bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of frailty on posttraumatic outcomes in older trauma patients: A systematic review and meta-analysis
Authors: Zhao Fangjie , Tang Bihan , Hu Chaoqun , Wang Bo , Wang Yincheng , Zhang Lulu 
Published: January 2020

BACKGROUND
Frailty is a risk factor for mortality among the elderly. However, evidence from longitudinal studies linking trauma and frailty is fragmented, and a comprehensive analysis of the relationship between frailty and adverse outcomes is lacking. Therefore, we conducted a systematic review and meta-analysis to examine whether frailty is predictive of posttraumatic results including mortality, adverse discharge, complications, and readmission in trauma patients.

METHODS
This systematic review was registered with the PROSPERO international prospective register of systematic reviews. Articles in PubMed, Embase, and Web of Science databases from January 1, 1990, to October 31, 2019, were systematically searched. Articles in McDonald et al.'s study (J Trauma Acute Care Surg. 2016;80(5):824-834) and Cubitt et al.'s study (Injury 2019;50(11):1795-1808) were included for studies evaluating the association between frailty and outcomes in trauma patients. Cohort studies, both retrospective and prospective, were included. Study population was patients suffering trauma injuries with an average age of 50 years and older. Multivariate adjusted odds ratios (ORs) were calculated through a random-effects model, and the Newcastle-Ottawa Quality Assessment Scale was used to assess studies.

RESULTS
We retrieved 11,313 entries. Thirteen studies including seven prospective and six retrospective cohort studies involving 50,348 patients were included in the meta-analysis. Frailty was a significant predictor of greater than 30-day mortality (OR, 2.41; 95% confidence interval [CI], 1.17–4.95; I
2 = 88.1%), in-hospital and 30-day mortality (OR, 4.05; 95% CI, 2.02–8.11; I
2 = 0%), postoperative complications (OR, 2.23; 95% CI, 1.34–3.73; I
2 = 78.2%), Clavien-Dindo IV complications (OR, 4.16; 95% CI, 1.70–10.17; I
2 = 0%), adverse discharge (OR, 1.80; 95% CI, 1.15–2.84; I
2 = 78.6%), and readmission (OR, 2.16; 95% CI, 1.19–3.91; I
2 = 21.5%) in elderly trauma patients. Subgroup analysis showed that prospective studies (OR, 3.06; 95% CI, 1.43–6.56) demonstrated a greater correlation between frailty and postoperative complications.

CONCLUSION
Frailty has significant adverse impacts on the occurrence of posttraumatic outcomes. Further studies should focus on interventions for patients with frailty. Given the number of vulnerable elderly trauma patients grows, further studies are needed to determine the accuracy of these measures in terms of trauma outcomes.

LEVEL OF EVIDENCE
Systematic review and meta-analysis, level IV.
Does computed tomography scan add any diagnostic value to the evaluation of stab wounds of the anterior abdominal wall? A systematic review and meta-analysis
Authors: Gachabayov Mahir , Gogna Shekhar , Samson David , Latifi Rifat 
Published: January 2020

BACKGROUND
The aim of this systematic review and meta-analysis was to evaluate whether computed tomography (CT) scan adds any diagnostic value in the evaluation of stab wounds of the anterior abdominal wall as compared with serial clinical examination (SCE).

METHODS
PubMed, EMBASE, Cochrane Library, and MEDLINE via Ovid were systematically searched for records published from 1980 to 2018 by two independent researchers (M.G., R.L.). Quality assessment, data extraction, and analysis were performed according to the Cochrane Handbook for Systematic Reviews of Interventions. Mantel-Haenszel method with odds ratio (OR) and 95% confidence interval (95% CI) as the measure of effect size was used for meta-analysis.

RESULTS
Three studies (1 randomized controlled trial and 2 observational studies) totaling 319 patients were included in the meta-analysis. Overall laparotomy rate was 12.8% (22 of 172 patients) in SCE versus 19% (28 of 147 patients) in CT. This difference was not significant (OR [95% CI], 0.63 [0.34–1.16]; p = 0.14). Negative laparotomy rate was 3.5% (6 of 172 patients) in SCE versus 5.4% (8 of 147 patients) in CT. The difference was not significant (OR [95% CI], 0.61 [0.20–1.83]; p = 0.37).

