tbuckley/cabot-search huggingface dataset:
Adult ependymal tumors: prognosis and the M. D. Anderson Cancer Center experience
Authors: T. S. Armstrong, E. Vera-Bolanos, B. N. Bekele, K. Aldape, M. R. Gilbert
Journal: Neuro-Oncology (2010)

Ependymomas in adults are rare and often misdiagnosed. This study reports on a series of adult patients with confirmed ependymoma treated at The University of Texas M. D. Anderson Cancer Center (MDACC). Patients aged >17 and with ependymoma were identified, and clinical data were collected by retrospective chart review. Descriptive statistics were used to describe the clinical data, Kaplan–Meier methods were used to generate survival curves, and Cox proportional hazards models were used to evaluate the association of clinical characteristics with survival. This series included 123 adult patients [51% male; median age 39 years (18–72)]. Forty had tumors in the brain, 80 in the spine, and 3 had both. The majority were Grade I/II lesions (108) vs Grade III (anaplastic; 15). Eighteen patients had tumors that were reclassified as ependymal tumors at MDACC. The most common presenting symptom was pain, with an average of 4 symptoms reported prior to diagnosis. Sixty-three percent of patients had a gross total resection, and 49% received radiation therapy. Average follow-up was 5.5 years, and 13% had died. Median time to recurrence was 21 months (Grade II) brain and 18 months (Grade III). Worse outcome measured by overall and progression-free survival were associated with brain location (P = .01, P = .04) and tumor anaplasia (P = .0025, P = .001). An MIB-1 > 10 was associated with worse outcome (P = .03). Tumor grade and brain location are associated with a worse prognosis. Reclassification of ependymoma by neuropathologists is common. Results of this study have lead to a multicenter study to further define important diagnostic and prognostic variables for adults with ependymoma.
Circulating Tumor Cells and Bone Marrow Micrometastasis
Authors: Catherine Alix-Panabières, Sabine Riethdorf, Klaus Pantel
Journal: Clinical Cancer Research (2008)

Abstract Sensitive immunocytochemical and molecular assays allow the detection of single circulating tumor cells (CTC) in the peripheral blood and disseminated tumor cells (DTC) in the bone marrow as a common and easily accessible homing organ for cells released by epithelial tumors of various origins. The results obtained thus far have provided direct evidence that tumor cell dissemination starts already early during tumor development and progression. Tumor cells are frequently detected in the blood and bone marrow of cancer patients without clinical or even histopathologic signs of metastasis. The detection of DTC and CTC yields important prognostic information and might help to tailor systemic therapies to the individual needs of a cancer patient. In the present review, we provide a critical review of (a) the current methods used for detection of CTC/DTC and (b) data on the molecular characterization of CTC/DTC with a particular emphasis on tumor dormancy, cancer stem cell theory, and novel targets for biological therapies; and we pinpoint to (c) critical issues that need to be addressed to establish CTC/DTC measurements in clinical practice.
The Irritable Bowel Syndrome: A Disease or a Response? Discussion Paper
Authors: M A Eastwood, J Eastwood, M J Ford
Journal: Journal of the Royal Society of Medicine (1987)

The irritable bowel syndrome is a problem commonly found in the population as a whole, in general practice and in general hospital and specialist gastroenterological clinical practice. A population survey found that 14% of those interviewed exhibited symptoms of the irritable bowel syndrome but did not present to their general practitioner. In the gastroenterology clinic it is said to represent approximately one-third to one-half of referrals 1 .
Experience with lung neuroendocrine tumors in three Portuguese hospitals
Authors: Gustavo Coimbra dos Reis, Vanda Areias, Joana Pimentel, Tiago Abreu, Rita Barata, Cristina Rodrigues, Margarida Felizardo, Encarnação Teixeira, Agostinho Costa, Renato Sotto-Mayor, Maria Teresa Almodovar
Journal: European Respiratory Journal (2012)

