bluuebunny/crossref_metadata_2025_split huggingface dataset:
Group exercise can improve participants' mobility in an outpatient rehabilitation setting: a randomized controlled trial
Authors: Sherrington Catherine , Pamphlett Patricia I , Jacka Jennifer A , Olivetti Lynnette M , Nugent Julie A , Hall Jillian M , Dorsch Simone , Kwan Marcella Mun-San , Lord Stephen R 
Published: May 2008

Objective: To establish the effects of group exercise on mobility and strength. Design: Randomized controlled trial. Setting: Two public hospital outpatient rehabilitation services. Participants: One hundred and seventy-three people (mean age 74.9 years, SD 10.8) with impaired mobility were randomized and 159 people (92%) completed the trial. Interventions: Five-week, twice-weekly `circuit-style' group exercise programme run by a physiotherapist (n = 85) and a no-intervention waiting list control group (n = 88). Main outcome measures: Three aspects of mobility: balance while standing and stepping (Step Test, semi-tandem and tandem stance times); sit-to-stand ability (rate and minimum height) and gait (6-metre and 6-minute walk tests). Lower limb muscle strength (knee flexion and extension). Results: At retest, exercise participants had improved significantly more than their control counterparts on measures of balance while stepping, sit to stand and gait. Exercise participants averaged 1.6 more steps on the 15-second Step Test (95% confidence interval (CI) 0.5 to 2.8, P=0.005), walked an average of 0.12 m/s faster (95% CI 0.05 to 0.2, P=0.002) and took 2.5 fewer steps in 6 metres (95% CI —4.2 to —0.8, P=0.004). Exercise participants also averaged 0.04 more sit-to-stands/second, (95% CI 0.003 to 0.08, P=0.037) and walked an average of 30.9 metres further in 6 minutes (95% CI 9.4 to 52.4, P=0.005). There were no clinically important or statistically significant between-group differences at retest for the measures of strength (knee extension and flexion), balance while standing or minimal sit-to-stand height. Conclusion: This short-duration circuit class programme improved mobility, but not strength.
Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+CD27+ B cells harbor the virus in X-linked lymphoproliferative disease patients
Authors: Chaganti Sridhar , Ma Cindy S. , Bell Andrew I. , Croom-Carter Debbie , Hislop Andrew D. , Tangye Stuart G. , Rickinson Alan B. 
Published: May 2008

AbstractEpstein-Barr virus (EBV) persists in healthy virus carriers within the immunoglobulin (Ig)D−CD27+ (class-switched) memory B-cell compartment that normally arises through antigen stimulation and germinal center transit. Patients with X-linked lymphoproliferative disease (XLP) lack such class-switched memory B cells but are highly susceptible to EBV infection, often developing fatal symptoms resembling those seen in EBV-associated hemophagocytic syndrome (EBV-AHS), a disease caused by aberrant virus entry into the NK- or T-cell system. Here we show that XLP patients who survive primary EBV exposure carry relatively high virus loads in the B-cell, but not the NK- or T-cell, compartment. Interestingly, in the absence of conventional class-switched memory B cells, the circulating EBV load was concentrated within a small population of IgM+IgD+CD27+ (nonswitched) memory cells rather than within the numerically dominant naive (IgM+IgD+CD27−) or transitional (CD10+CD27−) subsets. In 2 prospectively studied patients, the circulating EBV load was stable and markers of virus polymorphism detected the same resident strain over time. These results provide the first definitive evidence that EBV can establish persistence in the B-cell system in the absence of fully functional germinal center activity and of a class-switched memory B-cell compartment.
Heme oxygenase-1 deficiency leads to disrupted response to acute stress in stem cells and progenitors
Authors: Cao Yu-An , Wagers Amy J. , Karsunky Holger , Zhao Hui , Reeves Robert , Wong Ronald J. , Stevenson David K. , Weissman Irving L. , Contag Christopher H. 
Published: May 2008

