bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplex immune serum biomarker profiling in sarcoidosis and systemic sclerosis
Authors: Beirne P. , Pantelidis P. , Charles P. , Wells A. U. , Abraham D. J. , Denton C. P. , Welsh K. I. , Shah P. L. , du Bois R. M. , Kelleher P. 
Published: June 2009

Multiplex protein technology has the potential to identify biomarkers for the differentiation, classification and improved understanding of the pathogenesis of interstitial lung disease. The aim of this study was to determine whether a 30-inflammatory biomarker panel could discriminate between healthy controls, sarcoidosis and systemic sclerosis (SSc) patients independently of other clinical indicators. We also evaluated whether a panel of biomarkers could differentiate between the presence or absence of lung fibrosis in SSc patients.We measured 30 circulating biomarkers in 20 SSc patients, 21 sarcoidosis patients and 20 healthy controls using Luminex bead technology and used Fisher’s discriminant function analysis to establish the groups of classification mediators.There were significant differences in median concentration measurements between study groups for 20 of the mediators but with considerable range overlap between the groups, limiting group differentiation by single analyte measurements. However, a 17-analyte biomarker model correctly classified 90% of study individuals to their respective group and another 14-biomarker panel correctly identified the presence of lung fibrosis in SSc patients.These findings, if they are corroborated by independent studies in other centres, have potential for clinical application and may generate novel insights into the modulation of immune profiles during disease evolution.
Troponin T predicts in-hospital and 1-year mortality in patients with pulmonary embolism
Authors: Janata K. M. , Leitner J. M. , Holzer-Richling N. , Janata A. , Laggner A. N. , Jilma B. 
Published: June 2009

We aimed to determine the prognostic value of troponin T (TNT) for in-hospital and 1-yr mortality in a large sample of patients with pulmonary embolism (PE).Patients presenting at the emergency department of a tertiary care centre from January 1998 to December 2006 with PE were included. A blood sample was taken at the time of presentation. To determine in-hospital and 1-yr mortality, data from the hospital records and the national death register were used.TNT was determined in 563 out of 737 patients with proven PE. TNT was elevated (>0.03ng·mL−1) in 27%. In-hospital survival was 79% in TNT-positive patients compared with 94% in TNT-negative patients (p<0.001). 1-yr survival was 71% in TNT-positive patients compared with 90% in TNT-negative patients (p<0.001). Elevated TNT levels meant a four-times higher risk of in-hospital death and a three-times higher risk of 1-yr mortality, even after adjustment for the other most important risk factors of death in this population.Elevated TNT independently predicts in-hospital and 1-yr mortality in patients with acute PE.
Incidence, characteristics and outcomes of patients with severe community acquired-MRSA pneumonia
Authors: Vardakas K. Z. , Matthaiou D. K. , Falagas M. E. 
Published: June 2009

We evaluated the published data for the incidence, characteristics and outcomes of patients with community-acquired pneumonia (CAP) due to methicillin-resistantStaphylococcus aureus(MRSA). The estimated incidence of MRSA CAP is 0.51–0.64 cases per 100,000.We identified 74 articles reporting data on 114 patients. Influenza like symptoms was reported in 41% of patients. Pneumonia improved in 59 (54.1%) out of 109 patients; 49 (44.5%) out of 110 patients died. The duration of hospitalisation was 38.1±24.9 and 8.3±11.7 days, respectively. The duration of intensive care unit (ICU) stay was 18.9±13.6 and 6.8±9.7 days, respectively. 76 strains carried the Panton–Valentine leukocidin gene.The univariate analysis showed that multi-organ failure (p<0.001), leukopenia (p<0.001), admission to ICU (p<0.001), mechanical ventilation (p<0.001), use of aminoglycosides after culture results (p<0.001), shock (p = 0.001), acute respiratory distress syndrome (p = 0.001), influenza like symptoms (p = 0.008), disseminated intravascular coagulation (p = 0.042) and rash (p = 0.04) were the factors associated with death.
Incidence and outcome of weaning from mechanical ventilation according to new categories
Authors: Funk G-C. , Anders S. , Breyer M-K. , Burghuber O. C. , Edelmann G. , Heindl W. , Hinterholzer G. , Kohansal R. , Schuster R. , Schwarzmaier-D'Assie A. , Valentin A. , Hartl S. 
Published: June 2009