Introduction : Lung neuroendocrine tumors (NET) are rare and heterogeneous, with wide range of aggressiveness. Aim : Describe clinical and epidemiologic characteristics, stage, treatment and survival of patients with lung NET according to histological group -[typical carcinoid (TC), atypical carcinoid (AT), large cell neuroendocrine carcinoma (NEC). Methods: Retrospective longitudinal, multicenter study analyzing files of patients diagnosed with NET from 2005 to 2010. Small cell carcinoma was excluded. Comparisons among groups were done with X2. Survival curves were generated using Kaplan-Meier method. Results : 137 patients were included, mean age (SD) 59 (± 14) years; 71 (52%) male; 82 (60%) non-smokers. Histological classification: 54 TC, 49 NEC and 34 AC. Table below describes patients' characteristics. Follow-up ranged from 1 to 78 months. Twenty seven patients (20%) died, 1 in TC, 2 in AC, 23 in NEC. The median overall survival (OS) calculated for NEC was 42 months, for other patients median OS has not yet been reached. Conclusion: In our series few patients were asymptomatic, none had carcinoid syndrome and most had symptoms other than those due to endobronchial involvement, which was found in less than 50% pts. Most frequent histological pattern was TC. NEC was most aggressive, with more advanced stage and a higher mortality. Surgery was the most frequent treatment. Prognosis is generally good, although follow-up is still short.

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The Prevalence of Nonadherence in Difficult Asthma
Authors: Jacqueline Gamble, Michael Stevenson, Elizabeth McClean, Liam G. Heaney
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

With the advent of new and expensive therapies for severe refractory asthma, targeting the appropriate patients is important. An important issue is identifying nonadherence with current therapies. The extent of nonadherence in a population with difficult asthma has not been previously reported.To examine the prevalence of nonadherence to corticosteroid medication in a population with difficult asthma referred to a Specialist Clinic and to examine the relationship of poor adherence to asthma outcome.General practitioner prescription refill records for the previous 6 months for inhaled combination therapy and short-acting beta-agonists were compared with initial prescriptions and expressed as a percentage. Blood plasma prednisolone and cortisol assay levels were used to examine the utility of these measures in assessing adherence to oral prednisolone. Patient demographics, hospital admissions, lung function, oral prednisolone courses, and quality of life data were analyzed to indentify the variables associated with reduced medication adherence.A total of 182 patients were assessed. Sixty-three patients (35%) filled 50% or fewer inhaled medication prescriptions; 88% admitted poor adherence with inhaled therapy after initial denial. Twenty-one percent of patients filled more than 100% of presciptions, and 45% of subjects filled between 51 and 100% of prescriptions. Twenty-three of 51 patients (45%) prescribed oral steroids were found to be nonadherent.A significant proportion of patients with difficult-to-control asthma remained nonadherent to corticosteroid therapy. Objective surrogate and direct measures of adherence should be performed as part of a difficult asthma assessment and are important before prescibing expensive novel biological therapies.
Methylation Induced Gene Silencing of HtrA3 in Smoking-Related Lung Cancer
Authors: Daniah Beleford, Zhixue Liu, Ramandeep Rattan, Lucio Quagliuolo, Mariarosaria Boccellino, Alfonso Baldi, Jacie Maguire, Julie Staub, Julian Molina, Viji Shridhar
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Some 85% of lung cancers are smoking related. Here, we investigate the role of serine protease HtrA3 in smoking-related lung cancer. Experimental Design: We assess HtrA3 methylation and its corresponding expression in the human bronchial cell line BEAS-2B following cigarette smoke carcinogen treatment, in lung cancer cell lines and in primary lung tumors from light, moderate, and heavy smokers. We also show the effects of HtrA3 downregulation on MTT reduction and clonogenic survival with etoposide and cisplatin treatment and the corresponding effects of HtrA3 re-expression during treatment. Results: We show for the first time that HtrA3 expression is reduced or completely lost in over 50% of lung cancer cell lines and primary lung tumors from heavy smokers. Treatment of HtrA3-deficient cell lines with 5-aza-2′-deoxycytidine resulted in a dose-dependent increase in HtrA3 transcription. Further, sequence analysis of bisulfite-modified DNA from lung cancer cell lines and from primary lung tumors showed an increased frequency of methylation within the first exon of HtrA3 with a corresponding loss of HtrA3 expression, particularly in tumors from smokers. In BEAS-2B, treatment with the cigarette smoke carcinogen 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone resulted in HtrA3 downregulation with a corresponding increase in methylation. Additional studies indicate resistance to etoposide and cisplatin cytotoxicity as a functional consequence of HtrA3 loss. Finally, immunohistochemical analysis of primary lung tumors revealed a strong correlation between low HtrA3 expression and heavy smoking history. Conclusions: Collectively, these results suggest that cigarette smoke–induced methylation of HtrA3 could contribute to the etiology of chemoresistant disease in smoking-related lung cancer. Clin Cancer Res; 16(2); 398–409
Whole genome sequencing of a natural recombinant Toxoplasma gondii strain reveals chromosome sorting and local allelic variants
Authors: Irene Lindström Bontell, Neil Hall, Kevin E Ashelford, JP Dubey, Jon P Boyle, Johan Lindh, Judith E Smith
Journal: Genome biology (2009)

