tbuckley/cabot-search huggingface dataset:
From the Museum: the Art of Thinking. Part Nine: Imagination
Authors: Tom Kotsimbos
Journal: European Respiratory Journal (2014)

The Persistence of Memory is an unforgettable dreamscape composition that plays with the timelessness of time and juxtaposes photo-like reality painting with what can only be imagined. Everywhere hardness is juxtaposed with softness and transformation abounds (fading deterioration of each element alone versus the enduring celebrity of the melting clocks as an iconic whole). The sur- reality of time passed in all its phases is explored within the framed time of a clock face. At the top of the painting is a sun-streak underlined blue sky that could be either the sunset or sunrise of 6 o'clock in three of the four solidified melting watches. Immediately, hope and despair are as one. At 2 o'clock is a rocky Catalonian protrusion (Dali) with a lone smooth pebble isolated in front (Gala, his muse and mistress). At 3 o'clock and extending centrally is a lived-in, well-moustached, long eye-lashed self-portrait, whereas at 7–11 o'clock are several natural and man-made structures with dulling reflective surfaces. The water-cool blue that is bathed in the sunlight (consciousness) contrasts with the earth-warm brown background that is featureless and variably shaded (unconsciousness). The latter surrounds the four pocket watches that form the central motif of this picture and which represent the different phases of time contextualised by Dali-nean imagination.
Personalized management of essential thrombocythemia—application of recent evidence to clinical practice
Authors: A Tefferi, T Barbui
Journal: Leukemia (2013)

The World Health Organization (WHO) classification system has recently strengthened the diagnostic criteria for essential thrombocythemia (ET) by lowering the threshold platelet count, underscoring its morphological distinction from early/prefibrotic myelofibrosis (MF) and incorporating molecular markers of clonality. The International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) examined the clinical relevance of this process in 1104 cases of locally diagnosed 'ET' and showed worse overall, leukemia-free and fibrosis-free survival, and a higher risk of bleeding in early/prefibrotic MF (n=180) vs WHO-defined ET (n=891). The risk of thrombosis was similar between the two entities and, in WHO-defined ET, was predicted by thrombosis history, older age, cardiovascular risk factors and JAK2V617F. A prognostic model based on these risk factors identified patient groups in ET with residual risk of thrombosis, despite treatment with conventional therapy. The main objectives of the current perspective are to underscore the prognostic importance of morphological confirmation in the diagnosis of ET and provide management recommendations, in both WHO-defined ET and early/prefibrotic MF, based on observations from the aforementioned IWG-MRT and other studies. In so doing, we are fully cognizant and sympathetic of the fact that some of our recommendations need to be tested in prospective controlled studies.
Establishing a standard definition for child overweight and obesity worldwide: international survey
Authors: T. J Cole
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points. <b>Design:</b> International survey of six large nationally representative cross sectional growth studies. <b>Setting:</b> Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States <b>Subjects:</b> 97 876 males and 94 851 females from birth to 25 years of age <b>Main outcome measure:</b> Body mass index (weight/height2). <b>Results:</b> For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m2 for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years. <b>Conclusions:</b> The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
Immunomagnetic Enrichment, Genomic Characterization, and Prognostic Impact of Circulating Melanoma Cells
Authors: Anja Ulmer, Oleg Schmidt-Kittler, Jörg Fischer, Ulf Ellwanger, Gernot Rassner, Gert Riethmüller, Gerhard Fierlbeck, Christoph A. Klein
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The finding of melanoma cells in the peripheral blood, thus far mainly inferred from the PCR-based demonstration of tyrosinase mRNA, has been associated with metastatic melanoma. Neither the malignant nature nor the prognostic significance of circulating cells could be established. To address this question, we analyzed immunomagnetically isolated circulating melanoma cells for chromosomal aberrations and performed a clinical follow-up study of the enrolled patients. Experimental Design: In a prospective study, blood samples were taken from 164 melanoma patients and 50 donors without malignant disease. Circulating melanoma cells were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. To prove the malignant origin of the positive cells and to define their chromosomal aberrations, we analyzed the genomes of 15 individually isolated cells from seven patients by single-cell comparative genomic hybridization (SCOMP). Results: Absolute and relative frequencies of circulating melanoma cells were associated with stage and with the presence or absence of detectable tumor. The detection of two or more cells correlated significantly with a reduced survival of patients with metastatic melanoma. All of the cells that were analyzed by SCOMP displayed multiple chromosomal changes and carried aberrations typical for melanoma. Conclusions: Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.
Point Mutation in Essential Genes with Loss or Mutation of the Second Allele
Authors: Gabriele B. Beck-Engeser, Paul A. Monach, Dominik Mumberg, Farley Yang, Sherry Wanderling, Karin Schreiber, Rafael Espinosa, Michelle M. Le Beau, Stephen C. Meredith, Hans Schreiber
Journal: The Journal of Experimental Medicine (2001)

