bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving early exclusion of acute coronary syndrome in primary care: the added value of point-of-care troponin as stated by general practitioners
Authors: Kip Michelle M.A. , Noltes Amber M. , Koffijberg Hendrik , IJzerman Maarten J. , Kusters Ron 
Published: May 2017

AimTo investigate general practitioners’ (GPs’) desire and perceived added value of point-of-care (POC) troponin, its effect on referral decisions, and test requirements.BackgroundExcluding acute coronary syndrome (ACS) in primary care remains a diagnostic challenges for GPs. Consequently, referral rates of chest pain patients are high, while the incidence of a cardiovascular problem is only 8–15%. Previous studies have shown that GPs are interested in a POC troponin test. This test could enhance rapid exclusion of ACS, thereby preventing unnecessary patient distress, without compromising safety and while reducing costs. However, using this test is not recommended in current guidelines due to uncertainty in the test’s potential added value, and the lower sensitivity early after symptom onset as compared with troponin tests in a regular laboratory.MethodsAn online survey containing 34 questions was distributed among 837 Dutch GPs in June 2015.FindingsA total of 126 GPs (15.1%) completed at least 75% of the questions. 67.1% of GPs believe that POC troponin tests have moderate to very high added value. Although the availability of a POC test is expected to increase the frequency at which troponin tests are used, it likely decreases (immediate) referral rates. Of the responding GPs, 78.3% only accept 10 min as the maximum test duration, 78.1% think reimbursement of the POC device is required for implementation, and 68.9% consider it necessary that it can be performed with a finger prick blood sample. In conclusion, according to GPs, the POC troponin test can be of added value to exclude ACS early on. Actual test implementation will depend on test characteristics, including test duration, type of blood sample required, and reimbursement of the analyzer.
Public–private partnerships to improve primary healthcare surgeries: clarifying assumptions about the role of private provider activities
Authors: Mudyarabikwa Oliver , Tobi Patrick , Regmi Krishna 
Published: May 2017

Aim
To examine assumptions about public–private partnership (PPP) activities and their role in improving public procurement of primary healthcare surgeries.

Background
PPPs were developed to improve the quality of care and patient satisfaction. However, evidence of their effectiveness in delivering health benefits is limited.

Methods
A qualitative study design was employed. A total of 25 interviews with public sector staff (n=23) and private sector managers (n=2) were conducted to understand their interpretations of assumptions in the activities of private investors and service contractors participating in Local Improvement Finance Trust (LIFT) partnerships. Realist evaluation principles were applied in the data analysis to interpret the findings.

Results
Six thematic areas of assumed health benefits were identified: (i) quality improvement; (ii) improved risk management; (iii) reduced procurement costs; (iv) increased efficiency; (v) community involvement; and (vi) sustainable investment. Primary Care Trusts that chose to procure their surgeries through LIFT were expected to support its implementation by providing an environment conducive for the private participants to achieve these benefits. Private participant activities were found to be based on a range of explicit and tacit assumptions perceived helpful in achieving government objectives for LIFT.

Conclusion
The success of PPPs depended upon private participants’ (i) capacity to assess how PPP assumptions added value to their activities, (ii) effectiveness in interpreting assumptions in their expected activities, and (iii) preparedness to align their business principles to government objectives for PPPs. They risked missing some of the expected benefits because of some factors constraining realization of the assumptions. The ways in which private participants preferred to carry out their activities also influenced the extent to which expected benefits were achieved. Giving more discretion to public than private participants over critical decisions may help in ensuring that assumptions in PPP activities result in outcomes that match the anticipated health benefits.
Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling
Authors: Ishii Seiji , Torii Masaaki , Son Alexander I. , Rajendraprasad Meenu , Morozov Yury M. , Kawasawa Yuka Imamura , Salzberg Anna C. , Fujimoto Mitsuaki , Brennand Kristen , Nakai Akira , Mezger Valerie , Gage Fred H. , Rakic Pasko , Hashimoto-Torii Kazue 
Published: May 2017