Abstract Background Toxoplasma gondii is a zoonotic parasite of global importance. In common with many protozoan parasites it has the capacity for sexual recombination, but current evidence suggests this is rarely employed. The global population structure is dominated by a small number of clonal genotypes, which exhibit biallelic variation and limited intralineage divergence. Little is known of the genotypes present in Africa despite the importance of AIDS-associated toxoplasmosis. Results We here present extensive sequence analysis of eight isolates from Uganda, including the whole genome sequencing of a type II/III recombinant isolate, TgCkUg2. 454 sequencing gave 84% coverage across the approximate 61 Mb genome and over 70,000 single nucleotide polymorphisms (SNPs) were mapped against reference strains. TgCkUg2 was shown to contain entire chromosomes of either type II or type III origin, demonstrating chromosome sorting rather than intrachromosomal recombination. We mapped 1,252 novel polymorphisms and clusters of new SNPs within coding sequence implied selective pressure on a number of genes, including surface antigens and rhoptry proteins. Further sequencing of the remaining isolates, six type II and one type III strain, confirmed the presence of novel SNPs, suggesting these are local allelic variants within Ugandan type II strains. In mice, the type III isolate had parasite burdens at least 30-fold higher than type II isolates, while the recombinant strain had an intermediate burden. Conclusions Our data demonstrate that recombination between clonal lineages does occur in nature but there is nevertheless close homology between African and North American isolates. The quantity of high confidence SNP data generated in this study and the availability of the putative parental strains to this natural recombinant provide an excellent basis for future studies of the genetic divergence and of genotype-phenotype relationships.
The fatty Romanus lesion: a non-inflammatory spinal MRI lesion specific for axial spondyloarthropathy
Authors: A. N. Bennett, A. Rehman, E. M. A. Hensor, H. Marzo-Ortega, P. Emery, D. McGonagle
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Background</h3> Fatty changes at vertebral corners have been reported on MRI in ankylosing spondylitis but the distribution or specificity of these lesions to early axial spondyloarthropathy (axial-SpA) has not been determined. <h3>Objective</h3> To assess the diagnostic utility of fatty Romanus lesions (FRLs) for axial-SpA in a population with chronic back pain. <h3>Methods</h3> Axial-skeleton TI SE and fat-suppressed MRI were performed on 174 patients with back pain and 11 controls. MRI lesions including FRLs were scored blind. An imaging diagnosis was given on MRI findings alone and compared with the 'gold standard' treating doctor9s diagnosis. <h3>Results</h3> Twenty-nine patients had FRLs: 31% (20/64) of patients with spondyloarthropathy, 13% (6/45) with degenerative arthritis, 4% (2/45) with spinal malignancy, 5% (1/20) with 'other' diagnoses; none of 11 normal subjects had FRLs. The majority of the FRLs in SpA 60% (135/226) were present in the thoracic spine. The diagnostic utility of FRLs for SpA (likelihood ratio (LR) = 4.7) was significantly (p&lt;0.05) greater than for other diagnoses and increased further (LR = 12.6, p&lt;0.05) when more than five FRLs were present. Of note 5/20 (25%) patients with SpA with FRLs had no diagnostic bone-oedema lesions on fat-suppressed MRI, suggesting that FRLs may be useful diagnostically in axial-SpA. <h3>Conclusion</h3> This study defines the FRL as a diagnostic imaging feature of axial-SpA, which may be useful where inflammatory changes are absent on fat-suppression MRI and where radiography is normal.
Costs of Autism Spectrum Disorders in the United Kingdom and the United States
Authors: Ariane V. S. Buescher, Zuleyha Cidav, Martin Knapp, David S. Mandell
Journal: JAMA Pediatrics (2014)

