bluuebunny/crossref_metadata_2025_split huggingface dataset:
Best lung function equations for the very elderly selected by survival analysis
Authors: Miller Martin R. , Thinggaard Mikael , Christensen Kaare , Pedersen Ole F. , Sigsgaard Torben 
Published: February 2014

We evaluated which equations best predicted the lung function of a cohort of nonagenarians based on which best accounted for subsequent survival.In 1998, we measured lung function, grip strength and dementia score (Mini Mental State Examination (MMSE)) in a population-based sample of 2262 Danes born in 1905. Mortality was registered to 2011 when only five (0.2%) subjects were alive. In half the cohort, we recorded forced expiratory volume in 1 s (FEV1).Complete data were available in 592 subjects with results expressed as standardised residuals (SR) using various prediction equations. Cox proportional hazard regression found lower FEV1SR was a predictor of mortality having controlled for MMSE, grip strength and sex. The US National Health and Nutrition Examination Survey (NHANES) III (1999) equations gave a better spread of median survival by FEV1SR quartile: 3.94, 3.65, 3.51 and 2.61 years with a hazard ratio for death of 1, 1.16, 1.32 and 1.60 respectively, compared with equations derived with the inclusion of elderly subjects.We conclude that extrapolating from NHANES III equations to predict lung function in nonagenarians gave better survival predictions from spirometry than when employing equations derived using very elderly subjects with possible selection bias. These findings can help inform how future lung function equations for the elderly are derived.
Association of ambient air pollution with the prevalence and incidence of COPD
Authors: Schikowski Tamara , Adam Martin , Marcon Alessandro , Cai Yutong , Vierkötter Andrea , Carsin Anne Elie , Jacquemin Benedicte , Al Kanani Zaina , Beelen Rob , Birk Matthias , Bridevaux Pierre-Olivier , Brunekeef Bert , Burney Peter , Cirach Marta , Cyrys Josef , de Hoogh Kees , de Marco Roberto , de Nazelle Audrey , Declercq Christophe , Forsberg Bertil , Hardy Rebecca , Heinrich Joachim , Hoek Gerard , Jarvis Debbie , Keidel Dirk , Kuh Diane , Kuhlbusch Thomas , Migliore Enrica , Mosler Gioia , Nieuwenhuijsen Mark J. , Phuleria Harish , Rochat Thierry , Schindler Christian , Villani Simona , Tsai Ming-Yi , Zemp Elisabeth , Hansell Anna , Kauffmann Francine , Sunyer Jordi , Probst-Hensch Nicole , Krämer Ursula , Künzli Nino 
Published: February 2014

The role of air pollution in chronic obstructive pulmonary disease (COPD) remains uncertain.The aim was to assess the impact of chronic exposure to air pollution on COPD in four cohorts using the standardised ESCAPE exposure estimates. Annual average particulate matter (PM), nitrogen oxides (NOx) and road traffic exposure were assigned to home addresses using land-use regression models. COPD was defined by NHANES reference equation (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than the lower limit of normal) and the Global Initiative for Chronic Obstructive Lung Disease criterion (FEV1/FVC <0.70) and categorised by severity in non-asthmatics.We included 6550 subjects with assigned NOxand 3692 with PM measures. COPD was not associated with NO2or PM10in any individual cohort. In meta-analyses only NO2, NOx, PM10and the traffic indicators were positively, although not significantly, associated with COPD. The only statistically significant associations were seen in females (COPD prevalence using GOLD: OR 1.57, 95% CI 1.11–2.23; and incidence: OR 1.79, 95% CI 1.21–2.68).None of the principal results were statistically significant, the weak positive associations of exposure with COPD and the significant subgroup findings need to be evaluated in further well standardised cohorts followed up for longer time, and with time-matched exposure assignments.
Is continuous positive airway pressure necessarily an everyday therapy in patients with obstructive sleep apnoea?
Authors: Rossi Valentina A. , Schwarz Esther I. , Bloch Konrad E. , Stradling John R. , Kohler Malcolm 
Published: February 2014

