bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disproportionate elevation of N-terminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension
Authors: Mathai S. C. , Bueso M. , Hummers L. K. , Boyce D. , Lechtzin N. , Le Pavec J. , Campo A. , Champion H. C. , Housten T. , Forfia P. R. , Zaiman A. L. , Wigley F. M. , Girgis R. E. , Hassoun P. M. 
Published: July 2009

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of neurohormonal activation that is useful in the diagnosis and prognosis of various forms of pulmonary arterial hypertension (PAH). We sought to characterise and compare NT-proBNP in a cohort of PAH related to systemic sclerosis (PAH-SSc) and idiopathic PAH (IPAH) patients.NT-proBNP levels, collected from PAH-SSc and IPAH patients followed prospectively, were compared and correlated with haemodynamic variables. Cox proportional hazard models were created to assess the predictive value of NT-proBNP.98 patients (55 PAH-SSc, 43 IPAH) were included. Haemodynamics were similar, except for lower mean pulmonary arterial pressure in PAH-SSc. NT-proBNP levels were significantly higher in PAH-SSc (3,419±3,784versus1,393±1,633 pg·mL−1; p<0.01) and were more closely related to haemodynamics in PAH-SSc than IPAH. 28 patients died. NT-proBNP predicted survival (hazard ratio (HR) 3.18; p<0.01) in the overall cohort; however, when stratified by group, predicted survival only in PAH-SSc (HR 3.07, p<0.01versus2.02, p = 0.29 in IPAH).This is the first description showing NT-proBNP levels are 1) significantly higher in PAH-SSc than IPAH despite less severe haemodynamic perturbations, and 2) stronger predictors of survival in PAH-SSc, suggesting that neurohormonal regulation may differ between PAH-SSc and IPAH. Future studies to define pertinent mechanisms are warranted.
Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study
Authors: Eagan T. M. L. , Ueland T. , Wagner P. D. , Hardie J. A. , Mollnes T. E. , Damås J. K. , Aukrust P. , Bakke P. S. 
Published: July 2009

Chronic obstructive pulmonary disease (COPD) is considered an inflammatory pulmonary disorder with systemic inflammatory manifestations. The aim of this study was to assess the systemic levels of six inflammatory mediators in a large cohort of COPD patients and controls.409 COPD patients and 231 healthy subjects, aged 40–75 yrs, were included from the first phase of the Bergen COPD Cohort Study. All COPD patients were clinically diagnosed by a physician, and had a forced expiratory volume in 1 s/forced vital capacity ratio less than 0.7 and a smoking history of >10 pack-yrs. The plasma levels of C-reactive protein (CRP), soluble tumour necrosis factor receptor (sTNFR)-1, osteoprotegrin, neutrophil activating peptide-2, CXCL16 and monocyte chemoattractant protein-4 were determined by ELISA.After adjustment for all known confounders, COPD patients had significantly lower levels of osteoprotegrin than subjects without COPD (p<0.05), and higher levels of CRP (p<0.01). Among COPD patients, CRP was elevated in patients with frequent exacerbations (p<0.05). sTNFR-1 and osteoprotegrin were both related to Global Initiative for Chronic Obstructive Lung Disease stage and frequency of exacerbations in the last 12 months (p<0.05). In addition, sTNFR-1 was significantly associated with important comorbidities such as hypertension and depression (p<0.05).The present study confirms that certain circulating inflammatory mediators are an important phenotypic feature of COPD.
Mechanisms of emphysema in α1-antitrypsin deficiency: molecular and cellular insights
Authors: Gooptu B. , Ekeowa U. I. , Lomas D. A. 
Published: July 2009

