bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microsurgical Treatment of Ruptured True Posterior Communicating Artery Aneurysm in the Distal Portion of the Posterior Communicating Artery
Authors: Yang Yonglin , Meng Xiangfu , Song Jiangquan , Nie Xiutao , Zhao Chao , Su Wandong 
Published: October 2018

Abstract
The true posterior communicating artery (PCoA) aneurysms in the distal portion of the posterior communicating artery are rare. The authors describe a 63-year-old woman with 1 true PCoA aneurysms in the distal portion of the PCoA, which was treated surgically through modified pterional approach. No neurologic deficit was present at the postoperative period. Although endovascular intervention is more and more widely used in the treatment of aneurysms, the authors have also emphasized that true PCoA aneurysms in the distal portion of the PCoA can also be surgically treated in suitable patients.
Achondroplasia: Orocraniofacial Features and Orthodontic-Surgical Management Guidelines Proposal
Authors: Pineau Mallouel , Farrow Emilie , Nicot Romain , Ferri Joël 
Published: October 2018

Abstract
In this study, the authors aimed to describe orocraniofacial features and to suggest orthodontic-surgical managements in achondroplasia, based on a literature review. The authors focused on skeletal and dentoalveolar malocclusion in order to highlight the place of orthognathic surgery, based on our experience of 3 patients. Maxillary hypoplasia in achondroplasia typically results in an Angle class III malocclusion with an anterior open bite. The other orocraniofacial features include enlarged calvarium, prominent forehead and frontal bossing, midface hypoplasia, elongated lower face and saddle-shaped nose due to lack of development of the nasomaxillary complex.
All our patients had a typical facial appearance but each of them had their own particularities regarding medical history and severity of the dentoskeletal dysmorphosis. Two of them were successfully treated by orthognathic surgery; the other declined surgical treatment and underwent orthopedic treatment only (anchorage plates). The treatment failure of this 3rd patient raises the question of the efficiency of anchorage plates in achondroplasia. In the light of the literature and our results, the authors conclude the need for personalized management based on age, medical history, severity of the dentoskeletal dysmorphosis, functional and/or esthetic disorders, and the patient's needs and requests. In any patient, orthodontic management should be initiated at an early age, and orthognathic surgery modalities should be personalized and adapted to each situation.
Leukocyte Transcriptional Response in Sepsis
Authors: Skibsted Simon , Bhasin Manoj K. , Henning Daniel J. , Jaminet Shou Ching , Lewandowski Jeffrey , Kirkegaard Hans , Aird William C. , Shapiro Nathan I. 
Published: October 2018

ABSTRACT

Background:
The complex host response to sepsis is incompletely understood. The aim of this investigation is to use leukocyte RNA sequencing to characterize biological functions, cellular pathways, and key regulatory molecules driving sepsis pathophysiology.

Methods:
This was a prospective, observational study of emergency department patients with sepsis, at an urban, academic, tertiary care center. In the derivation cohort, we collected blood at enrollment and 90 days after hospital discharge allowing each patient to serve as an internal control. We performed RNA sequencing to quantify transcriptional expression changes during sepsis and non-sepsis states. We then performed unsupervised and supervised analyses, as well as functional and pathway analyses. We selected the top down and upregulated genes and key regulatory molecules for validation. Validation occurred in a cohort of septic and non-septic using real-time PCR.

Results:
The derivation cohort included 5 patients, and RNA sequencing revealed 916 unique mRNA transcripts differentially expressed during sepsis. Among these, 673 (73%) genes were upregulated, and 243 (27%) were downregulated. Functional enrichment analysis revealed a highly dynamic downstream effect of the transcriptional activity during sepsis. Of the 43 functional cellular pathways activated during sepsis, the top pathways were closely associated with inflammation and response to infection. Validation occurred in 18 septic and 25 non-septic control patients, with 34/45 (76%) of identified genes validated. The regulatory analysis identified several key regulators of sepsis.

Conclusions:
Highly dynamic transcriptional activity occurs in leukocytes during sepsis, activating key cellular pathways and master regulatory molecules that drive the sepsis process.
Accuracy Comparison Between Age-Adapted SOFA and SIRS in Predicting in-Hospital Mortality of Infected Children at China's PICU
Authors: Wu Zhiyuan , Liang Yafeng , Li Zhihao , Liu Guangjian , Zheng Jianbin , Zuo Yunlong , Li Lijuan , Cao Xiaojun , Zhang Jianhui , Liang Huiying 
Published: October 2018

ABSTRACT

Objectives:
Sepsis-3 consensus suggests “the need to develop similar updated definitions for pediatric populations.” Sequential organ failure assessment (SOFA) and systemic inflammatory response syndrome (SIRS) criteria are two systems widely used to define the status of infection. However, it is still unclear whether SOFA is more accurate than SIRS in predicting children mortality in low- and middle-income countries. Thus, we validated the accuracy of age-adapted SOFA and SIRS in predicating the poor prognosis of infected children in China's pediatric intensive care unit (PICU).

