tbuckley/cabot-search huggingface dataset:
Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis
Authors: D E A Greven, E S Cohen, D M Gerlag, J Campbell, J Woods, N Davis, A van Nieuwenhuijze, A Lewis, S Heasmen, M McCourt, D Corkill, A Dodd, J Elvin, G Statache, I P Wicks, I K Anderson, A Nash, M A Sleeman, P P Tak
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)–GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue and investigated the effects of anti-GM-CSFRα antibody treatment in vitro and in vivo in a preclinical model of RA. <h3>Methods</h3> We compared GM-CSFRα expression on macrophages positive for CD68 or CD163 on synovial biopsy samples from patients with RA or psoriatic arthritis (PsA) to disease controls. In addition, we studied the effects of CAM-3003, an anti-GM-CSFR antibody in a collagen induced arthritis model of RA in DBA/1 mice. The pharmacokinetic profile of CAM-3003 was studied in naïve CD1(ICR) mice (see online supplement) and used to interpret the results of the pharmacodynamic studies in BALB/c mice. <h3>Results</h3> GM-CSFRα was expressed by CD68 positive and CD163 positive macrophages in the synovium, and there was a significant increase in GM-CSFRα positive cells in patients in patients with RA as well as patients with PsA compared with patients with osteoarthritis and healthy controls. In the collagen induced arthritis model there was a dose dependent reduction of clinical arthritis scores and the number of F4/80 positive macrophages in the inflamed synovium after CAM-3003 treatment. In BALB/c mice CAM-3003 inhibited recombinant GM-CSF mediated margination of peripheral blood monocytes and neutrophils. <h3>Conclusions</h3> The findings support the ongoing development of therapies aimed at interfering with GM-CSF or its receptor in various forms of arthritis, such as RA and PsA.
Warrior values and social identity
Authors: Linnda R. Caporael
Journal: Behavioral and Brain Sciences (1999)

A single evolved psychological mechanism, social identity, may help explain the development of salient sex differences in aggression. Bearing children automatically provides a basis for positive social identity for females. Masculine identity is more problematic, especially where the range of possible cultural roles is small. Ethnohistorical data provides insight into the overlap between masculine values and warrior values.
80 KV CORONARY CT ANGIOGRAPHY FOR LOW-BODY WEIGHT PATIENTS
Authors: Sei Komatsu, Teruaki Kamata, Atsuko Imai, Jyunichi Yoshida, Tomoki Ohara, Kazuaki Miyaji, Yoshinobu Shimizu, Kazuisa Kodama
Journal: Journal of the American College of Cardiology (2010)
A French survey of 3,225 patients treated with CPAP for obstructive sleep apnoea: benefits, tolerance, compliance and quality of life
Authors: N Meslier, T Lebrun, V Grillier-Lanoir, N Rolland, C Henderick, JC Sailly, JL Racineux
Journal: European Respiratory Journal (1998)

