bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is There a Preoperative Morphine Equianalgesic Dose that Predicts Ability to Achieve a Clinically Meaningful Improvement Following Spine Surgery?
Authors: Wick Joseph B , Sivaganesan Ahilan , Chotai Silky , Archer Kristin R , Posey Samuel L , Evans Parker T , Campbell Joel R , Devin Clinton J 
Published: June 2017

Abstract

BACKGROUND
Preoperative opioid use is widespread and associated with worse patient-reported outcomes following spine surgery.

OBJECTIVE
To calculate a threshold preoperative morphine equianalgesic (MEA) dose beyond which patients are less likely to achieve the minimum clinically important difference (MCID) following elective surgery for degenerative spine disease.

METHODS
The study included 543 cervical and 1293 lumbar patients. Neck Disability Index and Oswestry Disability Index scores were collected at baseline and 12 mo postoperatively. Preoperative MEA doses were calculated retrospectively. Multivariate logistic regression was then performed to determine the relationship between MEA dose and the odds of achieving MCID. As a part of this regression, Bayesian inference and Markov Chain Monte Carlo methods were used to estimate the values of inflection points (or “thresholds”) in MEA.

RESULTS
Overall, 1020 (55.5%) patients used preoperative opioids. A total of 50.3% of cervical and 61.9% of lumbar patients achieved MCID. The final logistic regression model demonstrated that MCID achievement decreased significantly when mean preoperative MEA dose exceeded 47.8 mg/d, with a 95% credible interval of 29.0 to 60.0 mg/d.

CONCLUSION
Minimum and maximum MEA doses exist, between which increasing opioid dose is associated with decreased ability to achieve clinically meaningful improvement following spine surgery. Patients with preoperative MEA dose exceeding 29 mg/d, the lower limit of the 95% credible interval for the mean MEA dose above which patients exhibit significantly decreased achievement of MCID, may be considered for preoperative opioid weaning.
Structure of the human pro-myostatin precursor and determinants of growth factor latency
Authors: Cotton Thomas , Fischer Gerhard , Wang Xuelu , McCoy Jason , Czepnik Magdalena , Thompson Thomas B. , Hyvönen Marko 
Published: June 2017

ABSTRACTMyostatin, a key regulator of muscle mass in vertebrates, is biosynthesised as a latent precursor in muscle and is activated by sequential proteolysis of the pro-domain. To investigate the molecular mechanism by which pro-myostatin remains latent, we have solved the structure of unprocessed promyostatin and analysed the properties of the protein in its different forms. Crystal structures and SAXS analyses show that pro-myostatin adopts an open, V-shaped structure with a domain-swapped arrangement. The pro-mature complex, after cleavage of the furin site, has significantly reduced activity compared with mature growth factor and persists as a stable complex that is resistant to the natural antagonist follistatin. The latency appears to be conferred by a number of distinct features that collectively stabilise the interaction of the pro-domains with the mature growth factor, enabling a regulated step-wise activation process, distinct from the prototypical pro-TGF-β1. These results provide a basis for understanding the effect of missense mutations in pro-myostatin and pave the way for the design of novel myostatin inhibitors.
Whole genome amplification and sequencing of low cell numbers directly from a bacteria spiked blood model
Authors: Anscombe Catherine , Misra Raju.V , Gharbia Saheer 
Published: June 2017

AbstractWhilst next generation sequencing is frequently used to whole genome sequence bacteria from cultures, it’s rarely applied directly to clinical samples. Therefore, this study addresses the issue of applying NGS microbial diagnostics directly to blood samples. To demonstrate the potential of direct from blood sequencing a bacteria spiked blood model was developed. Horse blood was spiked with clinical samples ofE. coliandS. aureus, and a process developed to isolate bacterial cells whilst removing the majority of host DNA. One sample of each isolate was then amplified using ϕ29 multiple displacement amplification (MDA) and sequenced. The total processing time, from sample to amplified DNA ready for sequencing was 3.5 hours, significantly faster than the 18-hour overnight culture step which is typically required. Both bacteria showed 100% survival through the processing. The direct from sample sequencing resulted in greater than 92% genome coverage of the pathogens whilst limiting the sequencing of host genome (less than 7% of all reads). Analysis ofde novoassembled reads allowed accurate genotypic antibiotic resistance prediction. The sample processing is easily applicable to multiple sequencing platforms. Overall this model demonstrates potential to rapidly generate whole genome bacterial data directly from blood.
Recruitment of CRISPR-Cas systems by Tn7-like transposons
Authors: Peters Joseph E. , Makarova Kira S. , Shmakov Sergey , Koonin Eugene V. 
Published: June 2017

