bluuebunny/crossref_metadata_2025_split huggingface dataset:
A disruptive cue improves handwashing in school children in Zambia
Authors: Naluonde Tabonga , Wakefield Christina , Markle Laurie , Martin Anne , Tresphor Chanda , Abdullah Rim , Larsen David A 
Published: September 2018

Abstract
Behavioral economics hold great promise in changing patterns of behavior that influence human health. Handwashing with soap is one such behavior that is important in reducing exposure to pathogens, and in school-age children, handwashing helps reduce absenteeism through the prevention of respiratory and diarrheal diseases. However, the gap between knowledge on the importance of handwashing and actual handwashing practice, especially with soap, persists. Many traditional behavior change communication approaches have failed in achieving and sustaining improved handwashing practices. Cognitive psychology research on habits as well as nudge theory, a component of behavioral economics predicated on the idea of making a behavior as easy as possible to do, suggests that introducing a disruptive cue into the environment may be able to interrupt current habitual neurological patterns to effect and then sustain behavior change. We used a participatory process to identify and introduce a locally appropriate disruptive cue to improve handwashing behavior in schools in Zambia. We then utilized a school-randomized controlled trial to test the soap-on-a-rope in 50 government schools in Namwala District of Southern Province. Two outcomes were considered among school children; washing hands with water and using soap while washing hands. Following the intervention, soap use was more likely in intervention schools than control schools [Odds ratio = 7.23, 95% confidence interval = (1.76–29.71)], though both intervention and control schools saw an increase in handwashing without soap. This low-cost intervention could be scaled throughout Zambia and may work well in other countries of similar circumstances.
38 seconds above the 38th parallel: how short video clips produced by the US military can promote alignment despite antagonism between Japan and Korea
Authors: Asaba Yuki , Hahn Kyu S , Jang Seulgi , Kobayashi Tetsuro , Tago Atsushi 
Published: September 2018

Abstract
The effectiveness of public diplomacy is now increasingly the subject of scientific measurement and testing by researchers in the field of International Relations. While there are variety of empirical efforts to uncover the power of public diplomacy, extant studies have mostly focused on the activities initiated by the ministries in charge of external relations. In this article, rather than external relations ministries and agencies, we focus on the effectiveness of public diplomacy by the military. Specifically, we argue that figures, pictures and indeed videos created by military forces have power in changing perceptions among the receivers of the information. In this particular study, we show that a 38 second video made by the US military induces positive feelings for cooperation which would otherwise be difficult to sustain between South Korea and Japan — two countries which have suffered highly fractious relations, yet which are indispensable allies to the US in countering the rising threat from North Korea.
A search for optical transients associated with fast radio burst 150418
Authors: Niino Yuu , Tominaga Nozomu , Totani Tomonori , Morokuma Tomoki , Keane Evan , Possenti Andrea , Sugai Hajime , Yamasaki Shotaro 
Published: September 2018

Abstract
We have searched for optical variability in the host galaxy of the radio variable source possibly associated with fast radio burst (FRB) 150418. We compare images of the galaxy taken 1 day after the burst using Subaru/Suprime-Cam with images taken ∼1 yr after the burst using Gemini-South/GMOS. No optical variability is found between the two epochs with a limiting absolute magnitude ≳ −19 (AB). This limit applies to the optical variability of the putative active galactic nucleus in the galaxy on a timescale of ∼1 yr, and also to the luminosity of an optical counterpart of FRB 150418 one day after the burst should it have occurred in this galaxy.
Keeping up-to-date with diabetes care and education
Authors: Funnell Martha M. , Freehill Karein 
Published: September 2018

Abstract:
The American Diabetes Association publishes standards of care that are updated annually by a panel of experts in nursing, education, behavior, psychology, nutrition, pharmacology, and medicine. This article describes current evidence-based approaches to care and education for adults and highlights revisions in the 2018 Standards of Care that are relevant to nurses and patients with type 2 diabetes.
Neuromuscular blocking agents for adult patients with acute respiratory distress syndrome: A meta-analysis of randomized controlled trials
Authors: Tao Wei , Yang Liu-Qing , Gao Ju , Shao Jun 
Published: September 2018

BACKGROUND
To explore the effect of neuromuscular blocking agents (NMBAs) on adult patients with acute respiratory distress syndrome (ARDS) by meta-analysis.