The aim of this study was to investigate in a large population of patients with obstructive sleep apnoea and on long-term treatment with continuous positive airway pressure (CPAP) the patients' perception of symptomatic improvement, side-effects and quality of life. Questionnaires were mailed via local respiratory homecare associations to 5,339 French patients who had been treated at home for at least 6 months with CPAP machines and who continued their treatment. In total, 3,225 questionnaires were analysable. More than 80% of the responding patients reported that CPAP treatment had greatly improved their symptoms. Despite discomfort related to nasal problems and excess noise from the blower, the mean rate of use for the whole population was 6 h 36 min+/-2 h 15 min. The perceived health evaluated by the Nottingham Health Profile was good (mean score &lt;50) for at least 75% of the patients in each dimension explored. The perceived health was significantly related to the improvement in symptoms, the overall satisfaction and the objective compliance. This retrospective study indicates that patients who continued continuous positive airway pressure treatment for more than 6 months felt a great improvement in their symptoms, were satisfied with the treatment and had a relatively good perception of their health.
Bone Marrow Microenvironment Induces Stem Cell-Like Phenotype In Acute Myeloid Leukemia
Authors: Venkata L Battula, Juliana M Benito, Anitha Somanchi, Seshagiri Duvvuri, Lauren Hodgson, Ye Chen, Wencai Ma, Richard E. Davis, Ian K. McNiece, Elizabeth J Shpall, Marina Konopleva, Michael Andreeff
Journal: Blood (2013)
Vaccination with Viable Human Umbilical Vein Endothelial Cells Prevents Metastatic Tumors by Attack on Tumor Vasculature with Both Cellular and Humoral Immunity
Authors: Xin-Yuan Chen, Wei Zhang, Wang Zhang, Sheng Wu, Feng Bi, Yi-Jing Su, Xiang-Yang Tan, Jian-Ning Liu, Jing Zhang
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Because tumor endothelium is rarely targeted by immunity but is critically important for tumor growth, the immunity against tumor endothelium is to be developed as a novel antitumor strategy. Experimental Design: First, viable human umbilical vein endothelial cells (HUVEC) were immunized to C57BL/6 and BALB/c mice to evoke specific CTLs as well as antibodies against tumor endothelium. Lewis lung carcinoma or myeloma cells were subsequently inoculated to evaluate the effect on tumor growth by vaccination. Second, the effect on tumor metastasis by vaccination was studied using tumor-resected mice receiving HUVEC immunization 3 days after excision. Third, the immune sera and T lymphocytes from HUVEC-immunized mice were transferred to tumor-bearing mice and added to cultured HUVECs to investigate their antiproliferative effect. Results: Viable HUVEC immunization showed potent antitumor effects in Lewis lung carcinoma and myeloma tumor models. Both immune sera and CTL inhibited tumor growth and specifically suppressed proliferation of HUVECs. Particularly, tumors entirely disappeared on day 90 after tumor inoculation in four of six tumor-bearing mice receiving CTL therapy. In a metastatic tumor model, we found that the HUVEC vaccination prolonged life span from 30.9 to 41.5 days after tumor resection compared with PBS-treated mice without apparent side effects. Conclusions: Vaccination with viable HUVECs evoked both humoral and cellular immunity against tumor microvasculature, and therefore significantly inhibited tumor growth and prolonged life span of tumor-resected mice. This may provide with a novel treatment for metastatic tumors. Moreover, we have established a convenient method to evoke specific CTL against tumor angiogenesis.
p130Cas as a New Regulator of Mammary Epithelial Cell Proliferation, Survival, and HER2-Neu Oncogene–Dependent Breast Tumorigenesis
Authors: Sara Cabodi, Agata Tinnirello, Paola Di Stefano, Brigitte Bisarò, Elena Ambrosino, Isabella Castellano, Anna Sapino, Riccardo Arisio, Federica Cavallo, Guido Forni, Marina Glukhova, Lorenzo Silengo, Fiorella Altruda, Emilia Turco, Guido Tarone, Paola Defilippi
Journal: Cancer Research (2006)

Abstract To investigate the mechanisms through which p130Cas adaptor protein is linked to tumorigenesis, we generated mouse mammary tumor virus (MMTV)-p130Cas mice overexpressing p130Cas in the mammary gland. MMTVp130Cas transgenic mice are characterized by extensive mammary epithelial hyperplasia during development and pregnancy and by delayed involution at the end of lactation. These phenotypes are associated with activation of Src kinase, extracellular signal-regulated kinase 1/2, mitogen-activated protein kinase, and Akt pathways, leading to an increased rate of proliferation and a decreased apoptosis. A double-transgenic line derived from crossing MMTV-p130Cas with MMTV-HER2-Neu mice expressing the activated form of the HER2-Neu oncogene develops multifocal mammary tumors with a significantly shorter latency than the HER2-Neu parental strain alone. Mammary epithelial cells isolated from tumors of double-transgenic mice display increased tyrosine phosphorylation, c-Src, and Akt activation compared with cells derived from HER2-Neu tumors. In addition, p130Cas down-regulation by RNA interference increases apoptosis in HER2-Neu-expressing cells, indicating that p130Cas regulates cell survival. Consistently with the double-transgenic mice model, p130Cas is overexpressed in a significant subset of human breast cancers and high levels of p130Cas in association with HER2 expression correlate with elevated proliferation. These findings provide evidences for a role of p130Cas as a positive regulator of both proliferation and survival in normal and transformed mammary epithelial cells. Its overexpression contributes to HER2-Neu-induced breast tumorigenesis, thus identifying this protein as a putative target for clinical therapy. (Cancer Res 2006; 66(9): 4672-80)
Hierarchical Clustering Analysis of Tissue Microarray Immunostaining Data Identifies Prognostically Significant Groups of Breast Carcinoma
Authors: Nikita A. Makretsov, David G. Huntsman, Torsten O. Nielsen, Erika Yorida, Michael Peacock, Maggie C. U. Cheang, Sandra E. Dunn, Malcolm Hayes, Matt van de Rijn, Chris Bajdik, C. Blake Gilks
Journal: Clinical Cancer Research (2004)

