bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional lung function and heterogeneity of specific gas volume in healthy and emphysematous subjects
Authors: Aliverti Andrea , Pennati Francesca , Salito Caterina , Woods Jason C. 
Published: August 2012

The aim of our study was to study regional lung function by standard computed tomography (CT) and characterise regional variations of density and specific gas volume (SVg) between different lung volumes.We studied 10 healthy and 10 severely emphysematous subjects. Corresponding CT images taken at high and low lung volumes were registered by optical flow to obtain two-dimensional maps of pixel-by-pixel differences of density (ΔHU) and SVg (ΔSVg) at slice levels near the aortic arch, carina and top diaphragm.In healthy subjects, ΔHU was higher at all levels (p<0.001) with higher variability expressed as interquartile range (p<0.001), largely due to its differences between dorsal and ventral regions. In patients, median ΔSVg values were 3.2 times lower than healthy volunteers (p<0.001), while heterogeneity of ΔSVg maps, expressed as quartile coefficient of variation, was 5.4 times higher (p<0.001). In all patients, there were areas with negative values of ΔSVg.In conclusion, ΔSVg is uniform in healthy lungs and minimally influenced by gravity. The significant ΔSVg heterogeneity observed in emphysema allows identification of areas of alveolar destruction and gas trapping and suggests that ΔSVg maps provide useful information for evaluation and planning of emerging treatments that target trapped gas for removal.
Sweet talk: insights into the nature and importance of glucose transport in lung epithelium
Authors: Garnett James P. , Baker Emma H. , Baines Deborah L. 
Published: August 2012

For over 50 years, glucose has been recognised to cross the lung epithelial barrier and be transported by lung epithelial cells. However, until recently, research into these processes focused on their effects on lung liquid volume. Here, we consider a newly identified role for pulmonary glucose transport in maintaining low airway surface liquid (ASL) glucose concentrations and propose that this contributes to lung defence against infection.Glucose diffuses into ASLviaparacellular pathways at a rate determined by paracellular permeability and the transepithelial glucose gradient. Glucose is removed from ASL in proximal airwaysviafacilitative glucose transporters, down a concentration gradient generated by intracellular glucose metabolism. In the distal lung, glucose transportviasodium-coupled glucose transporters predominates. These processes vary between species but universally maintain ASL glucose at 3–20-fold lower concentrations than plasma.ASL glucose concentrations are increased in respiratory disease and by hyperglycaemia. Elevated ASL glucose in intensive care patients was associated with increasedStaphylococcus aureusinfection. Diabetic patients with and without chronic lung disease are at increased risk of respiratory infection. Understanding of mechanisms underlying lung glucose homeostasis could identify new therapeutic targets for control of ASL glucose and prevention and treatment of lung infection.
CFTR biomarkers: time for promotion to surrogate end-point
Authors: De Boeck K. , Kent L. , Davies J. , Derichs N. , Amaral M. , Rowe S.M. , Middleton P. , de Jonge H. , Bronsveld I. , Wilschanski M. , Melotti P. , Danner-Boucher I. , Boerner S. , Fajac I. , Southern K. , de Nooijer R.A. , Bot A. , de Rijke Y. , de Wachter E. , Leal T. , Vermeulen F. , Hug M.J. , Rault G. , Nguyen-Khoa T. , Barreto C. , Proesmans M. , Sermet-Gaudelus I. 
Published: August 2012

In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis.Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts.The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed.This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.
SharedPseudomonas aeruginosagenotypes are common in Australian cystic fibrosis centres
Authors: Kidd Timothy J. , Ramsay Kay A. , Hu Honghua , Marks Guy B. , Wainwright Claire E. , Bye Peter T. , Elkins Mark R. , Robinson Philip J. , Rose Barbara R. , Wilson John W. , Grimwood Keith , Bell Scott C. ,   the ACPinCF Investigator Group
Published: August 2012

Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways forPseudomonas aeruginosain patients with cystic fibrosis (CF). In Australia, there is only limited evidence of unrelated patients sharing indistinguishableP. aeruginosastrains. We therefore examined the point-prevalence, distribution, diversity and clinical impact ofP. aeruginosastrains in Australian CF patients nationally.983 patients attending 18 Australian CF centres provided 2887 sputumP. aeruginosaisolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant.Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres, respectively. AUST-01 was associated with significantly greater treatment requirements than uniqueP. aeruginosastrains.Multiple clusters of sharedP. aeruginosastrains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation. Longitudinal studies are now needed to determine the infection control implications of these findings.
Airway epithelial cell apoptosis and inflammation in COPD, smokers and nonsmokers
Authors: Comer David M. , Kidney Joseph C. , Ennis Madeleine , Elborn J. Stuart 
Published: August 2012

We hypothesised that primary bronchial epithelial cells (PBECs) from subjects with chronic obstructive pulmonary disease (COPD) respond differently toPseudomonas aeruginosalipopolysaccharide (LPS) after cigarette smoke extract (CSE) exposure than PBECs obtained from smokers without airflow obstruction and nonsmokers.PBECs from 16 COPD subjects, 10 smokers without airflow obstruction and nine nonsmokers were cultured at air–liquid interface. Cultures were incubated with CSE prior to stimulation withP. aeruginosaLPS. Interleukin (IL)-6 and IL-8 were measured by ELISA and Toll-like receptor (TLR)-4 expression by fluorescence-activated cell sorter. Activation of nuclear factor (NF)-κB was determined by Western blotting and ELISA, and MAPK and caspase-3 activity by Western blotting. Apoptosis was evaluated using Annexin-V staining and the terminal transferase-mediated dUTP nick end-labelling methods.Constitutive release of IL-8 and IL-6 was greatest from the COPD cultures. However, CSE pretreatment followed byP. aeruginosaLPS stimulation reduced IL-8 release from COPD PBECs, but increased it from cells of smokers without airflow obstruction and nonsmokers. TLR-4 expression, MAPK and NF-κB activation in COPD cultures were reduced after CSE treatment, but not in the smokers without airflow obstruction or nonsmoker groups, which was associated with increased apoptosis.CSE attenuates inflammatory responses to LPS in cells from people with COPD but not those from nonsmoking individuals and those who smoke without airflow obstruction.
Transmission of multidrug-resistant and extensively drug-resistant tuberculosis in a metropolitan city
Authors: Leung Eric Chung Ching , Leung Chi Chiu , Kam Kai Man , Yew Wing Wai , Chang Kwok Chiu , Leung Wai Man , Tam Cheuk Ming 
Published: August 2012

Multidrug-resistant (MDR)- tuberculosis (TB) and extensively drug resistant (XDR)-TB reportedly lead to increased household transmission.This is a retrospective cohort study of active TB occurring among household contacts exposed to MDR-TB.Of 704 contacts in 246 households, initial screening identified 12 (1.7%) TB cases (prevalent cases) and 17 (2.4%) contacts that subsequently developed active TB (secondary cases) after a median (range) duration of 17 (5–62.5) months. Eight prevalent cases and three secondary cases had MDR-TB. TB incidence rates per 100 000 person-years were 254.9 overall and 45.0 for MDR-TB. XDR-TB in the index MDR-TB patient significantly increased the odds of identifying a prevalent TB case to 4.8 (95% CI 1.02–22.5), and the hazard of finding a secondary TB case to 4.7 (95% CI 1.7–13.5). Molecular fingerprinting confirmed household transmission of MDR-TB. Of 20 retrievable isolates from 27 XDR-TB index cases, restriction fragment length polymorphism analysis showed clustering among 13 (65%), with 11 (55%) due to recent transmission by n-1 method and an identifiable household source in only three (27.2%) of the 11 cases.XDR-TB relative to MDR-TB significantly increases household transmission of TB, probably reflecting prolonged/higher infectivity, and indicating a need for prolonged household surveillance. XDR-TB may largely transmit outside of the household settings.
Defining race/ethnicity and explaining difference in research studies on lung function
Authors: Braun Lundy , Wolfgang Melanie , Dickersin Kay 
Published: August 2012