METHODS
Three databases including Cochrane central register of controlled trials, PubMed, and Wanfang Data were searched to find relevant articles. We included randomized controlled trials that evaluated NMBAs compared with placebo or usual treatment in adult patients with ARDS.

RESULTS
Five trials totaling 551 patients were identified eligible for inclusion. All the five trials were protective ventilation strategies based. All patients (the ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤ 200 mm Hg) met American-European Consensus Conference or the Berlin definition oxygenation criteria for ARDS. Neuromuscular blocking agents significantly reduced intensive care unit mortality (relative risk, 0.73; 95% confidence intervals [CI], 0.58–0.93; p = 0.009; I
2 = 0.0%; 4 trials, 455 patients) and 21- to 28-day mortality (relative risk, 0.63; 95% CI, 0.49–0.82; p = 0.001; I
2 = 0.0%; 4 trials, 527 patients). At 48 hours, NMBAs improved oxygenation (weighted mean differences [WMD], 27.98; 95% CI, 7.45–48.51; p = 0.008; I
2 = 44.2%; 4 trials, 212 patients). However, NMBAs have no effect on reduction of oxygenation at 24 hours (WMD, 26.83; 95% CI, −5.89 to 59.55; p = 0.108; I
2 = 82.4%; 4 trials, 447 patients), and plateau pressure (WMD, 0.43; 95% CI, −0.46 to 1.31; p = 0.345; 4 trials, 455 patients) as well as positive end expiratory pressure (WMD, 0.10; 95% CI, −0.47 to 0.67; p = 0.73; 4 trials, 455 patients) at 48 hours.

CONCLUSION
Protective ventilation strategies based NMBAs treatment reduces mortality in patients with moderate to severe ARDS.

LEVEL OF EVIDENCE
Systematic reviews & meta-analysis, level III.
A Chromosome-level Sequence Assembly Reveals the Structure of theArabidopsis thalianaNd-1 Genome and its Gene Set
Authors: Pucker Boas , Holtgräwe Daniela , Stadermann Kai Bernd , Frey Katharina , Huettel Bruno , Reinhardt Richard , Weisshaar Bernd 
Published: September 2018

AbstractBackgroundIn addition to the BAC-based reference sequence of the accession Columbia-0 from the year 2000, several short read assemblies of THE plant model organismArabidopsis thalianawere published during the last years. Also, a SMRT-based assembly of Landsbergerectahas been generated that identified translocation and inversion polymorphisms between two genotypes of the species.ResultsHere we provide a chromosome-arm level assembly of theA. thalianaaccession Niederzenz-1 (AthNd-1_v2c) based on SMRT sequencing data. The best assembly comprises 69 nucleome sequences and displays a contig length of up to 16 Mbp. Compared to an earlier Illumina short read-based NGS assembly (AthNd-1_v1), a 75 fold increase in contiguity was observed for AthNd-1_v2c. To assign contig locations independent from the Col-0 gold standard reference sequence, we used genetic anchoring to generate ade novoassembly. In addition, we assembled the chondrome and plastome sequences.ConclusionsDetailed analyses of AthNd-1_v2c allowed reliable identification of large genomic rearrangements betweenA. thalianaaccessions contributing to differences in the gene sets that distinguish the genotypes. One of the differences detected identified a gene that is lacking from the Col-0 gold standard sequence. Thisde novoassembly extends the known proportion of theA. thalianapan-genome.
Budding yeast complete DNA replication after chromosome segregation begins
Authors: Ivanova Tsvetomira , Maier Michael , Missarova Alsu , Ziegler-Birling Céline , Carey Lucas B. , Mendoza Manuel 
Published: September 2018

AbstractTo faithfully transmit genetic information, cells must replicate their entire genome before division. This is thought to be ensured by the temporal separation of replication and chromosome segregation. Here we show that in a substantial fraction of unperturbed yeast cells, DNA replication finishes during anaphase, late in mitosis. High cyclin-Cdk activity inhibits replication in metaphase, and the decrease in cyclin-Cdk activity during mitotic exit allows DNA replication to finish at difficult-to-replicate regions. Replication during late mitosis correlates with elevated mutation rates, including copy number variation. Thus, yeast cells temporally overlap replication and chromosome segregation during normal growth, possibly allowing cells to maximize population-level growth rate while simultaneously exploring greater genetic space.One Sentence SummaryCompletion of DNA replication is coupled to downregulation of Cyclin-Dependent Kinase during mitotic exit.
Differences in Therapeutic Efficacy in Pancreatic Cancer Between Interstitial and Superficial Light Delivery Strategies in Targeted Photo Therapy
Authors: De Magalhães Nzola ,   HTL(ASCP)CM
Published: September 2018