Abstract Prognostically relevant cluster groups, based on gene expression profiles, have been recently identified for breast cancers, lung cancers, and lymphoma. Our aim was to determine whether hierarchical clustering analysis of multiple immunomarkers (protein expression profiles) improves prognostication in patients with invasive breast cancer. A cohort of 438 sequential cases of invasive breast cancer with median follow-up of 15.4 years was selected for tissue microarray construction. A total of 31 biomarkers were tested by immunohistochemistry on these tissue arrays. The prognostic significance of individual markers was assessed by using Kaplan-Meier survival estimates and log-rank tests. Seventeen of 31 markers showed prognostic significance in univariate analysis (P ≤ 0.05) and 4 markers showed a trend toward significance (P ≤ 0.2). Unsupervised hierarchical clustering analysis was done by using these 21 immunomarkers, and this resulted in identification of three cluster groups with significant differences in clinical outcome. χ2 analysis showed that expression of 11 markers significantly correlated with membership in one of the three cluster groups. Unsupervised hierarchical clustering analysis with this set of 11 markers reproduced the same three prognostically significant cluster groups identified by using the larger set of markers. These cluster groups were of prognostic significance independent of lymph node metastasis, tumor size, and tumor grade in multivariate analysis (P = 0.0001). The cluster groups were as powerful a prognostic indicator as lymph node status. This work demonstrates that hierarchical clustering of immunostaining data by using multiple markers can group breast cancers into classes with clinical relevance and is superior to the use of individual prognostic markers.
EGTA treatment of human airways<i>in vitro</i>unmasks M1/MUC5AC mucin in submucosal glands
Authors: P. Roger, J-P. Gascard, J. Bara, E. Dulmet, C. Brink
Journal: European Respiratory Journal (2001)

Mucin staining can be used to evaluate secretory activity of human airways. However, mucin epitopes may be masked by physicochemical properties of the secretions. The aim of this investigation was to examine the effects of the calcium chelator, ethyleneglycol-bis-(β-aminoethylether)-N, N, N′, N′-tetraacetic acid (EGTA) on the detection of M1/MUC5AC mucin in isolated human bronchial preparations. Immunohistochemical investigation and immunoradiometric assays with anti-M1 monoclonal antibodies (Mabs) were used to detect M1/MUC5AC mucin derived from bronchial preparations with an intact surface epithelium, or in tissues where the epithelium had been removed (rubbed preparations). The Mabs labelled both epithelial goblet cells and submucosal glandular cells in EGTA (4 mM)-exposed bronchial preparations, while only goblet cells were stained in EGTA (0.4 mM)-exposed tissues. The quantities of M1/MUC5AC mucin detected in either the bronchial fluids derived from EGTA (4 mM)-exposed intact and rubbed preparations or in bronchial fluids treated with EGTA (4 mM) were significantly increased by two-fold when compared with untreated control values (p&lt;0.001). In addition, lactate dehydrogenase (LDH) activity and protein measurements were unaltered during exposure of human airways to EGTA (4 mM) suggesting that this treatment did not affect tissue viability. These results provide evidence that ethyleneglycol-bis-(β-aminoethylether)-N, N, N′, N′-tetraacetic acid (4 mM) facilitates the detection of M1/MUC5AC mucin by altering the physicochemical properties of respiratory mucin, thereby exposing epitopes with which anti-M1 monoclonal antibodies are reactive. This will allow more accurate measurement of secretory activity in human airways in vitro .
Characteristics of Walkable Built Environments and BMI <i>z</i> -Scores in Children: Evidence from a Large Electronic Health Record Database
Authors: Dustin T. Duncan, Mona Sharifi, Steven J. Melly, Richard Marshall, Thomas D. Sequist, Sheryl L. Rifas-Shiman, Elsie M. Taveras
Journal: Environmental Health Perspectives (2014)

