tbuckley/cabot-search huggingface dataset:
European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies
Authors: L Gossec, J S Smolen, C Gaujoux-Viala, Z Ash, H Marzo-Ortega, D van der Heijde, O FitzGerald, D Aletaha, P Balint, D Boumpas, J Braun, F C Breedveld, G Burmester, J D Cañete, M de Wit, H Dagfinrud, K de Vlam, M Dougados, P Helliwell, A Kavanaugh, T K Kvien, R Landewé, T Luger, M Maccarone, D McGonagle, N McHugh, I B McInnes, C Ritchlin, J Sieper, P P Tak, G Valesini, J Vencovsky, K L Winthrop, A Zink, P Emery
Journal: Annals of the Rheumatic Diseases (2011)

Background Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). Methods The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. Results Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. Conclusion These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.
The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry
Authors: S. O'Neill, J. Sweeney, C. C. Patterson, A. Menzies-Gow, R. Niven, A. H. Mansur, C. Bucknall, R. Chaudhuri, N. C. Thomson, C. E. Brightling, C. O'Neill, L. G. Heaney
Journal: Thorax (2014)

Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449). Significant predictors of costs were FEV<sub>1</sub>% predicted, location of care, maintenance oral corticosteroid treatment and body mass index. Treating individuals with severe refractory asthma presents a substantial cost to the health service.
Association of control and risk of severe asthma‐related events in severe or difficult‐to‐treat asthma patients
Authors: S. D. Sullivan, S. E. Wenzel, B. W. Bresnahan, B. Zheng, J. H. Lee, M. Pritchard, T. V. Kamath, S. T. Weiss
Journal: Allergy (2007)

Background: Clinical tools for predicting poor outcomes in asthma patients are lacking. This study investigated the association of asthma control and subsequent severe asthma‐related healthcare events in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Methods: The extent of asthma control problems was determined from baseline values of the Asthma Therapy Assessment Questionnaire (ATAQ). Patients self‐reported the presence of severe asthma‐related events at 6‐ and 12‐month follow up. Poisson regression models determined the adjusted association between baseline control and the likelihood of severe asthma‐related events. Results: At baseline, 2942 patients (mean age, 49.6 years; female, 71.9%) had an ATAQ score (no control problems, 17.0%; 1 control problem, 20.0%; 2 control problems, 30.8%; 3 or 4 control problems, 32.2%) and at least one severe asthma‐related event. After adjustment, subjects with three or four control problems were at greater risk for unscheduled office visits [relative risk (RR) = 2.8; 95% confidence interval (CI): 2.4–3.2], course of oral steroids (RR = 2.9; 95% CI: 2.5–3.3), emergency room visits (RR = 4.1; 95% CI: 2.7–6.2) or hospitalization (RR = 13.6; 95% CI: 7.4–24.9), vs no control problems. Progressively poorer levels of asthma control are associated with increasing risk of severe asthma‐related events. Conclusions: This study provides evidence of an association between poor asthma control and future severe asthma‐related healthcare events. A validated questionnaire may help clinicians identify patients requiring intervention to prevent future severe asthma‐related events.
Utilization of Non-Traditional and Alternative Therapies (CAM) in Inner City Under-Served Children with Asthma
Authors: K. Tai, M. Tsoukleris, V. Hsu, I.H. Zuckerman, M.E. Bollinger, K. Mudd, M. Donithan, A.M. Butz
Journal: Journal of Allergy and Clinical Immunology (2007)
NeuroD/BETA2 Gene G→A Polymorphism May Affect Onset Pattern of Type 1 Diabetes in Japanese
Authors: Satoru Yamada, Yoshiko Motohashi, Tatsuo Yanagawa, Taro Maruyama, Akira Kasuga, Hiroshi Hirose, Koichi Matsubara, Akira Shimada, Takao Saruta
Journal: Diabetes Care (2001)