The 2005 guidelines of the American Thoracic Society/European Respiratory Society recommend the use of race- and/or ethnic-specific reference standards for spirometry. Yet definitions of the key variables of race and ethnicity vary worldwide. The purpose of this study was to determine whether researchers defined race and/or ethnicity in studies of lung function and how they explained any observed differences.Using the methodology of the systematic review, we searched PubMed in July 2008 and screened 10 471 titles and abstracts to identify potentially eligible articles that compared “white” to “other racial and ethnic groups”.Of the 226 eligible articles published between 1922 and 2008, race and/or ethnicity was defined in 17.3%, with the proportion increasing to 70% in the 2000s for those using parallel controls. Most articles (83.6%) reported that “other racial and ethnic groups” have a lower lung capacity compared to “white”; 94% of articles failed to examine socioeconomic status. In the 189 studies that reported lower lung function in “other racial and ethnic groups”, 21.8% and 29.4% of explanations cited inherent factors and anthropometric differences, respectively, whereas 23.1% of explanations cited environmental and social factors.Even though researchers sought to determine differences in lung function by race/ethnicity, they typically failed to define their terms and frequently assumed inherent (or genetic) differences.
Effectiveness of sequential automatic-manual home respiratory polygraphy scoring
Authors: Masa Juan F. , Corral Jaime , Pereira Ricardo , Duran-Cantolla Joaquin , Cabello Marta , Hernández-Blasco Luis , Monasterio Carmen , Alonso-Fernandez Alberto , Chiner Eusebi , Vázquez-Polo Francisco-José , Montserrat Jose M. ,   the Spanish Sleep Group
Published: August 2012

Automatic home respiratory polygraphy (HRP) scoring functions can potentially confirm the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS) (obviating technician scoring) in a substantial number of patients. The result would have important management and cost implications. The aim of this study was to determine the diagnostic cost-effectiveness of a sequential HRP scoring protocol (automatic and then manual for residual cases) compared with manual HRP scoring, and with in-hospital polysomnography.We included suspected SAHS patients in a multicentre study and assigned them to home and hospital protocols at random. We constructed receiver operating characteristic (ROC) curves for manual and automatic scoring. Diagnostic agreement for several cut-off points was explored and costs for two equally effective alternatives were calculated.Of 366 randomised patients, 348 completed the protocol. Manual scoring produced better ROC curves than automatic scoring. There was no sensitive automatic or subsequent manual HRP apnoea–hypopnoea index (AHI) cut-off point. The specific cut-off points for automatic and subsequent manual HRP scorings (AHI >25 and >20, respectively) had a specificity of 93% for automatic and 94% for manual scorings. The costs of manual protocol were 9% higher than sequential HRP protocol; these were 69% and 64%, respectively, of the cost of the polysomnography.A sequential HRP scoring protocol is a cost-effective alternative to polysomnography, although with limited cost savings compared to HRP manual scoring.
Evaluation of QuantiFERON microtube, using 0.9 mL blood, for diagnosing tuberculosis infection
Authors: Rose Michala V. , Kimaro Godfather , Kroidl Inge , Hoelscher Michael , Bygbjerg Ib C. , Mfinanga Sayoki M. , Ravn Pernille 
Published: August 2012