Antigens that are tumor specific yet retained by tumor cells despite tumor progression offer stable and specific targets for immunologic and possibly other therapeutic interventions. Therefore, we have studied two CD4(+) T cell-recognized tumor-specific antigens that were retained during evolution of two ultraviolet-light-induced murine cancers to more aggressive growth. The antigens are ribosomal proteins altered by somatic tumor-specific point mutations, and the progressor (PRO) variants lack the corresponding normal alleles. In the first tumor, 6132A-PRO, the antigen is encoded by a point-mutated L9 ribosomal protein gene. The tumor lacks the normal L9 allele because of an interstitial deletion from chromosome 5. In the second tumor, 6139B-PRO, both alleles of the L26 gene have point mutations, and each encodes a different tumor-specific CD4(+) T cell-recognized antigen. Thus, for both L9 and L26 genes, we observe "two hit" kinetics commonly observed in genes suppressing tumor growth. Indeed, reintroduction of the lost wild-type L9 allele into the 6132A-PRO variant suppressed the growth of the tumor cells in vivo. Since both L9 and L26 encode proteins essential for ribosomal biogenesis, complete loss of the tumor-specific target antigens in the absence of a normal allele would abrogate tumor growth.
Gq-Dependent Signaling Upregulates COX2 in Glomerular Podocytes
Authors: Liming Wang, Patrick J. Flannery, Paul B. Rosenberg, Timothy A. Fields, Robert F. Spurney
Journal: Journal of the American Society of Nephrology (2008)

Accumulating evidence suggests that upregulation of cyclooxygenase 2 (COX2) in glomerular podocytes promotes podocyte injury. Because Gq signaling activates calcineurin and calcineurin-dependent mechanisms are known to mediate COX2 expression, this study investigated the role of Gqalpha in promoting COX2 expression in podocytes. A constitutively active Gq alpha subunit tagged with the TAT HIV protein sequence was introduced into an immortalized podocyte cell line by protein transduction. This stimulated inositol trisphosphate production, activated an nuclear factor of activated T cells-responsive reporter construct, and enhanced levels of both COX2 mRNA and protein compared with cells treated with a Gq protein lacking the TAT sequence. Induction of COX2 was associated with increased prostaglandin E(2) production and podocyte death, both of which were attenuated by selective COX2 inhibition. In vivo, levels of COX2 mRNA and protein were significantly enhanced in podocytes from transgenic mice that expressed podocyte-targeted constitutively active Gqalpha compared with nontransgenic littermates. These data suggest that Gq-dependent signaling cascades stimulate calcineurin and, in turn, upregulate COX2 mRNA and protein, increase eicosanoid production, and cause podocyte injury.
Insulin Resistance, Cystatin C, and Mortality Among Older Adults
Authors: Ian H. de Boer, Ronit Katz, Michel B. Chonchol, Linda F. Fried, Joachim H. Ix, Bryan Kestenbaum, Kenneth J. Mukamal, Carmen A. Peralta, David S. Siscovick
Journal: Diabetes Care (2012)

