bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neglected evidence in idiopathic pulmonary fibrosis: from history to earlier diagnosis
Authors: Cordier Jean-François , Cottin Vincent 
Published: April 2013

This perspective highlights some evidence that has hitherto been neglected, especially because it may not have been sufficiently explicated in the clinical respiratory medicine literature. Idiopathic pulmonary fibrosis (IPF) has appeared only in the second half of the 20th century and, like lung cancer and chronic obstructive pulmonary disease, may be a direct consequence of the cigarette smoking epidemic. It is a disease of lung ageing, with most affected patients being >70 years of age. The relationship between lung ageing and pulmonary fibrosis is further illustrated in the bleomycin mouse model, in which older males develop more fibrosis than young female mice.Earlier diagnosis of IPF is a prerequisite for significant progress to be made in the long-term outcome and prognosis. We consider that only two different yet complementary and realistic approaches could lead to earlier diagnosis of IPF and possibly to allowing more efficient disease management: 1) investigating any patients with early Velcro crackles at lung auscultation through proactive education of, and commitment from, primary care physicians; and 2) using current large-scale lung cancer screening strategies with low-dose high-resolution computed tomography in smokers for the detection of subclinical interstitial lung disease and especially early IPF.
The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study
Authors: Hoefsloot Wouter , van Ingen Jakko , Andrejak Claire , Ängeby Kristian , Bauriaud Rosine , Bemer Pascale , Beylis Natalie , Boeree Martin J. , Cacho Juana , Chihota Violet , Chimara Erica , Churchyard Gavin , Cias Raquel , Daza Rosa , Daley Charles L. , Dekhuijzen P.N. Richard , Domingo Diego , Drobniewski Francis , Esteban Jaime , Fauville-Dufaux Maryse , Folkvardsen Dorte Bek , Gibbons Noel , Gómez-Mampaso Enrique , Gonzalez Rosa , Hoffmann Harald , Hsueh Po-Ren , Indra Alexander , Jagielski Tomasz , Jamieson Frances , Jankovic Mateja , Jong Eefje , Keane Joseph , Koh Wo-Jung , Lange Berit , Leao Sylvia , Macedo Rita , Mannsåker Turid , Marras Theodore K. , Maugein Jeannette , Milburn Heather J. , Mlinkó Tamas , Morcillo Nora , Morimoto Kozo , Papaventsis Dimitrios , Palenque Elia , Paez-Peña Mar , Piersimoni Claudio , Polanová Monika , Rastogi Nalin , Richter Elvira , Ruiz-Serrano Maria Jesus , Silva Anabela , da Silva M. Pedro , Simsek Hulya , van Soolingen Dick , Szabó Nora , Thomson Rachel , Tórtola Fernandez Teresa , Tortoli Enrico , Totten Sarah E. , Tyrrell Greg , Vasankari Tuula , Villar Miguel , Walkiewicz Renata , Winthrop Kevin L. , Wagner Dirk 
Published: April 2013

A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide.To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country.We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated.Mycobacterium aviumcomplex (MAC) bacteria predominated in most countries, followed byM. gordonaeandM. xenopi. Important differences in geographical distribution of MAC species as well asM. xenopi, M. kansasiiand rapid-growing mycobacteria were observed.This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location.
Aetiology of paediatric pneumonia after the introduction of pneumococcal conjugate vaccine
Authors: Elemraid Mohamed A. , Sails Andrew D. , Eltringham Gary J.A. , Perry John D. , Rushton Stephen P. , Spencer David A. , Thomas Matthew F. , Eastham Katherine M. , Hampton Fiona , Gennery Andrew R. , Clark Julia E. 
Published: April 2013