CONCLUSION
This meta-analysis compared SCE with CT scan in patients presenting with stab wounds of the anterior abdominal wall and provided level II evidence showing no additional benefit in CT scan. Further observational and experimental clinical studies are needed to confirm the findings of this meta-analysis.

LEVEL OF EVIDENCE
Systematic review and meta-analysis, level II.
Crosslinking-guided geometry of a complete CXC receptor-chemokine complex and the basis of chemokine subfamily selectivity
Authors: Ngo Tony , Stephens Bryan S. , Gustavsson Martin , Holden Lauren G. , Abagyan Ruben , Handel Tracy M. , Kufareva Irina 
Published: January 2020

AbstractChemokines and their receptors are orchestrators of cell migration in humans. Because dysregulation of the receptor-chemokine system leads to inflammation and cancer, both chemokines and receptors are highly sought therapeutic targets. Yet one of the barriers for their therapeutic targeting is the limited understanding of the structural principles behind receptor-chemokine recognition and selectivity. The existing structures do not include CXC subfamily complexes and lack information about the receptor distal N-termini, despite the importance of the latter in signaling, regulation, and bias. Here we report the discovery of the geometry of the complex between full-length CXCR4, a prototypical CXC receptor and driver of cancer metastasis, and its endogenous ligand CXCL12. By comprehensive disulfide crosslinking, we establish the existence and the structure of a novel interface between the CXCR4 distal N-terminus and CXCL12 β1-strand, while also recapitulating earlier findings from NMR, modeling and crystallography of homologous receptors. A crosslinking-informed high-resolution model of the CXCR4-CXCL12 complex pinpoints the interaction determinants and reveals the occupancy of the receptor major subpocket by the CXCL12 proximal N-terminus. This newly found positioning of the chemokine proximal N-terminus provides a structural explanation of CXC receptor-chemokine selectivity against other subfamilies. Our findings challenge the traditional two-site understanding of receptor-chemokine recognition, suggest the possibility of new affinity and signaling determinants, and fill a critical void on the structural map of an important class of therapeutic targets. These results will aid the rational design of selective chemokine-receptor-targeting small molecules and biologics with novel pharmacology.
Maternally derived sex steroid hormones impact sex ratios of loggerhead sea turtles
Authors: Lockley Emma C. , Reischig Thomas , Eizaguirre Christophe 
Published: January 2020

AbstractGlobal warming could drive species with temperature-dependent sex determination to extinction by persistently skewing offspring sex ratios. Evolved mechanisms that buffer these biases are therefore paramount for their persistence. Here, we tested whether maternally-derived sex steroid hormones affect the sex-determination cascade and provide a physiological mechanism to buffer sex ratio bias in the endangered loggerhead sea turtle (Caretta caretta). We quantified estradiol and testosterone in nesting females and their egg yolks at oviposition, before incubating nests in situ at standardised temperatures. Upon hatchling emergence, we developed a new, non-lethal method to establish the sex of individuals. Despite standardised incubation temperatures, sex ratios varied widely among nests, correlating non-linearly with the estradiol:testosterone ratio in egg yolks. Males were produced at an equal ratio, with females produced either side of this optimum. This result provides evidence that maternal hormone transfer forms a physiological mechanism that impacts sex determination in this endangered species.
One-to-one innervation of vocal muscles allows precise control of birdsong
Authors: Adam I. , Maxwell A. , Rössler H. , Hansen E.B. , Vellema M. , Elemans C.P.H. 
Published: January 2020

SummaryThe motor control resolution of any animal behavior is limited to the minimal force step available when activating muscles, which is set by the number and size distribution of motor units (MUs) and muscle specific force [1, 2]. Birdsong is an excellent model system for understanding sequence learning of complex fine motor skills [3], but we know surprisingly little how the motor pool controlling the syrinx is organized [4] and how MU recruitment drives changes in vocal output [5]. Here we combine measurements of syringeal muscle innervation ratios with muscle stress and anin vitrosyrinx preparation to estimate MU size distribution and the control resolution of fundamental frequency (fo), a key vocal parameter, in zebra finches. We show that syringeal muscles have extremely small MUs, with 50% innervating ≤ 3, and 13 – 17% innervating a single muscle fiber. Combined with the lowest specific stress (5 mN/mm2) known to skeletal vertebrate muscle, small force steps by the majorfocontrolling muscle provide control of 50 mHz to 4.2 Hz steps per MU. We show that the song system has the highest motor control resolution possible in the vertebrate nervous system and suggest this evolved due to strong selection on fine gradation of vocal output. Furthermore, we propose that high-resolution motor control was a key feature contributing to the radiation of songbirds that allowed diversification of song and speciation by vocal space expansion.
The assembly of Hfq into foci-like structures in response to long-term nitrogen starvation inEscherichia coli
Authors: McQuail Josh , Switzer Amy , Burchell Lynn , Wigneshweraraj Sivaramesh 
Published: January 2020