Weaning from mechanical ventilation was categorised as simple, difficult or prolonged by an international task force of the American Thoracic Society/European Respiratory Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine/Sociéte de Réanimation de Langue Française in 2007. This new classification has not been tested in clinical practice. The objective of the present study was to determine the incidence and outcome of weaning according to the new categories.We included medical and surgical patients who required mechanical ventilation in a prospective, multicentre, 6-month cohort study.From an initial cohort of 510 patients, 257 intubated patients started weaning. Of these patients, the cumulative incidences of simple, difficult, and prolonged weaning were 152 (59%), 68 (26%) and 37 (14%), respectively. Hospital mortality was increased in patients with prolonged (32%) but not difficult (9%) weaning in comparison with those with simple weaning (13%), overall p = 0.0205. In a multivariate logistic regression model, prolonged but not difficult weaning was associated with an increased risk of death. Ventilator-free days and intensive care unit (ICU)-free days were decreased in both difficult and prolonged weaning.In conclusion, the new weaning category prolonged weaning is associated with increased mortality and morbidity in the ICU. The new category difficult to wean was associated with increased morbidity, but not mortality.
Control and severity of asthma during pregnancy are associated with asthma incidence in offspring: two-stage case–control study
Authors: Martel M-J. , Rey É. , Beauchesne M-F. , Malo J-L. , Perreault S. , Forget A. , Blais L. 
Published: June 2009

The extent to which childhood asthma incidence is influenced by asthma control and severity during pregnancy is unknown. We have studied this association during the child's first 10 yrs of life.A two-stage, case–control study, nested in a cohort of 8,226 children of asthmatic mothers, was conducted using three interlinked databases of Quebec, Canada, and mailed questionnaires. A total of 2,681 asthmatic children and 30,318 age-matched controls were selected (≤20 controls·case−1; stage 1), and 3,254 selected mothers were mailed questionnaires to obtain additional information (stage 2). Asthma control and severity was defined using validated indexes and childhood asthma incidence based on at least one asthma-related diagnosis and prescription received within 2 yrs. A total of 44 confounders were considered.Compared with children of mild controlled asthmatic mothers, children whose mothers had moderate-to-severe uncontrolled asthma during pregnancy had an increased risk of asthma (adjusted OR 1.27, 95% CI 1.06–1.52). No increased risk was observed for children of mild uncontrolled and moderate-to-severe controlled mothers.Based on one of the largest studies of children of asthmatic mothers, a significant increase in asthma risk was demonstrated among children whose mothers had poor control and increased severity of asthma during pregnancy, indicating that this element should be added to the expanding list of determinants of childhood asthma. As it constitutes a risk factor where pregnant asthmatic females can intervene, it is of great importance for physicians to optimally treat asthmatic females during pregnancy and to encourage females to be adherent to the prescribed asthma medications.
Signalling pathways involved in the contractile response to 5-HT in the human pulmonary artery
Authors: Rodat-Despoix L. , Aires V. , Ducret T. , Marthan R. , Savineau J-P. , Rousseau E. , Guibert C. 
Published: June 2009

Serotonin (5-hydroxytryptamine; 5-HT) is a potent pulmonary vasoconstrictor and mitogenic agent whose plasma level is increased in pulmonary hypertensive patients. Thus, we explored the signalling pathways involved in the contractile response to 5-HT in human pulmonary arteries (HPAs).Intact and β-escin permeabilised rings from HPAs mounted in an organ bath system were used to assess both tension and myofilament Ca2+-sensitisation. Microspectrofluorimetry was used for intracellular Ca2+recordings in cultured HPA smooth muscle cells.Voltage-operated Ca2+channel blockers (nitrendipine and nifedipine) partially reduced the contraction to 5-HT. Thapsigargin or cyclopiazonic acid (CPA), known to deplete sarcoplasmic reticulum Ca2+stores, also partially inhibited the contraction, whereas removal of extracellular Ca2+under these conditions further inhibited the contraction. Changing from Ca2+-free to Ca2+containing solution, in the presence of nitrendipine and CPA, a protocol known to stimulate store-operated Ca2+channels, induced HPA contractions that were blocked by nickel. Nickel or gadolinium also reduced the contraction to 5-HT. Finally, 5-HT increased intracellular Ca2+responses in cultured HPA smooth muscle cells and myofilament Ca2+-sensitisation in HPA rings.Collectively, these results indicate that voltage-operated and voltage-independent Ca2+channels, as well as Ca2+release and myofilament Ca2+-sensitisation, participate in 5-HT-induced contraction in HPAs.
Corticosteroid responsiveness and clinical characteristics in childhood difficult asthma
Authors: Bossley C. J. , Saglani S. , Kavanagh C. , Payne D. N. R. , Wilson N. , Tsartsali L. , Rosenthal M. , Balfour-Lynn I. M. , Nicholson A. G. , Bush A. 
Published: June 2009