The economic effect of autism spectrum disorders (ASDs) on individuals with the disorder, their families, and society as a whole is poorly understood and has not been updated in light of recent findings.To update estimates of age-specific, direct, indirect, and lifetime societal economic costs, including new findings on indirect costs, such as individual and parental productivity costs, associated with ASDs.A literature review was conducted of US and UK studies on individuals with ASDs and their families in October 2013 using the following keywords: age, autism spectrum disorder, prevalence, accommodation, special education, productivity loss, employment, costs, and economics. Current data on prevalence, level of functioning, and place of residence were combined with mean annual costs of services and support, opportunity costs, and productivity losses of individuals with ASDs with or without intellectual disability.Presence of ASDs.Mean annual medical, nonmedical, and indirect economic costs and lifetime costs were measured for individuals with ASDs separately for individuals with and without intellectual disability in the United States and the United Kingdom.The cost of supporting an individual with an ASD and intellectual disability during his or her lifespan was $2.4 million in the United States and £1.5 million (US $2.2 million) in the United Kingdom. The cost of supporting an individual with an ASD without intellectual disability was $1.4 million in the United States and £0.92 million (US $1.4 million) in the United Kingdom. The largest cost components for children were special education services and parental productivity loss. During adulthood, residential care or supportive living accommodation and individual productivity loss contributed the highest costs. Medical costs were much higher for adults than for children.The substantial direct and indirect economic effect of ASDs emphasizes the need to continue to search for effective interventions that make best use of scarce societal resources. The distribution of economic effect across many different service systems raises questions about coordination of services and sectors. The enormous effect on families also warrants policy attention.
The Effect of Experimental Diabetes Mellitus and Insulin Replacement on Hepatic Ultrastructure and Protein Synthesis
Authors: Eve P. Reaven, Daniel T. Peterson, Gerald M. Reaven
Journal: Journal of Clinical Investigation (1973)

The following study was conducted in order to define the specific alterations in hepatic ultrastructure responsible for the decrease in hepatic protein synthesis associated with experimental diabetes. Rats received intravenous alloxan (70 mg/kg) and 48 h later were either sacrificed or given insulin for 1, 2, 4, 6, or 24 h. Specimens for electron microscopic evaluation and morphometric analysis were taken from the same livers used to isolate ribosomes for measurement of in vitro protein synthesis. Our results show that hepatocytes from animals with untreated alloxan diabetes show varying degrees of disorganization and loss of rough endoplasmic reticulum (RER) which is directly related to the severity of the alloxan diabetes. A significant correlation existed between the severity of ultrastructural changes as judged by the loss of both membrane and polysome components of the RER and degree of inhibition of protein synthesis (P < 0.001). Abnormalities of hepatic ultrastructure and protein synthesis were reversed within 24 h of insulin administration. The data are consistent with the view that it is the relative decrease in hepatic polysomes that results from the loss of RER in alloxan diabetes that is responsible for the decrease in hepatic protein synthesis.
Pharmacogenetic control of bronchial obstruction in steroid depend asthma (SDBA) patients
Authors: Maria Simakova, Zhanna Mironova, Vasiliy Trofimov, Vasiliy Belash, Elena Iantchina, Michael Dubina
Journal: European Respiratory Journal (2011)

Multidrug resistance gene (MDR1) encodes P-glycoprotein 170 (Pgp170), which realize efflux of glucocorticosteroids (GCS) from the cell. C3435T of gene MDR1 in SDBA patients is supposed to be associated with dose of GCS, their anti-inflammatory activity, degree of bronchial obstruction.   Methods:  Blood samples were taken from 40 SDBA patients and 103 controls. Genotypes were analyzed using PCR-RLFP method.   Results:  Homozygous 3435C in SDBA patients were observed more frequently, than in controls: 35% (n=14) vs 8% (n=9) (χ2=15.56, p  In patients with allele C bronchial obstruction was less severe. However, if compared with TT genotype, post-broncholytic increase of velocity characteristics and Sgaw was not so marked.   Conclusion:  Patients with allele C require higher oGCS doses, probably, due to enhanced activity of Pgp170 and accelerated GCS efflux. In patients with TT genotype significant obstruction may be due to inadequate oGCS dose, while reversibility of distal obstruction may be due to intact function of bronchial smooth muscles and their sensitivity to GCS.
Short chain acyl-coenzyme A dehydrogenase (SCAD) deficiency. Immunochemical demonstration of molecular heterogeneity due to variant SCAD with differing stability.
Authors: E Naito, Y Indo, K Tanaka
Journal: Journal of Clinical Investigation (1989)