AbstractAn effective response to extreme hematopoietic stress requires an extreme elevation in hematopoiesis and preservation of hematopoietic stem cells (HSCs). These diametrically opposed processes are likely to be regulated by genes that mediate cellular adaptation to physiologic stress. Herein, we show that heme oxygenase-1 (HO-1), the inducible isozyme of heme degradation, is a key regulator of these processes. Mice lacking one allele of HO-1 (HO-1+/−) showed accelerated hematopoietic recovery from myelotoxic injury, and HO-1+/− HSCs repopulated lethally irradiated recipients with more rapid kinetics. However, HO-1+/− HSCs were ineffective in radioprotection and serial repopulation of myeloablated recipients. Perturbations in key stem cell regulators were observed in HO-1+/− HSCs and hematopoietic progenitors (HPCs), which may explain the disrupted response of HO-1+/− HPCs and HPCs to acute stress. Control of stem cell stress response by HO-1 presents opportunities for metabolic manipulation of stem cell–based therapies.
Effects of glucocorticoids in ventilated piglets with severe pneumonia
Authors: Sibila O. , Luna C. M. , Agustí C. , Baquero S. , Gando S. , Patrón J. R. , Morato J. G. , Absi R. , Bassi N. , Torres A. 
Published: May 2008

There is clinical evidence suggesting that glucocorticoids may be useful in severe pneumonia, but the pathogenic mechanisms explaining these beneficial effects are unknown.The aim of the present study was to determine the effects of adding glucocorticoids to antibiotic treatment in an experimental model of severe pneumonia.In total, 15 Lagerwhite-Landrace piglets were ventilated for 96 h. After intubation, a 75 mL solution containingPseudomonas aeruginosa(106 cfu·mL−1) was bronchoscopically inoculated. The animals were randomised into three groups 12 h after inoculation: 1) untreated; 2) treated with ciprofloxacin; and 3) treated with ciprofloxacin plus methylprednisolone. Physiological and laboratory parameters were monitored throughout the study. Pro-inflammatory cytokines were measured in serum and bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed.At the end of the study, piglets receiving the antibiotic plus glucocorticoids showed: 1) a decrease in the concentration of interleukin-6 in BAL; and 2) a decrease in the global bacterial burden both in BAL and lung tissue.In conclusion, in this experimental model of pneumonia, the association of glucocorticoids with antibiotics attenuates local inflammatory response and decreases bacterial burden in the lung.
Treatment with inhaled steroids in patients with symptoms suggestive of asthma but with normal lung function
Authors: Rytilä P. , Ghaly L. , Varghese S. , Chung W. , Selroos O. , Haahtela T. 
Published: May 2008

A total of 144 patients with lower airway symptoms suggestive of asthma, but who did not fulfil the functional criteria of asthma, were included in a randomised, double-blind, placebo-controlled 8-week “proof-of-concept” study with mometasone furoate (MF), 400 µg once daily. The primary efficacy variable was the mean change from baseline in six morning and evening weekly symptom scores: cough, sputum production, wheeze, shortness of breath, chest tightness and exercise-induced cough/wheeze. Total symptom scores were calculated after treatment for 4 and 8 weeks.Compared with placebo, MF improved total morning symptom score at 8 weeks. Changes in total evening symptom scores did not differ between treatments. MF improved all individual symptom scores more than placebo, although the differences in changes between treatments were not always statistically significant. Morning and evening peak expiratory flow rates increased with MF compared with placebo. MF reduced eosinophils and the levels of eosinophilic cationic protein in induced sputum.The results show that symptoms suggestive of asthma exist in patients without significant β2-agonist reversibility or diurnal variability in peak flow. Once-daily MF may benefit some of these patients and a short course with inhaled corticosteroids may be tried. Responders should be better identified in further studies.
Haem oxygenase-1 plays a central role in NNK-mediated lung carcinogenesis
Authors: Li M-Y. , Yip J. , Hsin M. K. Y. , Mok T. S. K. , Wu Y. , Underwood M. J. , Chen G. G. 
Published: May 2008