Background: Childhood obesity remains a prominent public health problem. Walkable built environments may prevent excess weight gain.Objectives: We examined the association of walkable built environment characteristics with body mass index (BMI) z-score among a large sample of children and adolescents.Methods: We used geocoded residential address data from electronic health records of 49,770 children and adolescents 4 to &lt; 19 years of age seen at the 14 pediatric practices of Harvard Vanguard Medical Associates from August 2011 through August 2012. We used eight geographic information system (GIS) variables to characterize walkable built environments. Outcomes were BMI z-score at the most recent visit and BMI z-score change from the earliest available (2008–2011) to the most recent (2011–2012) visit. Multivariable models were adjusted for child age, sex, race/ethnicity, and neighborhood median household income.Results: In multivariable cross-sectional models, living in closer proximity to recreational open space was associated with lower BMI z-score. For example, children who lived in closest proximity (quartile 1) to the nearest recreational open space had a lower BMI z-score (β = –0.06; 95% CI: –0.08, –0.03) compared with those living farthest away (quartile 4; reference). Living in neighborhoods with fewer recreational open spaces and less residential density, traffic density, sidewalk completeness, and intersection density were associated with higher cross-sectional BMI z-score and with an increase in BMI z-score over time.Conclusions: Overall, built environment characteristics that may increase walkability were associated with lower BMI z-scores in a large sample of children. Modifying existing built environments to make them more walkable may reduce childhood obesity.Citation: Duncan DT, Sharifi M, Melly SJ, Marshall R, Sequist TD, Rifas-Shiman SL, Taveras EM. 2014. Characteristics of walkable built environments and BMI z-scores in children: evidence from a large electronic health record database. Environ Health Perspect 122:1359–1365; http://dx.doi.org/10.1289/ehp.1307704
Effectiveness of screening and brief alcohol intervention in primary care (SIPS trial): pragmatic cluster randomised controlled trial
Authors: E. Kaner, M. Bland, P. Cassidy, S. Coulton, V. Dale, P. Deluca, E. Gilvarry, C. Godfrey, N. Heather, J. Myles, D. Newbury-Birch, A. Oyefeso, S. Parrott, K. Perryman, T. Phillips, J. Shepherd, C. Drummond
Journal: BMJ (2013)

<b>Objective</b> To evaluate the effectiveness of different brief intervention strategies at reducing hazardous or harmful drinking in primary care. The hypothesis was that more intensive intervention would result in a greater reduction in hazardous or harmful drinking. <b>Design</b> Pragmatic cluster randomised controlled trial. <b>Setting</b> Primary care practices in the north east and south east of England and in London. <b>Participants</b> 3562 patients aged 18 or more routinely presenting in primary care, of whom 2991 (84.0%) were eligible to enter the trial: 900 (30.1%) screened positive for hazardous or harmful drinking and 756 (84.0%) received a brief intervention. The sample was predominantly male (62%) and white (92%), and 34% were current smokers. <b>Interventions</b> Practices were randomised to three interventions, each of which built on the previous one: a patient information leaflet control group, five minutes of structured brief advice, and 20 minutes of brief lifestyle counselling. Delivery of the patient leaflet and brief advice occurred directly after screening and brief lifestyle counselling in a subsequent consultation. <b>Main outcome measures</b> The primary outcome was patients’ self reported hazardous or harmful drinking status as measured by the alcohol use disorders identification test (AUDIT) at six months. A negative AUDIT result (score &lt;8) indicated non-hazardous or non-harmful drinking. Secondary outcomes were a negative AUDIT result at 12 months, experience of alcohol related problems (alcohol problems questionnaire), health utility (EQ-5D), service utilisation, and patients’ motivation to change drinking behaviour (readiness to change) as measured by a modified readiness ruler. <b>Results</b> Patient follow-up rates were 83% at six months (n=644) and 79% at 12 months (n=617). At both time points an intention to treat analysis found no significant differences in AUDIT negative status between the three interventions. Compared with the patient information leaflet group, the odds ratio of having a negative AUDIT result for brief advice was 0.85 (95% confidence interval 0.52 to 1.39) and for brief lifestyle counselling was 0.78 (0.48 to 1.25). A per protocol analysis confirmed these findings. <b>Conclusions</b> All patients received simple feedback on their screening outcome. Beyond this input, however, evidence that brief advice or brief lifestyle counselling provided important additional benefit in reducing hazardous or harmful drinking compared with the patient information leaflet was lacking. <b>Trial registration</b> Current Controlled Trials ISRCTN06145674.
OC-076 Assessing knowledge of recognition and treatment of malnutrition among healthcare professionals
Authors: J G Powell-Tuck, J Connelly, H Haboubi, P Eadala
Journal: Gut (2012)