The majority of type 1 diabetes is considered to be autoimmune with, for the most part, abrupt development. However, type 1 diabetes with slow onset, or the so-called slowly progressive type 1 diabetes or latent autoimmune diabetes in adults, has been recently recognized and is considered to be autoimmune-related. Although some investigators tried to explain the difference in onset pattern by the genetic background, including HLA type, it has not been established thus far. We hypothesized that the difference in onset pattern may relate to regeneration or differentiation of pancreatic beta-cells, and we therefore focused on the NeuroD/BETA2 gene, which encodes a transcription factor for the insulin gene and beta-cell differentiation.We examined the NeuroD/BETA2 gene polymorphism in 105 Japanese type 1 diabetic patients and in 122 nondiabetic Japanese subjects in a case-control study, and we stratified the patients according to their onset pattern and islet-associated autoantibody positivity.Regardless of the existence of islet-associated autoantibody, we found a significant difference in A allele frequency between type 1 diabetic patients with acute-onset type and control subjects. However, no difference was found between type 1 slow-onset diabetic patients and control subjects.These results support our hypothesis that NeuroD/BETA2 may affect the ability of regeneration of beta-cells, leading to a difference in the onset pattern and clinical course of type 1 diabetes.
“They who dream by day”: Parallels between Openness to Experience and dreaming
Authors: Colin G. DeYoung, Rachael G. Grazioplene
Journal: Behavioral and Brain Sciences (2013)

Individuals high in the personality trait Openness to Experience appear to engage spontaneously (during wake) in processes of elaborative encoding similar to those Llewellyn identifies in both dreaming and the ancient art of memory (AAOM). Links between Openness and dreaming support the hypothesis that dreaming is part of a larger process of cognitive exploration that facilitates adaptation to new experiences.
Self-reported skin complaints: validation of a questionnaire for population surveys
Authors: F. Dalgard, A. Svensson, J.O. Holm, J. Sundby
Journal: British Journal of Dermatology (2003)

Estimation of skin diseases in the community is challenging because we do not easily have access to the nonhealthcare-seeking population. A potential tool is a questionnaire asking for self-reported skin complaints. Such an instrument has not yet been developed.To validate a simple instrument assessing skin morbidity in the general adult population, to predict clinical skin morbidity from self-reported skin complaints.A questionnaire was drawn up in Norwegian and validated against clinical signs in two samples of an urban population, 100 healthcare-seeking adults in a dermatological clinic, and 100 nonhealthcare-seeking adults. A total self-reported score was calculated and validated against severity of clinical signs (no sign, trivial, moderate or severe). The inter-rater agreement was assessed in a small study including 16 patients from a dermatological clinic.The participation rate was 98%. The sensitivity was 61%, the specificity 69% and the positive predictive value 82% when the caseness criterion was any clinical sign of skin disease. The agreement was good between the two observers for clinical skin morbidity, with kappa = 0.67.This questionnaire is a simple tool to evaluate skin morbidity in an adult population. The use of self-reported complaints to predict clinical morbidity may be of value in quantifying and exploring skin diseases at the population level. Further studies are needed to improve the instrument. It is our intention to demonstrate the potential usefulness of this questionnaire in a forthcoming population survey in Norway.
SEQUENCE OF MORPHOLOGICAL CHANGES IN EPITHELIAL CELL CULTURES INFECTED WITH POLIOVIRUS
Authors: Magdalena Reissig, David W. Howes, Joseph L. Melnick
Journal: The Journal of Experimental Medicine (1956)