The tobacco-specific nitrosamine, 4-(N-methyl-N-nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent lung cancer inducer. However, how NNK induces lung cancer is still largely unknown.Haem oxygenase (HO)-1 was evaluated in 30 pairs of lung cancer tumour samples and matched nontumour tissues from patients with a history of cigarette smoking. Expression of HO-1, p21Cip1/Waf1/Cid1(p21), B-cell lymphoma (Bcl)-2 family members, mitogen-activated protein kinase and nuclear factor (NF)-κB was also studied in lung cancer cells treated with NNK.The levels of HO-1 and p21 were significantly increased in lung tumour tissues. There was a positive relationship between these two proteins in the tumour. NNK stimulated lung cell proliferation and elevated the levels of HO-1, p21, inhibitor of apoptosis protein (c-IAP)2 and Bcl-2, but downregulated Bad. These effects of NNK were blocked by zinc protoporphyrin-XII, an HO-1 inhibitor. The NNK-mediated expression of HO-1 was governed by NF-κB and extracellular signal-regulated kinase 1/2, since blocking either of these prevented the stimulatory effect of NNK on HO-1, as well as molecules downstream of HO-1, such as p21, c-IAP2, Bcl-2 and Bad.In conclusion, haem oxygenase-1 plays a central role in NNK-mediated cell proliferation by promoting the expression of p21Cip1/Waf1/Cid1, inhibitor of apoptosis protein 2 and B-cell lymphoma-2 but inhibiting the activity of Bad. Nuclear factor-κB and extracellular signal-regulated kinase 1/2 function upstream of haem oxygenase-1. Therefore, haem oxygenase-1 is likely to be a potential target in the treatment of smoking-related lung cancer.
Can CAP guideline adherence improve patient outcome in internal medicine departments?
Authors: Blasi F. , Iori I. , Bulfoni A. , Corrao S. , Costantino S. , Legnani D. 
Published: May 2008

The impact of compliance with Italian guidelines on the outcome of hospitalised community-acquired pneumonia (CAP) in internal medicine departments was evaluated.All Fine class IV or V CAP patients were included in this multicentre, interventional, before-and-after study, composed of three phases: 1) a retrospective phase (RP; 1,443 patients); 2) a guideline implementation phase; and 3) a prospective phase (PP; 1,404 patients).Antibiotic prescription according to the guidelines increased significantly in the PP. The risk of failure at the end of the firstline therapy was significantly lower in the PPversusthe RP (odds ratio (OR) 0.83, 95% confidence interval (CI) 0.69–1.00), particularly in Fine class V patients (OR 0.71, 95% CI 0.51–0.98). Analysis of outcome in the overall population (2,847 patients) showed a statistically significant advantage for compliantversusnoncompliant therapies in terms of failure rate (OR 0.74, 95% CI 0.60–0.90) and an advantage in terms of mortality (OR 0.77, 95% CI 0.58–1.04). Antipneumococcal cephalosporin monotherapy was associated with a low success rate (68.6%) and the highest mortality (16.2%); levofloxacin alone and the combination of cephalosporin and macrolide resulted in higher success rates (79.1 and 76.7%, respectively) and significantly lower mortalities (9.1 and 5.7%, respectively).Overall, a low compliance with guidelines in the prospective phase (44%) was obtained, indicating the need for future more aggressive and proactive approaches.
Efficacy of a cell phone-based exercise programme for COPD
Authors: Liu W-T. , Wang C-H. , Lin H-C. , Lin S-M. , Lee K-Y. , Lo Y-L. , Hung S-H. , Chang Y-M. , Chung K.F. , Kuo H-P. 
Published: May 2008

The application of a supervised endurance exercise training programme in a home setting offering convenience and prolonged effects is a challenge.In total, 48 patients were initially assessed by the incremental shuttle walk test (ISWT), spirometry and the Short Form-12 (SF-12) quality-of-life questionnaire, and then every 4 weeks for 3 months thereafter and again after 1 yr. During the first 3 months, 24 patients in the cell phone group were asked to perform daily endurance walking at 80% of their maximal capacity by following the tempo of music from a program installed on a cell phone. The level of endurance walking at home was readjusted monthly according to the result of ISWT. In the control group, 24 patients received the same protocol and were verbally asked to take daily walking exercise at home.Patients in the cell phone group significantly improved their ISWT distance and duration of endurance walking after 8 weeks. The improvements in ISWT distance, inspiratory capacity and SF-12 scoring at 12 weeks persisted until the end of the study, with less acute exacerbations and hospitalisations.In the present pilot study, the cell phone-based system provides an efficient, home endurance exercise training programme with good compliance and clinical outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease.
Outdoor swimming pools and the risks of asthma and allergies during adolescence
Authors: Bernard A. , Nickmilder M. , Voisin C. 
Published: May 2008