The severe, early onset emphysema that occurs in patients with circulating deficiency of α1-antitrypsin (α1-AT) attests to the importance of this protease inhibitor in maintaining lung parenchymal integrity. It has led to the powerful concept of protease:antiprotease balance being crucial to alveolar homeostasis.Pathogenic mutations cause α1-AT to self-associate into polymer chains that accumulate intracellularly rather than proceeding along the secretory pathway. Polymerisation of α1-AT abolishes antiprotease activity and confers toxic gain-of-function effects. Since α1-AT is predominantly synthesised in the liver, where it does not play a major homeostatic role, the directly toxic effects of polymerisation are clearest here. However, data from molecular, cellular, animal andex vivostudies indicate that intrapulmonary polymerisation of α1-AT and inflammatory positive feedback loops may augment the destructive effects of decreased antiprotease levels in the lung.This review integrates the findings from these different approaches and highlights how multiple pathways may converge to give the severe, panacinar emphysema phenotype seen in α1-AT deficiency.
Rapid reduction in hospitalisations after an intervention to manage severe asthma
Authors: Souza-Machado C. , Souza-Machado A. , Franco R. , Ponte E. V. , Barreto M. L. , Rodrigues L. C. , Bousquet J. , Cruz A. A. 
Published: July 2009

Asthma is the third cause of hospitalisations due to clinical illnesses in Brazil. The Programme for Control of Asthma in Bahia (ProAR) leads an initiative in Salvador City (Brazil) to manage severe asthma for free. The aim of this study was to identify trends in asthma hospitalisation in the entire city and to evaluate the impact of ProAR.Information on asthma hospitalisations from 1998 to 2006 was collected. We analysed trends in Salvador (2.8 million inhabitants) before and after ProAR, taking pneumonia and myocardial infarction into account for local comparison. As an external control we obtained information on asthma from Recife, which is the most comparable Brazilian city.In Salvador, asthma hospital admissions declined by 82.3% (1998–2006). A greater proportion of this reduction (74%) occurred after 2003, in parallel with the implementation of ProAR. The reduction in asthma admissions in Recife was smaller. The rates of hospitalisation in 2006 were 2.25 per 10,000 inhabitants in Salvador and 17.06 in Recife. In Salvador, we found an inverse correlation between the provision of medication for asthma and hospitalisation (-0.801; p<0.0001).A rapid reduction in asthma admissions in the entire city of Salvador was associated with ProAR, a public health intervention targeting severe asthma.
Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis
Authors: Scherf D. B. , Dally H. , Müller P. , Werle-Schneider G. , Jäger B. , Edler L. , Tuengerthal S. , Fischer J. R. , Drings P. , Bartsch H. , Risch A. 
Published: July 2009

The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1,MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated.For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS).The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage- and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods.None of the investigated polymorphisms modified response significantly in the whole patient population.However, tumour stage IIIB variant allele carriers ofMMP2 C-735Tshowed a significantly worse response. PFS was significantly prolonged inMMP1 G-1607GGvariant allele carriers and OS in small cell lung cancer patients carrying theMMP12 A-82Gvariant allele.In conclusion, this study identified SNPs inMMP1,MMP2, MMP7andMMP12for further investigation as possible predictors of chemotherapy outcome in lung cancer patients.
Discharge planning and home care for end-stage COPD patients
Authors: Escarrabill J. 
Published: July 2009

Discharge support for the most seriously ill chronic obstructive pulmonary disease (COPD) patients is a key issue in minimising the impact of the acute episode and preventing future relapses.Alternatives to hospitalisation are crucial in the cost minimisation of COPD care. However, besides efficiency, there are clinical reasons for promoting alternatives to conventional hospital admission. Hospital stay itself conveys a risk to patients.The discharge process is a key element in the healthcare continuum. Hospital at home is a safe alternative to hospital admission, but it is not the only means of supporting discharge. Some home care schedules, mainly supported by nurses, have been proven to be good alternatives.Home care is also useful in the prevention of hospital admission. Integrated care is a comprehensive response to the needs of severely affected COPD patients achieved through models of shared care utilising all relevant health providers and promoting self-management. The framework for integrated care is the so-called chronic care model, centred on the promotion of self-management, the holistic appraisal of the patient, the most appropriate design of healthcare delivery responding effectively to the needs of the patient and a good system of shared and accessible information.
Chronic respiratory care for neuromuscular diseases in adults
Authors: Ambrosino N. , Carpenè N. , Gherardi M. 
Published: July 2009