AbstractThe purpose of this study was to determine if therapeutic efficacy of a Cetuximab based near-infrared (NIR) targeted photo therapy (TPT) was dependent on light delivery strategies. We examined the cytotoxic effects of TPT in a pancreatic cancer mouse model, when administered to tumors interstitially and superficially.A subcutaneous mouse model of pancreatic cancer using BXPC-3 -GFP cells was established in male athymic (nu/nu) mice. The mice received intravenous (IV) injection of Cetuximab-IR700DX, 24 hours prior to near-infrared light irradiation. Interstitial illumination was administered at a 400mW/cm fixed power output, at a light dose of 100 J/cm to half the mice and at 300 J/cm to the remaining mice. Superficial illumination was administered at a 150mw/cm2fixed power density at a dose of 50 J/cm2to half the mice, and at 250 J/cm2to the other half. Cellular damage and decrease in cell viability was determined by the decrease in GFP fluorescence intensity levels in whole animal images and in relative intensity measurements.Interstitially administered TPT resulted in greater long-term permanent damage (72 hours post treatment) to tumor cells (0% recovery at low dose, and 11% recovery at high dose) compared to superficially administered TPT (1% recovery at low dose, and 44% recovery at high dose). While these results demonstrated that near-infrared targeted photo therapy efficacy was dependent on the type of light delivery strategy, overall, both superficial and interstitial Cet-IR700DX based near-infrared targeted photo therapy can effect significant long-term damage (less signal recovery) to pancreatic cancer cellsin vivoat lower doses regimens, compared to higher dose regimens (higher signal recovery).
Distinct pathogenic genes causing intellectual disability and autism exhibit overlapping effects on neuronal network development
Authors: Frega Monica , Selten Martijn , Mossink Britt , Keller Jason M. , Linda Katrin , Moerschen Rebecca , Qu Jieqiong , Koerner Pierre , Jansen Sophie , Bijvank Elske , Oudakker Astrid , Kleefstra Tjitske , Bokhoven Hans van , Zhou Huiqing , Schubert Dirk , Kasri Nael Nadif 
Published: September 2018

AbstractAn intriguing question in medical biology is how mutations in functionally distinct genes can lead to similar clinical phenotypes. For example, patients with mutations in distinct epigenetic regulators EHMT1, MBD5, MLL3 or SMARCB1 share the core clinical features of intellectual disability (ID), autism spectrum disorder (ASD) and facial dysmorphisms. To elucidate how these phenotypic similarities are reflected by convergence at the molecular, cellular and neuronal network level, we directly compared the effects of their loss of function in neurons. Interestingly, knockdown of each gene resulted in hyperactive neuronal networks with altered patterns of synchronized activity. At the single-cell level, we found genotype-specific changes in intrinsic excitability and excitatory-inhibitory balance, but in all cases leading to increased excitability. Congruent with our physiological findings, we identified dysregulated genes that converge on biological and cellular pathways related to neuronal excitability and synaptic function, including genes previously implicated in ID/ASD. Yet, our data suggests that the common cellular phenotypes depend on the ensemble of dysregulated genes engaged in neuronal excitability rather than the direction of transcriptional changes of individual genes. The demonstration of increasing convergence from molecular pathways to neuronal networks may be a paradigm for other types of ID/ASD.
A Type I Restriction-Modification System Associated withEnterococcus faeciumSubspecies Separation
Authors: Huo Wenwen , Adams Hannah M. , Trejo Cristian , Badia Rohit , Palmer Kelli L. 
Published: September 2018