AbstractRepetitive prenatal exposure to identical or similar doses of harmful agents results in highly variable and unpredictable negative effects on fetal brain development ranging in severity from high to little or none. However, the molecular and cellular basis of this variability is not well understood. This study reports that exposure of mouse and human embryonic brain tissues to equal doses of harmful chemicals, such as ethanol, activates the primary stress response transcription factor heat shock factor 1 (Hsf1) in a highly variable and stochastic manner. While Hsf1 is essential for protecting the embryonic brain from environmental stress, excessive activation impairs critical developmental events such as neuronal migration. Our results suggest that mosaic activation of Hsf1 within the embryonic brain in response to prenatal environmental stress exposure may contribute to the resulting generation of phenotypic variations observed in complex congenital brain disorders.
Effect of Bacillus subtilis on Aeromonas hydrophila-induced intestinal mucosal barrier function damage and inflammation in grass carp (Ctenopharyngodon idella)
Authors: Kong Weiguang , Huang Can , Tang Ying , Zhang Ding , Wu Zhixin , Chen Xiaoxuan 
Published: May 2017

AbstractOur study explored the effect of oral intubation of Bacillus subtilis on Aeromonas hydrophila-induced intestinal mucosal barrier function damage and inflammation in grass carp. The mid-intestine mucosal tissue was collected for ATPase activity measurement. Intestinal mucosa was also ultrastructurally examined with transmission electron microscope (TEM), and its permeability was determined using Evans blue (EB) and D-lactic acid. The mid-intestine pro-inflammation cytokine, MyD88 and tight junction (TJ) protein mRNA expression levels were measured using real-time quantitative PCR. The results revealed that B. subtilis was found to prevent the decrease in the activity of Na+, K+-ATPase and Ca2+, Mg2+-ATPase, as well as the increase in EB and D-lactic acid concentration and inflammation induced by A. hydrophila in grass carp. Compared with A. hydrophila groups, B. subtilis safeguarded the integrity of intestinal villi and tight junction structure and restrained A. hydrophila-induced down-regulation of TJ proteins zonula occludens-1 (ZO-1) and occludin. B. subtilis also restrained up-regulation of TJ protein claudin b, pro-inflammation cytokine tumour necrosis factor α (TNF-α), cytokine interleukin 8 (IL-8), IL-1β, and adaptor protein myeloid differentiation factor 88 (MyD88) mRNA levels. Thus, oral intubation of B. subtilis could reduce A. hydrophila-induced intestinal mucosal barrier function damage and inflammation.
Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete
Authors: Kao Wei-Chien Andrew , Pětrošová Helena , Ebady Rhodaba , Lithgow Karen V. , Rojas Pablo , Zhang Yang , Kim Yae-Eun , Kim Yae-Ram , Odisho Tanya , Gupta Nupur , Moter Annette , Cameron Caroline E. , Moriarty Tara J. 
Published: May 2017

AbstractTreponema pallidum subsp. pallidum, the causative agent of syphilis, is a highly invasive spirochete pathogen that uses the vasculature to disseminate throughout the body. Identification of bacterial factors promoting dissemination is crucial for syphilis vaccine development. An important step in dissemination is bacterial adhesion to blood vessel surfaces, a process mediated by bacterial proteins that can withstand forces imposed on adhesive bonds by blood flow (vascular adhesins). The study of T. pallidum vascular adhesins is hindered by the uncultivable nature of this pathogen. We overcame these limitations by expressing T. pallidum adhesin Tp0751 (pallilysin) in an adhesion-attenuated strain of the cultivable spirochete Borrelia burgdorferi. Under fluid shear stress representative of conditions in postcapillary venules, Tp0751 restored bacterial-vascular interactions to levels similar to those observed for infectious B. burgdorferi and a gain-of-function strain expressing B. burgdorferi vascular adhesin BBK32. The strength and stability of Tp0751- and BBK32-dependent endothelial interactions under physiological shear stress were similar, although the mechanisms stabilizing these interactions were distinct. Tp0751 expression also permitted bacteria to interact with postcapillary venules in live mice as effectively as BBK32-expressing strains. These results demonstrate that Tp0751 can function as a vascular adhesin.
A simple and cost-effective setup for super-resolution localization microscopy
Authors: Ma Hongqiang , Fu Rao , Xu Jianquan , Liu Yang 
Published: May 2017

