bluuebunny/crossref_metadata_2025_split huggingface dataset:
Educational interventions encouraging appropriate use of blood transfusions
Authors: Abelow A. , Gafter‐Gvili A. , Tadmor B. , Lahav M. , Shepshelovich D. 
Published: February 2017

Background and ObjectivesThe integration of a restrictive packed red blood cells (PRBC) transfusion strategy into daily clinical practice presents a challenge. This study describes the effect of an intervention including educational presentations and computerized alerts on PRBC utilization at a tertiary hospital.Materials and MethodsDuring December 2014, lectures describing recommended PRBC transfusion indications were presented to all non‐intensive care departments. Starting from January 2015, an alert was added to the electronic drug ordering system recommending transfusions at a haemoglobin (Hb) level <7 g/dl or Hb < 8 g/dl in symptomatic patients. The physician was not required to acknowledge the alert. Data regarding measured Hb preceding transfusions were collected. The primary end‐point was defined as the percentage of PRBC administered at Hb ≥ 8 g/dl in 2015 compared with 2014. Secondary end‐points were the percentage of PRBC administered to patients with Hb < 7 g/dl and the absolute number of PRBC transfused in 2015 compared with 2014.ResultsCompared to 2014, in 2015, the percentage of PRBC transfused when the Hb ≥ 8 g/dl was reduced by 18·8% (P < 0·001) and made up 29% of the total PRBC transfused. The absolute number of PRBC transfused decreased by 7·7%. The percentage of PRBC transfused when the Hb < 7 g/dl increased by 25·9% (P < 0·001).ConclusionsFollowing the described intervention, there was a significant improvement in the appropriateness of PRBC transfusions in our medical centre. These changes occurred despite the lack of interruption of the physician's workflow from the computerized alert. This simple strategy might be of use in implementing a restrictive PRBC transfusion strategy.
Driving variables for eutrophication in lakes of Hanoi by data‐driven technique
Authors: Hoang Thu‐Huong Thi , Van Anh Dieu , Nguyen Hien Thi Thu 
Published: February 2017

AbstractTo investigate eutrophication in 31 freshwater lakes in Hanoi, Vietnam, water quality and Chlorophyll‐a content were monitored to calculate trophic indices. Twelve of the 15 urban lakes investigated were eutrophic, of which five were hypertrophic, while only seven of the 16 suburban lakes were eutrophic. The Trophic Index (TRIX) was the best predictive index to identify the eutrophication level of the lakes. Classification trees (CTs) were applied to study the trophic status of lakes and identify the driving variables. The results demonstrated that eutrophication in the lakes of Hanoi was driven by nutrients and organic enrichment, as well as by inappropriate management such as unplanned embankment and water uses. DIN, BOD, lake size and embankment were the key parameters controlling eutrophication in the lakes of Hanoi.
Benefits of a Regional Evidence‐Based Practice Fellowship Program: A Test of the ARCC Model
Authors: Kim Son Chae , Ecoff Laurie , Brown Caroline E. , Gallo Ana‐Maria , Stichler Jaynelle F. , Davidson Judy E. 
Published: February 2017

ABSTRACTBackgroundThe Advancing Research and Clinical practice through close Collaboration (ARCC) model postulates that improvement in nurses’ evidence‐based practice (EBP) beliefs results in improved EBP implementation, which in turn improves nurse‐related outcomes, such as nurses’ job satisfaction and group cohesion. However, there is a dearth of interventional studies that evaluate the relationships among these variables.AimsThis study evaluated whether a regional EBP fellowship program improved participants’ EBP beliefs, EBP implementation, job satisfaction, group cohesion, and group attractiveness, and examined the relationships among these improvements, using structural equation modeling.MethodsA pretest–posttest design was used among three annual cohorts of a regional, 9‐month EBP fellowship program, from 2012 to 2014, in San Diego, California. Matched pretest and posttest questionnaires, including EBP Beliefs, EBP Implementation, Job Satisfaction, Group Cohesion, and Group Attractiveness scales, were analyzed (N = 120).ResultsPaired t‐tests showed statistically significant improvements in EBP beliefs, EBP implementation, job satisfaction, and group cohesion (p < .05). Structural equation modeling showed that improvement in EBP implementation had no direct effect on improvements in job satisfaction, group cohesion, or group attractiveness. However, improvement in EBP beliefs had direct effects on improvements in job satisfaction (β = .24; p = .002) and group attractiveness (β = .22; p = .010).Linking Evidence to ActionA regional, collaborative EBP fellowship program was effective in improving EBP beliefs, EBP implementation, job satisfaction, and group cohesion. Improvement in EBP beliefs appears to have had direct effects on improvements in job satisfaction and group attractiveness. Regional fellowship programs that educate and support EBP champions and their mentors may enhance EBP adoption in nursing practice across multiple health care institutions.
Pain management in total knee arthroplasty: efficacy of a multimodal opiate-free protocol
Authors: Canata Gian , Casale Valentina , Chiey Alfredo 
Published: February 2017