ABSTRACTThe gastrointestinal colonizerEnterococcus faeciumis a leading cause of hospital-acquired infections. Multidrug-resistant (MDR)E. faeciumare particularly concerning for infection treatment. Previous comparative genomic studies revealed that subspecies referred to as Clade A and Clade B exist withinE. faecium. MDRE. faeciumbelong to Clade A, while Clade B consists of drug-susceptible fecal commensalE. faecium. Isolates from Clade A are further grouped into two sub-clades, A1 and A2. In general, Clade A1 isolates are hospital epidemic isolates whereas Clade A2 isolates are isolates from animals and sporadic human infections. Such phylogenetic separation indicates that reduced gene exchange occurs between the clades. We hypothesize that endogenous barriers to gene exchange exist betweenE. faeciumclades. Restriction-modification (R-M) systems are such barriers in other microbes. We utilized bioinformatics analysis coupled with second generation and third generation deep sequencing platforms to characterize the methylome of two representativeE. faeciumstrains, one from Clade A1 and one from Clade B. We identified a Type I R-M system that is Clade A1-specific, is active for DNA methylation, and significantly reduces transformability of Clade A1E. faecium. Based on our results, we conclude that R-M systems act as barriers to horizontal gene exchange inE. faeciumand propose that R-M systems contribute toE. faeciumsubspecies separation.IMPORTANCEEnterococcus faeciumis a leading cause of hospital-acquired infections around the world. Rising antibiotic resistance in certainE. faeciumlineages leaves fewer treatment options. The overarching aim of the attached work was to determine whether restriction-modification (R-M) systems contribute to the structure of theE. faeciumspecies, wherein hospital-epidemic and non-hospital-epidemic isolates have distinct evolutionary histories and highly resolved clade structures. R-M provides bacteria with a type of innate immunity to horizontal gene transfer (HGT). We identified a Type I R-M system that is enriched in the hospital-epidemic clade and determined that it is active for DNA modification activity and significantly impacts HGT. Overall, this work is important because it provides a mechanism for the observed clade structure ofE. faeciumas well as a mechanism for facilitated gene exchange among hospital-epidemicE. faecium.
Identification of novel protein lysine acetyltransferases inEscherichia coli
Authors: Christensen David G. , Meyer Jesse G. , Baumgartner Jackson T. , D’Souza Alexandria K. , Nelson William C. , Payne Samuel H. , Kuhn Misty L. , Schilling Birgit , Wolfe Alan J. 
Published: September 2018

AbstractPost-translational modifications, such as Nε-lysine acetylation, regulate protein function. Nε-lysine acetylation can occur either non-enzymatically or enzymatically. The non-enzymatic mechanism uses acetyl phosphate (AcP) or acetyl coenzyme A (AcCoA) as acetyl donors to modify an Nε-lysine residue of a protein. The enzymatic mechanism uses Nε-lysine acetyltransferases (KATs) to specifically transfer an acetyl group from AcCoA to Nε-lysine residues on proteins. To date, only one KAT (YfiQ, also known as Pka and PatZ) has been identified inE. coli. Here, we demonstrate the existence of 4 additionalE. coliKATs: RimI, YiaC, YjaB, and PhnO. In a genetic background devoid of all known acetylation mechanisms (most notably AcP and YfiQ) and one deacetylase (CobB), overexpression of these putative KATs elicited unique patterns of protein acetylation. We mutated key active site residues and found that most of them eliminated enzymatic acetylation activity. We used mass spectrometry to identify and quantify the specificity of YfiQ and the four novel KATs. Surprisingly, our analysis revealed a high degree of substrate specificity. The overlap between KAT-dependent and AcP-dependent acetylation was extremely limited, supporting the hypothesis that these two acetylation mechanisms play distinct roles in the post-translational modification of bacterial proteins. We further showed that these novel KATs are conserved across broad swaths of bacterial phylogeny. Finally, we determined that one of the novel KATs (YiaC) and the known KAT (YfiQ) can negatively regulate bacterial migration. Together, these results emphasize distinct and specific non-enzymatic and enzymatic protein acetylation mechanisms present in bacteria.ImportanceNε-lysine acetylation is one of the most abundant and important post-translational modifications across all domains of life. One of the best-studied effects of acetylation occurs in eukaryotes, where acetylation of histone tails activates gene transcription. Although bacteria do not have true histones, Nε-lysine acetylation is prevalent; however, the role of these modifications is mostly unknown. We constructed anE. colistrain that lacked both known acetylation mechanisms to identify four new Nε-lysine acetyltransferases (RimI, YiaC, YjaB, and PhnO). We used mass spectrometry to determine the substrate specificity of these acetyltransferases. Structural analysis of selected substrate proteins revealed site-specific preferences for enzymatic acetylation that had little overlap with the preferences of the previously reported acetyl-phosphate non-enzymatic acetylation mechanism. Finally, YiaC and YfiQ appear to regulate flagellar-based motility, a phenotype critical for pathogenesis of many organisms. These acetyltransferases are highly conserved and reveal deeper and more complex roles for bacterial post-translational modification.
Innolysins: A novel approach to engineer endolysins to kill Gram-negative bacteria
Authors: Zampara Athina , Holst Sørensen Martine C. , Grimon Dennis , Antenucci Fabio , Briers Yves , Brøndsted Lone 
Published: September 2018