This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction (FeNO) and no bronchodilator responsiveness (BDR <12%)) is uncommon in paediatric DA.We report on 102 children, mean±sdage 11.6±2.8 yrs, with DA in a cross-sectional study. 89 children underwent spirometry, BDR andFeNObefore and after 2 weeks of systemic corticosteroids (corticosteroid response study). Bronchoscopy was performed after the corticosteroid trial.Of the 102 patients in the cross-sectional study, 88 (86%) were atopic, 60 (59%) were male and 52 (51%) had additional or alternative diagnoses. Out of the 81 patients in the corticosteroid response study, nine (11%) were complete responders. Of the 75 patients with symptom data available, 37 (49%) responded symptomatically, which was less likely if there were smokers in the home (OR 0.31, 95% CI 0.02–0.82). Of the 75 patients with available spirometry data, 35 (46%) had normal spirometry, with associations being BAL eosinophilia (OR 5.43, 95% CI 1.13–26.07) and high baseline forced expiratory volume in 1 s (FEV1) (OR 1.08, 95% CI 1.02–1.12). Of these 75 patients, BDR data were available in 64, of whom 36 (56%) had <12% BDR.FeNOdata was available in 70 patients, of whom 53 (75%) had normalFeNO. Airflow limitation data was available in 75 patients, of whom 17 (26%) had persistent airflow limitation, which was associated with low baseline FEV1(OR 0.93, 95% CI 0.90–0.97).Only 11% of DA children exhibited complete corticosteroid responsiveness. The rarity of complete corticosteroid responsiveness suggests alternative therapies are needed for children with DA.
Admission hypoglycaemia is associated with adverse outcome in community-acquired pneumonia
Authors: Singanayagam A. , Chalmers J. D. , Hill A. T. 
Published: June 2009

The aim of our study was to investigate if hypoglycaemia correlates with outcome in community-acquired pneumonia (CAP).We performed a prospective, observational study of consecutive patients presenting with a primary diagnosis of CAP in Lothian (UK). Admission plasma glucose was measured and, on this basis, patients were divided into two groups, hypoglycaemic (<4.4 mmol·L−1or <79.0 mg·dL−1) and nonhypoglycaemic (≥4.4 mmol·L−1or ≥79.0 mg·dL−1). Outcomes of interest were 30-day mortality, need for mechanical ventilation and inotropic support. Multivariable logistic regression was used to compare these outcomes in hypoglycaemic patients to nonhypoglycaemic patients, adjusting for diabetes mellitus, prior statin use and Pneumonia Severity Index.In total, 1,050 patients were included in the study with 5.4% classified as hypoglycaemic. Increased rates of 30-day mortality (28.1%versus7.5%, p<0.0001), need for mechanical ventilation (29.8%versus6.5%, p<0.0001) and need for inotropic support (21.1%versus4.8%, p<0.0001) were observed in hypoglycaemic patients compared with nonhypoglycaemic patients. On multivariable analysis, hypoglycaemia was independently associated with increased 30-day mortality (OR 2.25, 95% CI 1.1–4.7; p = 0.03), need for mechanical ventilation (OR 3.8, 95% CI 1.9–7.5; p = 0.0002) and need for inotropic support (OR, 2.9, 95% CI 1.4–6.3; p = 0.0006).Admission hypoglycaemia is associated with increased 30-day mortality, need for mechanical ventilation and inotropic support in patients presenting with CAP.
Biomarkers of infection for the differential diagnosis of pleural effusions
Authors: Porcel J. M. , Vives M. , Cao G. , Bielsa S. , Ruiz-González A. , Martínez-Iribarren A. , Esquerda A. 
Published: June 2009

