bluuebunny/crossref_metadata_2025_split huggingface dataset:
Window of Opportunity to Mitigate Trauma-induced Coagulopathy
Authors: Leeper Christine M. , Strotmeyer Stephen J. , Neal Matthew D. , Gaines Barbara A. 
Published: July 2019

Objective:
The aim of this study was to delineate the kinetics of coagulation dysregulation after injury in children.

Summary Background Data:
Trauma-induced coagulopathy is common and portends poor outcomes in severely-injured children. Transfer to pediatric trauma centers is common; time from injury to laboratory testing is therefore highly variable.

Methods:
Records of severely injured children age <18 years with rapid thromboelastography (TEG) on arrival and documented time of injury were queried. Standard definitions of hyperfibrinolysis (LY30 ≥3), fibrinolysis shutdown (SD; LY30 ≤0.8), and physiologic (LY30 = 0.9–2.9) were applied. Abbreviated Injury Scale score ≥3 defined severe traumatic brain injury (TBI). Variables of interest included demographics, injury mechanism, medications, mortality, and functional disability. Wilcoxon rank-sum and Kruskal-Wallis testing were utilized for skewed continuous data, and Chi-square or Fisher exact test was used for categorical data. To determine independent predictors of SD, multivariable logistic regression modeling was performed using the time from injury variable as well as variables determined a priori to be clinically relevant contributors to the development of SD (TBI, injury mechanism, and age).

Results:
A total of 285 patients were included: median (interquartile range) age = 11 (6–15), injury severity score = 17 (10–25), 75% blunt mechanism, 32% severe TBI, 11% mortality, 28% functional disability. None received antifibrinolytics or blood products before TEG testing. Physiologic phenotype was predominant within 1 hour of injury (51%); beyond 1 hour, fibrinolysis SD was the predominant phenotype (1–3 hours = 46%, >3 hours = 59%). Patients with TBI had significant increase in incidence of fibrinolysis SD beyond 1 hour after injury as compared to non-TBI patients. Physiologic fibrinolysis was associated with survival at all timepoints (P = 0.005).

Conclusions:
Fibrinolysis SD is a reactive, compensatory mechanism that is evident soon after injury. There appears to be an early and brief window of opportunity for intervention to mitigate the progression to TIC. Further studies should focus on understanding the dynamic events occurring immediately after injury to identify specific targets for intervention.
Medicare Patient Referral Networks to Female Pelvic Medicine and Reconstructive Surgeons Across the United States
Authors: Muffly Tyler M. , Gonzalez Javier , Khorshid Arian , Hajagos Janos , Kropat Georg 
Published: July 2019

Objective
The source of urogynecology patient referrals remains poorly understood. We used novel methods to identify referral networks to female pelvic medicine and reconstructive surgeons (FPMRS) and to determine factors associated with physician connections.

Methods
A retrospective analysis of Centers for Medicare and Medicaid Services data with physician sharing relationships spanning 180 days during 2015 was performed. All patients studied were Medicare beneficiaries. Provider patient-sharing networks were modeled using social network analytics. To visualize the resulting flow of patients from referring providers to FPMRS, we encoded the node and edge data and mapped the data to a map of the United States.

Results
We studied 206,568 Medicare beneficiaries who were seen by 618 different board-certified FPMRS. Internal medicine physicians followed by nurse practitioners referred the most patients to FPMRS. Over half of referrals were made locally, with patients traveling less than 5 miles from the referring provider to the female pelvic surgeon. The median number of incoming Medicare patient referrals per FPMRS provider was 15 (interquartile range, 12–20) over a 6-month period. The high modularity of the referral network indicates that most providers refer their patients to a few female pelvic surgeons.

Conclusions
Medicare patient referrals to FPMRS are primarily and proportionally the highest from local internal medicine physicians.
Palliative Care in trauma: Not just for the dying
Authors: Fiorentino Michele , Hwang Franchesca , Pentakota Sri Ram , Livingston David H. , Mosenthal Anne C. 
Published: July 2019

BACKGROUND
Palliative Care (PC) is indicated in patients with functional dependency and advanced care needs in addition to those with life-threatening conditions. Older trauma patients have PC needs due to increased risk of mortality and poor long-term outcomes. We hypothesized that older trauma patients discharged alive with poor outcomes are not easily identified nor receive PC interventions.

