bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Changes in Ejection Fraction in Heart Failure Patients With Preserved and Reduced Ejection Fraction
Authors: Dunlay Shannon M. , Roger Véronique L. , Weston Susan A. , Jiang Ruoxiang , Redfield Margaret M. 
Published: September 2012

Background—
Heart failure (HF) can occur in patients with preserved (HFpEF, EF≥50%) or reduced (HFrEF, EF<50%) ejection fraction (EF), but changes in EF after HF diagnosis are not well described.

Methods and Results—

Among a community cohort of incident HF patients diagnosed from 1984 to 2009 in Olmsted County, Minnesota, we obtained all EFs assessed by echocardiography from initial HF diagnosis until death or last follow-up through March 2010. Mixed effects models fit a unique linear regression line for each person using serial EF data. Compiled results allowed estimates of the change in EF over time in HFpEF and HFrEF. Among 1233 HF patients (48.3% male, mean age 75.0 years, mean follow-up 5.1 years), 559 (45.3%) had HFpEF at diagnosis. In HFpEF, on average, EF decreased by 5.8% over 5 years (
P
<0.001) with greater declines in older individuals and those with coronary disease. Conversely, EF increased in HFrEF (average increase 6.9% over 5 years,
P
<0.001). Greater increases were noted in women, younger patients, individuals without coronary disease, and those treated with evidence-based medications. Overall, 39% of HFpEF patients had an EF<50% and 39% of HFrEF patients had an EF≥50% at some point after diagnosis. Decreases in EF over time were associated with reduced survival whereas increases in EF were associated with improved survival.

Conclusions—
These data suggest that progressive contractile dysfunction may contribute to the pathophysiology of HFpEF. Prospective longitudinal studies are needed to confirm these observations and establish the mechanism and clinical relevance of decline in EF over time in HFpEF.
Changes in the Risk of Extratropical Cyclones in Eastern Australia
Authors: Dowdy Andrew J. , Mills Graham A. , Timbal Bertrand , Wang Yang 
Published: September 2012

Abstract
The east coast of Australia is a region of the world where a particular type of extratropical cyclone, known locally as an east coast low, frequently occurs with severe consequences such as extreme rainfall, winds, and waves. The likelihood of formation of these storms is examined using an upper-tropospheric diagnostic applied to three reanalyses and three global climate models (GCMs). Strong similarities exist among the results derived from the individual reanalyses in terms of their seasonal variability (e.g., winter maxima and summer minima) and interannual variability. Results from reanalyses indicate that the threshold value used in the diagnostic method is dependent on the spatial resolution. Results obtained when applying the diagnostic to two of the three GCMs are similar to expectations given their spatial resolutions, and produce seasonal cycles similar to those from the reanalyses. Applying the methodology to simulations from these two GCMs for both current and future climate in response to increases in greenhouse gases indicates a reduction in extratropical cyclone occurrence of about 30% from the late twentieth century to the late twenty-first century for eastern Australia. In addition to the absolute risk of formation of these extratropical cyclones, spatial climatologies of occurrence are examined for the broader region surrounding eastern Australia. The influence of large-scale modes of atmospheric and oceanic variability on the occurrence of these storms in this region is also discussed.
Crosswinds from a Single-Aperture Scintillometer Using Spectral Techniques
Authors: van Dinther Daniëlle , Hartogensis Oscar K. , Moene Arnold F. 
Published: September 2012

Abstract
In this study, spectral techniques to obtain crosswinds from a single large-aperture scintillometer (SLAS) time series are investigated. The crosswind is defined as the wind component perpendicular to a path. A scintillometer obtains a path-averaged estimate of the crosswind. For certain applications this can be advantageous (e.g., monitoring crosswinds along airport runways). The essence of the spectral techniques lies in the fact that the scintillation power spectrum shifts linearly along the frequency domain as a function of the crosswind. Three different algorithms are used, which are called herein the corner frequency (CF), maximum frequency (MF), and cumulative spectrum (CS) techniques. The algorithms track the frequency shift of a characteristic point in different representations of the scintillation power spectrum. The spectrally derived crosswinds compare well with sonic anemometer estimates. The CS algorithm obtained the best results for the crosswind when compared with the sonic anemometer. However, the MF algorithm was most robust in obtaining the crosswind. Over short time intervals (&lt;1 min) the crosswind can be obtained with the CS algorithm using wavelet instead of fast Fourier transformation to calculate the power scintillation spectra.
Effect of organomodified montmorillonite on acoustic properties of wood–plastic nanocomposites
Authors: Kord Behzad , Tajik Milad 
Published: September 2012