There are limited data on the evolution of obstructive sleep apnoea (OSA) during continuous positive airway pressure (CPAP) therapy and whether this treatment is required every night.125 OSA patients with an original oxygen desaturation index (ODI) >10 events per hour, established on CPAP, were asked to withdraw CPAP for four nights and performed ambulatory nocturnal pulse oximetry on the fourth night of CPAP withdrawal. An ODI >10 events per hour during pulse oximetry was considered to indicate persistent OSA. Patients not experiencing recurrence of OSA underwent repeat ambulatory pulse oximetry after a further 2-week period off CPAP.In 71% of the patients, OSA recurred after four nights of CPAP withdrawal (group 1); thus, OSA did not recur in 29% (group 2). 55% of group 2 had an ODI >10 events per hour after 2 weeks off CPAP; thus, 45% remained without a recurrence. In multivariate analysis, higher original ODI, longer duration of CPAP therapy, current smoking status and larger neck circumference were independently associated with a higher ODI after four nights of CPAP withdrawal (all p<0.05).Following CPAP withdrawal, a third of CPAP-treated patients do not experience significant recurrence of oxygen desaturations after 4 days and ∼10% do not after 2 weeks. Thus, a significant proportion of patients may be able to stop CPAP for short periods.
Prevalence of night-time dyspnoea in COPD and its implications for prognosis
Authors: Lange Peter , Marott Jacob Louis , Vestbo Jørgen , Nordestgaard Børge Grønne 
Published: February 2014

The information on night-time symptoms in chronic obstructive pulmonary disease (COPD) is sparse.We investigated the prevalence of night-time dyspnoea in 6616 individuals with COPD recruited from the general population in the Copenhagen area, Denmark, and described characteristics and prognosis of subjects with this symptom.The prevalence of night-time dyspnoea was 4.3%: 2.1% in Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A, 12.9% in GOLD B, 2.6% in GOLD C and 16.3% in GOLD D. Compared with individuals without night-time dyspnoea, those with night time dyspnoea had lower forced expiratory volume in 1 s, higher daytime dyspnoea scores (modified Medical Research Council scale) and more wheezing, more often had chronic mucus hypersecretion, ischaemic heart disease and atrial fibrillation, and more often reported stress, nervousness and tiredness. After adjustment for age and sex, the presence of night-time dyspnoea was associated with future COPD exacerbations (hazard ratio (HR) 2.3, 95% CI 1.7–3.0), hospital admissions due to COPD (HR 3.2, 95% CI 2.3–4.4) and mortality (HR 1.7, 95% CI 1.2–2.3).Prevalence of night-time dyspnoea in COPD increases with disease severity according to both spirometric and clinical GOLD classification, and is associated with presence of daytime respiratory symptoms and cardiac comorbidities. Night-time dyspnoea is a significant predictor of poor prognosis in individuals with COPD.
Inferring clonal evolution of tumors from single nucleotide somatic mutations
Authors: Jiao Wei , Vembu Shankar , Deshwar Amit G , Stein Lincoln , Morris Quaid 
Published: February 2014

Abstract

Background
High-throughput sequencing allows the detection and quantification of frequencies of somatic single nucleotide variants (SNV) in heterogeneous tumor cell populations. In some cases, the evolutionary history and population frequency of the subclonal lineages of tumor cells present in the sample can be reconstructed from these SNV frequency measurements. But automated methods to do this reconstruction are not available and the conditions under which reconstruction is possible have not been described.

Results
We describe the conditions under which the evolutionary history can be uniquely reconstructed from SNV frequencies from single or multiple samples from the tumor population and we introduce a new statistical model, PhyloSub, that infers the phylogeny and genotype of the major subclonal lineages represented in the population of cancer cells. It uses a Bayesian nonparametric prior over trees that groups SNVs into major subclonal lineages and automatically estimates the number of lineages and their ancestry. We sample from the joint posterior distribution over trees to identify evolutionary histories and cell population frequencies that have the highest probability of generating the observed SNV frequency data. When multiple phylogenies are consistent with a given set of SNV frequencies, PhyloSub represents the uncertainty in the tumor phylogeny using a “partial order plot”. Experiments on a simulated dataset and two real datasets comprising tumor samples from acute myeloid leukemia and chronic lymphocytic leukemia patients demonstrate that PhyloSub can infer both linear (or chain) and branching lineages and its inferences are in good agreement with ground truth, where it is available.