METHODS
Prospective observational study of trauma patients 55 years or older. Patients with poor functional outcomes defined by discharge Glasgow Outcome Scale Extended (GOSE) 1–4 or death at 6-month follow-up were analyzed for rate and timing of PC interventions including goals of care conversation (GOCC), do-not-resuscitate (DNR) order, do not intubate (DNI) order, and withdrawal of life supporting measures. Logistic regression was performed for having and timing of GOCC.

RESULTS
Three hundred fifteen (54%) of 585 patients had poor outcomes. Of patients who died, 94% had GOCC compared with 31% of patients who were discharged with GOSE 3 or 4. In patients who died, 85% had DNR order, 18% had DNI order, and 56% had withdrawal of ventilator. Only 24% and 9% of patients with GOSE of 3 or 4, respectively, had DNR orders. Fifty percent of the patients who were dead at 6-month follow-up had GOCC during initial hospitalization. The median time to DNR in patients that died was 2 days compared with 5 days and 1 day in GOSE 3 and 4 (p = 0.046). Age, injury severity scale, and preexisting limited physiological reserve were predictive of having a GOCC.

CONCLUSION
The PC utilization was very high for older trauma patients who died in hospital. In contrast, the majority of those who were discharged alive, but with poor outcomes, did not have PC. Development of triggers to identify older trauma patients, who would benefit from PC, could close this gap and improve quality of care and outcomes.
Coordination of Tissue Cell Polarity by Auxin Transport and Signaling
Authors: Verna Carla , Ravichandran Sree Janani , Sawchuk Megan G. , Linh Nguyen Manh , Scarpella Enrico 
Published: July 2019

AbstractCoordination of polarity between cells in tissues is key to multicellular organism development. In animals, coordination of this tissue cell polarity often requires direct cell-cell interactions and cell movements, which are precluded in plants by a wall that separates cells and holds them in place; yet plants coordinate the polarity of hundreds of cells during the formation of the veins in their leaves. Overwhelming experimental evidence suggests that the plant signaling molecule auxin coordinates tissue cell polarity to induce vein formation, but how auxin does so is unclear. The prevailing hypothesis proposes that GNOM, a regulator of vesicle formation during protein trafficking, positions auxin transporters of the PIN-FORMED family to the correct side of the plasma membrane. The resulting cell-to-cell, polar transport of auxin would coordinate tissue cell polarity and would induce vein formation. Here we tested this hypothesis by means of a combination of cellular imaging, molecular genetic analysis, and chemical induction and inhibition. Contrary to predictions of the hypothesis, we find that auxin-induced vein formation occurs in the absence of PIN-FORMED proteins or any known intercellular auxin transporter, that the residual auxin-transport-independent vein-patterning activity relies on auxin signaling, and that aGNOM-dependent signal that coordinates tissue cell polarity to induce vein formation acts upstream of both auxin transport and signaling. Our results reveal synergism between auxin transport and signaling, and their unsuspected control byGNOM, in the coordination of tissue cell polarity during vein patterning, one of the most spectacular and informative expressions of tissue cell polarization in plants.
Clonal transmission and new mechanism of resistance to trimethoprim-sulfamethoxazole in Stenotrophomonas maltophilia strains isolated in a neonatology unit at Antananarivo, Madagascar, deciphered by whole genome sequence analysis
Authors: Noah Rabenandrasana Mamitina Alain , Andrianoelina Volasoa , Bonneault Melanie , Herindrainy Perlinot , Garin Benoit , Breurec Sebastien , Delarocque-Astagneau Elisabeth , Andrianirina Zafitsara Zo , Enouf Vincent , Huynh Bich-Tram , Opatowski Lulla , Collard Jean-Marc 
Published: July 2019