AbstractSingle molecule localization microscopy (SMLM) has become a powerful imaging tool for biomedical research, but it is mostly available in imaging facilities and a small number of laboratories due to its high cost. Here, we evaluate the possibility of replacing high-cost components on standard SMLM with appropriate low-cost alternatives and build a simple but high-performance super-resolution SMLM setup. Through numerical simulation and biological experiments, we demonstrate that our low-cost SMLM setup can yield similar localization precision and spatial resolution compared to the standard SMLM equipped with state-of-the-art components, but at a small fraction of their cost. Our low-cost SMLM setup can potentially serve as a routine laboratory microscope with high-performance super-resolution imaging capability.
Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3
Authors: Guo Shuyu , Zhang Yuxin , Zhou Tingting , Wang Dongyue , Weng Yajuan , Wang Lin , Ma Junqing 
Published: May 2017

AbstractTranscription factor GATA4 regulates cardiac and osteoblast differentiation. However, its role in tooth development is not clear. Therefore, we generated Wnt1-Cre;GATA4
fl/fl
mice, with conditional inactivation of the GATA4 gene in the dental papilla mesenchymal cells. Phenotypic analysis showed short root deformity along with reduced expressions of odonto/osteogenic markers. Proliferation (but not apoptosis) of cells around the apical area of the root was attenuated. In vitro, we knocked down GATA4 expression in stem cells of dental apical papilla (SCAPs). Proliferation, migration and odonto/osteogenic differentiation of SCAPs were affected in the shGATA4 group. Overexpression of GATA4 in SCAPs increased mineralization. Based on our previous iTRAQ results, guanine nucleotide binding proteins 3 (GNAI3) is one of the distinct proteins after GATA4 deletion. G protein signaling is involved in bone development, remodeling, and disease. In this study, both GATA4 deletion in the mouse root and knock-down in human SCAPs decreased the expression of GNAI3. Dual-luciferase and ChIP assay confirmed the direct binding of GATA4 to the GNAI3 promoter, both in vitro and in vivo. GNAI3 knock-down significantly decreased the odonto/osteogenic differentiation ability of SCAPs. We thus establish the role of GATA4 as a novel regulator of root development and elucidate its downstream molecular events.
BAMClipper: removing primers from alignments to minimize false-negative mutations in amplicon next-generation sequencing
Authors: Au Chun Hang , Ho Dona N. , Kwong Ava , Chan Tsun Leung , Ma Edmond S. K. 
Published: May 2017

AbstractAmplicon-based next-generation sequencing (NGS) has been widely adopted for genetic variation detection in human and other organisms. Conventional data analysis paradigm includes primer trimming before read mapping. Here we introduce BAMClipper that removes primer sequences after mapping original sequencing reads by soft-clipping SAM/BAM alignments. Mutation detection accuracy was affected by the choice of primer handling approach based on real NGS datasets of 7 human peripheral blood or breast cancer tissue samples with known BRCA1/BRCA2 mutations and >130000 simulated NGS datasets with unique mutations. BAMClipper approach detected a BRCA1 deletion (c.1620_1636del) that was otherwise missed due to edge effect. Simulation showed high false-negative rate when primers were perfectly trimmed as in conventional practice. Among the other 6 samples, variant allele frequencies of 5 BRCA1/BRCA2 mutations (indel or single-nucleotide variants) were diluted by apparently wild-type primer sequences from an overlapping amplicon (17 to 82% under-estimation). BAMClipper was robust in both situations and all 7 mutations were detected. When compared with Cutadapt, BAMClipper was faster and maintained equally high primer removal effectiveness. BAMClipper is implemented in Perl and is available under an open source MIT license at https://github.com/tommyau/bamclipper.
Evolution of sex-dependent mtDNA transmission in freshwater mussels (Bivalvia: Unionida)
Authors: Guerra Davide , Plazzi Federico , Stewart Donald T. , Bogan Arthur E. , Hoeh Walter R. , Breton Sophie 
Published: May 2017