In this study, the effect of organomodified montmorillonite (OMMT) on the acoustic properties and clay dispersion of polypropylene (PP)/wood flour (WF) composites was investigated. To meet this objective, the blend composites were prepared through the melt mixing of PP/WF at 50% weight ratios, with various amounts of OMMT (0, 3, and 6 per hundred compounds (phc)) in hake internal mixer then the samples made by injection molding. The amount of coupling agent was fixed at 2 phc for all formulations. The acoustic properties such as speed of sound propagation, time of sound propagation, and sound energy absorbance were evaluated. Results indicated that the time of sound propagation and sound energy absorbance of composites increased with increase in OMMT. However, the speed of sound propagation decreased with the increase in OMMT loading. Also, the biggest improvement of the tensile modulus can be achieved for the nanoclay loading at 3 phc. X-Ray diffraction patterns and transmission electron microscopy revealed that the nanocomposites formed were intercalated. Also, morphological findings showed that samples containing 3 phc of OMMT had higher order of intercalation.
Therapeutic misconception in research subjects: Development and validation of a measure
Authors: Appelbaum Paul S , Anatchkova Milena , Albert Karen , Dunn Laura B , Lidz Charles W 
Published: September 2012

Background Therapeutic misconception (TM), which occurs when research subjects fail to appreciate the distinction between the imperatives of clinical research and ordinary treatment, may undercut the process of obtaining meaningful consent to clinical research participation. Previous studies have found that TM is widespread, but progress in addressing TM has been stymied by the absence of a validated method for assessing its presence. Purpose The goal of this study was to develop and validate a theoretically grounded measure of TM, assess its diagnostic accuracy, and test previous findings regarding TM’s prevalence. Methods A total of 220 participants were recruited from clinical trials at four academic medical centers in the United States. Participants completed a 28-item Likert-type questionnaire to assess the presence of beliefs associated with TM, and a semistructured TM interview designed to elicit their perceptions of the nature of the clinical trial in which they were participating. Data from the questionnaires were subjected to factor analysis, and items with poor factor loadings were excluded. This resulted in a 10-item scale, with three strongly correlated factors and excellent internal consistency; the fit indices of the model across 10 training sets were consistent with the original results, suggesting a stable factor solution. Results The scale was validated against the TM interview, with significantly higher scores among subjects coded as displaying evidence of TM. Receiver operating curve (ROC) analysis based on a 10-fold internal cross-validation yielded area under the ROC (AUC) = 0.682 for any evidence of TM. When sensitivity (0.72) and specificity (0.61) were both optimized, positive predictive value was 0.65 and negative predictive value was 0.68, with a positive likelihood ratio of 1.89 and a negative likelihood ratio of 0.47. In all, 50.5% (n = 101) of the participants manifested evidence of TM on the TM interview, a somewhat lower rate than in most previous studies. Limitations The predictive value of the scale compared with the ‘gold standard’ clinical interview is modest, although similar to other instruments based on self-report assessing states of mind rather than discrete symptoms. Thus, although the scale can offer evidence of which subjects are at risk for distortions in their decisions and to what degree, it will not allow researchers to conclude definitively that TM is present in a given subject. Conclusions The development of a reliable and valid TM scale, even with modest predictive power, should permit investigators in clinical trials to identify subjects with tendencies to misinterpret the nature of the situation and to provide additional information to them. It should also stimulate research on how best to decrease TM and facilitate meaningful informed consent to clinical research.
A Rare Case of Tuberculosis of the Midfoot
Authors: Ferguson Kim B. , Elias Jones Cameron , Thomson Allan George , Moir John Stuart 
Published: September 2012