Exposure to indoor chlorinated swimming pools can be detrimental to the airways of swimmers and increase asthma risks but it is unknown whether these effects concern outdoor pools.The present study examined 847 secondary school adolescents who had attended residential or nonresidential outdoor chlorinated pools at a variable rate. The main outcomes were: ever asthma (physician-diagnosed at any time); current asthma (ever asthma under medication and/or with exercise-induced bronchoconstriction); elevated exhaled nitric oxide; and aeroallergen-specific immunoglobulin (Ig)E in serum.The prevalence of ever and current asthma significantly increased with the lifetime number of hours spent in outdoor pools by up to four and eight times, respectively, among adolescents with the highest attendance (>500 h) and a low exposure to indoor pools (<250 h). Odds for asthma were significantly increased among adolescents with total serum IgE >25 kIU·L−1, on average by 1–2 units for each 100-h increase in pool attendance. Use of residential outdoor pools was also associated with higher risks of elevated exhaled nitric oxide and sensitisation to cat or house dust mite allergens.Outdoor chlorinated swimming pool attendance is associated with higher risks of asthma, airways inflammation and some respiratory allergies.
Exhaled nitric oxide predicts lung function decline in difficult-to-treat asthma
Authors: van Veen I. H. , ten Brinke A. , Sterk P. J. , Sont J. K. , Gauw S. A. , Rabe K. F. , Bel E. H. 
Published: May 2008

A subset of patients with asthma is known to have progressive loss of lung function despite treatment with corticosteroids. The aim of the present study was to identify risk factors of decline in forced expiratory volume in one second (FEV1) in patients with difficult-to-treat asthma.In total, 136 nonsmoking patients with difficult-to-treat asthma were recruited between 1998 and 1999. Follow-up assessment was performed 5–6 yrs later in 98 patients. The predictive effect of clinical characteristics and inflammatory markers were analysed at baseline (asthma onset and duration, atopy, airway hyperresponsiveness, blood and sputum eosinophils, and the fraction of nitric oxide in exhaled air (FeNO)) on subsequent decline in post-bronchodilator FEV1.Patients with highFeNO(≥20 ppb) had an excess decline of 40.3 (95% confidence interval (CI) 7.3–73.2) mL·yr−1compared to patients with lowFeNO.FeNO≥20 ppb was associated with a relative risk of 1.9 (95% CI, 1.1–2.6) of having an accelerated (≥25 mL·yr−1) decline in FEV1. In patients with baseline FEV1≥80% of predicted, this relationship was even stronger: 90versus29% had accelerated decline in FEV1(FeNO≥20 ppbversusFeNO<20 ppb respectively; relative risk 3.1 (95% CI, 1.7–3.4).Exhaled nitric oxide is a predictor of accelerated decline in lung function in patients with difficult-to-treat asthma, particularly if forced expiratory volume in one second is still normal.
Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma
Authors: Wu S-G. , Gow C-H. , Yu C-J. , Chang Y-L. , Yang C-H. , Hsu Y-C. , Shih J-Y. , Lee Y-C. , Yang P-C. 
Published: May 2008

Malignant pleural effusions (MPEs) are often observed in lung cancer, especially adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in lung adenocarcinoma. The purpose of the present study was to investigate theEGFRmutation rate in MPEs of lung adenocarcinoma.Between June 2005 and December 2006, 136 MPEs from lung adenocarcinoma were collected forEGFRmutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of lung adenocarcinoma from patients without MPEs were assessed forEGFRmutation.TheEGFRmutation rate was significantly higher in the patients with MPEs than in the patients without (68.4%versus50.5%). TheEGFRmutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0–1, andEGFRmutation were significantly associated with a longer overall survival for lung adenocarcinoma patients with MPEs.The patients with malignant pleural effusions related to lung adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for lung adenocarcinoma with malignant pleural effusions in east Asia.
Nutritional deficit as a negative prognostic factor in patients with miliary tuberculosis
Authors: Kim D. K. , Kim H. J. , Kwon S-Y. , Yoon H-I. , Lee C-T. , Kim Y. W. , Chung H. S. , Han S. K. , Shim Y-S. , Lee J-H. 
Published: May 2008