Purpose: this study was conducted to identify the most effective method of postoperative pain management, comparing the intravenous opiate infusion protocol with the use of a single periarticular local anesthetic infiltration (LAI) in patients undergoing total knee arthroplasty (TKA) surgery.
Methods: 50 patients submitted to TKA surgery between 2013 and 2015 were divided into two groups. Buprenorphine was administered intravenously to the patients in Group A, while the Group B patients received a single periarticular LAI (ropivacaine and ketorolac) during surgery.Pain was assessed using a visual analog scale (VAS) and the knee injury and osteoarthritis outcome score. Hemoglobin and hematocrit were measured in the early postoperative period and at 40 days post-surgery. Range of motion and inflammatory markers were also assessed. Statistical analysis was performed using Student’s t-test.
Results: student’s t-test showed no significant difference between the groups in functional outcomes or blood values, but a difference in VAS score on the day of surgery was found (p < 0.0001), in favor of Group B.
Conclusions: LAI considerably reduces postoperative pain, allowing rapid mobilization and accelerating functional recovery.
Level of evidence: Level I, prospective single-blind randomized trial.
Understanding Zika Virus Stability and Developing a Chimeric Vaccine through Functional Analysis
Authors: Xie Xuping , Yang Yujiao , Muruato Antonio E. , Zou Jing , Shan Chao , Nunes Bruno T. D. , Medeiros Daniele B. A. , Vasconcelos Pedro F. C. , Weaver Scott C. , Rossi Shannan L. , Shi Pei-Yong 
Published: February 2017

ABSTRACT

Compared with other flaviviruses, Zika virus (ZIKV) is uniquely associated with congenital diseases in pregnant women. One recent study reported that (i) ZIKV has higher thermostability than dengue virus (DENV [a flavivirus closely related to ZIKV]), which might contribute to the disease outcome; (ii) the higher thermostability of ZIKV could arise from an extended loop structure in domain III of the viral envelope (E) protein and an extra hydrogen-bond interaction between E molecules (V. A. Kostyuchenko, E. X. Y. Lim, S. Zhang, G. Fibriansah, T.-S. Ng, J. S. G. Ooi, J. Shi, and S.-M. Lok, Nature 533:425–428, 2016,
https://doi.org/10.1038/nature17994
). Here we report the functional analysis of the structural information in the context of complete ZIKV and DENV-2 virions. Swapping the prM-E genes between ZIKV and DENV-2 switched the thermostability of the chimeric viruses, identifying the prM-E proteins as the major determinants for virion thermostability. Shortening the extended loop of the E protein by 1 amino acid was lethal for ZIKV assembly/release. Mutations (Q350I and T351V) that abolished the extra hydrogen-bond interaction between the E proteins did not reduce ZIKV thermostability, indicating that the extra interaction does not increase the thermostability. Interestingly, mutant T351V was attenuated in A129 mice defective in type I interferon receptors, even though the virus retained the wild-type thermostability. Furthermore, we found that a chimeric ZIKV with the DENV-2 prM-E and a chimeric DENV-2 with the ZIKV prM-E were highly attenuated in A129 mice; these chimeric viruses were highly immunogenic and protective against DENV-2 and ZIKV challenge, respectively. These results indicate the potential of these chimeric viruses for vaccine development.