Neuromuscular diseases (NMD) may affect respiratory muscles, leading to respiratory failure. Studies show that long-term noninvasive mechanical ventilation (NIV) improves symptoms, gas exchange, quality of life and survival. NIV improved these parameters in muscular dystrophies and also in patients with amyotrophic lateral sclerosis without severe bulbar dysfunction. NIV should be started at the onset of nocturnal hypoventilation. In selected cases, NIV may be simpler, better accepted by patients and cheaper than invasive mechanical ventilation, but it cannot be used as an alternative. Tracheostomy may be preferred by patients unable to protect their airways and wishing to survive as long as possible, or by ventilator-dependent patients.Glossopharyngeal breathing consists of taking air and propelling it into the lungs. Chest percussions and vibrations can help to mobilise airway secretions but they cannot substitute coughing. Manually assisted coughing requires substantial lung inflation through air stacking or deep lung insufflation, followed by an abdominal thrust with open glottis. The combination of mechanical in-exsufflation with an abdominal thrust is a mechanically assisted cough.In conclusion, recent advances in respiratory care of NMD have improved prognosis and many caregivers have changed from a traditional noninterventional to a more aggressive, supportive approach.
Inspiratory muscle dysfunction in patients with severe obstructive sleep apnoea
Authors: Chien M-Y. , Wu Y-T. , Lee P-L. , Chang Y-J. , Yang P-C. 
Published: July 2009

Repetitive inspiratory effort against an obstructed airway and intermittent hypoxia may be deleterious to the inspiratory muscles in patients with obstructive sleep apnoea (OSA).We investigated muscular dysfunction by comparing the strength, endurance and fatigability of inspiratory muscles and knee extensors in patients with newly diagnosed severe OSA compared with matched controls. The measurements included strength and endurance tests of both muscles, and a fatigue trial with simultaneous surface electromyography of the diaphragm and the vastus lateralis during voluntary contractions and in response to magnetic stimulation. To our knowledge, this is the first investigation to assess peripheral muscle performance in severe OSA patientsversuscontrols.Patients in the OSA group exhibited significantly lower strength and endurance in both muscles than the control group. The fatigue index decreased significantly exclusively in the inspiratory muscles of OSA patients. Magnetic stimulation-evoked compound muscle action potential latencies increased and the amplitudes decreased significantly in the diaphragm, but not in the vastus lateralis after a fatigue test in the OSA group.In conclusion, a significantly lower functional performance was shown for both inspiratory muscles and knee extensors in the OSA group. However, higher fatigability was only seen in the inspiratory muscles of patients with severe OSA.
Primer fabrication using polymerase mediated oligonucleotide synthesis
Authors: Cairns Murray J , Thomas Torsten , Beltran Carolina E , Tillett Daniel 
Published: July 2009

Abstract

Background
Custom solid phase oligonucleotide synthesis is an important foundation supporting nearly every aspect of current genomics. In spite of the demand for oligonucleotide primers, their synthesis remains relatively expensive, time consuming and in many circumstances a wasteful process. In this methodology, described as polymerase mediated oligonucleotide synthesis (PMOS), a DNA polymerase is used to increase the hybridization affinity of one oligonucleotide by using another as a template for DNA synthesis. This self-assembly process provides an opportunity to instantly generate a very large number of useful gene-specific primers from a small library of simple precursors. PMOS can be used to generate primers directly in the end-users laboratory within the context of any DNA polymerase chemistry such as in PCR or sequencing reactions

Results
To demonstrate the utility of PMOS, a universal 768-member oligonucleotide library (UniSeq) was designed, fabricated and its performance optimized and evaluated in a range of PCR and DNA sequencing reactions. This methodology used to derive specific 11-mers, performed well in each of these activities and produced the desired amplification or sequencing analysis with results comparable to primers made by time consuming and expensive custom synthesis.