AbstractThe initial adaptive responses to nutrient depletion in bacteria often occur at the level of RNA metabolism. Hfq is an RNA-binding protein present in diverse bacterial lineages and contributes to many different aspects of RNA metabolism. We demonstrate that Hfq forms a distinct and reversible focus-like structure inE. colispecifically experiencing long-term nitrogen (N) starvation. Using the ability of T7 phage to replicate in N starved bacteria as a biological probe ofE. colicell function during N starvation, we demonstrate that Hfq foci have a role in the adaptive response to long-term N starvation. We further show that Hfq foci formation does not depend on gene expression during N starvation and occurs independently of the N regulatory protein C (NtrC) activated initial adaptive response to N starvation. The results serve as a paradigm to demonstrate that bacterial adaptation to long-term nutrient starvation can be spatiotemporally coordinated and can occur independently ofde novogene expression during starvation.Significance StatementBacteria have evolved complex strategies to cope with conditions of nitrogen (N) adversity. We now reveal a role for a widely studied RNA binding protein, Hfq, in the processes involved in howEscherichia colicopes with N starvation. We demonstrate that Hfq forms a distinct and reversible focus-like structure in long-term N starvedE. coli. We provide evidence to suggest that the Hfq foci are important features required for adjustingE. colicell function during N starvation for optimal adaptation to long-term N starvation. The results have broad implications for our understanding of bacterial adaptive processes in response to stress.
Stromal Amyloid β drives Neutrophil extracellular trap formation to augment tumour growth
Authors: Munir Hafsa , Jones James O. , Janowitz Tobias , Martins Carla P. , Welsh Sarah J. , Shields Jacqueline D. 
Published: January 2020

AbstractTumors are comprised of cancer cells and a network of non-cancerous stromal cells. Cancer-associated fibroblasts (CAFs) are well known to support tumorigenesis and are emerging as immune modulators. While many leukocyte populations are well studied in cancer, neutrophils have received less attention. Neutrophils can release histone-bound nuclear DNA and cytotoxic granules as extracellular traps (NETs) in a process termed NETosis. Here, we show that CAFs induce formation of NETs both within the tumor microenvironment and at systemic levels in the blood and bone marrow. These tumor-induced NETs (t-NETs) are driven by a ROS-mediated pathway dependent on PAD4 and CD11b. Remarkably, CAF-derived Amyloid β was identified as the key factor driving t-NETosis, a protein with significance in both neurodegenerative and inflammatory disorders. Therapeutic inhibition of NETs in established tumors prevented growth, skewing neutrophils to a pro-inflammatory phenotype. Reciprocally, t-NETs enhanced CAF activation phenotypes. Mirroring murine observations, NETs were detected juxtaposed to CAFs in human melanoma and pancreatic adenocarcinoma, and elevated expression of amyloid and β-Secretase correlated with poor prognosis. In summary, we report the existence of cross-talk between CAFs and neutrophils within the tumour microenvironment whereby CAF-induced t-NETosis supports cancer progression, identifying Amyloid β as the protagonist and potential therapeutic target.SignificanceThis study defines the existence of a pro-tumor immunomodulatory function of the stroma showing the induction of Neutrophil Extracellular Traps through CAF-derived Amyloid β. We term this novel process “Tumor-induced NETosis” (t-NETosis) and propose that therapeutic inhibition of this mechanism, which we observe in human melanoma and pancreatic cancer, has the potential to improve patient outcome.
Generation of Monophasic Action Potentials and Intermediate Forms
Authors: Iravanian Shahriar , Uzelac Ilija , Herndon Conner , Langberg Jonathan J , Fenton Flavio H 
Published: January 2020