OBJECTIVE Insulin resistance is a risk factor for cardiovascular and noncardiovascular diseases. Impaired kidney function is linked with insulin resistance and may affect relationships of insulin resistance with health outcomes. RESEARCH DESIGN AND METHODS We performed a cohort study of 3,138 Cardiovascular Health Study participants (age ≥65 years) without diabetes. Insulin sensitivity index (ISI) was calculated from fasting and 2-h postload insulin and glucose concentrations. Associations of ISI and fasting insulin concentration with all-cause mortality were tested using Cox proportional hazards models, adjusting for demographic variables, prevalent cardiovascular disease, lifestyle variables, waist circumference, and LDL cholesterol. Subsequent models were additionally adjusted for or stratified by glomerular filtration rate estimated using serum cystatin C (eGFR). RESULTS A total of 1,810 participants died during the 14.7-year median follow-up. Compared with the highest quartile of ISI, the lowest quartile (most insulin resistant) was associated with 21% (95% CI 6–41) and 11% (−3 to 29) higher risks of death without and with adjustment for eGFR, respectively. Compared with the lowest quartile of fasting insulin concentration, the highest quartile was associated with 22% (4–43) and 4% (−12 to 22) higher risks of death without and with adjustment for eGFR, respectively. Similar attenuation by eGFR was observed when blood pressure, triglycerides, HDL cholesterol, and C-reactive protein were included in models. CONCLUSIONS Insulin resistance measured as ISI or fasting insulin concentration is associated with increased risk of death among older adults, adjusting for conventional confounding characteristics. Impaired kidney function may mediate or confound this relationship.
Adalimumab effectively reduces the signs and symptoms of active ankylosing spondylitis in patients with total spinal ankylosis
Authors: D van der Heijde, A L Pangan, M H Schiff, J Braun, M Borofsky, J Torre, J C Davis, R L Wong, H Kupper, E Collantes
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To evaluate the long-term safety and efficacy of adalimumab in patients with ankylosing spondylitis (AS) and total spinal ankylosis (TSA). <h3>Design:</h3> Patients (n = 315) with active AS were randomised in a 2:1 ratio to receive adalimumab 40 mg every other week or placebo for 24 weeks followed by open-label adalimumab for up to 5 years. Two-year efficacy and safety data for 11 patients with investigator-defined TSA were evaluated. The primary end point was the ASsessment in AS International Working Group criteria for 20% improvement (ASAS20) at Week 12. On or after Week 12, ASAS20 non-responders could switch to open-label adalimumab. Other efficacy measurements included ASAS40, ASAS 5/6, ASAS partial remission, and 50% improvement in the Bath AS Disease Activity Index (BASDAI 50). <h3>Results:</h3> 6 of 11 TSA patients were randomised to adalimumab and 5 to placebo. At Week 12, 50% of the adalimumab-treated patients achieved an ASAS20 response and 33% achieved an ASAS40, ASAS 5/6 and BASDAI 50. No placebo-treated patients achieved any response criteria at Week 12. 4 placebo- and 2 adalimumab-treated patients switched to open-label adalimumab before Week 24. After 1 year of adalimumab treatment, 8 of 11 patients achieved an ASAS20 response. After 2 years, 6 of the remaining 8 patients with TSA reported an ASAS20 response. There were no serious adverse events or adverse event-related study discontinuations. <h3>Conclusion:</h3> In patients with TSA, adalimumab treatment resulted in rapid and clinically significant improvement in the signs and symptoms of active disease. Adalimumab effectiveness and safety were sustained for at least 2 years. <h3>Trial registration number:</h3> NCT00085644.
Competition for hydrogen by human faecal bacteria: evidence for the predominance of methane producing bacteria.
Authors: A Strocchi, J K Furne, C J Ellis, M D Levitt
Journal: Gut (1991)