We describe the aetiology of community-acquired pneumonia in children before and after the introduction of the pneumococcal conjugate vaccination (PCV) programme in 2006.Prospective studies were conducted in 2001–2002 (pre-vaccine) and 2009–2011 (post-vaccine) of children aged 0–16 years with radiologically confirmed pneumonia seen in hospital. Investigations included culture, serology, immunofluorescence antibody and urine antigen testing, with an increased use of PCR assays and expanded panels of pathogens in the post-vaccine study.241 and 160 children were enrolled in the pre- and post-vaccine studies, respectively (73% aged <5 years). Identification of a causative pathogen was higher post-vaccination (61%) than pre-vaccination (48.5%) (p=0.019). Rates of bacterial infections were not different between post- and pre-vaccine studies (17.5%versus24%, p=0.258). Viral (31%) and mixed (12.5%) infections were found more often post-vaccination (19.5%, p=0.021) than pre-vaccination (5%, p=0.015). Rates of identified pneumococcal infections were comparable between pre- and post-vaccine studies (14.7%versus17.4%, p=0.557). Diagnosis of pneumococcal infection post-vaccination improved when PCR was used compared to culture (21.6%versus6%, p=0.0004). Serotypes included in PCV13 but not PCV7 were identified in 75% (18 out of 24) post-vaccination.Infection with nonvaccine pneumococcal serotypes continues to be a significant cause of pneumonia in children in the UK.
Hermite-Hadamard-type inequalities for "Equation missing" -convex dominated functions
Authors: Özdemir Muhamet Emin , Gürbüz Mustafa , Kavurmacı Havva 
Published: April 2013

Abstract
In this paper, we introduce the notion of

(
g
,

φ
h

)

-convex dominated function and present some properties of them. Finally, we present a version of Hermite-Hadamard-type inequalities for

(
g
,

φ
h

)

-convex dominated functions. Our results generalize the Hermite-Hadamard-type inequalities in Dragomir et al. (Tamsui Oxford Univ. J. Math. Sci. 18(2):161-173, 2002), Kavurmacı et al. (New Definitions and Theorems via Different Kinds of Convex Dominated Functions, 2012) and Özdemir et al. (Two new different kinds of convex dominated functions and inequalities via Hermite-Hadamard type, 2012).

MSC:26D15, 26D10, 05C38.
Convergent evolution of [D-Leucine1] microcystin-LR in taxonomically disparate cyanobacteria
Authors: Shishido Tânia Keiko , Kaasalainen Ulla , Fewer David P , Rouhiainen Leo , Jokela Jouni , Wahlsten Matti , Fiore Marli Fátima , Yunes João Sarkis , Rikkinen Jouko , Sivonen Kaarina 
Published: April 2013

Abstract

Background
Many important toxins and antibiotics are produced by non-ribosomal biosynthetic pathways. Microcystins are a chemically diverse family of potent peptide toxins and the end-products of a hybrid NRPS and PKS secondary metabolic pathway. They are produced by a variety of cyanobacteria and are responsible for the poisoning of humans as well as the deaths of wild and domestic animals around the world. The chemical diversity of the microcystin family is attributed to a number of genetic events that have resulted in the diversification of the pathway for microcystin assembly.

Results
Here, we show that independent evolutionary events affecting the substrate specificity of the microcystin biosynthetic pathway have resulted in convergence on a rare [D-Leu1] microcystin-LR chemical variant. We detected this rare microcystin variant from strains of the distantly related genera Microcystis, Nostoc, and Phormidium. Phylogenetic analysis performed using sequences of the catalytic domains within the mcy gene cluster demonstrated a clear recombination pattern in the adenylation domain phylogenetic tree. We found evidence for conversion of the gene encoding the McyA2 adenylation domain in strains of the genera Nostoc and Phormidium. However, point mutations affecting the substrate-binding sequence motifs of the McyA2 adenylation domain were associated with the change in substrate specificity in two strains of Microcystis. In addition to the main [D-Leu1] microcystin-LR variant, these two strains produced a new microcystin that was identified as [Met1] microcystin-LR.

Conclusions
Phylogenetic analysis demonstrated that both point mutations and gene conversion result in functional mcy gene clusters that produce the same rare [D-Leu1] variant of microcystin in strains of the genera Microcystis, Nostoc, and Phormidium. Engineering pathways to produce recombinant non-ribosomal peptides could provide new natural products or increase the activity of known compounds. Our results suggest that the replacement of entire adenylation domains could be a more successful strategy to obtain higher specificity in the modification of the non-ribosomal peptides than point mutations.
Evolution and variability of Solanum RanGAP2, a cofactor in the incompatible interaction between the resistance protein GPA2 and the Globodera pallida effector Gp-RBP-1
Authors: Carpentier Jean , Grenier Eric , Esquibet Magalie , Hamel Louis-Philippe , Moffett Peter , Manzanares-Dauleux Maria J , Kerlan Marie-Claire 
Published: April 2013