Despite the increasing prevalence of tuberculosis in developed countries, tuberculous osteomyelitis of the foot remains an uncommon complication. The relative rarity of such a diagnosis means that delays are often incurred before clinicians can correctly identify the pathogen and therefore instigate appropriate chemotherapy. The authors present a case of midfoot pain secondary to tuberculous osteomyelitis. Levels of Evidence: Therapeutic, Level IV: Case Study
Adaptor protein Lnk binds to and inhibits normal and leukemic FLT3
Authors: Lin De-Chen , Yin Tong , Koren-Michowitz Maya , Ding Ling-Wen , Gueller Saskia , Gery Sigal , Tabayashi Takayuki , Bergholz Ulla , Kazi Julhash U. , Rönnstrand Lars , Stocking Carol , Koeffler H. Phillip 
Published: September 2012

Abstract
Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase with important roles in hematopoietic progenitor cell survival and proliferation. It is mutated in approximately one-third of AML patients, mostly by internal tandem duplications (ITDs). Adaptor protein Lnk is a negative regulator of hematopoietic cytokine signaling. In the present study, we show that Lnk interacts physically with both wild-type FLT3 (FLT3-WT) and FLT3-ITD through the SH2 domains. We have identified the tyrosine residues 572, 591, and 919 of FLT3 as phosphorylation sites involved in direct binding to Lnk. Lnk itself was tyrosine phosphorylated by both FLT3 ligand (FL)–activated FLT3-WT and constitutively activated FLT3-ITD. Both shRNA-mediated depletion and forced overexpression of Lnk demonstrated that activation signals emanating from both forms of FLT3 are under negative regulation by Lnk. Moreover, Lnk inhibited 32D cell proliferation driven by different FLT3 variants. Analysis of primary BM cells from Lnk-knockout mice showed that Lnk suppresses the expansion of FL-stimulated hematopoietic progenitors, including lymphoid-primed multipotent progenitors. The results of the present study show that through direct binding to FLT3, Lnk suppresses FLT3-WT/ITD–dependent signaling pathways involved in the proliferation of hematopoietic cells. Therefore, modulation of Lnk expression levels may provide a unique therapeutic approach for FLT3-ITD–associated hematopoietic disease.
Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype
Authors: Robinson Claire M , Neary Roisin , Levendale Ashleigh , Watson Chris J , Baugh John A 
Published: September 2012

Abstract

Background
Pulmonary fibrosis is a debilitating and lethal disease with no effective treatment options. Understanding the pathological processes at play will direct the application of novel therapeutic avenues. Hypoxia has been implicated in the pathogenesis of pulmonary fibrosis yet the precise mechanism by which it contributes to disease progression remains to be fully elucidated. It has been shown that chronic hypoxia can alter DNA methylation patterns in tumour-derived cell lines. This epigenetic alteration can induce changes in cellular phenotype with promoter methylation being associated with gene silencing. Of particular relevance to idiopathic pulmonary fibrosis (IPF) is the observation that Thy-1 promoter methylation is associated with a myofibroblast phenotype where loss of Thy-1 occurs alongside increased alpha smooth muscle actin (α-SMA) expression. The initial aim of this study was to determine whether hypoxia regulates DNA methylation in normal human lung fibroblasts (CCD19Lu). As it has been reported that hypoxia suppresses Thy-1 expression during lung development we also studied the effect of hypoxia on Thy-1 promoter methylation and gene expression.

Methods
CCD19Lu were grown for up to 8 days in hypoxia and assessed for global changes in DNA methylation using flow cytometry. Real-time PCR was used to quantify expression of Thy-1, α-SMA, collagen I and III. Genomic DNA was bisulphite treated and methylation specific PCR (MSPCR) was used to examine the methylation status of the Thy-1 promoter.

Results
Significant global hypermethylation was detected in hypoxic fibroblasts relative to normoxic controls and was accompanied by increased expression of myofibroblast markers. Thy-1 mRNA expression was suppressed in hypoxic cells, which was restored with the demethylating agent 5-aza-2′-deoxycytidine. MSPCR revealed that Thy-1 became methylated following fibroblast exposure to 1% O2.