A sequential study is reported of the cytological changes induced in cultures of monkey kidney epithelial cells by poliovirus. The pattern of cytological changes was followed through a single cycle of virus multiplication. Morphological alterations were correlated with the appearance of new infective virus within the cells and in the culture fluid. Alteration of the chromatin pattern of the nucleus, and Type B acidophilic intranuclear inclusions, were seen as early as 4 hours after virus inoculation. Later wrinkling and shrivelling of the nucleus occurred, and eosinophilic cytoplasmic masses appeared. The rounded, pycnotic cell, customarily used as an index of the cytopathic response, was found only during the last stages of the infective process. On the basis of these changes, infected cells could be classified into six different types. Differential cell counts were made on the stained cultures, and the stage of cytopathic degeneration was correlated with the appearance of virus in the cells and in the culture fluid. Newly formed virus could be detected within the infected cells at about the same time that the first nuclear alterations and intranuclear inclusions were seen. The virus-induced morphological changes exhibited a specificity distinct from the classical pycnosis of autolytic degeneration.
Defective IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells
Authors: Masako Saito, Masayuki Nagasawa, Hidetoshi Takada, Toshiro Hara, Shigeru Tsuchiya, Kazunaga Agematsu, Masafumi Yamada, Nobuaki Kawamura, Tadashi Ariga, Ikuya Tsuge, Shigeaki Nonoyama, Hajime Karasuyama, Yoshiyuki Minegishi
Journal: The Journal of Experimental Medicine (2011)

Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by recurrent staphylococcal infections and atopic dermatitis associated with elevated serum IgE levels. Although defective differentiation of IL-17–producing CD4+ T cells (Th17) partly accounts for the susceptibility to staphylococcal skin abscesses and pneumonia, the pathogenesis of atopic manifestations in HIES still remains an enigma. In this study, we examined the differentiation and function of Th1, Th2, regulatory T cells (Treg cells), and dendritic cells (DCs) in HIES patients carrying either STAT3 or TYK2 mutations. Although the in vitro differentiation of Th1 and Th2 cells and the number and function of Treg cells in the peripheral blood were normal in HIES patients with STAT3 mutations, primary and monocyte-derived DCs showed defective responses to IL-10 and thus failed to become tolerogenic. When treated with IL-10, patient DCs showed impaired up-regulation of inhibitory molecules on their surface, including PD-L1 and ILT-4, compared with control DCs. Moreover, IL-10–treated DCs from patients displayed impaired ability to induce the differentiation of naive CD4+ T cells to FOXP3+ induced Treg cells (iTreg cells). These results suggest that the defective generation of IL-10–induced tolerogenic DCs and iTreg cells may contribute to inflammatory changes in HIES.
Endocrine Receptors in Relation to Cancer
Authors: J. T. Shirlaw
Journal: BMJ (1947)

and also in primary suppurative meningitis due to the pneumo- coccus and nmany due to H. influenzae (Pfeiffer) is not ques- tioned, but in meningococcal cases its superiority to oral and systemic sulphonamides has not been established, and its use is attended with unjustifiable risks.-Iam, etc.,
Cubilin Is Essential for Albumin Reabsorption in the Renal Proximal Tubule
Authors: Sabine Amsellem, Jakub Gburek, Ghislaine Hamard, Rikke Nielsen, Thomas E. Willnow, Olivier Devuyst, Ebba Nexo, Pierre J. Verroust, Erik I. Christensen, Renata Kozyraki
Journal: Journal of the American Society of Nephrology (2010)

Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubule. This process involves two interacting receptors, megalin and cubilin, which form a complex with amnionless. Whether these proteins function in parallel or as part of an integrated system is not well understood. Here, we report the renal effects of genetic ablation of cubilin, with or without concomitant ablation of megalin, using a conditional Cre-loxP system. We observed that proximal tubule cells did not localize amnionless to the plasma membrane in the absence of cubilin, indicating a mutual dependency of cubilin and amnionless to form a functional membrane receptor complex. The cubilin-amnionless complex mediated internalization of intrinsic factor-vitamin B12 complexes, but megalin considerably increased the uptake. Furthermore, cubilin-deficient mice exhibited markedly decreased uptake of albumin by proximal tubule cells and resultant albuminuria. Inactivation of both megalin and cubilin did not increase albuminuria, indicating that the main role of megalin in albumin reabsorption is to drive the internalization of cubilin-albumin complexes. In contrast, cubulin deficiency did not affect urinary tubular uptake or excretion of vitamin D-binding protein (DBP), which binds cubilin and megalin. In addition, we observed cubilin-independent reabsorption of the "specific" cubilin ligands transferrin, CC16, and apoA-I, suggesting a role for megalin and perhaps other receptors in their reabsorption. In summary, with regard to albumin, cubilin is essential for its reabsorption by proximal tubule cells, and megalin drives internalization of cubilin-albumin complexes. These genetic models will allow further analysis of protein trafficking in the progression of proteinuric renal diseases.
Adult rabbit cardiomyocytes undergo hibernation-like dedifferentiation when co-cultured with cardiac fibroblasts
Authors: G Dispersyn
Journal: Cardiovascular Research (2001)