Abstract

Background
The Ran GTPase Activating Protein 2 (RanGAP2) was first described as a regulator of mitosis and nucleocytoplasmic trafficking. It was then found to interact with the Coiled-Coil domain of the Rx and GPA2 resistance proteins, which confer resistance to Potato Virus X (PVX) and potato cyst nematode Globodera pallida, respectively. RanGAP2 is thought to mediate recognition of the avirulence protein GP-RBP-1 by GPA2. However, the Gpa2-induced hypersensitive response appears to be relatively weak and Gpa2 is limited in terms of spectrum of efficiency as it is effective against only two nematode populations. While functional and evolutionary analyses of Gp-Rbp-1 and Gpa2 identified key residues in both the resistance and avirulence proteins that are involved in recognition determination, whether variation in RanGAP2 also plays a role in pathogen recognition has not been investigated.

Results
We amplified a total of 147 RanGAP2 sequences from 55 accessions belonging to 18 different di-and tetraploid Solanum species from the section Petota. Among the newly identified sequences, 133 haplotypes were obtained and 19.1% of the nucleotide sites were found to be polymorphic. The observed intra-specific nucleotide diversity ranges from 0.1 to 1.3%. Analysis of the selection pressures acting on RanGAP2 suggests that this gene evolved mainly under purifying selection. Nonetheless, we identified polymorphic positions in the protein sequence at the intra-specific level, which could modulate the activity of RanGAP2. Two polymorphic sites and a three amino-acid deletion in RanGAP2 were found to affect the timing and intensity of the Gpa2-induced hypersensitive response to avirulent GP-RBP-1 variants even though they did not confer any gain of recognition of virulent GP-RBP-1 variants.

Conclusions
Our results highlight how a resistance gene co-factor can manage in terms of evolution both an established role as a cell housekeeping gene and an implication in plant parasite interactions. StRanGAP2 gene appears to evolve under purifying selection. Its variability does not seem to influence the specificity of GPA2 recognition but is able to modulate this activity by enhancing the defence response. It seems therefore that the interaction with the plant resistance protein GPA2 (and/or Rx) rather than with the nematode effector was the major force in the evolution of the RanGAP2 locus in potato. From a mechanistic point of view these results are in accordance with a physical interaction of RanGAP2 with GPA2 and suggest that RBP-1 would rather bind the RanGAP2-GPA2 complex than the RanGAP2 protein alone.
Bone formation in rabbit cancellous bone explant culture model is enhanced by mechanical load
Authors: Zong ming Wan , Jian yu Li , Rui xin Li , Hao Li , Yong Guo , Lu Liu , Xin chang Zhang , Xi zheng Zhang 
Published: April 2013

Abstract

Background
When studying and designing an artificial bone in vitro with similar features and functionality of natural bone by tissue engineering technology, the culturing environment, especially the mechanical environment is supposed to be an important factor, because a suitable mechanical environment in vitro may improve the adaptability of the planted-in tissue engineering bone in the body. Unfortunately, up to now, the relationship between mechanical stimuli and natural bone growth has not yet been precisely determined, and it is so imperative for a prior study on effect of mechanical loading on growth of the natural bone cultured in vitro.

Methods
Under sterile conditions, explant models of rabbit cancellous bone with 3 mm in thickness and 8 mm in diameter were prepared and cultured in a dynamic loading and circulating perfusion bioreactor system. By Micro-CT scanning, a 3D model for finite element (FEM) analysis was achieved. According to the results of FEM analysis and physiological load bearing capacity of the natural bone, these models were firstly subjected to mechanical load with 1Hz frequency causing average apparent strain of 1000 μϵ, 2000 μϵ, 3000 μϵ and 4000 μϵ respectively for 30 min every day, activities of alkaline phosphatase (AKP) were detected on the 5th and the 14th loading day and on the 14th and the 21st day, mechanical properties, tissue mineral density (TMD) of the bone explant models were investigated and Von-kossa staining and fluorescence double labeling assays were conducted to evaluate whether there were fresh osteoid in the bone explant models. In addition, Western blot, Elisa and Real-time PCR were employed to analyze expression of Collagen-I (COL-1), bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG) protein and RNA.