Studies of sludge have shown that some species of sulphate reducing bacteria outcompete methane producing bacteria for the common substrate H2. A similar competition may exist in human faeces where the methane (CH4) producing status of an individual depends on the faecal concentration of sulphate reducing bacteria. To determine if non-methanogenic faeces outcompete CH4 producing faeces for H2, aliquots of each type of faeces were incubated alone or mixed together, with or without addition of 10% H2 and/or 20 mmol/l sulphate. Methane producing faeces consumed H2 significantly more rapidly and reduced faecal H2 tension to a lower value compared with non-methanogenic faeces. The mixture of the two types of faeces yielded significantly more CH4 than CH4 producing faeces alone (mean (SD) 8.5 (1.3) v 2.9 (0.45) mmol/l of homogenate per 24 hours, p less than 0.01). Faecal sulphide concentrations were similar in CH4 producing and non-producing homogenates both before and after 24 hours of incubation. The addition of sulphate to the homogenates did not significantly influence CH4 production or sulphide formation. Our results suggest that in human faeces methane producing bacteria outcompete other H2 consuming bacteria for H2.
Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663
Authors: Pan Jian, Zhao Wen Li, Tao Yan Fang, Wang Jian, Zhou Zhuan, Liao Xin Mei, Wu Shui Yan, Ni Jian
Journal: Journal of Hematology & Oncology (2011)

Differentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized. Using bioinformatics and in vitro experiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation. Six microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV) backbone incorporating the spleen focus forming virus (SFFV-F) promoter to drive miR-663 expression, as the CMV (Cytomegalovirus) promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiation in vitro. Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies
Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis; an association with disease activity at 28 and 52 weeks of follow-up
Authors: Erik H Vogelzang, Eva L Kneepkens, Michael T Nurmohamed, Arno W R van Kuijk, Theo Rispens, Gertjan Wolbink, Charlotte L M Krieckaert
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To investigate the relationship between antidrug antibodies (ADA), adalimumab concentrations and clinical response in patients with psoriatic arthritis (PsA) during 52 weeks of follow-up. <h3>Methods</h3> This prospective cohort study included 103 consecutive patients with PsA. Disease Activity Score of 28 joints (DAS28), Erythrocyte Sedimentation Rate, C reactive protein and Psoriasis Area and Severity Index were assessed. Adalimumab concentrations and ADA were measured in serum trough samples, using an ELISA and a radio immunoassay, respectively. <h3>Results</h3> Adalimumab concentrations were significantly lower at 28 and 52 weeks in patients with detectable ADA compared with patients without detectable ADA (at week 28: 1.3 mg/L (IQR 0.0–3.2) versus 8.7 mg/L (IQR 5.7–11.5), p&lt;0.001; at week 52: 0.9 mg/L (IQR 0.0–2.9) vs 9.4 mg/L (IQR 5.7–12.1), p=0.0001). DAS28 at 28 weeks (2.16 vs 2.95, p=0.023) and 52 weeks (2.19 vs 2.95, p=0.024) showed a significant difference; patients with detectable ADA had a poorer clinical outcome than patients without. <h3>Conclusions</h3> Patients with detectable ADA had lower adalimumab concentrations and a significantly poorer clinical outcome compared with patients in whom ADA were not detected.
Somatostatin-Induced Changes in Insulin and Glucagon Secretion in Normal and Diabetic Dogs
Authors: Hideo Sakurai, Richard Dobbs, Roger H. Unger
Journal: Journal of Clinical Investigation (1974)

In conscious dogs intravenously infused somatostatin (3.3 mug per min for 1 h) caused prompt and sustained declines in mean plasma insulin and glucagon, even during alanine infusion and intraduodenal casein hydrolysate feeding; plasma glucose declined, but not significantly. 6.7 mug per min of somatostatin significantly lowered pancreatoduodenal vein glucagon and insulin within 2.5 min and profoundly suppressed their secretion throughout the infusion. Consistent bihormonal suppression occurred at rates as low as 24 ng per kg per min, but was variable at 12 and 2.4 ng per kg per min. When somatostatin-induced (3.3 mug per min) hypoglucagonemia was corrected by exogenous glucagon, hyperglycemia occurred. In dogs with long-standing insulin-requiring alloxan diabetes 3.3 mug per min of somatostatin suppressed glucagon to 55 pg per ml throughout the 30-min infusion and lowered glucose by 36.4+/-6.1 mg per dl, about 1 mg per dl per min. Glucagon suppression was maintained despite alanine infusion, and glucose, which rose 29 mg per dl during alanine infusion without somatostatin, declined 58 mg per dl in the somatostatin-treated diabetic dogs despite alanine. Continuous infusion of somatostatin for 24 h in five insulin-requiring alloxan-diabetic dogs suppressed glucagon and lowered glucose significantly, usually to below normal. It is concluded that in normal dogs pharmacologic doses of somatostatin virtually abolish insulin and glucagon secretion in the basal state and during hyperaminoacidemia. Hyperglycemia occurs during somatostatin-induced insulin lack only if hypoglucagonemia is corrected. Somatostatin suppresses glucagon in diabetic dogs and lowers their plasma glucose approximately 1 mg per dl per min, even when the gluconeogenic substrate alanine is abundant. Glucagon suppression can be maintained for several hours in such dogs and hyperglycemia is thereby reduced.
Nosocomial and community-acquired Legionella pneumonia: clinical comparative analysis
Authors: ML Pedro-Botet, M Sabria-Leal, M Haro, C Rubio, G Gimenez, N Sopena, J Tor
Journal: European Respiratory Journal (1995)