Little is known about the causal factors which induce the typical structural changes accompanying cardiomyocyte dedifferentiation in vivo such as in chronic hibernating myocardium. For identifying important factors involved in cardiomyocyte dedifferentiation, as seen in chronic hibernation, an in vitro model mimicking those morphological changes, would be extremely helpful.Adult rabbit cardiomyocytes were co-cultured with cardiac fibroblasts. The typical changes induced by this culturing paradigm were investigated using morphometry, electron microscopy and immunocytochemical analysis of several structural proteins, which were used as dedifferentiation markers, i.e., titin, desmin, cardiotin and alpha-smooth muscle actin.Close apposition of fibroblasts with adult rabbit cardiomyocytes induced hibernation-like dedifferentiation, similar to the typical changes seen in chronic hibernation in vivo. Both changes in ultrastructure and in the protein expression pattern of dedifferentiation markers as seen in chronic hibernating myocardium were seen in the co-cultured cardiomyocytes.Hibernation-like changes can be induced by co-culturing adult rabbit cardiomyocytes with fibroblasts. This cellular model can be a valuable tool in identifying and characterizing the pathways involved in the dedifferentiation phenotype in vivo, and already suggests that many of the structural changes accompanying dedifferentiation are not per se dependent on a decreased oxygen availability.
Integrative Genomic Analyses of Sporadic Clear Cell Renal Cell Carcinoma Define Disease Subtypes and Potential New Therapeutic Targets
Authors: Vijay R. Dondeti, Bradley Wubbenhorst, Priti Lal, John D. Gordan, Kurt D'Andrea, Edward F. Attiyeh, M. Celeste Simon, Katherine L. Nathanson
Journal: Cancer Research (2011)

Sporadic clear cell renal cell carcinoma (ccRCC), the most common type of adult kidney cancer, is often associated with genomic copy number aberrations on chromosomes 3p and 5q. Aberrations on chromosome 3p are associated with inactivation of the tumor suppressor gene von-Hippel Lindau (VHL), which activates the hypoxia-inducible factors HIF1α and HIF2α. In contrast, ccRCC genes on chromosome 5q remain to be defined. In this study, we conducted an integrated analysis of high-density copy number and gene expression data for 54 sporadic ccRCC tumors that identified the secreted glycoprotein STC2 (stanniocalcin 2) and the proteoglycan VCAN (versican) as potential 5q oncogenes in ccRCCs. In functional assays, STC2 and VCAN each promoted tumorigenesis by inhibiting cell death. Using the same approach, we also investigated the two VHL-deficient subtypes of ccRCC, which express both HIF1α and HIF2α (H1H2) or only HIF2α (H2). This analysis revealed a distinct pattern of genomic aberrations in each group, with the H1H2 group displaying, on average, a more aberrant genome than the H2 group. Together our findings provide a significant advance in understanding ccRCCs by offering a molecular definition of two subtypes with distinct characteristics as well as two potential chromosome 5q oncogenes, the overexpression of which is sufficient to promote tumorigenesis by limiting cell death.
Regulation of hormone-sensitive calcium influx by the adenylyl cyclase system in renal epithelial cells.
Authors: K Kitamura, R T Miller
Journal: Journal of Clinical Investigation (1994)