ABSTRACTThe Monophasic Action Potential (MAP) is a near replica of the transmembrane potential recorded when an electrode is pushed firmly against cardiac tissue. Despite its many practical uses, the mechanism of MAP signal generation and the reason it is so different from unipolar recordings is not completely known and is a matter of controversy. It is hypothesized that partial depolarization of the cells directly underneath the electrode contributes to the generation of MAP signals. In this paper, we describe a parametric, semi-quantitative method to generate realistic MAP and intermediate forms – multiphasic electrograms different from an ideal MAP – that does not require the partial depolarization hypothesis. The key ideas of our method are the formation of junctional spaces, i.e., electrically isolated pockets between the surface of an electrode and tissue, and the presence of a complex network of passive components that acts as a high-pass filter to distort the signal that reaches the recording amplifier. The passive network is formed by the interaction between the passive tissue properties and the double-layer capacitance of electrodes. We show that it is possible to generate different electrograms by the change of the model parameters and that both the MAP and intermediate forms reside on a continuum of signals. Our model helps to decipher the mechanisms of signal generation and can lead to a better design for electrodes, recording amplifiers, and experimental setups.SIGNIFICANCERecording the Monophasic Action Potential (MAP) is potentially very useful in both experimental and clinical cardiac electrophysiology and can provide valuable information about the repolarization phase of the action potential. However, despite its benefits, it currently has only a small and niche role. The main challenge is the technical difficulties of recording an ideal MAP. Our results provide a better understanding of the mechanisms of the generation of cardiac electrograms and may help to optimize experiments and improve tools to achieve the full potentials of recording the MAP signals.
An image-computable model of human visual shape similarity
Authors: Morgenstern Yaniv , Hartmann Frieder , Schmidt Filipp , Tiedemann Henning , Prokott Eugen , Maiello Guido , Fleming Roland W. 
Published: January 2020

AbstractShape is a defining feature of objects. Yet, no image-computable model accurately predicts how similar or different shapes appear to human observers. To address this, we developed a model (‘ShapeComp’), based on over 100 shape features (e.g., area, compactness, Fourier descriptors). When trained to capture the variance in a database of >25,000 animal silhouettes, ShapeComp predicts human shape similarity judgments almost perfectly (r2>0.99) without fitting any parameters to human data. To test the model, we created carefully selected arrays of complex novel shapes using a Generative Adversarial Network trained on the animal silhouettes, which we presented to observers in a wide range of tasks. Our findings show that human shape perception is inherently multidimensional and optimized for comparing natural shapes. ShapeComp outperforms conventional metrics, and can also be used to generate perceptually uniform stimulus sets, making it a powerful tool for investigating shape and object representations in the human brain.
Identification ofPhotorhabdussymbionts by MALDI-TOF mass spectrometry
Authors: Hill Virginia , Kuhnert Peter , Erb Matthias , Machado Ricardo A. R. 
Published: January 2020

AbstractSpecies of the bacterial genusPhotorhabuslive in a symbiotic relationship withHeterorhabditisentomopathogenic nematodes. Besides their use as biological control agents against agricultural pests, somePhotorhabdusspecies are also a source of natural products and are of medical interest due to their ability to cause tissue infections and subcutaneous lesions in humans. Given the diversity ofPhotorhabdusspecies, rapid and reliable methods to resolve this genus to the species level are needed. In this study, we evaluated the potential of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the identification ofPhotorhabdusspecies. To this end, we established a collection of 54 isolates consisting of type strains and multiple field strains that belong to each of the validly described species and subspecies of this genus. Reference spectra for the strains were generated and used to complement a currently available database. The extended reference database was then used for identification based on the direct transfer sample preparation method and protein fingerprint of single colonies. High discrimination of distantly related species was observed. However, lower discrimination was observed with some of the most closely related species and subspecies. Our results, therefore, suggest that MALDI-TOF MS can be used to correctly identifyPhotorhabdusstrains at the genus and species level, but has limited resolution power for closely related species and subspecies. Our study demonstrates the suitability and limitations of MALDI-TOF-based identification methods for the assessment of the taxonomical position and identification ofPhotorhabdusisolates.Impact StatementSpecies of the bacterial genusPhotorhabuslive in close association with soil-born entomopathogenic nematodes. Under natural conditions, these bacteria are often observed infecting soil-associated arthropods, but under certain circumstances, can also infect humans. They produce a large variety of natural products including antibiotics, insecticides, and polyketide pigments that have substantial agricultural, biotechnological and medical potential. In this study, we implement MALDI-TOF MS-based identification method to resolve the taxonomic identity of this bacterial genus, providing thereby a rapid identification tool to understanding its taxonomic diversity to boost scientific progress in medical, agricultural, and biotechnological settings.
Genomic rearrangements generate hypervariable mini-chromosomes in host-specific lineages of the blast fungus
Authors: Langner Thorsten , Harant Adeline , Gomez-Luciano Luis B. , Shrestha Ram K. , Win Joe , Kamoun Sophien 
Published: January 2020