The performance of QuantiFERON microtube (QFT-MT), using 0.9 mL blood, and QuantiFERON-TB Gold in-tube test (QFT-IT) (3 mL blood), for diagnosing tuberculosis (TB) was compared in children and adults in an endemic setting.In 152 children with suspected TB and 87 adults with confirmed TB, QFT-IT was compared with two QFT-MT concentrations (QFT-MT A and B). Proportions of positive and indeterminate results, interferon (IFN)-γ responses, interassay agreement and sensitivity were assessed.We found similar proportions of indeterminate results, levels of IFN-γ and comparable sensitivity. The interassay agreement was moderate in all children (QFT-ITversusQFT-MT A: 85%, k=0.44 and QFT-ITversusQFT-MT B: 88%, k=0.50) and adults (QFT-ITversusQFT-MT A: 88%, k=0.50 and QFT-ITversusQFT-MT B: 89%, k=0.49). Sensitivity was low (QFT-IT 23%, QFT-MT A 18% and B 19%) in children with confirmed or highly probable TB compared with adults (83%, 86% and 88%, respectively).The QFT-MT test can be reliably performed using less than one-third of the blood volume used in QFT-IT. The reduced volume may be useful for research and future diagnosis of paediatric TB. The poor sensitivity and high indeterminate rate of both IFN-γ release assays in severely ill children, with immature or impaired immunity in an endemic setting, warrants further investigations.
Hospital admissions of adults with community-acquired pneumonia in Portugal between 2000 and 2009
Authors: Froes Filipe , Diniz António , Mesquita Margarida , Serrado Margarida , Nunes Baltazar 
Published: August 2012

Recent studies in the USA and northern Europe have shown an increase in community-acquired pneumonia (CAP). In southern Europe, this increase has not yet been documented.We carried out a retrospective analysis from encoded information from the Portuguese database for hospital admissions that included all individuals aged ≥18 years, with a primary diagnosis of pneumonia, who were discharged between 2000 and 2009. We excluded patients infected with HIV, individuals immunocompromised as a result of anti-cancer or immunosuppressive treatment, and transplant recipients.Of the 294 027 admissions for CAP, 56% were male. The mean age was 73.1 years and the median age 77 years. Between 2000 and 2009, there was a 5% increase in the average age of patients admitted with CAP.Admissions for CAP represented 3.7% of total admissions of adult patients. The average annual rate of hospital admissions for adults with CAP was 3.61 per 1000 total population, rising to 13.4 for those aged ≥65 years. Between 2000–2004 and 2005–2009 the average annual rate of hospital admission for CAP per 1000 population increased by 28.2%.Hospital admissions for CAP in Portugal increased between 2000 and 2009. It has grown consistently over time, varying according to age with males over-represented.
Distinct gene loci control the host response to influenza H1N1 virus infection in a time-dependent manner
Authors: Nedelko Tatiana , Kollmus Heike , Klawonn Frank , Spijker Sabine , Lu Lu , Heßman Manuela , Alberts Rudi , Williams Robert W , Schughart Klaus 
Published: August 2012

Abstract

Background
There is strong but mostly circumstantial evidence that genetic factors modulate the severity of influenza infection in humans. Using genetically diverse but fully inbred strains of mice it has been shown that host sequence variants have a strong influence on the severity of influenza A disease progression. In particular, C57BL/6J, the most widely used mouse strain in biomedical research, is comparatively resistant. In contrast, DBA/2J is highly susceptible.

Results
To map regions of the genome responsible for differences in influenza susceptibility, we infected a family of 53 BXD-type lines derived from a cross between C57BL/6J and DBA/2J strains with influenza A virus (PR8, H1N1). We monitored body weight, survival, and mean time to death for 13 days after infection. Qivr5 (quantitative trait for influenza virus resistance on chromosome 5) was the largest and most significant QTL for weight loss. The effect of Qivr5 was detectable on day 2 post infection, but was most pronounced on days 5 and 6. Survival rate mapped to Qivr5, but additionally revealed a second significant locus on chromosome 19 (Qivr19). Analysis of mean time to death affirmed both Qivr5 and Qivr19. In addition, we observed several regions of the genome with suggestive linkage. There are potentially complex combinatorial interactions of the parental alleles among loci. Analysis of multiple gene expression data sets and sequence variants in these strains highlights about 30 strong candidate genes across all loci that may control influenza A susceptibility and resistance.