Conclusion
These data suggest that global and gene-specific changes in DNA methylation may play an important role in fibroblast function in hypoxia.
Sequencing and analysis of a South Asian-Indian personal genome
Authors: Gupta Ravi , Ratan Aakrosh , Rajesh Changanamkandath , Chen Rong , Kim Hie Lim , Burhans Richard , Miller Webb , Santhosh Sam , Davuluri Ramana V , Butte Atul J , Schuster Stephan C , Seshagiri Somasekar , Thomas George 
Published: September 2012

Abstract

Background
With over 1.3 billion people, India is estimated to contain three times more genetic diversity than does Europe. Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost. While genomes from people of European and Asian descent have been sequenced, only recently has a single male genome from the Indian subcontinent been published at sufficient depth and coverage. In this study we have sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala.

Results
We identified over 3.4 million SNPs in this genome including over 89,873 private variations. Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes. Analysis of the SAIF mitochondrial genome showed that it was closely related to the U1 haplogroup which has been previously observed in Kerala. We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases. In analyzing SNPs that modulate drug response, we found a variation that predicts a favorable response to metformin, a drug used to treat diabetes. SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin. In addition, we report the presence of several additional SNPs of medical relevance.

Conclusions
This is the first study to report the complete whole genome sequence of a female from the state of Kerala in India. The availability of this complete genome and variants will further aid studies aimed at understanding genetic diversity, identifying clinically relevant changes and assessing disease burden in the Indian population.
The lavender plumage colour in Japanese quail is associated with a complex mutation in the region of MLPH that is related to differences in growth, feed consumption and body temperature
Authors: Bed’hom Bertrand , Vaez Mohsen , Coville Jean-Luc , Gourichon David , Chastel Olivier , Follett Sarah , Burke Terry , Minvielle Francis 
Published: September 2012

Abstract

Background
The lavender phenotype in quail is a dilution of both eumelanin and phaeomelanin in feathers that produces a blue-grey colour on a wild-type feather pattern background. It has been previously demonstrated by intergeneric hybridization that the lavender mutation in quail is homologous to the same phenotype in chicken, which is caused by a single base-pair change in exon 1 of MLPH.

Results
In this study, we have shown that a mutation of MLPH is also associated with feather colour dilution in quail, but that the mutational event is extremely different. In this species, the lavender phenotype is associated with a non-lethal complex mutation involving three consecutive overlapping chromosomal changes (two inversions and one deletion) that have consequences on the genomic organization of four genes (MLPH and the neighbouring PRLH, RAB17 and LRRFIP1). The deletion of PRLH has no effect on the level of circulating prolactin. Lavender birds have lighter body weight, lower body temperature and increased feed consumption and residual feed intake than wild-type plumage quail, indicating that this complex mutation is affecting the metabolism and the regulation of homeothermy.

Conclusions
An extensive overlapping chromosome rearrangement was associated with a non-pathological Mendelian trait and minor, non deleterious effects in the lavender Japanese quail which is a natural knockout for PRLH.
Pregnancy loss and role of infant HIV status on perinatal mortality among HIV-infected women
Authors: Kim Hae-Young , Kasonde Prisca , Mwiya Mwiya , Thea Donald M , Kankasa Chipepo , Sinkala Moses , Aldrovandi Grace , Kuhn Louise 
Published: September 2012

Abstract

Background
HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth) and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status.

Methods
A total of 1229 HIV-infected pregnant women were enrolled (2001–2004) in Lusaka, Zambia and followed to pregnancy outcome. Live-born infants were tested for HIV by PCR at birth, 1 week and 5 weeks. Obstetric and neonatal data were collected after delivery and the rates of neonatal (<28 days) and early mortality (<70 days) were described using Kaplan-Meier methods.