IMPORTANCE
Analysis of a recently observed high-resolution structure of ZIKV led to a hypothesis that its unusual stability may contribute to the associated, unique disease outcomes. Here we performed a functional analysis to demonstrate that viral prM-E genes are the main determinants for the high stability of ZIKV. The extra hydrogen-bond interaction (observed in the high-resolution structure) between ZIKV E proteins did not enhance virion stability, whereas the extended loop of E protein (CD loop in domain III) was essential for ZIKV assembly. More importantly, we found that a chimeric ZIKV with DENV-2 prM-E genes and a chimeric DENV-2 with ZIKV prM-E genes were highly attenuated in A129 mice. Mice immunized with these chimeric viruses generated robust neutralizing antibody responses and were fully protected from DENV-2 and ZIKV challenge, respectively, indicating that these chimeric viruses could be further developed as vaccine candidates.
Selective Whole-Genome Amplification Is a Robust Method That Enables Scalable Whole-Genome Sequencing of
Plasmodium vivax
from Unprocessed Clinical Samples
Authors: Cowell Annie N. , Loy Dorothy E. , Sundararaman Sesh A. , Valdivia Hugo , Fisch Kathleen , Lescano Andres G. , Baldeviano G. Christian , Durand Salomon , Gerbasi Vince , Sutherland Colin J. , Nolder Debbie , Vinetz Joseph M. , Hahn Beatrice H. , Winzeler Elizabeth A. 
Published: February 2017

ABSTRACT

Whole-genome sequencing (WGS) of microbial pathogens from clinical samples is a highly sensitive tool used to gain a deeper understanding of the biology, epidemiology, and drug resistance mechanisms of many infections. However, WGS of organisms which exhibit low densities in their hosts is challenging due to high levels of host genomic DNA (gDNA), which leads to very low coverage of the microbial genome. WGS of
Plasmodium vivax
, the most widely distributed form of malaria, is especially difficult because of low parasite densities and the lack of an
ex vivo
culture system. Current techniques used to enrich
P. vivax
DNA from clinical samples require significant resources or are not consistently effective. Here, we demonstrate that selective whole-genome amplification (SWGA) can enrich
P. vivax
gDNA from unprocessed human blood samples and dried blood spots for high-quality WGS, allowing genetic characterization of isolates that would otherwise have been prohibitively expensive or impossible to sequence. We achieved an average genome coverage of 24×, with up to 95% of the
P. vivax
core genome covered by ≥5 reads. The single-nucleotide polymorphism (SNP) characteristics and drug resistance mutations seen were consistent with those of other
P. vivax
sequences from a similar region in Peru, demonstrating that SWGA produces high-quality sequences for downstream analysis. SWGA is a robust tool that will enable efficient, cost-effective WGS of
P. vivax
isolates from clinical samples that can be applied to other neglected microbial pathogens.

IMPORTANCE
Malaria is a disease caused by
Plasmodium
parasites that caused 214 million symptomatic cases and 438,000 deaths in 2015.
Plasmodium vivax
is the most widely distributed species, causing the majority of malaria infections outside sub-Saharan Africa. Whole-genome sequencing (WGS) of
Plasmodium
parasites from clinical samples has revealed important insights into the epidemiology and mechanisms of drug resistance of malaria. However, WGS of
P. vivax
is challenging due to low parasite levels in humans and the lack of a routine system to culture the parasites. Selective whole-genome amplification (SWGA) preferentially amplifies the genomes of pathogens from mixtures of target and host gDNA. Here, we demonstrate that SWGA is a simple, robust method that can be used to enrich
P. vivax
genomic DNA (gDNA) from unprocessed human blood samples and dried blood spots for cost-effective, high-quality WGS.
ATP-Dependent Persister Formation in
Escherichia coli
Authors: Shan Yue , Brown Gandt Autumn , Rowe Sarah E. , Deisinger Julia P. , Conlon Brian P. , Lewis Kim 
Published: February 2017

ABSTRACT

Persisters are dormant variants that form a subpopulation of cells tolerant to antibiotics. Persisters are largely responsible for the recalcitrance of chronic infections to therapy. In
Escherichia coli
, one widely accepted model of persister formation holds that stochastic accumulation of ppGpp causes activation of the Lon protease that degrades antitoxins; active toxins then inhibit translation, resulting in dormant, drug-tolerant persisters. We found that various stresses induce toxin-antitoxin (TA) expression but that induction of TAs does not necessarily increase persisters. The 16S rRNA promoter
rrnB
P1 was proposed to be a persister reporter and an indicator of toxin activation regulated by ppGpp. Using fluorescence-activated cell sorting (FACS), we confirmed the enrichment for persisters in the fraction of
rrnB
P1
-gfp
dim cells; however, this is independent of toxin-antitoxins.
rrnB
P1 is coregulated by ppGpp and ATP. We show that
rrnB
P1 can report persisters in a
relA
/
spoT
deletion background, suggesting that
rrnB
P1 is a persister marker responding to ATP. Consistent with this finding, decreasing the level of ATP by arsenate treatment causes drug tolerance. Lowering ATP slows translation and prevents the formation of DNA double-strand breaks upon ﬂuoroquinolone treatment. We conclude that variation in ATP levels leads to persister formation by decreasing the activity of antibiotic targets.

