Antiretroviral Therapy) by HIV-1 Infected Patients with Allergic Asthma is Associated with Selective Suppression of Serum IgE but Not of Exhaled Breath Nitric Oxide (NO).
Authors: P. Brown, M. Findley, J. DeHovitz, R. Joks, H.G. Durkin, M. Nowakowski
Journal: Journal of Allergy and Clinical Immunology (2009)
Environmental exposure to air pollution and allergensand peak flow changes
Authors: B G Higgins, H C Francis, C Yates, C J Warburton, A M Fletcher, C A Pickering, A A Woodcock
Journal: European Respiratory Journal (2000)

Laboratory-based studies have shown that ozone and nitrogen dioxide can potentiate the effect of allergen in sensitized asthmatic subjects, but it is not known whether this interaction is important under natural exposure conditions. Thirty-five subjects with clinical diagnoses of asthma or chronic obstructive pulmonary disease and with a provocative dose causing a 20% fall in forced expiratory volume in one second methacholine <12.25 micromol (using the Yan method) kept peak expiratory flow (PEF) records for a 4-week period during late summer, with concurrent measurement of spore and pollen counts and pollution levels. Multiple regression analysis was then used to determine the effect on PEF of aeroallergen, and of the interaction between aeroallergen and pollutant levels. A statistically significant interaction was demonstrated between total spore count and ozone, but not nitrogen dioxide. Mean PEF fell in association with increasing spore count (same-day and 24-h lag level) and PEF variability increased with increasing spore count (24-h lag level only); both changes were greater the higher the prior ozone level. These results suggest that ozone can potentiate the effect of aeroallergens in subjects with bronchial hyperreactivity under natural exposure conditions. However, the effect was small, and the clinical significance of the interaction requires further study.
Poor-Prognosis Estrogen Receptor–Positive Breast Cancer Identified by Histopathologic Subclassification
Authors: Lucy R. Webster, Shu-Fen Lee, Clare Ringland, Adrienne L. Morey, Andrew M. Hanby, Graeme Morgan, Karen Byth, Patricia A. Mote, Pamela J. Provan, Ian O. Ellis, Andrew R. Green, Gillian Lamoury, Peter Ravdin, Christine L. Clarke, Robyn L. Ward, Rosemary L. Balleine, Nicholas J. Hawkins
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Identification of biologically and clinically distinct breast cancer subtypes could improve prognostic assessment of primary tumors. The characteristics of “molecular” breast cancer subtypes suggest that routinely assessed histopathologic features in combination with limited biomarkers may provide an informative classification for routine use. Experimental Design: Hierarchical cluster analysis based on components of histopathologic grade (tubule formation, nuclear pleomorphism, and mitotic score), expression of ER, cytokeratin 5/6, and HER2 amplification identified four breast cancer subgroups in a cohort of 270 cases. Cluster subgroup membership was compared with observed and Adjuvant! Online predicted 10-year survival. Survival characteristics were confirmed in an independent cohort of 300 cases assigned to cluster subgroups using a decision tree model. Results: Four distinct breast cancer cluster subgroups (A-D) were identified that were analogous to molecular tumor types and showed a significant association with survival in both the original and validation cohorts (P &amp;lt; 0.001). There was a striking difference between survival for patients in cluster subgroups A and B with ER+ breast cancer (P &amp;lt; 0.001). Outcome for all tumor types was well estimated by Adjuvant! Online, with the exception of cluster B ER+ cancers where Adjuvant! Online was too optimistic. Conclusions: Breast cancer subclassification based on readily accessible pathologic features could improve prognostic assessment of ER+ breast cancer.