Results
The explant models of rabbit cancellous bone prepared under sterile conditions grew well in the bioreactor system. With the increasing culturing time and load levels, bone explant models in groups with 1000 μϵ and 2000 μϵ average apparent strain experienced improving mechanical properties and TMD (P<0.05), and results of Von-kossa staining and fluorescence double labeling also showed apparent fresh osteoid formation. Under the same loading conditions, a up-regulations in protein and RNA of COL-1, BMP-2 and OPG were detected, especially, relative genes notably expressed after 21 days.

Conclusion
Our study demonstrated that mechanical load could improve function and activity of osteoblasts in explant models of cancellous bone. Through regulations of COL-1, OPG and BMP-2 secreted by osteoblasts, the mechanical load could improve the tissue structural density and stiffness due to formation of fresh osteoid.
PAG/Cbp suppression reveals a contribution of CTLA-4 to setting the activation threshold in T cells
Authors: Smida Michal , Cammann Clemens , Gurbiel Slavyana , Kerstin Nadja , Lingel Holger , Lindquist Sabine , Simeoni Luca , Brunner-Weinzierl Monika C , Suchanek Miloslav , Schraven Burkhart , Lindquist Jonathan A 
Published: April 2013

AbstractBackgroundPAG/Cbp represents a ubiquitous mechanism for regulating Src family kinases by recruiting Csk to the plasma membrane, thereby controlling cellular activation. Since Src kinases are known oncogenes, we used RNA interference in primary human T cells to test whether the loss of PAG resulted in lymphocyte transformation.ResultsPAG-depletion enhanced Src kinase activity and augmented proximal T-cell receptor signaling; exactly the phenotype expected for loss of this negative regulator. Surprisingly, rather than becoming hyper-proliferative, PAG-suppressed T cells became unresponsive. This was mediated by a Fyn-dependent hyper-phosphorylation of the inhibitory receptor CTLA-4, which recruited the protein tyrosine phosphatase Shp-1 to lipid rafts. Co-suppression of CTLA-4 abrogates this inhibition and restores proliferation to T cells.ConclusionWe have identified a fail-safe mechanism as well as a novel contribution of CTLA-4 to setting the activation threshold in T cells.
Bio-fabrication of gold nanoparticles using aqueous extract of red tomato and its use as a colorimetric sensor
Authors: Barman Gadadhar , Maiti Swarnali , Laha Jayasree Konar 
Published: April 2013

Abstract
In this work, we report a green method for the synthesis of gold nanoparticles (GNP) using the aqueous extract of red tomato (Lycopersicon esculentum). We believe that citric acid and ascorbic acid present in tomato juice are responsible for the reduction of gold ions. This biosynthesized GNP in the presence of sodium dodecyl sulfate has been used as a colorimetric sensor to detect and estimate the pesticide, methyl parathion. The GNP in the presence of methyl parathion shows a new peak at 400 nm due to the formation of 4-nitrophenolate ion by catalytic hydrolysis of methyl parathion in alkaline medium. A calibration curve between the absorption coefficients of the 400-nm peak versus the concentration of the pesticide allows the quantitative estimation of the 4-nitrophenolate ion, thereby enabling indirect estimation of methyl parathion present in the system.
Mixed protein-templated luminescent metal clusters (Au and Pt) for H2O2 sensing
Authors: Li Min , Yang Da-Peng , Wang Xiansong , Lu Jianxin , Cui Daxiang 
Published: April 2013

Abstract
A simple and cost-effective method to synthesize the luminescent noble metal clusters (Au and Pt) in chicken egg white aqueous solution at room temperature is reported. The red-emitting Au cluster is used as fluorescent probe for sensitive detection of H2O2.
miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs
Authors: Riaz Muhammad , van Jaarsveld Marijn TM , Hollestelle Antoinette , Prager-van der Smissen Wendy JC , Heine Anouk AJ , Boersma Antonius WM , Liu Jingjing , Helmijr Jean , Ozturk Bahar , Smid Marcel , Wiemer Erik A , Foekens John A , Martens John WM 
Published: April 2013

Abstract
Introduction
Breast cancer is a genetically and phenotypically complex disease. To understand the role of miRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer cell lines to identify miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations.