AbstractA survey of bacterial and archaeal genomes shows that many Tn7-like transposons contain ‘minimal’ type I-F CRISPR-Cas systems that consist of fused cas8f and cas5f, cas7f and cas6f genes, and a short CRISPR array. Additionally, several small groups of Tn7-like transposons encompass similarly truncated type I-B CRISPR-Cas systems. This gene composition of the transposon-associated CRISPR-Cas systems implies that they are competent for pre-crRNA processing yielding mature crRNAs and target binding but not target cleavage that is required for interference. Here we present phylogenetic analysis demonstrating that evolution of the CRISPR-Cas containing transposons included a single, ancestral capture of a type I-F locus and two independent instances of type I-B loci capture. We further show that the transposon-associated CRISPR arrays contain spacers homologous to plasmid and temperate phage sequences, and in some cases, chromosomal sequences adjacent to the transposon. A hypothesis is proposed that the transposon-encoded CRISPR-Cas systems generate displacement (R-loops) in the cognate DNA sites, targeting the transposon to these sites and thus facilitating their spread via plasmids and phages. This scenario fits the “guns for hire” concept whereby mobile genetic elements can capture host defense systems and repurpose them for different stages in the life cycle of the element.ImportanceCRISPR-Cas is an adaptive immunity system that protects bacteria and archaea from mobile genetic elements. We present comparative genomic and phylogenetic analysis of degenerate CRISPR-Cas variants associated with distinct families of transposable elements and develop the hypothesis that such repurposed defense systems contribute to the transposable element propagation by facilitating transposition into specific sites. Such recruitment of defense systems by mobile elements supports the “guns for hire” concept under which the same enzymatic machineries can be alternately employed for transposon proliferation or host defense.
Soil community assembly varies across body sizes in a tropical forest
Authors: Zinger Lucie , Taberlet Pierre , Schimann Heidy , Bonin Aurélie , Boyer Frédéric , Barba Marta De , Gaucher Philippe , Gielly Ludovic , Giguet-Covex Charline , Iribar Amaia , Réjou-Méchain Maxime , Rayé Gilles , Rioux Delphine , Schilling Vincent , Tymen Blaise , Viers Jérôme , Zouiten Cyril , Thuiller Wilfried , Coissac Eric , Chave Jérôme 
Published: June 2017

ABSTRACTThe relative influence of deterministic niche-based (i.e. abiotic conditions, biotic interactions) and stochastic-distance dependent neutral processes (i.e. demography, dispersal) in shaping communities has been extensively studied for various organisms, but is far less explored jointly across the tree of life, in particular in soil environments. Here, using a thorough DNA-based census of the whole soil biota in a large tropical forest plot, we show that soil aluminium, topography, and plant species identity are all important drivers of soil richness and community composition. Body size emerges as an important feature of the comparative ecology of the different taxa at the studied spatial scale, with microorganisms being more importantly controlled by environmental factors, while soil mesofauna rather display random spatial distribution. We infer that niche-based processes contribute differently to community assembly across trophic levels due to spatial scaling. Body size could hence help better quantifying important properties of multitrophic assemblages.
The structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35
Authors: Mock Jee-Young , Xu Yue , Ye Yihong , Clemons William M. 
Published: June 2017

