bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble epoxide hydrolase inhibitory activity of phenolic components from the rhizomes and roots of Gentiana scabra
Authors: Li Wei , Kim Jang Hoon , Zhou Wei , Shim Sang Hee , Ma Jin Yeul , Kim Young Ho 
Published: January 2015

Abstract
Two new (1 and 2) and seven known phenolic compounds were isolated from a methanol extract of the rhizomes and roots of Gentiana scabra. Their structures were identified by spectroscopic analysis and comparing with reported values. The inhibitory effects of each compound on soluble epoxide hydrolase (sEH) were evaluated. Among them, compounds 2, 6, and 9 potently inhibited sEH activity.
R Wave in aVL Lead Is a Robust Index of Left Ventricular Hypertrophy: A Cardiac MRI Study
Authors: Courand Pierre-Yves , Grandjean Adrien , Charles Paul , Paget Vinciane , Khettab Fouad , Bricca Giampiero , Boussel Loïc , Lantelme Pierre , Harbaoui Brahim 
Published: January 2015

BACKGROUND
In patients free from overt cardiac disease, R wave in aVL lead (RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by transthoracic echocardiography. The aim of the present study was to extend this finding to other settings (cardiomyopathy or conduction disorders), by comparing ECG criteria of left ventricular hypertrophy (LVH) to cardiac MRI (CMR).

METHODS
In 501 patients, CMR and ECG were performed within a median-period of 5 days. CMR LVH cut-offs used were 83g/m2 in men and 67g/m2 in women.

RESULTS
RaVL was independently correlated with LVMI in patients with or without myocardial infarction (MI) (N = 300 and N = 201, respectively). SV3 was independently correlated with LVMI and LV enlargement only in patients without MI. In the whole cohort, RaVL had area under receiver-operating characteristic curve of 0.729 (specificity 98.3%, sensitivity 19.6%, optimal cut-off 1.1 mV). The performance of RaVL was remarkable in women, in Caucasians, and in the presence of right bundle branch block. It decreased in case of MI. Overall, it is proposed that below 0.5 mV and above 1.0 mV, RaVL is sufficient to exclude or establish LVH. Between 0.5 and 1 mV, composite indices (Cornell voltage or product) should be used. Using this algorithm allowed classifying appropriately 85% of the patients.

CONCLUSIONS
Our results showed that RaVL is a good index of LVH with a univocal threshold of 1.0 mV in various clinical conditions. SV3 may be combined to RaVL in some conditions, namely LV enlargement to increase its performance.
The transcriptomic response of Acinetobacter baumannii to colistin and doripenem alone and in combination in an in vitro pharmacokinetics/pharmacodynamics model
Authors: Henry Rebekah , Crane Bethany , Powell David , Deveson Lucas Deanna , Li Zhifeng , Aranda Jesús , Harrison Paul , Nation Roger L. , Adler Ben , Harper Marina , Boyce John D. , Li Jian 
Published: January 2015

Abstract

Objectives
Colistin remains a last-line treatment for MDR Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against MDR strains. In order to understand the bacterial responses to these antibiotics, we analysed the transcriptome of A. baumannii following exposure to each.

Methods
RNA sequencing was employed to determine changes in the transcriptome following treatment with colistin and doripenem, both alone and in combination, using an in vitro pharmacokinetics (PK)/pharmacodynamics model to mimic the PK of both antibiotics in patients.

Results
After treatment with colistin (continuous infusion at 2 mg/L), &gt;400 differentially regulated genes were identified, including many associated with outer membrane biogenesis, fatty acid metabolism and phospholipid trafficking. No genes were differentially expressed following treatment with doripenem (Cmax 25 mg/L, t1/2 1.5 h) for 15 min, but 45 genes were identified as differentially expressed after 1 h of growth under this condition. Treatment of A. baumannii with both colistin and doripenem together for 1 h resulted in &gt;450 genes being identified as differentially expressed. More than 70% of these gene expression changes were also observed following colistin treatment alone.