AbstractSupernumerary mini-chromosomes–a unique type of genomic structural variation–have been implicated in the emergence of virulence traits in plant pathogenic fungi. However, the mechanisms that facilitate the emergence and maintenance of mini-chromosomes across fungi remain poorly understood. In the blast fungusMagnaporthe oryzae, mini-chromosomes have been first described in the early 1990s but, until very recently, have been overlooked in genomic studies. Here we investigated structural variation in four isolates of the blast fungusM. oryzaefrom different grass hosts and analyzed the sequences of mini-chromosomes in the rice, foxtail millet and goosegrass isolates. The mini-chromosomes of these isolates turned out to be highly diverse with distinct sequence composition. They are enriched in repetitive elements and have lower gene density than core-chromosomes. We identified several virulence-related genes in the mini-chromosome of the rice isolate, including the polyketide synthaseAce1and the effector geneAVR-Pik. Macrosynteny analyses around these loci revealed structural rearrangements, including inter-chromosomal translocations between core- and mini-chromosomes. Our findings provide evidence that mini-chromosomes independently emerge from structural rearrangements of core-chromosomes and might contribute to adaptive evolution of the blast fungus.Author summaryThe genomes of plant pathogens often exhibit an architecture that facilitates high rates of dynamic rearrangements and genetic diversification in virulence associated regions. These regions, which tend to be gene sparse and repeat rich, are thought to serve as a cradle for adaptive evolution. Supernumerary chromosomes, i.e. chromosomes that are only present in some but not all individuals of a species, are a special type of structural variation that have been observed in plants, animals, and fungi. Here we identified and studied supernumerary mini-chromosomes in the blast fungusMagnaporthe oryzae, a pathogen that causes some of the most destructive plant diseases. We found that rice, foxtail millet and goosegrass isolates of this pathogen contain mini-chromosomes with distinct sequence composition. All mini-chromosomes are rich in repetitive genetic elements and have lower gene densities than core-chromosomes. Further, we identified virulence-related genes on the mini-chromosome of the rice isolate. We observed large-scale genomic rearrangements around these loci, indicative of a role of mini-chromosomes in facilitating genome dynamics. Taken together, our results indicate that mini-chromosomes facilitate genome rearrangements and possibly adaptive evolution of the blast fungus.
The Architecture of GluD2 Ionotropic Delta Glutamate Receptor Elucidated by cryo-EM
Authors: Burada Ananth Prasad , Kumar Janesh 
Published: January 2020

AbstractGluD2 receptors belong to the orphan delta receptor family of glutamate receptor ion channels. These receptors play key roles in synaptogenesis and synaptic plasticity and are associated with multiple neuronal disorders like schizophrenia, autism spectrum disorder, cerebellar ataxia, intellectual disability, paraplegia, retinal dystrophy, etc. Despite the importance of these receptors in CNS, insights into full-length GluD2 receptor structure is missing till-date. Here we report cryo-electron microscopy structure of the rat GluD2 receptor in the presence of calcium ions and the ligand 7-chlorokynurenic acid, elucidating its 3D architecture. The structure reveals a non-swapped architecture at the extracellular aminoterminal (ATD), and ligand-binding domain (LBD) interface similar to that observed in GluD1; however, the organization and arrangement of the ATD and LBD domains are unique. While our results demonstrate that non-swapped architecture is conserved in the delta receptor family, they also highlight the differences that exist between the two member receptors; GluD1 and GluD2.