<h3>Introduction</h3> Malnutrition is common in hospitals, affecting up to 40% of patients.<sup>1</sup> Malnourished patients are vulnerable to ill health and are known to be at increased risk of complications during inpatient stays.<sup>2</sup> In 1999 Nightingale <i>et al</i> studied healthcare professionals9 knowledge of nutrition and despite recognition of its importance, understanding was found to be poor.<sup>3</sup> We aim to assess whether there has been any improvement in healthcare professionals9 knowledge of nutrition. <h3>Methods</h3> We approached healthcare staff from a tertiary referral centre and two district general hospitals to complete questionnaires to evaluate their understanding of assessment and treatment of under nutrition. The questionnaire contained 18 multiple choice questions in which staff were asked to select the correct answer from five possibilities. All questions were constructed from the 2006 NICE guidelines: Nutrition Support in Adults.<sup>2</sup> <h3>Results</h3> We obtained 114 responses from 67 doctors, 10 nurses, 12 pharmacists, 10 dietitians and 15 final year medical students. Dietitians9 average score was significantly higher than all other groups (81.7%, p&lt;0.001). Medical students scored lowest (25.4%). Pharmacists averaged 42.6%, doctors 35.8% and nurses 25.4%. There was no statistically significant difference between medical and surgical specialties (36.6% vs 33.6%, p=0.4). Consultants and registrars both averaged 43.8%, SHOs 32.4% and F1s 28.8%. Only 8.9% of doctors felt that they had received adequate nutritional training. 90.0% of nurses and 30.0% of doctors surveyed did not know how to calculate body mass index (BMI). Only 34.8% of doctors could correctly identify the BMI below which one would be considered underweight. 50.0% of doctors did not know an average person9s daily fluid requirements. Knowledge of parenteral feeding and the nutritional needs of septic patients was also particularly poor among all health professionals except dietitians. <h3>Conclusion</h3> These results suggest that basic understanding of nutrition remains poor. There needs to be greater emphasis on both undergraduate and postgraduate training in nutrition to ensure that recognition and treatment of malnutrition can be improved. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Barker L</b>, <i>et al.</i> Hospital malnutrition: prevalence, identification and impact on patients and the healthcare system. <i>Int J Environ Res Public Health</i> 2011;<b>8</b>:514–27. 2. <b>National Collaborating Centre for Acute Care</b>. <i>Nutritional Support in Adults, Oral Nutritional Support, Enteral Tube Feeding and Parenteral Nutrition</i>. London: National Collaborating Centre for Acute Care, 2006. 3. <b>Nightingale J</b>, Reeves J. Knowledge about the assessment and management of undernutrition: a pilot questionnaire in a UK teaching hospital. <i>Clin Nutr</i> 1999;<b>18</b>:23–7.
The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers
Authors: A. Ihbe-Heffinger, B. Ehlken, R. Bernard, K. Berger, C. Peschel, H.-G. Eichler, R. Deuson, J. Thödtmann, F. Lordick
Journal: Annals of Oncology (2004)
No Blood Testing in Relative Adrenal Insufficiency: Just Treat!
Authors: Djillali Annane
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

In their recent article, Djillali Annane and colleagues report that 83.5% of the septic patients they studied with the cosyntropin and metyrapone stimulation tests have primary or secondary adrenal insufficiency (respectively, 12.5 and 71%) (1). In their editorial in the same issue, Nuala J. Meyer and Jesse B. Hall conclude that we now have been provided with an elegant algorithm for the diagnosis of (relative) adrenal insufficiency in severe sepsis and septic shock (2). Given the fact that more than 80% of the septic patients studied appear to have (relative) adrenal insufficiency and that low-dose steroids have beneficial effects on hemodynamics and few side effects, we think it is even easier to skip these stimulation tests and just start low-dose steroid treatment (3–5)!
Generalized lichen nitidus successfully treated with an antituberculous agent
Authors: Y. Kubota, H. Kiryu, J. Nakayama
Journal: British Journal of Dermatology (2002)

Summary We describe a Japanese girl with generalized lichen nitidus. She had been exposed to Mycobacterium tuberculosis at 6 years of age via her teacher. At 8 years of age, she developed severe contact dermatitis on sun‐exposed areas after contact with Japanese lacquer trees. Shortly after, numerous tiny, shiny, flesh‐coloured papules developed over the upper part of her body. At 10 years of age, she was exposed to a school outbreak of M. tuberculosis. Her eruption showed no response to topical corticosteroids or oral tranilast, but most of the papules completely disappeared after she had received oral isoniazid for 6 months.