Conclusions
These data suggest that colistin causes gross damage to the outer membrane, facilitates lipid exchange between the inner and outer membrane and alters the normal asymmetric outer membrane composition. The transcriptional response to colistin was highly similar to that observed for an LPS-deficient strain, indicating that many of the observed changes are responses to outer membrane instability resulting from LPS loss.
The 2015 Nucleic Acids Research Database Issue and Molecular Biology Database Collection
Authors: Galperin Michael Y. , Rigden Daniel J. , Fernández-Suárez Xosé M. 
Published: January 2015

Abstract
The 2015 Nucleic Acids Research Database Issue contains 172 papers that include descriptions of 56 new molecular biology databases, and updates on 115 databases whose descriptions have been previously published in NAR or other journals. Following the classification that has been introduced last year in order to simplify navigation of the entire issue, these articles are divided into eight subject categories. This year's highlights include RNAcentral, an international community portal to various databases on noncoding RNA; ValidatorDB, a validation database for protein structures and their ligands; SASBDB, a primary repository for small-angle scattering data of various macromolecular complexes; MoonProt, a database of ‘moonlighting’ proteins, and two new databases of protein–protein and other macromolecular complexes, ComPPI and the Complex Portal. This issue also includes an unusually high number of cancer-related databases and other databases dedicated to genomic basics of disease and potential drugs and drug targets. The size of NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/a/, remained approximately the same, following the addition of 74 new resources and removal of 77 obsolete web sites. The entire Database Issue is freely available online on the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).
Opposing roles of H3- and H4-acetylation in the regulation of nucleosome structure—a FRET study
Authors: Gansen Alexander , Tóth Katalin , Schwarz Nathalie , Langowski Jörg 
Published: January 2015

Abstract
Using FRET in bulk and on single molecules, we assessed the structural role of histone acetylation in nucleosomes reconstituted on the 170 bp long Widom 601 sequence. We followed salt-induced nucleosome disassembly, using donor–acceptor pairs on the ends or in the internal part of the nucleosomal DNA, and on H2B histone for measuring H2A/H2B dimer exchange. This allowed us to distinguish the influence of acetylation on salt-induced DNA unwrapping at the entry–exit site from its effect on nucleosome core dissociation. The effect of lysine acetylation is not simply cumulative, but showed distinct histone-specificity. Both H3- and H4-acetylation enhance DNA unwrapping above physiological ionic strength; however, while H3-acetylation renders the nucleosome core more sensitive to salt-induced dissociation and to dimer exchange, H4-acetylation counteracts these effects. Thus, our data suggest, that H3- and H4-acetylation have partially opposing roles in regulating nucleosome architecture and that distinct aspects of nucleosome dynamics might be independently controlled by individual histones.
DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes
Authors: Cohen Isadora S. , Bar Carmit , Paz-Elizur Tamar , Ainbinder Elena , Leopold Karoline , de Wind Niels , Geacintov Nicholas , Livneh Zvi 
Published: January 2015

Abstract
DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells.
Sequences spanning the leader-repeat junction mediate CRISPR adaptation to phage in Streptococcus thermophilus
Authors: Wei Yunzhou , Chesne Megan T. , Terns Rebecca M. , Terns Michael P. 
Published: January 2015

Abstract
CRISPR-Cas systems are RNA-based immune systems that protect prokaryotes from invaders such as phages and plasmids. In adaptation, the initial phase of the immune response, short foreign DNA fragments are captured and integrated into host CRISPR loci to provide heritable defense against encountered foreign nucleic acids. Each CRISPR contains a ∼100–500 bp leader element that typically includes a transcription promoter, followed by an array of captured ∼35 bp sequences (spacers) sandwiched between copies of an identical ∼35 bp direct repeat sequence. New spacers are added immediately downstream of the leader. Here, we have analyzed adaptation to phage infection in Streptococcus thermophilus at the CRISPR1 locus to identify cis-acting elements essential for the process. We show that the leader and a single repeat of the CRISPR locus are sufficient for adaptation in this system. Moreover, we identified a leader sequence element capable of stimulating adaptation at a dormant repeat. We found that sequences within 10 bp of the site of integration, in both the leader and repeat of the CRISPR, are required for the process. Our results indicate that information at the CRISPR leader-repeat junction is critical for adaptation in this Type II-A system and likely other CRISPR-Cas systems.
Antiretroviral Regimen and Suboptimal Medication Adherence Are Associated With Low-Level Human Immunodeficiency Virus Viremia
Authors: Konstantopoulos Christina , Ribaudo Heather , Ragland Kathleen , Bangsberg David R. , Li Jonathan Z. 
Published: January 2015

AbstractEpisodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification.
Impaired Autophagosome Clearance Contributes to Local Anesthetic Bupivacaine-induced Myotoxicity in Mouse Myoblasts
Authors: Li Rongrong , Ma He , Zhang Xiaojin , Li Chuanfu , Xiong Jingwei , Lu Ting , Mao Yu , Dai Juncheng , Liu Li , Ding Zhengnian 
Published: January 2015

AbstractAbstract
Bupivacaine stimulates autophagosome formation as a stress response and impairs autophagosome clearance by interfering with autophagosome–lysosome fusion, resulting in muscle cell injury. Rapamycin attenuates bupivacaine myotoxicity by increasing both autophagosome formation and autophagosome–lysosome fusion.
Supplemental Digital Content is available in the text.

Background:
The current study examined the role(s) of autophagy in myotoxicity induced by bupivacaine in mouse myoblast C2c12 cells.

Methods:
C2c12 cells were treated with bupivacaine. Myotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (n = 3 to 30), live/dead assay (n = 3 to 4), and morphological alterations (n = 3). Autophagosome formation was reflected by microtubule-associated protein light chain 3 conversion (n = 4 to 12) and light chain 3 punctation (n = 4 to 5). Autophagosome clearance was evaluated by p62 protein level (n = 4) and autolysosomes generation (n = 3).

Results:
Bupivacaine induced significant cell damage. Notably, there was a significant increase in autophagosome generation as evidenced by light chain 3 puncta formation (72.7 ± 6.9 vs. 2.1 ± 1.2) and light chain 3 conversion (2.16 ± 0.15 vs. 0.33 ± 0.04) in bupivacaine-treated cells. Bupivacaine inactivated the protein kinase B/mammalian target of rapamycin/p70 ribosomal protein S6 kinase signaling. However, cellular levels of p62 protein were significantly increased upon bupivacaine treatment (1.29 ± 0.15 vs. 1.00 ± 0.15), suggesting that the drug impaired autophagosome clearance. Further examination revealed that bupivacaine interrupted autophagosome–lysosome fusion (10.87% ± 1.48% vs. 32.94% ± 4.22%). Administration of rapamycin increased autophagosome clearance and, most importantly, improved the survival in bupivacaine-treated cells. However, knockdown of autophagy-related protein 5 (atg5) exacerbated bupivacaine-induced impairment of autophagosome clearance and myotoxicity.

Conclusions:
The data suggest that autophagosome formation was induced as a stress response mechanism after bupivacaine challenge; however, autophagosome clearance was impaired due to inadequate autophagosome–lysosome fusion. Therefore, impairment of autophagosome clearance appears to be a novel mechanism underlying bupivacaine-induced myotoxicity.
Modular continuing professional development for emergency physicians – the MNSHA masterclass programme
Authors: van den Berg Eefje E.P. , Bracey Amanda , van Driel A. Pieter G. , Geijsel Femke E.C. , Manders Sander 
Published: January 2015