Previous reports have suggested that nosocomial and community Legionella pneumonia cases are similar. However, community and hospital characteristics, such as aquatic environment, antibiotic pressure (usage) and populations, are quite different, leading to the suspicion that Legionella infection may differ in the two settings. Univariate and multivariate analyses were performed to compare demographic data, risk factors, clinical, radiological and outcome data between 125 nosocomial and 33 community-acquired cases of Legionella pneumophila infection. Patients in the nosocomially acquired Legionella pneumonia (NALP) group were older than those in the community-acquired Legionella pneumonia (CALP) group. Univariate analysis showed that smoking habit, cough, thoracic pain, and extrapulmonary manifestations were more prevalent in the CALP group, whilst chronic lung disease and cancer were more prevalent in the NALP group. Moreover, patients in the NALP group were more likely to have received oxygen and corticosteroid therapy and also to have altered creatinine values than patients in the CALP group, whilst more patients in the latter group had altered alanine amino-transferase values. However, multivariate analysis failed to confirm most of these differences. Smoking habit and blood creatinine levels were the only variables remaining significant. In conclusion, demographic, clinical, laboratory, radiological and outcome data in nosocomial and community-acquired Legionella pneumonia are quite similar.
Strong Association Between Time Watching Television and Blood Glucose Control in Children and Adolescents With Type 1 Diabetes
Authors: Hanna D. Margeirsdottir, Jakob R. Larsen, Cathrine Brunborg, Leiv Sandvik, Knut Dahl-Jørgensen
Journal: Diabetes Care (2007)

To examine the relationship between blood glucose control and the time spent watching television in Norwegian children and adolescents with type 1 diabetes in a population-based study.A total of 538 children and adolescents from 9 hospitals in the eastern part of Norway participated in the study; 70% of eligible subjects participated. The time spent watching television and time using a computer was recorded separately by interview together with clinical data. Mean (+/-SD) age was 13.1 +/- 3.7 years, mean diabetes duration was 5.4 +/- 3.4 years, and mean A1C was 8.6 +/- 1.3% (reference range 4.1-6.4).Sixty-two patients (11%) watched television <1 h daily (mean A1C 8.2 +/- 0.9%), 189 patients (35%) watched television between 1 and 2 h daily (8.4 +/- 1.2%), 166 patients (31%) watched television 2-3 h daily (8.7 +/- 1.4%), 75 patients (14%) watched television 3-4 h daily (8.8 +/- 1.2%), and 46 patients (9%) watched television > or =4 h daily (9.5 +/- 1.6%). This trend was highly significant (P < 0.001). The association between television viewing and A1C remained significant, even after adjusting for age and BMI and insulin dose. No correlation between A1C and the use of a personal computer was observed.Extensive television watching is associated with poor blood glucose control in children and adolescents with type 1 diabetes.
Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer
Authors: Michael Thomas, Christian Rübe, Petra Hoffknecht, Hans N Macha, Lutz Freitag, Albert Linder, Norman Willich, Michael Hamm, Gerhard W Sybrecht, Dieter Ukena, Karl-Matthias Deppermann, Cornelia Dröge, Dorothea Riesenbeck, Achim Heinecke, Cristina Sauerland, Klaus Junker, Wolfgang E Berdel, Michael Semik
Journal: The Lancet Oncology (2008)