ABSTRACTBacteriophage-encoded endolysins degrading the essential peptidoglycan of bacteria are promising alternative antimicrobials to handle the global threat of antibiotic resistant bacteria. However, endolysins have limited use against Gram-negative bacteria, since their outer membrane prevents access to the peptidoglycan. Here we present Innolysins, a novel concept for engineering endolysins that allows the enzymes to pass through the outer membrane, hydrolyse the peptidoglycan and kill the target bacterium. Innolysins combine the enzymatic activity of endolysins with the binding capacity of phage receptor binding proteins (RBPs). As our proof of concept, we used phage T5 endolysin and receptor binding protein Pb5, which binds irreversibly to the phage receptor FhuA involved in ferrichrome transport inEscherichia coli. In total, we constructed twelve Innolysins fusing endolysin with Pb5 or the binding domain of Pb5 with or without flexible linkers in between. While the majority of the Innolysins maintained their muralytic activity, Innolysin#6 also showed bactericidal activity againstE. colireducing the number of bacteria by 1 log, thus overcoming the outer membrane barrier. Using anE. coli fhuAdeletion mutant, we demonstrated that FhuA is required for bactericidal activity, supporting that the specific binding of Pb5 to its receptor onE. coliis needed for the endolysin to access the peptidoglycan. Accordingly, Innolysin#6 was able to kill other bacterial species that carry conserved FhuA homologs such asShigella sonneiandPseudomonas aeruginosa. In summary, the Innolysin approach expands recent protein engineering strategies allowing customization of endolysins by exploiting phage RBPs to specifically target Gram-negative bacteria.IMPORTANCEThe extensive use of antibiotics has led to the emergence of antimicrobial resistant bacteria responsible for infections causing more than 50,000 deaths per year across Europe and the US. In response, the World Health Organization has stressed an urgent need to discover new antimicrobials to control in particular Gram-negative bacterial pathogens, due to their extensive multi-drug resistance. However, the outer membrane of Gram-negative bacteria limits the access of many antibacterial agents to their targets. Here, we developed a new approach, Innolysins that enable endolysins to overcome the outer membrane by exploiting the binding specificity of phage receptor binding proteins. As proof of concept, we constructed Innolysins againstE. coliusing the endolysin and the receptor binding protein of phage T5. Given the rich diversity of phage receptor binding proteins and their different binding specificities, our proof of concept paves the route for creating an arsenal of pathogen specific alternative antimicrobials.
Human CtIP forms a tetrameric dumbbell-shaped particle which binds and bridges complex DNA end structures for double-strand break repair
Authors: Wilkinson O.J. , Martín-González A. , Kang H.J. , Northall S.J. , Wigley D.B. , Moreno-Hererro F. , Dillingham M.S. 
Published: September 2018

SummaryCtIP is involved in the resection of double-stranded DNA breaks during the S and G2 phases of the cell cycle for repair by homologous recombination. Acting in concert with the MRN complex, it plays a particularly important role in handling complex DNA end structures by localised nucleolytic processing of DNA termini in preparation for longer range resection. Here we show that human CtIP is a tetrameric protein adopting a dumbbell architecture in which DNA binding domains are connected by long coiled-coils. The protein complex binds two short DNA duplexes with high affinity and bridges DNA molecules in trans. DNA binding is potentiated by dephosphorylation and is not specific for DNA end structures per se. However, the affinity for linear DNA molecules is increased if the DNA terminates with more complex structures including forked ssDNA overhangs and model nucleoprotein conjugates. This work provides a biochemical and structural basis for the function of CtIP at complex DNA breaks.