We aimed to investigate whether pleural fluid concentrations of biomarkers for bacterial infection, namely triggering receptor expressed on myeloid cells (sTREM-1), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP), might identify infectious effusions and discriminate between complicated (CPPEs) and uncomplicated parapneumonic effusions (UPPEs).Stored pleural fluid samples from 308 patients with different causes of pleural effusion were used to measure the four biomarkers. Receiver-operating characteristic analysis determined the accuracy of the new tests.Median pleural fluid levels of CRP, sTREM-1 and LBP were significantly higher in CPPE compared with those in other aetiologies. The area under the curve for distinguishing infectious (parapneumonics and tuberculosis) from noninfectious effusions was 0.87 for CRP, 0.86 for sTREM-1, 0.57 for PCT and 0.87 for LBP. Regarding the discrimination of nonpurulent CPPEversusUPPE, a multivariate analysis found that pleural fluid glucose ≤60 mg·dL−1, LBP ≥17 μg·mL−1and CRP ≥80 mg·L−1were the best parameters. Individually, none of the new biomarkers achieved better performance characteristics than pH, glucose or lactate dehydrogenase in labelling CPPE.In conclusion, elevated pleural fluid levels of CRP, sTREM and LBP identify patients with infectious effusions, particularly those with CPPE. PCT has no value for the differential diagnosis of pleural effusions.
Maternal diabetes alters transcriptional programs in the developing embryo
Authors: Pavlinkova Gabriela , Salbaum J Michael , Kappen Claudia 
Published: June 2009

AbstractBackgroundMaternal diabetes is a well-known risk factor for birth defects, such as heart defects and neural tube defects. The causative molecular mechanisms in the developing embryo are currently unknown, and the pathogenesis of developmental abnormalities during diabetic pregnancy is not well understood. We hypothesized that the developmental defects are due to alterations in critical developmental pathways, possibly as a result of altered gene expression. We here report results from gene expression profiling of exposed embryos from a mouse diabetes model.ResultsIn comparison to normal embryos at mid-gestation, we find significantly altered gene expression levels in diabetes-exposed embryos. Independent validation of altered expression was obtained by quantitative Real Time Polymerase Chain Reaction. Sequence motifs in the promoters of diabetes-affected genes suggest potential binding of transcription factors that are involved in responses to oxidative stress and/or to hypoxia, two conditions known to be associated with diabetic pregnancies. Functional annotation shows that a sixth of the de-regulated genes have known developmental phenotypes in mouse mutants. Over 30% of the genes we have identified encode transcription factors and chromatin modifying proteins or components of signaling pathways that impinge on transcription.ConclusionExposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs.
Case report: Malignant teratoma of the uterine corpus
Authors: Newsom-Davis Thomas , Poulter Daniel , Gray Rebecca , Ameen Mohammed , Lindsay Iain , Papanikolaou Kyriakos , Butler-Manuel Simon , Christmas Timothy , Townsend Peter , Seckl Michael 
Published: June 2009

Abstract

Background
Teratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix.

Case Presentation
We report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection.

Conclusion
In this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.
Technology assessment and resource allocation for predictive genetic testing: A study of the perspectives of Canadian genetic health care providers
Authors: Adair Alethea , Hyde-Lay Robyn , Einsiedel Edna , Caulfield Timothy 
Published: June 2009

Abstract

Background
With a growing number of genetic tests becoming available to the health and consumer markets, genetic health care providers in Canada are faced with the challenge of developing robust decision rules or guidelines to allocate a finite number of public resources. The objective of this study was to gain Canadian genetic health providers' perspectives on factors and criteria that influence and shape resource allocation decisions for publically funded predictive genetic testing in Canada.

Methods
The authors conducted semi-structured interviews with 16 senior lab directors and clinicians at publically funded Canadian predictive genetic testing facilities. Participants were drawn from British Columbia, Alberta, Manitoba, Ontario, Quebec and Nova Scotia. Given the community sampled was identified as being relatively small and challenging to access, purposive sampling coupled with snowball sampling methodologies were utilized.