Conclusions
PhyloSub can be applied to frequencies of any “binary” somatic mutation, including SNVs as well as small insertions and deletions. The PhyloSub and partial order plot software is available from https://github.com/morrislab/phylosub/.
uPEPperoni: An online tool for upstream open reading frame location and analysis of transcript conservation
Authors: Skarshewski Adam , Stanton-Cook Mitchell , Huber Thomas , Al Mansoori Sumaya , Smith Ross , Beatson Scott A , Rothnagel Joseph A 
Published: February 2014

Abstract

Background
Several small open reading frames located within the 5′ untranslated regions of mRNAs have recently been shown to be translated. In humans, about 50% of mRNAs contain at least one upstream open reading frame representing a large resource of coding potential. We propose that some upstream open reading frames encode peptides that are functional and contribute to proteome complexity in humans and other organisms. We use the term uPEPs to describe peptides encoded by upstream open reading frames.

Results
We have developed an online tool, termed uPEPperoni, to facilitate the identification of putative bioactive peptides. uPEPperoni detects conserved upstream open reading frames in eukaryotic transcripts by comparing query nucleotide sequences against mRNA sequences within the NCBI RefSeq database. The algorithm first locates the main coding sequence and then searches for open reading frames 5′ to the main start codon which are subsequently analysed for conservation. uPEPperoni also determines the substitution frequency for both the upstream open reading frames and the main coding sequence. In addition, the uPEPperoni tool produces sequence identity heatmaps which allow rapid visual inspection of conserved regions in paired mRNAs.

Conclusions
uPEPperoni features user-nominated settings including, nucleotide match/mismatch, gap penalties, Ka/Ks ratios and output mode. The heatmap output shows levels of identity between any two sequences and provides easy recognition of conserved regions. Furthermore, this web tool allows comparison of evolutionary pressures acting on the upstream open reading frame against other regions of the mRNA. Additionally, the heatmap web applet can also be used to visualise the degree of conservation in any pair of sequences. uPEPperoni is freely available on an interactive web server at http://upep-scmb.biosci.uq.edu.au.
Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies
Authors: Kalko Susana Graciela , Paco Sonia , Jou Cristina , Rodríguez Maria Angels , Meznaric Marija , Rogac Mihael , Jekovec-Vrhovsek Maja , Sciacco Monica , Moggio Maurizio , Fagiolari Gigliola , De Paepe Boel , De Meirleir Linda , Ferrer Isidre , Roig-Quilis Manel , Munell Francina , Montoya Julio , López-Gallardo Ester , Ruiz-Pesini Eduardo , Artuch Rafael , Montero Raquel , Torner Ferran , Nascimento Andres , Ortez Carlos , Colomer Jaume , Jimenez-Mallebrera Cecilia 
Published: February 2014

Abstract

Background
Mutations in the gene encoding thymidine kinase 2 (TK2) result in the myopathic form of mitochondrial DNA depletion syndrome which is a mitochondrial encephalomyopathy presenting in children. In order to unveil some of the mechanisms involved in this pathology and to identify potential biomarkers and therapeutic targets we have investigated the gene expression profile of human skeletal muscle deficient for TK2 using cDNA microarrays.

Results
We have analysed the whole transcriptome of skeletal muscle from patients with TK2 mutations and compared it to normal muscle and to muscle from patients with other mitochondrial myopathies. We have identified a set of over 700 genes which are differentially expressed in TK2 deficient muscle. Bioinformatics analysis reveals important changes in muscle metabolism, in particular, in glucose and glycogen utilisation, and activation of the starvation response which affects aminoacid and lipid metabolism. We have identified those transcriptional regulators which are likely to be responsible for the observed changes in gene expression.