ABSTRACTStenotrophomonas maltophilia has been recognized as an emerging multidrug resistant organism in hospital settings due to its resistance to a broad range of antimicrobial agents. These include β-lactams and aminoglycosides, afforded by the existence of intrinsic and acquired resistance mechanisms. Trimethoprim/sulfamethoxazole (SXT) is recommended as one of the best treatment choices against S. maltophilia infections; however increasing resistance to SXT has complicated the treatment. From July 2014 to March 2015, individuals and surfaces from a neonatology ward in Antananarivo, Madagascar, were longitudinally followed to assess the transmission of bacteria resistant to antibiotics between neonates, individuals (parents and nurses) and ward environments. Four S. maltophilia strains were successively isolated from a water-tap (N=1), from feces obtained from a newborn (N=1), and nursing staff (N=2). Antimicrobial susceptibility testing and whole genome sequencing were performed on each isolate. Based on coregenome alignment, all strains were identical and belonged to the new sequence type ST-288. They were resistant to trimethoprim-sulfamethoxazole, carbapenems and intermediate to levofloxacin. Each isolate carried the aadB, strA, strB and sul1 genes located in a class I integron but variants of the dfrA gene were absent. We assessed by PROVEAN analysis the single nucleotide mutations found in folA, folC and folM genes and only the mutation in folA (A114T:GCC→ACC) has an effect on the activity of trimethoprim. Our findings demonstrated the prolonged presence of SXT-resistant S. maltophilia in a clinical setting with consecutive transfers from the environment to a newborn and staff based on the isolation dates. We also hypothesized that single nucleotide mutations in folA could be responsible for trimethoprim resistance.
Transfer of CRISPR-like activity of MIMIVIRE into Bacteria
Authors: Said Azza , Bernard La Scola , Anthony Levasseur , Pierre Perrin , Eric Chabrière , Didier Raoult 
Published: July 2019

AbstractMIMIVIRE is a defence system utilized by lineage A Mimiviruses against Zamilon virophages. It is composed of a helicase, a nuclease and a gene of unknown function here named trcg (for Target Repeat-Containing gene), which contains four 15-bp repeats identical to the Zamilon sequence. Their silencing restored susceptibility to Zamilon, and the CRISPR-Cas4-like activity of the nuclease was recently characterised. We expressed these 3 genes after transformation of a modified strain of Escherichia coli made resistant to ampicillin, chloramphenicol and tetracycline. The virophage repeats were replaced with four repeats of 15 nucleotides identical to a sequence in the tetracycline resistance gene. The induction of the MIMIVIRE genes restored E. coli sensitivity to tetracycline; the tetracycline operon and its supporting plasmid harbouring the chloramphenicol resistance gene vanished. We therefore efficiently transferred the defence system MIMIVIRE from giant Mimivirus against virophage to E. coli to clear it from a plasmid.
Deciphering the functioning of microbial communities: shedding light on the critical steps in metaproteomics
Authors: Géron Augustin , Werner Johannes , Wattiez Ruddy , Lebaron Philippe , Matallana-Surget Sabine 
Published: July 2019

AbstractUnraveling the complex structure and functioning of microbial communities is essential to accurately predict the impact of perturbations and/or environmental changes. From all molecular tools available today to resolve the dynamics of microbial communities, metaproteomics stands out, allowing the establishment of phenotype-genotype linkages. Despite its rapid development, this technology has faced many technical challenges that still hamper its potential power. How to maximize the number of protein identification, improve quality of protein annotation and provide reliable ecological interpretation, are questions of immediate urgency. In our study, we used a robust metaproteomic workflow combining two protein fractionation approaches (gel-basedversusgel-free) and four protein search databases derived from the same metagenome to analyze the same seawater sample. The resulting eight metaproteomes provided different outcomes in terms of (i) total protein numbers, (ii) taxonomic structures, and (iii) protein functions. The characterization and/or representativeness of numerous proteins from ecologically relevant taxa such asPelagibacterales,RhodobacteralesandSynechococcales, as well as crucial environmental processes, such as nutrient uptake, nitrogen assimilation, light harvesting and oxidative stress response were found to be particularly affected by the methodology. Our results provide clear evidences that the use of different protein search databases significantly alters the biological conclusions in both gel-free and gel-based approaches. Our findings emphasize the importance of diversifying the experimental workflow for a comprehensive metaproteomic study.
Differential attention-dependent adjustment of frequency, power and phase in primary sensory and frontoparietal areas
Authors: Suess Nina , Hartmann Thomas , Weisz Nathan 
Published: July 2019