IMPORTANCE
Persisters are a subpopulation of antibiotic-tolerant cells responsible for the recalcitrance of chronic infections. Our current understanding of persister formation is primarily based on studies of
E. coli
. The activation of toxin-antitoxin systems by ppGpp has become a widely accepted model for persister formation. In this study, we found that stress-induced activation of mRNA interferase-type toxins does not necessarily cause persister formation. We also found that the persister marker
rrnB
P1 reports persister cells because it detects a drop in cellular ATP levels. Consistent with this, lowering the ATP level decreases antibiotic target activity and, thus, leads to persister formation. We conclude that stochastic variation in ATP is the main mechanism of persister formation. A decrease in ATP provides a satisfactory explanation for the drug tolerance of persisters, since bactericidal antibiotics act by corrupting energy-dependent targets.
A Ferredoxin- and F
420
H
2
-Dependent, Electron-Bifurcating, Heterodisulfide Reductase with Homologs in the Domains
Bacteria
and
Archaea
Authors: Yan Zhen , Wang Mingyu , Ferry James G. 
Published: February 2017

ABSTRACT

Heterodisulfide reductases (Hdr) of the HdrABC class are ancient enzymes and a component of the anaerobic core belonging to the prokaryotic common ancestor. The ancient origin is consistent with the widespread occurrence of genes encoding putative HdrABC homologs in metabolically diverse prokaryotes predicting diverse physiological functions; however, only one HdrABC has been characterized and that was from a narrow metabolic group of obligate CO
2
-reducing methanogenic anaerobes (methanogens) from the domain
Archaea
. Here we report the biochemical characterization of an HdrABC homolog (HdrA2B2C2) from the acetate-utilizing methanogen
Methanosarcina acetivorans
with unusual properties structurally and functionally distinct from the only other HdrABC characterized. Homologs of the HdrA2B2C2 archetype are present in phylogenetically and metabolically diverse species from the domains
Bacteria
and
Archaea
. The expression of the individual HdrA2, HdrB2, and HdrB2C2 enzymes in
Escherichia coli
, and reconstitution of an active HdrA2B2C2 complex, revealed an intersubunit electron transport pathway dependent on ferredoxin or coenzyme F
420
(F
420
H
2
) as an electron donor. Remarkably, HdrA2B2C2 couples the previously unknown endergonic oxidation of F
420
H
2
and reduction of ferredoxin with the exergonic oxidation of F
420
H
2
and reduction of the heterodisulfide of coenzyme M and coenzyme B (CoMS-SCoB). The unique electron bifurcation predicts a role for HdrA2B2C2 in Fe(III)-dependent anaerobic methane oxidation (ANME) by
M. acetivorans
and uncultured species from ANME environments. HdrA2B2C2, ubiquitous in acetotrophic methanogens, was shown to participate in electron transfer during acetotrophic growth of
M. acetivorans
and proposed to be essential for growth in the environment when acetate is limiting.

IMPORTANCE
Discovery of the archetype HdrA2B2C2 heterodisulfide reductase with categorically unique properties extends the understanding of this ancient family beyond CO
2
-reducing methanogens to include diverse prokaryotes from the domains
Bacteria
and
Archaea
. The unprecedented coenzyme F
420
-dependent electron bifurcation, an emerging fundamental principle of energy conservation, predicts a role for HdrA2B2C2 in diverse metabolisms, including anaerobic CH
4
-oxidizing pathways. The results document an electron transport role for HdrA2B2C2 in acetate-utilizing methanogens responsible for at least two-thirds of the methane produced in Earth’s biosphere. The previously unavailable heterologous production of individual subunits and the reconstitution of HdrA2B2C2 with activity have provided an understanding of intersubunit electron transfer in the HdrABC class and a platform for investigating the principles of electron bifurcation.
Widespread compression associated with Eocene Tonga-Kermadec subduction initiation
Authors: Sutherland R. , Collot J. , Bache F. , Henrys S. , Barker D. , Browne G.H. , Lawrence M.J.F. , Morgans H.E.G. , Hollis C.J. , Clowes C. , Mortimer N. , Rouillard P. , Gurnis M. , Etienne S. , Stratford W. 
Published: February 2017