Methods
Using a microarray carrying LNA™ modified oligonucleotide capture probes), expression levels of 725 human miRNAs were measured in 51 breast cancer cell lines. Differential miRNA expression was explored by unsupervised cluster analysis and was then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer.

Results
Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 breast cancer cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of breast cancer cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group, 39 miRNAs were associated with ERBB2 overexpression and 24 with E-cadherin gene mutations, which are frequent in this subtype of breast cancer cell lines. In contrast, 31 miRNAs were associated with E-cadherin promoter hypermethylation, which, contrary to E-cadherin mutation, is exclusively observed in breast cancer cell lines that are not of luminal origin. Thirty miRNAs were associated with p16
INK4
status while only a few miRNAs were associated with BRCA1, PIK3CA/PTEN and TP53 mutation status. Twelve miRNAs were associated with DNA copy number variation of the respective locus.

Conclusion
Luminal-basal and epithelial-mesenchymal associated miRNAs determine the subdivision of miRNA transcriptome of breast cancer cell lines. Specific sets of miRNAs were associated with ERBB2 overexpression, p16
INK4a
or E-cadherin mutation or E-cadherin methylation status, which implies that these miRNAs may contribute to the driver role of these genetic aberrations. Additionally, miRNAs, which are located in a genomic region showing recurrent genetic aberrations, may themselves play a driver role in breast carcinogenesis or contribute to a driver gene in their vicinity. In short, our study provides detailed molecular miRNA portraits of breast cancer cell lines, which can be exploited for functional studies of clinically important miRNAs.
A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients: a double-blinded, randomised controlled trial
Authors: Robinson Sian , Zincuk Aleksander , Larsen Ulla Lei , Ekstrøm Claus , Nybo Mads , Rasmussen Bjarne , Toft Palle 
Published: April 2013

Abstract
Introduction
Critically ill patients are predisposed to venous thromboembolism. We hypothesized that higher doses of enoxaparin would improve thromboprophylaxis without increasing the risk of bleeding. Peak anti-factor Xa (anti-Xa) levels of 0.1 to 0.4 IU/ml reflect adequate thromboprophylaxis for general ward patients. Studies conducted in orthopaedic patients demonstrated a statistically significant relationship between anti-Xa levels and wound haematoma and thrombosis. Corresponding levels for critically ill patients may well be higher, but have never been validated in large studies.

Methods
Eighty critically ill patients weighing 50 to 90 kilograms were randomised in a double-blinded study to receive subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40 mg BID, or 1 mg/kg QD, each administered for three days. Anti-Xa activity was measured at baseline, and daily at 4, 12, 16 and 24 hours post administration. Antithrombin, fibrinogen, and platelets were measured at baseline and twice daily thereafter.

Results
Two patients were transferred prior to participation. On day 1, doses of 40 mg QD (n = 20) and 40 mg BID (n = 19) yielded mean peak anti-Xa of 0.20 IU/ml and 0.17 IU/ml respectively. A dose of 30 mg BID (n = 20) resulted in much lower levels (0.08 IU/ml). Patients receiving 1 mg/kg QD (n = 19) achieved near steady-state mean peak anti-Xa levels from day 1 (0.34 IU/ml). At steady state (day 3), mean peak anti-Xa levels of 0.13 IU/ml and 0.15 IU/ml were achieved with doses of 40 mg QD and 30 mg BID respectively. This increased significantly to 0.33 IU/ml and 0.40 IU/ml for doses of 40 mg BID and 1 mg/kg QD respectively. Thus anti-Xa response profiles differed significantly over the three days between enoxaparin treatment groups (P <0.0001). Doses of 40 mg BID and1 mg/kg QD enoxaparin yielded target anti-Xa levels for over 80% of the study period. There were no adverse effects.

Conclusions
Doses of 40 mg QD enoxaparin (Europe) or 30 mg BID (North America) yield levels of anti-Xa which may be inadequate for critically ill patients. A weight-based dose yielded the best anti-Xa levels without bioaccumulation, and allowed the establishment of near steady-state levels from the first day of enoxaparin administration.

Trial registration
Current Controlled Trials ISRCTN91570009.