IntroductionEmergency physician (EP) training in the Netherlands is currently a 3-year competency-based programme. Upon its completion, many Dutch EPs feel that they lack some of the skills and the knowledge necessary to be fully prepared for the challenges of emergency medicine. We perceived a need for new methods to deliver continuing professional development (CPD).MethodsA needs analysis survey was conducted to ascertain whether our perceived need for a new CPD programme was genuine. A new course was developed, incorporating innovative learning methods. The results of the needs analysis were incorporated into the programme. Another survey was held among participants of the first two editions of the programme.Results, discussion and conclusionModular CPD for Emergency Physicians (Dutch: MNSHA) is a modular programme that aims to deliver CPD to Dutch EPs. It combines innovative educational methods, such as asynchronous learning in a flipped classroom, with web-based mentoring. The aim is for participants to develop effective, individualized and sustainable methods to gain and maintain knowledge and skills as a part of their ongoing professional education. The participant survey showed encouraging results, strongly suggesting an improvement in confidence. A more robust study would be required to better assess the outcomes of our programme.
Efficacy and Safety of Adalimumab After Infliximab Failure in Pediatric Crohn Disease
Authors: Fumery Mathurin , Jacob Anne , Sarter Hélène , Michaud Laurent , Spyckerelle Claire , Mouterde Olivier , Savoye Guillaume , Colombel Jean‐Frédéric , Peyrin‐Biroulet Laurent , Gower‐Rousseau Corinne , Turck Dominique ,   EPIMAD Group
Published: January 2015

ABSTRACTObjectives:The objective of the present study was to evaluate the effectiveness and safety of adalimumab (ADA) in children with Crohn disease (CD) who experienced infliximab (IFX) failure at the population level.Methods:The present retrospective study included all of the children with CD from a pediatric‐onset population‐based cohort who received ADA before 18 years because of IFX failure or intolerance. Efficacy of ADA was evaluated using the physician's global assessment score, C‐reactive protein and orosomucoid, and nutritional and growth indicators.Results:A total of 27 children with CD received ADA. Median age at CD diagnosis and at ADA initiation was 11 years (Q1 = 9; Q3 = 12) and 15 years (12; 15), respectively. After a median follow‐up of 16 (8; 26) months after ADA initiation, ADA had clinical benefit as measured by the physical global assessment score in 19 patients (70%). Cumulative probability of failure to ADA treatment was 38% at 6 months and 55% at 1 year. Eight patients had a primary failure (30%) and 5 of 19 (26%) a secondary failure to ADA. Furthermore, 11 patients (40%) experienced a total of 19 adverse effects. No serious adverse effects were observed and none resulted in ADA discontinuation. There was no significant change in growth and nutritional patterns during the study period, but we found a significant decrease in median C‐reactive protein (15 mg/L [4; 44] vs 9 mg/L [3; 19]; P = 0.05) and orosomucoid (1.6 g/L [1.5; 2.6] vs 1.1 g/L [0.8; 1.9]; P = 0.001) from ADA initiation to maximal follow‐up in patients responding to ADA.Conclusions:In the present population‐based cohort of pediatric‐onset CD with IFX failure, treatment with ADA was safe and effective in two‐thirds of patients.
Epidemiology of Irritable Bowel Syndrome in Children and Adolescents in Asia
Authors: Devanarayana Niranga M. , Rajindrajith Shaman , Pathmeswaran Arunasalam , Abegunasekara Chithra , Gunawardena Nipul K. , Benninga Marc A. 
Published: January 2015

ABSTRACTObjectives:Several cross‐sectional surveys have been conducted to study the prevalence of irritable bowel syndrome (IBS) in children. The aim of the present study was to conduct a systematic review and a meta‐analysis of published literature to estimate the prevalence of IBS among Asian children.Method:A computer‐assisted search of MEDLINE, EMBASE, PsycINFO, and regional databases of Asia was carried out. Selected articles were reviewed in depth and data were extracted. Pooled prevalence, sex differences, and 95% confidence intervals were calculated. Heterogeneity of the studies was assessed using the I2 test.Results:A total of 16 cross‐sectional studies that reported prevalence of IBS (in children and adolescents) and qualified to be included were taken into the final analysis containing 38,076 patients. Selected studies are from China, Korea, Japan, Iran, Sri Lanka, and Saudi Arabia. Studies showed a marked heterogeneity with I2 of 98.59 (P < 0.0001). Prevalence of IBS ranges from 2.8% to 25.7%, with a pooled prevalence of 12.41% (95% confidence interval 9.87–14.95). Prevalence risk ratio of girl:boy is 1.39. Prevalence of subtypes is diverse and varies between studies.Conclusions:The published data indicate that IBS is a significant problem among Asian children and adolescents. Female sex predisposes children and adolescents to develop IBS.
The Ecological Forecast Horizon, and examples of its uses and determinants
Authors: Petchey Owen L. , Pontarp Mikael , Massie Thomas M. , Kéfi Sonia , Ozgul Arpat , Weilenmann Maja , Palamara Gian Marco , Altermatt Florian , Matthews Blake , Levine Jonathan M. , Childs Dylan Z. , McGill Brian J. , Schaepman Michael E. , Schmid Bernhard , Spaak Piet , Beckerman Andrew P. , Pennekamp Frank , Pearse Ian S. 
Published: January 2015