Results
Surveyed lab directors and clinicians indicated that predictive genetic tests were funded provincially by one of two predominant funding models, but they themselves played a significant role in how these funds were allocated for specific tests and services. They also rated and identified several factors that influenced allocation decisions and patients' decisions regarding testing. Lastly, participants provided recommendations regarding changes to existing allocation models and showed support for a national evaluation process for predictive testing.

Conclusion
Our findings suggest that largely local and relatively ad hoc decision making processes are being made in relation to resource allocations for predictive genetic tests and that a more coordinated and, potentially, national approach to allocation decisions in this context may be appropriate.
The complete genome of klassevirus – a novel picornavirus in pediatric stool
Authors: Greninger Alexander L , Runckel Charles , Chiu Charles Y , Haggerty Thomas , Parsonnet Julie , Ganem Donald , DeRisi Joseph L 
Published: June 2009

Abstract

Background
Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not found in approximately 30–50% of cases. Picornaviral genera such as enterovirus, kobuvirus, cosavirus, parechovirus, hepatovirus, teschovirus, and cardiovirus have all been found in human and animal diarrhea. Modern technologies, especially deep sequencing, allow rapid, high-throughput screening of clinical samples such as stool for new infectious agents associated with human disease.

Results
A pool of 141 pediatric gastroenteritis samples that were previously found to be negative for known diarrheal viruses was subjected to pyrosequencing. From a total of 937,935 sequence reads, a collection of 849 reads distantly related to Aichi virus were assembled and found to comprise 75% of a novel picornavirus genome. The complete genome was subsequently cloned and found to share 52.3% nucleotide pairwise identity and 38.9% amino acid identity to Aichi virus. The low level of sequence identity suggests a novel picornavirus genus which we have designated klassevirus. Blinded screening of 751 stool specimens from both symptomatic and asymptomatic individuals revealed a second positive case of klassevirus infection, which was subsequently found to be from the index case's 11-month old twin.

Conclusion
We report the discovery of human klassevirus 1, a member of a novel picornavirus genus, in stool from two infants from Northern California. Further characterization and epidemiological studies will be required to establish whether klasseviruses are significant causes of human infection.
Male-Biased Effects of Gonadotropin-Releasing Hormone Neuron-Specific Deletion of the Phosphoinositide 3-Kinase Regulatory Subunit p85α on the Reproductive Axis
Authors: Acosta-Martínez Maricedes , Luo Ji , Elias Carol , Wolfe Andrew , Levine Jon E. 
Published: June 2009

Abstract
GnRH neurosecretion is subject to regulation by insulin, IGF-I, leptin, and other neuroendocrine modulators whose effects may be conveyed by activation of phosphoinositide 3-kinase (PI3K)-mediated pathways. It is not known, however, whether any of these regulatory actions are exerted directly, via activation of PI3K in GnRH neurons, or whether they are primarily conveyed via effects on afferent circuitries governing GnRH neurosecretion. To investigate the role of PI3K signaling in GnRH neurons, we used conditional gene targeting to ablate expression of the major PI3K regulatory subunit, p85α, in GnRH neurons. Combined in situ hybridization and immunohistochemistry confirmed reduction of p85α mRNA expression in GnRH neurons of GnRH-p85α knockout (KO) animals. Females of both genotypes exhibited estrous cyclicity and had comparable serum LH, estradiol-17β, and FSH levels. In male GnRH-p85αKO mice, serum LH, testosterone, and sperm counts were significantly reduced compared with wild type. To investigate the role of the other major regulatory subunit, p85β, on the direct control of GnRH neuronal function, we generated mice with a GnRH-neuron-specific p85α deletion on a global βKO background. No additional reproductive effects in male or female mice were found, suggesting that p85β does not substitute p85 activity toward PI3K function in GnRH neurons. Our results suggest that p85α, and thus PI3K activity, participates in the control of GnRH neuronal activity in male mice. The sex-specific phenotype in these mice raises the possibility that PI3K activation during early development may establish sex differences in GnRH neuronal function.