AbstractDoubly uniparental inheritance (DUI) describes a mode of mtDNA transmission widespread in gonochoric freshwater mussels (Bivalvia: Palaeoheterodonta: Unionida). In this system, both female- and male-transmitted mtDNAs, named F and M respectively, coexist in the same species. In unionids, DUI is strictly correlated to gonochorism and to the presence of the atypical open reading frames (ORFans) F-orf and M-orf, respectively inside F and M mtDNAs, which are hypothesized to participate in sex determination. However, DUI is not found in all three Unionida superfamilies (confirmed in Hyrioidea and Unionoidea but not in Etherioidea), raising the question of its origin in these bivalves. To reconstruct the co-evolution of DUI and of ORFans, we sequenced the mtDNAs of four unionids (two gonochoric with DUI, one gonochoric and one hermaphroditic without DUI) and of the related gonochoric species Neotrigonia margaritacea (Palaeoheterodonta: Trigoniida). Our analyses suggest that rearranged mtDNAs appeared early during unionid radiation, and that a duplicated and diverged atp8 gene evolved into the M-orf associated with the paternal transmission route in Hyrioidea and Unionoidea, but not in Etherioidea. We propose that novel mtDNA-encoded genes can deeply influence bivalve sex determining systems and the evolution of the mitogenomes in which they occur.
Grass and forbs respond differently to nitrogen addition: a meta-analysis of global grassland ecosystems
Authors: You Chengming , Wu Fuzhong , Gan Youmin , Yang Wanqin , Hu Zhongmin , Xu Zhenfeng , Tan Bo , Liu Lin , Ni Xiangyin 
Published: May 2017

AbstractNitrogen (N) deposition has increased globally and has profoundly influenced the structure and function of grasslands. Previous studies have discussed how N addition affects aboveground biomass (AGB), but the effects of N addition on the AGB of different functional groups in grasslands remain unclear. We conducted a meta-analysis to identify the responses of AGB and the AGB of grasses (AGBgrass) and forbs (AGBforb) to N addition across global grasslands. Our results showed that N addition significantly increased AGB and AGBgrass by 31 and 79%, respectively, but had no significant effect on AGBforb. The effects of N addition on AGB and AGBgrass increased with increasing N addition rates, but which on AGBforb decreased. Although study durations did not regulate the response ratio of N addition for AGB, which for AGBgrass increased and for AGBforb decreased with increasing study durations. Furthermore, the N addition response ratios for AGB and AGBgrass increased more strongly when the mean annual precipitation (MAP) was 300–600 mm but decreased with an increase in the mean annual temperature (MAT). AGBforb was only slightly affected by MAP and MAT. Our findings suggest that an acceleration of N deposition will increase grassland AGB by altering species composition.
Detecting the Molecular System Signatures of Idiopathic Pulmonary Fibrosis through Integrated Genomic Analysis
Authors: Gangwar Indu , Kumar Sharma Nitesh , Panzade Ganesh , Awasthi Supriya , Agrawal Anurag , Shankar Ravi 
Published: May 2017

AbstractIdiopathic Pulmonary Fibrosis (IPF) is an incurable progressive fibrotic disease of the lungs. We currently lack a systematic understanding of IPF biology and a systems approach may offer new therapeutic insights. Here, for the first time, a large volume of high throughput genomics data has been unified to derive the most common molecular signatures of IPF. A set of 39 differentially expressed genes (DEGs) was found critical to distinguish IPF. Using high confidence evidences and experimental data, system level networks for IPF were reconstructed, involving 737 DEGs found common across at least two independent studies. This all provided one of the most comprehensive molecular system views for IPF underlining the regulatory and molecular consequences associated. 56 pathways crosstalks were identified which included critical pathways with specified directionality. The associated steps gained and lost due to crosstalk during IPF were also identified. A serially connected system of five crucial genes was found, potentially controlled by nine miRNAs and eight transcription factors exclusively in IPF when compared to NSIP and Sarcoidosis. Findings from this study have been implemented into a comprehensive molecular and systems database on IPF to facilitate devising diagnostic and therapeutic solutions for this deadly disease.
Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen
Authors: Itani Farah R. , Sinha Sushmita , Brate Ashley A. , Pewe Lecia L. , Gibson-Corley Katherine N. , Harty John T. , Karandikar Nitin J. 
Published: May 2017