Conclusion
On the basis of these experiments, we believe this novel system would be broadly applicable and could in many circumstances replace the need for conventional oligonucleotide synthesis.
Mosquito immune responses and compatibility between Plasmodium parasites and anopheline mosquitoes
Authors: Jaramillo-Gutierrez Giovanna , Rodrigues Janneth , Ndikuyeze Georges , Povelones Michael , Molina-Cruz Alvaro , Barillas-Mury Carolina 
Published: July 2009

Abstract

Background
Functional screens based on dsRNA-mediated gene silencing identified several Anopheles gambiae genes that limit Plasmodium berghei infection. However, some of the genes identified in these screens have no effect on the human malaria parasite Plasmodium falciparum; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different Plasmodium species.

Results
Four new An. gambiae (G3) genes were identified that, when silenced, have a different effect on P. berghei (Anka 2.34) and P. falciparum (3D7) infections. Orthologs of these genes, as well as LRIM1 and CTL4, were also silenced in An. stephensi (Nijmegen Sda500) females infected with P. yoelii (17XNL). For five of the six genes tested, silencing had the same effect on infection in the P. falciparum-An. gambiae and P. yoelii-An. stephensi parasite-vector combinations. Although silencing LRIM1 or CTL4 has no effect in An. stephensi females infected with P. yoelii, when An. gambiae is infected with the same parasite, silencing these genes has a dramatic effect. In An. gambiae (G3), TEP1, LRIM1 or LRIM2 silencing reverts lysis and melanization of P. yoelii, while CTL4 silencing enhances melanization.

Conclusion
There is a broad spectrum of compatibility, the extent to which the mosquito immune system limits infection, between different Plasmodium strains and particular mosquito strains that is mediated by TEP1/LRIM1 activation. The interactions between highly compatible animal models of malaria, such as P. yoelii (17XNL)-An. stephensi (Nijmegen Sda500), is more similar to that of P. falciparum (3D7)-An. gambiae (G3).
Mass spectrometry analysis of the variants of histone H3 and H4 of soybean and their post-translational modifications
Authors: Wu Tao , Yuan Tiezheng , Tsai Sau-Na , Wang Chunmei , Sun Sai-Ming , Lam Hon-Ming , Ngai Sai-Ming 
Published: July 2009

Abstract

Background
Histone modifications and histone variants are of importance in many biological processes. To understand the biological functions of the global dynamics of histone modifications and histone variants in higher plants, we elucidated the variants and post-translational modifications of histones in soybean, a legume plant with a much bigger genome than that of Arabidopsis thaliana.

Results
In soybean leaves, mono-, di- and tri-methylation at Lysine 4, Lysine 27 and Lysine 36, and acetylation at Lysine 14, 18 and 23 were detected in HISTONE H3. Lysine 27 was prone to being mono-methylated, while tri-methylation was predominant at Lysine 36. We also observed that Lysine 27 methylation and Lysine 36 methylation usually excluded each other in HISTONE H3. Although methylation at HISTONE H3 Lysine 79 was not reported in A. thaliana, mono- and di-methylated HISTONE H3 Lysine 79 were detected in soybean. Besides, acetylation at Lysine 8 and 12 of HISTONE H4 in soybean were identified. Using a combination of mass spectrometry and nano-liquid chromatography, two variants of HISTONE H3 were detected and their modifications were determined. They were different at positions of A31F41S87S90 (HISTONE variant H3.1) and T31Y41H87L90 (HISTONE variant H3.2), respectively. The methylation patterns in these two HISTONE H3 variants also exhibited differences. Lysine 4 and Lysine 36 methylation were only detected in HISTONE H3.2, suggesting that HISTONE variant H3.2 might be associated with actively transcribing genes. In addition, two variants of histone H4 (H4.1 and H4.2) were also detected, which were missing in other organisms. In the histone variant H4.1 and H4.2, the amino acid 60 was isoleucine and valine, respectively.