Conclusions
We have mapped influenza susceptibility loci to chromosomes 2, 5, 16, 17, and 19. Body weight and survival loci have a time-dependent profile that presumably reflects the temporal dynamic of the response to infection. We highlight candidate genes in the respective intervals and review their possible biological function during infection.
GhWRKY15, a member of the WRKY transcription factor family identified from cotton (Gossypium hirsutumL.), is involved in disease resistance and plant development
Authors: Yu Feifei , Huaxia Yifeng , Lu Wenjing , Wu Changai , Cao Xuecheng , Guo Xingqi 
Published: August 2012

Abstract

Background
As a large family of regulatory proteins, WRKY transcription factors play essential roles in the processes of adaptation to diverse environmental stresses and plant growth and development. Although several studies have investigated the role of WRKY transcription factors during these processes, the mechanisms underlying the function of WRKY members need to be further explored, and research focusing on the WRKY family in cotton crops is extremely limited.

Results
In the present study, a gene encoding a putative WRKY family member, GhWRKY15, was isolated from cotton. GhWRKY15 is present as a single copy gene, and a transient expression analysis indicated that GhWRKY15 was localised to the nucleus. Additionally, a group of cis-acting elements associated with the response to environmental stress and plant growth and development were detected in the promoter. Consistently, northern blot analysis showed that GhWRKY15 expression was significantly induced in cotton seedlings following fungal infection or treatment with salicylic acid, methyl jasmonate or methyl viologen. Furthermore, GhWRKY15-overexpressing tobacco exhibited more resistance to viral and fungal infections compared with wild-type tobacco. The GhWRKY15-overexpressing tobacco also exhibited increased RNA expression of several pathogen-related genes, NONEXPRESSOR OF PR1, and two genes that encode enzymes involved in ET biosynthesis. Importantly, increased activity of the antioxidant enzymes POD and APX during infection and enhanced expression of NtAPX1 and NtGPX in transgenic tobacco following methyl viologen treatment were observed. Moreover, GhWRKY15 transcription was greater in the roots and stems compared with the expression in the cotyledon of cotton, and the stems of transgenic plants displayed faster elongation at the earlier shooting stages compared with wide type tobacco. Additionally, exposure to abiotic stresses, including cold, wounding and drought, resulted in the accumulation of GhWRKY15 transcripts.

Conclusion
Overall, our data suggest that overexpression of GhWRKY15 may contribute to the alteration of defence resistance to both viral and fungal infections, probably through regulating the ROS system via multiple signalling pathways in tobacco. It is intriguing that GhWRKY15 overexpression in tobacco affects plant growth and development, especially stem elongation. This finding suggests that the role of the WRKY proteins in disease resistance may be closely related to their function in regulating plant growth and development.
Effects of a combined lifestyle score on 10-year mortality in Korean men and women: a prospective cohort study
Authors: Yun Ji Eun , Won Soyoung , Kimm Heejin , Jee Sun Ha 
Published: August 2012

Abstract

Background
Most studies that have evaluated the association between combined lifestyle factors and mortality outcomes have been conducted in populations of Caucasian origin. The objective of this study was to examine the association between combined lifestyle scores and the risk of mortality in Korean men and women.

Methods
The study population included 59,941 Koreans, 30–84 years of age, who had visited the Severance Health Promotion Center between 1994 and 2003. Cox regression models were fitted to establish the association between combined lifestyle factors (current smoker, heavy daily alcohol use, overweight or obese weight, physical inactivity, and unhealthy diet) and mortality outcomes.

Results
During 10.3 years of follow-up, there were 2,398 cases of death from any cause. Individual and combined lifestyle factors were found to be associated with the risk of mortality. Compared to those having none or only one risk factor, in men with a combination of four lifestyle factors, the relative risk for cancer mortality was 2.04-fold, for non-cancer mortality 1.92-fold, and for all-cause mortality 2.00-fold. In women, the relative risk was 2.00-fold for cancer mortality, 2.17-fold for non-cancer mortality, and 2.09-fold for all-cause mortality. The population attributable risks for all-cause mortality for the four risk factors combined was 44.5% for men and 26.5% for women.

Conclusion
This study suggests that having a high (unhealthy) lifestyle score, in contrast to a low (healthy) score, can substantially increase the risk of death by any cause, cancer, and non-cancer in Korean men and women.