AbstractCD8 T-cells predominate in CNS lesions of MS patients and display oligoclonal expansion. However, the role of myelin-specific CD8 T-cells in disease remains unclear, with studies showing protective and pathogenic roles in EAE. We demonstrated a disease-suppressive function for CNS-specific CD8 T-cells in a model where the antigen is exogenously administeredin vivoand used forin vitroactivation. To probe the nature of the CD8 response elicited by endogenously presented myelin antigensin vivo, we developed a novel approach utilizing infection withListeria monocytogenes(LM) encoding proteolipid protein peptide (PLP) amino acids 178-191 (LM-PLP). LM-PLP infection preferentially induced PLP-specific CD8 T-cell responses. Despite the induction of PLP-specific CD8 T-cells, LM-PLP infection did not result in disease. In fact, LM-PLP infection resulted in significant amelioration of PLP178-191-induced EAE. Disease suppression was not observed in mice deficient in CD8 T-cells, IFN-γ or perforin. DTH responses and CNS infiltration were reduced in protected mice, and their CD4 T-cells had reduced capacity to induce tissue inflammation. Importantly, infection with LM-PLP ameliorated established disease. Our studies indicate that CD8 T-cells induced by endogenous presentation of PLP178-191 attenuate CNS autoimmunity in models of EAE, implicating the potential of this approach as a novel immunotherapeutic strategy.
Maternal depression attenuates newborn vitamin D concentrations in winter-spring: a prospective population-based study
Authors: Zhou Qi-fan , Zhang Meng-xiao , Tong Shi-lu , Tao Rui-xue , Hao Jia-hu , Huang Kun , Tao Fang-biao , Zhu Peng 
Published: May 2017

AbstractWe aimed to investigate whether the newborns of mothers with maternal depression (MD) had lower vitamin D levels than newborns of non-MD (NMD) mothers and identify the potential mechanism underlying this association. Maternal depressive symptoms in late pregnancy and concentrations of cord blood 25 hydroxyvitamin D (25(OH)D) were measured in 1491 mother-infant pairs. Data on maternal sociodemographic characteristics, health status, lifestyle and birth outcomes were prospectively collected. For infants born in winter-spring, the infants of MD mothers had significantly reduced concentrations of 25(OH) D (adjusted β = −3.51 nmol/L; 95% CI: −6.19, −0.84; P = 0.010) and lower birth weight (3267 ± 470 g vs 3348 ± 598 g, F = 4.64, P = 0.031), compared with the infants of NMD mothers. A significant, inverse linear relationship was noted between maternal depression scores and the concentration of 25(OH)D for infants born in winter-spring (adjusted β = −0.158; 95% CI: −0.259, −0.057). The significant, inverse linear relationship between maternal depression scores and fetomaternal ratios of 25(OH) D was also observed among the infants born in winter-spring (adjusted β = −0.005; 95% CI: −0.008, −0.003). MD appears to significantly attenuate the vitamin D concentrations and birth weight of infants born in winter-spring. A decreased fetomaternal ratio of 25(OH)D might be involved in this biological pathway.
Asymmetrical barcode adapter-assisted recovery of duplicate reads and error correction strategy to detect rare mutations in circulating tumor DNA
Authors: Ahn Jinwoo , Hwang Byungjin , Young Kim Ha , Jang Hoon , Kim Hwang-Phill , Han Sae-Won , Kim Tae-You , Hyun Lee Ji , Bang Duhee 
Published: May 2017

AbstractDeep sequencing is required for the highly sensitive detection of rare variants in circulating tumor DNA (ctDNA). However, there remains a challenge for improved sensitivity and specificity. Maximum-depth sequencing is crucial to detect minority mutations that contribute to cancer progression. The associated costs become prohibitive as the numbers of targets and samples increase. We describe the targeted sequencing of KRAS in plasma samples using an efficient barcoding approach to recover discarded reads marked as duplicates. Combined with an error-removal strategy, we anticipate that our method could improve the accuracy of genotype calling, especially to detect rare mutations in the monitoring of ctDNA.