Using a [35S]methionine labeling/immunoprecipitation technique, we have previously shown that cultured skin fibroblast from three patients with short chain acyl-CoA dehydrogenase (SCAD) deficiency each synthesize a normal-sized (41 kD) variant SCAD in an amount comparable to that of normal cells. In the current study, these same cell lines were reexamined with immunoblot analysis. In one cell line (YH2065) no SCAD protein was detectable. In the other two deficient cell lines, the amount of variant SCAD was similar to, or only slightly less than, normal. These results suggested that SCAD-YH2065 is labile. In the pulse-labeling experiments, labeled SCAD was readily detectable for at least 30 h in a normal control and two other SCAD-deficient cell lines. In contrast, the labeled SCAD band in YH2065 cells was barely detectable at 6 h and undetectable at 20 h. [35S]Methionine-labeling in the presence of rhodamine 6G demonstrated that SCAD-YH2065 was synthesized as a 44-kD precursor and imported normally into mitochondria, as were the normal SCAD and two other variant SCADs, excluding the possibility that SCAD-YH2065 is a truncated precursor that cannot be imported into mitochondria. These results indicate that the mutations responsible for SCAD deficiency are heterogeneous, and emphasize the importance of using both radiolabeling and immunoblotting when evaluating such genetic defects at the protein level.
Do developing B cells need antigen?
Authors: Jean-Claude Weill, Claude-Agnès Reynaud
Journal: The Journal of Experimental Medicine (2005)

Just as potentially useful T cells are positively selected by MHC–peptide complexes in the thymus, it has been proposed that self or commensal bacterial epitopes might select B cell populations with the capacity to recognize polysaccharide or protein structures on pathogens. Recent studies indicate that the repertoire of B cells entering the periphery is not shaped by specific stimuli, but that mature B cell subsets may be under different selective pressures.
P137 Internal validation of the DECAF score as a predictor of inpatient mortality in acute exacerbations of COPD: Abstract P137 Table 1.
Authors: C Echevarria, J Steer, G J Gibson, S C Bourke
Journal: Thorax (2013)

<h3>Introduction</h3> In patients presenting with an acute exacerbation of COPD (AECOPD), accurate prediction of in-hospital mortality may help inform the most appropriate place and level of care. The DECAF score was developed for this purpose and designed to be simple to apply at the bedside using variables that are routinely collected on admission: Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial Fibrillation. Whilst the performance of the tool within the derivation cohort was strong,[1] before recommending use in clinical practice further validation is required. <h3>Methods</h3> Both external and internal validation of the DECAF score are currently in progress; for each, a cohort of 840 patients consecutively admitted with AECOPD is being recruited. To optimise data capture, patients are identified by screening admissions units and coding records. Indices that comprise the DECAF score and other independent predictors of mortality and readmission are collected. Dyspnoea is assessed using the extended MRC dyspnoea score.[1] Inclusion criteria are: primary diagnosis of AECOPD, age 35 or older, 10 pack years or more smoking history, and obstructive spirometry. Exclusion criteria are: other illness likely to limit survival to less than one year (principally metastatic malignancy) and previous inclusion in the validation study. We present an analysis of the performance of DECAF in the first 623 patients recruited to the internal validation cohort. <h3>Results</h3> <h3>Discussion</h3> As in the derivation study, DECAF is a good predictor of inpatient mortality (AUROC = 0.82), with a stepwise increase in mortality with DECAF score. The DECAF score accurately identifies low risk (DECAF score 0–1) and high risk patients (3 or greater) admitted with an exacerbation of COPD, potentially helping select patients for early supported discharge schemes, or for intensified medical treatment or early palliation. <h3>References</h3> Steer, J., J. Gibson, and S. C. Bourke, The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease. <i>Thorax</i>, 2012. <b>67</b>(11): p. 970–6.