1AbstractForecasts of ecological dynamics in changing environments are increasingly important, and are available for a plethora of variables, such as species abundance and distribution, community structure, and ecosystem processes. There is, however, a general absence of knowledge about how far into the future, or other dimensions (space, temperature, phylogenetic distance), useful ecological forecasts can be made, and about how features of ecological systems relate to these distances. The ecological forecast horizon is the dimensional distance for which useful forecasts can be made. Five case studies illustrate the influence of various sources of uncertainty (e.g. parameter uncertainty, environmental , and demographic stochasticity, evolution), level of ecological organisation (e.g. population or community), organismal properties (e.g. body size or number of trophic links) on temporal, spatial, and phylogenetic forecast horizons. Insights from these case studies demonstrate that the ecological forecast horizon is a flexible and powerful tool for researching and communicating ecological predictability. It also has potential for motivating and guiding agenda setting for ecological forecasting research and development.
Oxford Nanopore Sequencing, Hybrid Error Correction, andde novoAssembly of a Eukaryotic Genome
Authors: Goodwin Sara , Gurtowski James , Ethe-Sayers Scott , Deshpande Panchajanya , Schatz Michael C. , McCombie W. Richard 
Published: January 2015

AbstractMonitoring the progress of DNA molecules through a membrane pore has been postulated as a method for sequencing DNA for several decades. Recently, a nanopore-based sequencing instrument, the Oxford Nanopore MinION, has become available that we used for sequencing theS. cerevisiaegenome. To make use of these data, we developed a novel open-source hybrid error correction algorithm Nanocorr (https://github.com/jgurtowski/nanocorr) specifically for Oxford Nanopore reads, as existing packages were incapable of assembling the long read lengths (5-50kbp) at such high error rate (between ∼5 and 40% error). With this new method we were able to perform a hybrid error correction of the nanopore reads using complementary MiSeq data and produce ade novoassembly that is highly contiguous and accurate: the contig N50 length is more than ten-times greater than an Illumina-only assembly (678kb versus 59.9kbp), and has greater than 99.88% consensus identity when compared to the reference. Furthermore, the assembly with the long nanopore reads presents a much more complete representation of the features of the genome and correctly assembles gene cassettes, rRNAs, transposable elements, and other genomic features that were almost entirely absent in the Illumina-only assembly.Reviewer link to datahttp://schatzlab.cshl.edu/data/nanocorr/
Multi –omics and metabolic modelling pipelines: challenges and tools for systems microbiology
Authors: Fondi Marco , Liò Pietro 
Published: January 2015

AbstractIntegrated -omics approaches are quickly spreading across microbiology research labs, leading to i) the possibility of detecting previously hidden features of microbial cells like multi-scale spatial organisation and ii) tracing molecular components across multiple cellular functional states. This promises to reduce the knowledge gap between genotype and phenotype and poses new challenges for computational microbiologists. We underline how the capability to unravel the complexity of microbial life will strongly depend on the integration of the huge and diverse amount of information that can be derived today from - omics experiments. In this work, we present opportunities and challenges of multi –omics data integration in current systems biology pipelines. We here discuss which layers of biological information are important for biotechnological and clinical purposes, with a special focus on bacterial metabolism and modelling procedures. A general review of the most recent computational tools for performing large-scale datasets integration is also presented, together with a possible framework to guide the design of systems biology experiments by microbiologists.