The effects of malnutrition on outcomes in miliary tuberculosis (MTB) are not well described. The aim of the present study was to find predictors for the development of acute respiratory failure (ARF) and survival in MTB patients, focusing on parameters reflecting nutritional condition.Out of the patients from three hospitals who had microbiologically or histopathologically confirmed tuberculosis, 56 patients presenting with typical disseminated pulmonary nodules on radiographs were retrospectively enrolled. A four-point nutritional risk score (NRS) was defined according to the presence of four nutritional factors: low body mass index (BMI; <18.5 kg·m−2), hypoalbuminaemia (<30.0 g·L−1), hypocholesterolaemia (<2.33 mmol·L−1) and severe lymphocytopenia (<7×105 cells·L−1).The male to female ratio was 1:3. ARF developed in 25% of patients (14 out of 56), with a 50% fatality rate. A high NRS (≥3 points) was an independent risk factor for the development of ARF and fatality. In 90-day survival analysis, ARF, severe lymphocytopenia, hypocholesterolaemia, low BMI and higher NRS were risk factors for poor outcome. In multivariate analysis, only high NRS was an independent risk factor for 90-day survival rate in patients with MTB.A high nutritional risk score was a good predictor of poor outcome in miliary tuberculosis patients. Additional approaches to recover the nutritional deficits may become a focus in future management of miliary tuberculosis.
Sequencing and genotypic analysis of the triosephosphate isomerase (TPI1) locus in a large sample of long-lived Germans
Authors: Ralser Markus , Nebel Almut , Kleindorp Rabea , Krobitsch Sylvia , Lehrach Hans , Schreiber Stefan , Reinhardt Richard , Timmermann Bernd 
Published: May 2008

Abstract

Background
Triosephosphate isomerase (TPI) is a central and conserved glycolytic enzyme. In humans, TPI is encoded by a single gene on 12p13, and associated with a rare genetic disorder, TPI deficiency. Reduced TPI activity can increase specific oxidant resistances of model organisms and TPI null-alleles have been hypothesized to promote a heterozygote advantage in man. However, comprehensive genetic information about the TPI1 locus is still lacking.

Results
Here, we sequenced the TPI1 locus in a sample of 357 German long-lived individuals (LLI) aged 95 to 110 years. We identified 17 different polymorphisms, of which 15 were rare and previously unknown. The two remaining SNPs occurred at much higher frequency and were tested for association with the longevity phenotype in larger samples of LLI (n = 1422) and younger controls (n = 967). Neither of the two markers showed a statistically significant difference in allele or genotype frequency between LLI and control subjects.

Conclusion
This study marks the TPI1 locus as extraordinarily conserved, even when analyzing intronic and non-coding regions of the gene. None of the identified sequence variations affected the amino acid composition of the TPI protein and hence, are unlikely to impact the catalytic activity of the enzyme. Thus, TPI variants occur less frequent than expected and inactive alleles are not enriched in German centenarians.
Exploiting orthologue diversity for systematic detection of gain-of-function phenotypes
Authors: Martelli Maria Luisa , Isella Claudio , Mira Alessia , Fu Limin , Cantarella Daniela , Medico Enzo 
Published: May 2008

Abstract

Background
Systematic search for genes whose gain-of-function by exogenous expression confers an advantage in cell-based selective screenings is a powerful method for unbiased functional exploration of the genome, and has the potential to disclose new targets for cancer therapy. A major limit of this approach resides in the labor-intensive cloning of resistant cells, identification of the integrated genes and validation of their ability to confer a selective advantage. Moreover, the selection has to be drastic and genes conferring a limited advantage are typically missed.

Results
We developed a new functional screening strategy based on transduction of mammalian cells of a given species with an expression library from another species, followed by one-shot quantitative tracing with DNA microarrays of all library-derived transcripts before and after selection. In this way, exogenous transcripts enriched after selection, and therefore likely to confer resistance, are readily detected. We transduced a retroviral cDNA expression library from mouse testis into human and canine cells, and optimized the use of commercial murine gene expression arrays for species-specific detection of library-derived transcripts. We then conducted a functional screening by growing library-transduced canine MDCK cells in suspension, to enrich for cDNAs conferring anchorage independence. Notably, these cells show partial resistance to loss of anchorage, and the selection can be of limited stringency, compromising approaches based on clonal selection or anyway requiring high stringency. Microarray analysis revealed reproducible enrichment after three weeks of growth on polyhema for seven genes, among which the Hras proto-oncogene and Sox5. When individually transduced into MDCK cells, Sox5 specifically promoted anchorage-independent growth, thereby confirming the validity and specificity of the approach.

Conclusion
The procedure described here brings substantial advantages to the field of expression cloning, being faster, more systematic and more sensitive. Indeed, this strategy allowed identification and validation of genes promoting anchorage-independent growth of epithelial cells under selection conditions not amenable to conventional expression cloning.