Conclusion
Our data point towards the tumor suppressor p53 as the regulator at the centre of a network of genes which are responsible for a coordinated response to TK2 mutations which involves inflammation, activation of muscle cell death by apoptosis and induction of growth and differentiation factor 15 (GDF-15) in muscle and serum. We propose that GDF-15 may represent a potential novel biomarker for mitochondrial dysfunction although further studies are required.
Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines
Authors: Li Liang , Fridley Brooke L , Kalari Krishna , Niu Nifang , Jenkins Gregory , Batzler Anthony , Abo Ryan P , Schaid Daniel , Wang Liewei 
Published: February 2014

Abstract

Background
Two cytidine analogues, gemcitabine and cytosine arabinoside (AraC), are widely used in the treatment of a variety of cancers with a large individual variation in response. To identify potential genetic biomarkers associated with response to these two drugs, we used a human lymphoblastoid cell line (LCL) model system with extensive genomic data, including 1.3 million SNPs and 54,000 basal expression probesets to perform genome-wide association studies (GWAS) with gemcitabine and AraC IC50 values.

Results
We identified 11 and 27 SNP loci significantly associated with gemcitabine and AraC IC50 values, respectively. Eleven candidate genes were functionally validated using siRNA knockdown approach in multiple cancer cell lines. We also characterized the potential mechanisms of genes by determining their influence on the activity of 10 cancer-related signaling pathways using reporter gene assays. Most SNPs regulated gene expression in a trans manner, except 7 SNPs in the PIGB gene that were significantly associated with both the expression of PIGB and gemcitabine cytotoxicity.

Conclusion
These results suggest that genetic variation might contribute to drug response via either cis- or trans- regulation of gene expression. GWAS analysis followed by functional pharmacogenomics studies might help identify novel biomarkers contributing to variation in response to these two drugs and enhance our understanding of underlying mechanisms of drug action.
Aberrant phenotype and transcriptome expression during fiber cell wall thickening caused by the mutation of the Im gene in immature fiber (im) mutant in Gossypium hirsutum L
Authors: Wang Cheng , Lv Yuanda , Xu Wentin , Zhang Tianzhen , Guo Wangzhen 
Published: February 2014

AbstractBackgroundThe immature fiber (im) mutant ofGossypium hirsutumL. is a special cotton fiber mutant with non-fluffy fibers. It has low dry weight and fineness of fibers due to developmental defects in fiber secondary cell wall (SCW).ResultsWe compared the cellulose content in fibers, thickness of fiber cell wall and fiber transcriptional profiling during SCW development inimmutant and its near-isogenic wild-type line (NIL) TM-1. Theimmutant had lower cellulose content and thinner cell walls than TM-1 at same fiber developmental stage. During 25 ~ 35 day post-anthesis (DPA), sucrose content, an important carbon source for cellulose synthesis, was also significantly lower inimmutant than in TM-1. Comparative analysis of fiber transcriptional profiling from 13 ~ 25 DPA indicated that the largest transcriptional variations between the two lines occurred at the onset of SCW development. TM-1 began SCW biosynthesis approximately at 16 DPA, whereas the same fiber developmental program inimmutant was delayed until 19 DPA, suggesting an asynchronous fiber developmental program between TM-1 andimmutant. Functional classification and enrichment analysis of differentially expressed genes (DEGs) between the two NILs indicated that genes associated with biological processes related to cellulose synthesis, secondary cell wall biogenesis, cell wall thickening and sucrose metabolism, respectively, were significantly up-regulated in TM-1. Twelve genes related to carbohydrate metabolism were validated by quantitative reverse transcription PCR (qRT-PCR) and confirmed a temporal difference at the earlier transition and SCW biosynthesis stages of fiber development between TM-1 andimmutant.ConclusionsWe propose thatImis an important regulatory gene influencing temporal differences in expression of genes related to fiber SCW biosynthesis. This study lays a foundation for cloning theImgene, elucidating molecular mechanism of fiber SCW development and further genetic manipulation for the improvement of fiber fineness and maturity.
Smoking cessation advice recorded during pregnancy in United Kingdom primary care
Authors: Hardy Bethany , Szatkowski Lisa , Tata Laila J , Coleman Tim , Dhalwani Nafeesa N 
Published: February 2014