AbstractThe metazoan protein BCL2-associated athanogene cochaperone 6 (Bag6) forms a hetero-trimeric complex with ubiquitin-like 4A (Ubl4A) and transmembrane domain recognition complex 35 (TRC35). This Bag6 complex is involved in tail-anchored protein targeting and various protein quality control pathways in the cytosol as well as regulating transcription and histone methylation in the nucleus. Here we present a crystal structure of Bag6 and its cytoplasmic retention factor TRC35, revealing that TRC35 is remarkably conserved throughout opisthokont lineage except at the C-terminal Bag6-binding groove, which evolved to accommodate a novel metazoan factor Bag6. Remarkably, while TRC35 and its fungal homolog guided entry of tail-anchored protein 4 (Get4) utilize a conserved hydrophobic patch to bind their respective C-terminal binding partners Bag6 and Get5, Bag6 wraps around TRC35 on the opposite face relative to the Get4-5 interface. We further demonstrate that the residues involved in TRC35 binding are not only critical for occluding the Bag6 nuclear localization sequence from karyopherin α binding to retain Bag6 in the cytosol, but also for preventing TRC35 from succumbing to RNF126-mediated ubiquitylation and degradation. The results provide a mechanism for regulation of Bag6 nuclear localization and the functional integrity of the Bag6 complex in the cytosol.
Distinct representations of planned reach trajectories in human premotor and posterior parietal cortex
Authors: Pilacinski Artur , Lindner Axel 
Published: June 2017

ABSTRACTGoal-directed movements of the hand are often directed straight at the target, e.g. when swatting a fly; but when drawing or avoiding obstacles, hand trajectories can also become quite complex. Studies on movement planning have largely neglected the latter case and the question of whether the same neural machinery is planning straight, saccade-like vs. complex hand trajectories. Using time-resolved fMRI during delayed response tasks we examined planning activity in human superior parietal lobule (SPL) and dorsal premotor cortex (PMd). We show that the recruitment of both areas in trajectory planning differs significantly: PMd represented both straight and complex hand trajectories while SPL only those that led straight to the target. This implies that complex and computationally demanding reach planning is governed by a frontal pathway while a parietal route could warrant an alternative and faster way to put simple plans into action.
Head-on replication-transcription collisions lead to formation of life threatening R-loops
Authors: Lang Kevin S. , Hall Ashley N. , Merrikh Christopher N. , Ragheb Mark , Merrikh Houra 
Published: June 2017

ABSTRACTEncounters between transcription and DNA replication machineries lead to conflicts that shape genomes, influence evolution, and lead to genetic diseases in humans. Although unclear why, head-on transcription (lagging strand genes) is especially disruptive to replication, increases DNA breaks, and promotes mutagenesis. Here, we show that head-on replication-transcription conflicts lead to pervasive RNA:DNA hybrid formation inBacillus subtilis. We find that replication beyond head-on conflict regions requires the activity of a RNA:DNA hybrid processing enzyme, RNase HIII. Remarkably, pervasive RNA:DNA hybrid formation at head-on genes completely stops replication and inhibits gene expression in a replication-dependent manner. Accordingly, we find that resolution of head-on conflicts by RNase HIII is crucial for survival upon exposure to various stresses, as many stress response genes are encoded head-on to replication. We conclude that R-loops, RNA:DNA hybrids formed outside of the transcription bubble, exacerbate head-on replication-transcription conflicts, thereby threatening life, especially upon exposure to environmental stresses.
Rhodosporidium toruloides:A new platform organism for conversion of lignocellulose into terpene biofuels and bioproducts
Authors: Yaegashi Junko , Kirby James , Ito Masakazu , Sun Jian , Dutta Tanmoy , Mirsiaghi Mona , Sundstrom Eric R. , Rodriguez Alberto , Baidoo Edward , Tanjore Deepti , Pray Todd , Sale Kenneth , Singh Seema , Keasling Jay D. , Simmons Blake A. , Singer Steven W. , Magnuson Jon K. , Arkin Adam P. , Skerker Jeffrey M. , Gladden John M. 
Published: June 2017