Conclusion
This work revealed several distinct variants of soybean histone and their modifications that were different from A. thaliana, thus providing important biological information toward further understanding of the histone modifications and their functional significance in higher plants.
Educational intervention to improve physician reporting of adverse drug reactions (ADRs) in a primary care setting in complementary and alternative medicine
Authors: Tabali Manuela , Jeschke Elke , Bockelbrink Angelina , Witt Claudia M , Willich Stefan N , Ostermann Thomas , Matthes Harald 
Published: July 2009

Abstract

Background
Recent studies have shown that adverse drug reactions (ADRs) are underreported. This may be particularly true of ADRs associated with complementary and alternative medicine (CAM). Data on CAM-related ADRs, however, are sparse.
Objective was to evaluate the impact of an educational intervention and monitoring programme designed to improve physician reporting of ADRs in a primary care setting.

Methods
A prospective multicentre study with 38 primary care practitioners specialized in CAM was conducted from January 2004 through June 2007. After 21 month all physicians received an educational intervention in terms of face-to-face training to assist them in classifying and reporting ADRs. The study centre monitored the quantity and quality of ADR reports and analysed the results.
To measure changes in the ADR reporting rate, the median number of ADR reports and interquartile range (IQR) were calculated before and after the educational intervention. The pre-intervention and post-intervention quality of the reports was assessed in terms of changes in the completeness of data provided for obligatory items. Interrater reliability between the physicians and the study centre was calculated using Cohen's kappa with a 95% confidence interval (CI). We used Mann Whitney U-test for testing continuous data and chi-square test was used for categorical data. The level of statistical significance was set at P < 0.05.

Results
A total of 404 ADRs were reported during the complete study period. An initial 148% increase (P = 0.001) in the number of ADR reports was observed after the educational intervention. Compared to baseline the postinterventional number of ADR reportings was statistically significant higher (P < 0.005) through the first 16 months after the intervention but not significant in the last 4-month period (median: 8.00 (IQR [2.75; 8.75]; P = 0.605). The completeness of the ADR reports increased from 80.3% before to 90.7% after the intervention. The completeness of the item for classifying ADRs as serious or non-serious increased significantly (P < 0.001) after the educational intervention. The quality of ADR reports increased from kappa 0.15 (95% CI: 0.08; 0.29) before to 0.43 (95% CI: 0.23; 0.63) after the intervention.

Conclusion
The results of the present study demonstrate that an educational intervention can increase physician awareness of ADRs. Participating physicians were able to incorporate the knowledge they had gained from face-to-face training into their daily clinical practice. However, the effects of the intervention were temporary.
A generic method for assignment of reliability scores applied to solvent accessibility predictions
Authors: Petersen Bent , Petersen Thomas Nordahl , Andersen Pernille , Nielsen Morten , Lundegaard Claus 
Published: July 2009

Abstract

Background
Estimation of the reliability of specific real value predictions is nontrivial and the efficacy of this is often questionable. It is important to know if you can trust a given prediction and therefore the best methods associate a prediction with a reliability score or index. For discrete qualitative predictions, the reliability is conventionally estimated as the difference between output scores of selected classes. Such an approach is not feasible for methods that predict a biological feature as a single real value rather than a classification. As a solution to this challenge, we have implemented a method that predicts the relative surface accessibility of an amino acid and simultaneously predicts the reliability for each prediction, in the form of a Z-score.

Results
An ensemble of artificial neural networks has been trained on a set of experimentally solved protein structures to predict the relative exposure of the amino acids. The method assigns a reliability score to each surface accessibility prediction as an inherent part of the training process. This is in contrast to the most commonly used procedures where reliabilities are obtained by post-processing the output.

Conclusion
The performance of the neural networks was evaluated on a commonly used set of sequences known as the CB513 set. An overall Pearson's correlation coefficient of 0.72 was obtained, which is comparable to the performance of the currently best public available method, Real-SPINE. Both methods associate a reliability score with the individual predictions. However, our implementation of reliability scores in the form of a Z-score is shown to be the more informative measure for discriminating good predictions from bad ones in the entire range from completely buried to fully exposed amino acids. This is evident when comparing the Pearson's correlation coefficient for the upper 20% of predictions sorted according to reliability. For this subset, values of 0.79 and 0.74 are obtained using our and the compared method, respectively. This tendency is true for any selected subset.