Results
The ratio of miscarriage and stillbirth per 100 live-births were 3.1 and 2.6, respectively. Higher maternal plasma viral load (adjusted odds ratio [AOR] for each log10 increase in HIV RNA copies/ml = 1.90; 95% confidence interval [CI] 1.10–3.27) and being symptomatic were associated with an increased risk of stillbirth (AOR = 3.19; 95% CI 1.46–6.97), and decreasing maternal CD4 count by 100 cells/mm3 with an increased risk of miscarriage (OR = 1.25; 95% CI 1.02–1.54). The neonatal mortality rate was 4.3 per 100 increasing to 6.3 by 70 days. Intrauterine HIV infection was not associated with neonatal morality but became associated with mortality through 70 days (adjusted hazard ratio = 2.76; 95% CI 1.25–6.08). Low birth weight and cessation of breastfeeding were significant risk factors for both neonatal and early mortality independent of infant HIV infection.

Conclusions
More advanced maternal HIV disease was associated with adverse pregnancy outcomes. Excess neonatal mortality in HIV-infected women was not primarily explained by infant HIV infection but was strongly associated with low birth weight and prematurity. Intrauterine HIV infection contributed to mortality as early as 70 days of infant age. Interventions to improve pregnancy outcomes for HIV-infected women are needed to complement necessary therapeutic and prophylactic antiretroviral interventions.
Identifying obesity indicators which best correlate with type 2 diabetes in a Chinese population
Authors: Xin Zhong , Liu Chang , Niu Wen-Yan , Feng Jian-Ping , Zhao Lei , Ma Ya-Hong , Hua Lin , Yang Jin-Kui 
Published: September 2012

Background
Obesity has been shown to be a prognostic indicator of type 2 diabetes (T2D); however, the power of different obesity indicators in the detection of T2D remains controversial. This study evaluates the detecting power of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHTR) for the presence of T2D in undiagnosed diabetics among the Chinese population.

Methods

Individuals were selected from an ongoing large-scale population-based Beijing Community Pre-Diabetes (BCPD) study cohort. The oral glucose tolerance tests (OGTT) were performed to diagnose diabetes. A total of 220 new cases of T2D and 1,868 normal blood glucose subjects were analyzed. ROC curve analyses were used to compare the association of different obesity indicators with T2D and determine the optimal cut-off points of the best predictor for identifying T2D in men and women.

Results

All indicators positively correlated with presence of T2D in both men and women. In women, WC, WHR and WHTR were similar, but were better in identifying T2D when compared to BMI (P < 0.0001, P=0.0016 and P=0.0001, respectively). In men, WC, WHTR and BMI were similar, but WC and WHTR were better than WHR (P=0.0234, P=0.0101, respectively). For women, 86 cm was the optimal WC cut-off point, and its sensitivity and specificity were 0.714 and 0.616; for men, the optimal cut-off point was 90 cm, and its sensitivity and specificity were 0.722 and 0.571.

Conclusion

Compared with BMI, WHR and WHTR, WC is a simple and accurate measure for predicting T2D in the Chinese population.
Electro-acupuncture on functional peripheral nerve regeneration in mice: a behavioural study
Authors: Hoang Ngoc Son , Sar Chamroeun , Valmier Jean , Sieso Victor , Scamps Frédérique 
Published: September 2012

Abstract

Background
The improvement of axonal regeneration is a major objective in the treatment of peripheral nerve injuries. The aim of this study was to evaluate the effects of electro-acupuncture on the functional recovery of sensorimotor responses following left sciatic nerve crush in mice.

Methods
Sciatic nerve crush was performed on seven week old female mice. Following the injury, the control group was untreated while the experimental group received an electro-acupuncture application to the injured limb under isoflurane anesthesia at acupoints GB 30 and GB 34. Mechanical and heat sensitivity tests were performed to evaluate sensory recovery. Gait analysis was performed to assess sensorimotor recovery.

Results
Our results show that normal sensory recovery is achieved within five to six weeks with a two-week period of pain preceding the recovery to normal sensitivity levels. While electro-acupuncture did not accelerate sensory recovery, it did alleviate pain-related behaviour but only when applied during this period. Application before the development of painful symptoms did not prevent their occurrence. The analysis of gait in relation to the sensory tests suggests that the electro-acupuncture specifically improved motor recovery.

Conclusions
This study demonstrates that electro-acupuncture exerts a positive influence on motor recovery and is efficient in the treatment of pain symptoms that develop during target re-innervation.