Abstract
Eocene onset of subduction in the western Pacific was accompanied by a global reorganization of tectonic plates and a change in Pacific plate motion relative to hotspots during the period 52–43 Ma. We present seismic-reflection and rock sample data from the Tasman Sea that demonstrate that there was a period of widespread Eocene continental and oceanic compressional plate failure after 53–48 Ma that lasted until at least 37–34 Ma. We call this the Tectonic Event of the Cenozoic in the Tasman Area (TECTA). Its compressional nature is different from coeval tensile stresses and back-arc opening after 50 Ma in the Izu-Bonin-Mariana region. Our observations imply that spatial and temporal patterns of stress evolution during western Pacific Eocene subduction initiation were more varied than previously recognized. The evolving Eocene geometry of plates and boundaries played an important role in determining regional differences in stress state.
Climate-driven thaw of permafrost preserved glacial landscapes, northwestern Canada
Authors: Kokelj Steven V. , Lantz Trevor C. , Tunnicliffe Jon , Segal Rebecca , Lacelle Denis 
Published: February 2017

Abstract
Ice-marginal glaciated landscapes demarcate former boundaries of the continental ice sheets. Throughout circumpolar regions, permafrost has preserved relict ground ice and glacigenic sediments, delaying the sequence of postglacial landscape change that transformed temperate environments millennia earlier. Here we show that within 7 × 106 km2 of glaciated permafrost terrain, extensive landscapes remain poised for major climate-driven change. Across northwestern Canada, 60–100-km-wide concentric swaths of thaw slump–affected terrain delineate the maximum and recessional positions of the Laurentide Ice Sheet. These landscapes comprise ∼17% of continuous permafrost terrain in a 1.27 × 106 km2 study area, indicating widespread preservation of late Pleistocene ground ice. These thaw slump, relict ground ice, and glacigenic terrain associations are also evident at the circumpolar scale. Recent intensification of thaw slumping across northwestern Canada has mobilized primary glacial sediments, triggering a cascade of fluvial, lacustrine, and coastal effects. These geologically significant processes, highlighted by the spatial distribution of thaw slumps and patterns of fluvial sediment mobilization, signal the climate-driven renewal of deglaciation and postglacial permafrost landscape evolution.
Alternating Southern and Northern Hemisphere climate response to astronomical forcing during the past 35 m.y.
Authors: De Vleeschouwer David , Vahlenkamp Maximilian , Crucifix Michel , Pälike Heiko 
Published: February 2017

Abstract
Earth’s climate has undergone different intervals of gradual change as well as abrupt shifts between climate states. Here we aim to characterize the corresponding changes in climate response to astronomical forcing in the icehouse portion of the Cenozoic, from the latest Eocene to the present. As a tool, we use a 35-m.y.-long δ18Obenthic record compiled from different high-resolution benthic isotope records spliced together (what we refer to as a megasplice).We analyze the climate response to astronomical forcing during four 800-k.y.-long time windows. During the mid-Miocene Climatic Optimum (ca. 15.5 Ma), global climate variability was mainly dependent on Southern Hemisphere summer insolation, amplified by a dynamic Antarctic ice sheet; 2.5 m.y. later, relatively warm global climate states occurred during maxima in both Southern Hemisphere and Northern Hemisphere summer insolation. At that point, the Antarctic ice sheet grew too big to pulse on the beat of precession, and the Southern Hemisphere lost its overwhelming influence on the global climate state. Likewise, we juxtapose response regimes of the Miocene (ca. 19 Ma) and Oligocene (ca. 25.5 Ma) warming periods. Despite the similarity in δ18Obenthic values and variability, we find different responses to precession forcing. While Miocene warmth occurs during summer insolation maxima in both hemispheres, Oligocene global warmth is consistently triggered when Earth reaches perihelion in the Northern Hemisphere summer. This pattern is in accordance with previously published paleoclimate modeling results, and suggests an amplifying role for Northern Hemisphere sea ice.