To study signaling pathways regulated by alpha s and alpha i1 in renal epithelial cells, we expressed mutant, activated forms of alpha s and alpha i1 in a continuous proximal tubule cell line (MCT cells). alpha sQ227L increased cAMP production, and alpha ilQ204L reduced forskolin-sensitive cAMP production. alpha ilQ204L increased and alpha sQ227L decreased bradykinin-induced Ca influx across the cell membrane, but neither mutant affected bradykinin-stimulated intracellular Ca release or basal Ca influx. Bradykinin-stimulated Ca influx was reduced by dibutyryl cAMP, isoproterenol, and forskolin. Expression of a mutant regulatory type I subunit for cAMP-dependent protein kinase with reduced affinity for cAMP and treatment with KT-5720, a specific cAMP-dependent protein kinase inhibitor, enhanced Ca influx to a degree similar to that in cells expressing alpha ilQ204L. Bradykinin-stimulated c-fos mRNA expression is partially dependent on extracellular Ca. alpha sQ227L reduced and alpha ilQ204L enhanced bradykinin-stimulated c-fos expression. Consequently, in bradykinin-stimulated cells, the adenylyl cyclase system regulates Ca influx through cAMP-dependent protein kinase, but not intracellular Ca release. Furthermore, the Ca influx mechanism acts as an integrator of two signaling pathways such that Ca-dependent signals are damped by activators of adenylyl cyclase and enhanced by inhibitors of adenylyl cyclase.
Niche construction: A pervasive force in evolution?
Authors: Wim J. van der Steen
Journal: Behavioral and Brain Sciences (2000)

Industrial melanism, according to the traditional explanation, amounts to niche construction since it involves changes in predation pressure. Indeed, it would be difficult to imagine selection without niche construction. This cannot be what Laland, Odling-Smee &amp; Feldman mean. They offer convincing examples, but they should provide a better definition of “niche construction” to indicate how their view supplements traditional evolutionary biology.
D,L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase deficiency (MADD)
Authors: Johan LK Van Hove, Stephanie Grünewald, Jaak Jaeken, Philippe Demaerel, Peter E Declercq, Pierre Bourdoux, Klary Niezen-Koning, John E Deanfeld, James V Leonard
Journal: The Lancet (2003)
Liposomal-entrapped doxorubicin: an active agent in AIDS-related Kaposi's sarcoma.
Authors: M Harrison, D Tomlinson, S Stewart
Journal: Journal of Clinical Oncology (1995)

PURPOSE A phase II study was performed of single-agent liposomally entrapped doxorubicin ([LED] Doxil; Liposome Technology Inc, Menlo Park, CA) against locally advanced cutaneous/systemic AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS Thirty-four patients with AIDS-related advanced cutaneous/systemic KS were treated with 20 mg/m2 of LED every 3 weeks on an outpatient basis. The median age was 39 years and the median Karnofsky score was 70. All patients had poor prognostic disease as judged by AIDS Clinical Trials Group (ACTG) criteria. Nineteen of 34 patients had received prior chemotherapy for KS, although no patient had received prior anthracyclines. RESULTS An overall response rate of 73.5% (25 of 34) was observed. Partial responses (PRs) occurred in 67.7% (23 of 34) and complete responses (CRs) in 5.8% (two of 34). In patients who had received previous chemotherapy, the response rate was 68.4% (13 of 19), and all responses were PRs. The median time to response was 6 weeks. The median duration of response was 9 weeks. Toxicity according to World Health Organization (WHO) criteria was as follows: neutropenia (grade &gt; or = 3), 34%; alopecia (grade 1 only), 9%; and nausea and vomiting (grade 1), 18%. One patient died of heart failure, which was not considered to be anthracycline-induced. CONCLUSION LED appears to be highly active against AIDS-related KS. The major toxicity is neutropenia, which seems to be progressive in patients who receive several cycles of therapy. Comparative studies of LED versus conventional chemotherapy are needed.
Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study
Authors: S. Mathoulin-Pélissier, C. Chevreau, C. Bellera, E. Bauvin, M. Savès, P. Grosclaude, S. Albert, J. Goddard, S. Le Guellec, M. Delannes, B.N. Bui, J. Mendiboure, E. Stoeckle, J.M. Coindre, G. Kantor, M. Kind, A. Cowppli-Bony, S. Hoppe, A. Italiano
Journal: Annals of Oncology (2013)