AbstractContinuously prioritizing behaviourally relevant information from the environment for improved stimulus processing is a crucial function of attention. Low-frequency phase alignment of neural activity in primary sensory areas, with respect to attended/ignored features has been suggested to support top-down prioritization. Phase adjustment in frontoparietal regions has not been widely studied, despite general implication of these in top-down selection of information. In the current MEG study, we investigated how ongoing oscillatory activity of both sensory and non-sensory brain regions are differentially impacted by attentional focus. Participants performed an established intermodal selective attention task, where low-frequency auditory (1.6 Hz) and visual (1.8 Hz) stimuli were presented simultaneously. We instructed participants to either attend to the auditory or to the visual stimuli and to detect targets while ignoring the other stimulus stream. As expected, the strongest phase adjustment was observed in primary sensory regions for auditory and for visual stimulation, independent of attentional focus. We found greater differences in phase locking between attended and ignored stimulation for the visual modality. Interestingly, auditory temporal regions show small but significant attention-dependent entrainment even for visual stimulation. Extending findings from invasive recordings in non-human primates, we demonstrate an effect of attentional focus on the phase of the entrained oscillations in auditory and visual cortex which may be driven by phase locked increases of induced power. In contrast to the effects in sensory areas, attentional focus adjusted the peak frequencies in nonsensory areas. Spatially these areas show a striking overlap with core regions of the dorsal attention network and the frontoparietal network. This suggests that these areas prioritize the attended modality by optimally exploiting the temporal structure of stimulation. Overall, our study complements and extends previous work by showing a differential effect of attentional focus on entrained oscillations in primary sensory areas and frontoparietal areas.
Finding and extending ancient simple sequence repeat-derived regions in the human genome
Authors: Shortt Jonathan A. , Ruggiero Robert P. , Cox Corey , Wacholder Aaron C. , Pollock David D. 
Published: July 2019

AbstractBackgroundPreviously, 3% of the human genome has been annotated as simple sequence repeats (SSRs), similar to the proportion annotated as protein coding. The origin of much of the genome is not well annotated, however, and some of the unidentified regions are likely to be ancient SSR-derived regions not identified by current methods. The identification of these regions is complicated because SSRs appear to evolve through complex cycles of expansion and contraction, often interrupted by mutations that alter both the repeated motif and mutation rate. We applied an empirical, kmer-based, approach to identify genome regions that are likely derived from SSRs.ResultsThe sequences flanking annotated SSRs are enriched for similar sequences and for SSRs with similar motifs, suggesting that the evolutionary remains of SSR activity abound in regions near obvious SSRs. Using our previously described P-clouds approach, we identified ‘SSR-clouds’, groups of similar kmers (or ‘oligos’) that are enriched near a training set of unbroken SSR loci, and then used the SSR-clouds to detect likely SSR-derived regions throughout the genome.ConclusionsOur analysis indicates that the amount of likely SSR-derived sequence in the human genome is 6.77%, over twice as much as previous estimates, including millions of newly identified ancient SSR-derived loci. SSR-clouds identified poly-A sequences adjacent to transposable element termini in over 74% of the oldest class ofAlu(roughly,AluJ), validating the sensitivity of the approach. Poly-A’s annotated by SSR-clouds also had a length distribution that was more consistent with their poly-A origins, with mean about 35 bp even in olderAlus. This work demonstrate that the high sensitivity provided by SSR-Clouds improves the detection of SSR-derived regions and will enable deeper analysis of how decaying repeats contribute to genome structure.
Discovery of powdery mildew resistance gene candidates fromAegilops biuncialischromosome 2Mbbased on transcriptome sequencing
Authors: Li Huanhuan , Dong Zhenjie , Ma Chao , Tian Xiubin , Xiang Zhiguo , Xia Qing , Ma Pengtao , Liu Wenxuan 
Published: July 2019