Abstract

Background
United Kingdom (UK) national guidelines recommend that all pregnant women who smoke should be advised to quit at every available opportunity, and brief cessation advice is an efficient and cost-effective means to increase quit rates. The Quality and Outcomes Framework (QOF) implemented in 2004 requires general practitioners to document their delivery of smoking cessation advice in patient records. However, no specific targets have been set in QOF for the recording of this advice in pregnant women. We used a large electronic primary care database from the UK to quantify the pregnancies in which women who smoked were recorded to have been given smoking cessation advice, and the associated maternal characteristics.

Methods
Using The Health Improvement Network database we calculated annual proportions of pregnant smokers between 2000 and 2009 with cessation advice documented in their medical records during pregnancy. Logistic regression was used to assess variation in the recording of cessation advice with maternal characteristics.

Results
Among 45,296 pregnancies in women who smoked, recorded cessation advice increased from 7% in 2000 to 37% in 2004 when the QOF was introduced and reduced slightly to 30% in 2009. Pregnant smokers from the youngest age group (15–19) were 21% more likely to have a record of cessation advice compared to pregnant smokers aged 25–29 (OR 1.21, 95% CI 1.10-1.35) and pregnant smokers from the most deprived group were 38% more likely to have a record for cessation advice compared to pregnant smokers from the least deprived group (OR 1.38, 95% CI 1.14-1.68). Pregnant smokers with asthma were twice as likely to have documentation of cessation advice in their primary care records compared to pregnant smokers without asthma (OR 1.97, 95% CI 1.80-2.16). Presence of comorbidities such as diabetes, hypertension and mental illness also increased the likelihood of having smoking cessation advice recorded. No marked variations were observed in the recording of cessation advice with body mass index.

Conclusion
Recorded delivery of smoking cessation advice for pregnant smokers in primary care has increased with some fluctuation over the years, especially after the implementation of the QOF, and varies with maternal characteristics.
Is the Timed Up and Go test a useful predictor of risk of falls in community dwelling older adults: a systematic review and meta- analysis
Authors: Barry Emma , Galvin Rose , Keogh Claire , Horgan Frances , Fahey Tom 
Published: February 2014

Abstract

Background
The Timed Up and Go test (TUG) is a commonly used screening tool to assist clinicians to identify patients at risk of falling. The purpose of this systematic review and meta-analysis is to determine the overall predictive value of the TUG in community-dwelling older adults.

Methods
A literature search was performed to identify all studies that validated the TUG test. The methodological quality of the selected studies was assessed using the QUADAS-2 tool, a validated tool for the quality assessment of diagnostic accuracy studies. A TUG score of ≥13.5 seconds was used to identify individuals at higher risk of falling. All included studies were combined using a bivariate random effects model to generate pooled estimates of sensitivity and specificity at ≥13.5 seconds. Heterogeneity was assessed using the variance of logit transformed sensitivity and specificity.

Results
Twenty-five studies were included in the systematic review and 10 studies were included in meta-analysis. The TUG test was found to be more useful at ruling in rather than ruling out falls in individuals classified as high risk (>13.5 sec), with a higher pooled specificity (0.74, 95% CI 0.52-0.88) than sensitivity (0.31, 95% CI 0.13-0.57). Logistic regression analysis indicated that the TUG score is not a significant predictor of falls (OR = 1.01, 95% CI 1.00-1.02, p = 0.05).

Conclusion
The Timed Up and Go test has limited ability to predict falls in community dwelling elderly and should not be used in isolation to identify individuals at high risk of falls in this setting.