AbstractBackgroundEconomical conversion of lignocellulosic biomass into biofuels and bioproducts is central to the establishment of a robust bioeconomy. This requires a conversion host that is able to both efficiently assimilate the major lignocellulose-derived carbon sources and divert their metabolites toward specific bioproducts.ResultsIn this study, the carotenogenic yeastRhodosporidium toruloideswas examined for its ability to convert lignocellulose into two non-native sesquiterpenes with biofuel (bisabolene) and pharmaceutical (amorphadiene) applications. We found thatR. toruloidescan efficiently convert a mixture of glucose and xylose from hydrolyzed lignocellulose into these bioproducts, and unlike many conventional production hosts, its growth and productivity were enhanced in lignocellulosic hydrolysates relative to purified substrates. This organism was demonstrated to have superior growth in corn stover hydrolysates prepared by two different pretreatment methods, one using a novel biocompatible ionic liquid (IL) choline α-ketoglutarate, which produced 261 mg/L of bisabolene at bench-scale, and the other using an alkaline pretreatment, which produced 680 mg/L of bisabolene in a high gravity fed-batch bioreactor. Interestingly,R. toruloideswas also observed to assimilatep-coumaric acid liberated from acylated grass lignin in the IL hydrolysate, a finding we verified with purified substrates.R. toruloideswas also able to consume several additional compounds with aromatic motifs similar to lignin monomers, suggesting that this organism may have the metabolic potential to convert depolymerized lignin streams alongside lignocellulosic sugars.ConclusionsThis study highlights the natural compatibility ofR. toruloideswith bioprocess conditions relevant to lignocellulosic biorefineries and demonstrates its ability to produce non-native terpenes.
Olfactory and vomeronasal innervation of the olfactory bulbs are not essential for GnRH-1 neuronal migration to the brain
Authors: Taroc Ed Zandro , Prasad Aparna , Lin Jennifer M. , Forni Paolo E. 
Published: June 2017

AbstractGonadotropin releasing hormone-1 (GnRH-1) neurons migrate from the developing olfactory pit into the hypothalamus during embryonic development. Migration of the GnRH-1 neurons is required for mammalian reproduction as these cells control release of gonadotropins from the anterior pituitary gland. Disturbances in GnRH-1 cell migration, GnRH-1 synthesis, secretion or signaling lead to varying degrees of hypogonadotropic hypogonadism (HH), which impairs pubertal onset and fertility. HH associated with congenital olfactory defects is clinically defined as Kallmann Syndrome (KS).The association of olfactory defects with HH in KS suggested potential direct relationship between defective olfactory axonal routing, lack of olfactory bulbs and aberrant GnRH-1 cell migration. However, it has never been experimentally proven that the formation of axonal connections of the olfactory and vomeronasal neurons to their functional targets are necessary for the migration GnRH-1 neurons to the hypothalamus. Loss-of-function of theArx-1homeobox gene leads to the lack of proper formation of the olfactory bulbs with abnormal axonal termination of olfactory sensory neurons (Yoshihara et al., 2005). We exploited the Arx-1nullmouse line to investigate the role of the olfactory system (olfactory/vomeronasal fibers and OBs) in controlling GnRH-1 migration to the hypothalamus. Our data proves that correct development of the OBs, and axonal connection of the olfactory and vomeronasal sensory neurons to the forebrain are not needed for GnRH-1 neuronal migration. Moreover, we prove that the terminal nerve, which forms the GnRH-1 migratory scaffold, follows different guidance cues and differs in its genetic expression from olfactory and vomeronasal sensory neurons.Significance StatementGonadotropin Releasing Hormone-1 (GnRH-1) neurons control the reproductive axis of vertebrates. During embryonic development, these neurons migrate from the olfactory pit to the hypothalamus. GnRH-1 cell migration is commonly believed to take place along the olfactory axons. Our work reveals that correct olfactory bulb development and targeting of the olfactory and vomeronasal sensory neurons to the brain are not required for this migration. Our work challenges the idea that GnRH-1 neuronal migration to the hypothalamus relies on correct routing of the olfactory and vomeronasal sensory neurons. We provide a new basis for interpreting genetic correlations between anosmia, lack of olfactory bulbs, and hypogonadotropic hypogonadism in Kallmann Syndrome.
The Association of Health Literacy With Preventable Emergency Department Visits: A Cross‐sectional Study
Authors: Balakrishnan Meenakshi P. , Herndon Jill Boylston , Zhang Jingnan , Payton Thomas , Shuster Jonathan , Carden Donna L. 
Published: June 2017