AbstractPowdery mildew is one of the most widespread diseases of wheat. Breeding resistant varieties by utilization of resistance genes is considered as the most economic and effective method of controlling this disease. Previous study showed that the gene(s) at 2Mbin Chinese Spring (CS)-Aegilops biuncialis2Mbdisomic addition line TA7733 conferred high resistance to powdery mildew. In this study, 15Bgtisolates prevalent in different regions of China were used to further test the resistance spectrum of TA7733. As a result, TA7733 was high resistance to all tested isolates, indicating that the gene(s) on chromosome 2Mbwas broad-spectrum powdery mildew resistance. In order to mine resistance gene candidates and develop 2Mb-specific molecular markers to assist the transfer resistance gene(s) at chromosome 2Mb, RNA-seq of TA7733 and CS was conducted before and afterBgt-infection, generating a total of 158,953 unigenes. Of which, 7,278 unigenes were TA7733-specific which were not expressed in CS, and 295 out of these 7,278 unigenes were annotated as R genes. Based on Blastn against with CS Ref Seq v1.0, 61 R genes were further mapped to homoeologous group 2. Analysis of R gene-specific molecular markers designed from R gene sequences verified 40 out of 61 R genes to be 2Mbspecific. Annotation of these 40 R genes showed most genes encoded nucleotide binding leucine rich repeat (NLR) protein, being most likely resistance gene candidates. The broad-spectrum powdery mildew resistance gene(s), disease resistance gene candidates, and functional molecular markers of 2Mb-specific in present study will not only lay foundations for transferring disease resistance gene(s) from 2Mbto common wheat by inducing CS-Ae. biuncialishomoeologous recombination, but also provide useful candidates for isolating and cloning resistance gene(s) and dissecting molecular and genetic mechanisms of disease resistance from 2Mb.
The mammalian plasma membrane is defined by transmembrane asymmetries in lipid unsaturation, leaflet packing, and protein shape
Authors: Lorent JH , Levental KR , Ganesan L , Rivera-Longsworth G , Sezgin E. , Doktorova MD , Lyman E , Levental I 
Published: July 2019

SUMMARYA fundamental feature of cellular plasma membranes (PM) is asymmetric lipid distribution between the bilayer leaflets. However, neither the detailed, comprehensive compositions of individual PM leaflets, nor how these contribute to structural membrane asymmetries have been defined. We report the distinct lipidomes and biophysical properties of both monolayers in living mammalian PMs. Phospholipid unsaturation is dramatically asymmetric, with the cytoplasmic leaflet being ∼2-fold more unsaturated than the exoplasmic. Atomistic simulations and spectroscopy of leaflet-selective fluorescent probes reveal that the outer PM leaflet is more packed and less diffusive than the inner leaflet, with this biophysical asymmetry maintained in the endocytic system. The structural asymmetry of the PM is reflected in asymmetric structures of protein transmembrane domains (TMD). These structural asymmetries are conserved throughout Eukaryota, suggesting fundamental cellular design principles.
Regulation of nuclear-cytoplasmic partitioning by thelin-28-lin-46pathway reinforces microRNA repression of HBL-1 to confer robust cell-fate progression inC. elegans
Authors: Ilbay Orkan , Ambros Victor 
Published: July 2019

AbstractMicroRNAs target complementary mRNAs for degradation or translational repression, reducing or preventing protein synthesis. InC. elegans, the transcription factor HBL-1 (Hunchback-like 1) promotes early larval (L2) stage cell-fate, and thelet-7-family microRNAs temporally down-regulate HBL-1 to enable the L2-to-L3 cell-fate progression. In parallel tolet-7-family microRNAs, the conserved RNA binding protein LIN-28 and its downstream genelin-46, also act upstream of HBL-1 in regulating the L2-to-L3 cell-fate progression. The molecular function of LIN-46, and how thelin-28-lin-46pathway regulates HBL-1, are not understood. Here, we report that the regulation of HBL-1 by thelin-28-lin-46pathway is independent of thelet-7/lin-4microRNA complementary sites (LCSs) in thehbl-13’UTR, and involves a stage-specific post-translational regulation of HBL-1 nuclear accumulation. We find that LIN-46 is necessary and sufficient to prevent nuclear accumulation of HBL-1. Our results illuminate that the robust progression from L2 to L3 cell-fates depends on the combination of two distinct modes of HBL-1 down-regulation: decreased synthesis of HBL-1 vialet-7-family microRNA activity, and decreased nuclear accumulation of HBL-1 via action of thelin-28-lin-46pathway. Like HBL-1, many microRNA targets are transcription factors (TFs); and cooperation between regulation of nuclear accumulation and microRNA-mediated control of synthesis rate may be required to increase the precision of or confer robustness to down-regulation of these microRNA target TFs, which can be critical to achieve the optimal phenotypes.