AbstractBackgroundPolicymakers argue that emergency department (ED) visits for conditions preventable with high‐quality outpatient care contribute to waste in the healthcare system. However, access to ambulatory care is uneven, especially for vulnerable populations like minorities, the poor, and those with limited health literacy. The impact of limited health literacy on ED visits that are preventable with timely, high‐quality ambulatory care is unknown.ObjectiveThe objective was to determine the association of health literacy with preventable ED visits.MethodsWe conducted an observational cross‐sectional study of potentially preventable ED visits (outcome) among adults (≥18 years old) in an ED serving an urban community. We assessed health literacy (predictor) through structured interviews with the Rapid Estimate of Adult Literacy in Medicine (REALM). We recorded age, sex, race, employment, payer, marital and health status, and number of comorbidities through structured interviews or electronic record review. We identified potentially preventable ED visits in the 2 years before the index ED visit by applying Agency for Healthcare Research and Quality technical specifications to identify ambulatory care sensitive conditions using ED discharge diagnoses in hospital administrative data. We used Poisson regression to evaluate the number of preventable ED visits among patients with limited (REALM < 61) versus adequate (REALM ≥ 61) health literacy after adjusting for covariates.ResultsOf 1,201 participants, 709 (59%) were female, 370 (31%) were African American, mean age was 41.6 years, and 394 (33%) had limited health literacy. Of 4,444 total ED visits, 423 (9.5%) were potentially preventable. Of these, 260 (61%) resulted in hospital admission and 163 (39%) were treat and release. After covariates were adjusted for, patients with limited literacy had 2.3 (95% confidence interval [CI] = 1.7–3.1) times the number of potentially preventable ED visits resulting in hospital admission compared to individuals with adequate health literacy, 1.4 (95% CI = 1.0–2.0) times the number of treat‐and‐release visits, and 1.9 (95% CI = 1.5–2.4) times the number of total preventable ED visits.ConclusionsOur results suggest that the ED may be an important site to deploy universal literacy‐sensitive precautions and to test literacy‐sensitive interventions with the goal of reducing the burden of potentially preventable ED visits on patients and the healthcare system.
Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases
Authors: Gu Ming , Zhang Yu , Liu Chuhe , Wang Dongshan , Feng Li , Fan Shengjie , Yang Baican , Tong Qingchun , Ji Guang , Huang Cheng 
Published: June 2017

Background and PurposeMorin is a natural occurring flavonoid in many dietary plants and has a wide range of beneficial effects on metabolism; however, the mechanism underlying its action remains elusive.Experimental ApproachA reporter assay and the time‐resolved FRET assay were used to identify morin as a dual antagonist of liver X receptor (LXR)‐α and ‐β. Morin (100 mg.100 g‐1 diet) was administered to high‐fat diet‐induced obese or LXRβ−/− mice. The pharmacological effects and mechanism of action of morin were evaluated by Western blot and RT‐PCR analyses.Key ResultsFrom the in vitro assays, morin was shown to be a dual antagonist of LXRα and LXRβ. In vivo, morin blunted the development of liver hepatic steatosis, reduced body weight gains, lowered triglyceride levels and improved glucose and insulin tolerance in mice fed a high‐fat diet. Mechanistically, morin inhibited 3T3‐L1 adipocyte differentiation and lipid formation in human hepatic HepG2 cells and suppressed the mRNA expression of genes downstream of LXR. Consistently, the effects of morin on metabolic disorders were attenuated in LXRβ−/− mice.Conclusion and ImplicationsOur data reveal that morin is a dual antagonist of LXRα and LXRβ and suggest that morin may alleviate hepatic steatosis and other associated metabolic disorders via the suppression of LXR signalling and, therefore, shows promise as a novel therapy or nutraceutical for nonalcoholic fatty liver disease.
Surgical site infection after occlusion of the internal carotid artery with a thrombectomy catheter: Can this be prevented?
Authors: Freeman D. E. 
Published: June 2017

SummaryBased on available evidence, the embolisation methods guided by fluoroscopy (nitinol plugs and transarterial coil embolisation) are preferred when available to occlude the bleeding artery in horses with guttural pouch mycosis. All attempts should be made to submit suitable candidates to hospitals with the necessary equipment and expertise for these procedures. However, when this opportunity is not available, the nondetachable balloon catheter could still offer a viable and effective alternative. Although the risk of surgical site infection is a delayed complication of this method, risk of infection can be reduced by planned removal at 10–14 days after catheter placement.