Methods:
We performed a retrospective and observational cohort study of children admitted for infection to PICU in the hospital between January 1, 2009 and December 31, 2017. The indexes within 24 h after intensive care unit (ICU) admission were analyzed according to age-adapted SOFA and SIRS, and all data were sourced from the hospital's electronic health record database. The prognosis was illustrated with primary outcome and secondary outcome. Primary outcome referred to in-hospital mortality, and secondary outcome to in-hospital mortality or ICU length of stay ≥ 7 days. The predictive power of age-adapted SOFA and SIRS was compared using crude and adjusted area under the receiver operating characteristic curve (AUROC).

Results:
Of 1,831 PICU-admitted children due to infection, 164 (9.0%) experienced primary outcome, and 948 (51.8%) secondary outcome. Of 164 deaths, 65.9% were males (median age of 7.53 months, range of 2.67–41.00 months). Children who scored ≥ 2 in age-adapted SOFA or met two SIRS criteria accounted for 92.5% and 73.3%, respectively. In addition, age-adapted SOFA score of ≥2 predicted adverse outcome more accurately than pediatric SIRS (adjusted AUROC, 0.753; 0.713–0.796 vs. 0.674; 0.631–0.702; P < 0.001).

Conclusion:
Compared with SIRS criteria, age-adapted SOFA score of ≥ 2 enjoys a more accuracy in predicting in-hospital mortality of PICU-admitted children, and a higher sensitivity in identifying children with severe infection.
In Situ Simulation to Mitigate Threats to Participation in a Multicenter Clinical Trial in High-Acuity, Low-Frequency Setting
Authors: Chan Steven , Babcock Lynn , Geis Gary , Frey Mary , Robinson Venita , Kerrey Benjamin 
Published: October 2018

Introduction
Multicenter clinical trials of high-acuity, low-frequency emergencies are expensive and resource intensive. Current standards for trial preparation have significant limitations. Our objective is to describe our use of in situ simulation (ISS) to identify and mitigate threats to enrollment, protocol adherence, and patient safety in preparation for a multicenter clinical trial of antiepileptics for status epilepticus in the emergency department.

Methods
This is a descriptive study of ISS conducted in the emergency department at a free-standing, academic pediatric institution. We designed two scenarios, one for an eligible and ineligible patient, to allow care teams to complete all study procedures. All study training was completed before the first ISS. Participants included physicians, nurses, patient care assistants, paramedics, research coordinators, and pharmacists. Ten-minute simulations were followed by 10-minute debriefings, led by trained facilitators using a standard template. Data on threats to enrollment, protocol adherence, and patient safety were recorded. Mitigation strategies were developed by the study team and local experts in ISS.

Results
Ten of 18 planned simulations were conducted. Seven of 10 completed simulations were study eligible patients, with 73 total participants. Nine threats to enrollment and five to protocol adherence were identified. Five of 14 were also threats to patient safety. Mitigation strategies included creation of decision aid tools, targeted education during debriefings, adapting study material for use, and revision of status epilepticus treatment algorithm.

Conclusions
The addition of ISS to standard preparation for a multicenter clinical trial facilitated the identification and mitigation of threats to study participation and patient safety.
Greater loss of female embryos during human pregnancy: A novel mechanism
Authors: Mulley John F 
Published: October 2018

SummaryGiven an equal sex ratio at conception, we can only explain the excess of human males at birth by greater loss of females during pregnancy. I propose that the bias against females during human development is the result of a greater degree of genetic and metabolic “differentness” between female embryos and maternal tissues than for similarly aged males, and that successful implantation and placentation represents a threshold dichotomy, where the acceptance threshold shifts depending on maternal condition, especially stress. Right and left ovaries are not equal, and neither are the eggs and follicular fluid that they produce, and I further hypothesise that during times of stress, the implantation threshold is shifted sufficiently to favour survival of females, most likely those originating from the right ovary, and that this, rather than simply a greater loss of males, explains at least some of the variability in the human sex ratio at birth.
Toward single particle reconstruction without particle picking: Breaking the detection limit
Authors: Bendory Tamir , Boumal Nicolas , Leeb William , Levin Eitan , Singer Amit 
Published: October 2018

AbstractSingle-particle cryo-electron microscopy (cryo-EM) has recently joined X-ray crystallography and NMR spectroscopy as a high-resolution structural method for biological macromolecules. In a cryo-EM experiment, the microscope produces images called micrographs. Projections of the molecule of interest are embedded in the micrographs at unknown locations, and under unknown viewing directions. Standard imaging techniques first locate these projections (detection) and then reconstruct the 3-D structure from them. Unfortunately, high noise levels hinder detection. When reliable detection is rendered impossible, the standard techniques fail. This is a problem especially for small molecules, which can be particularly hard to detect. In this paper, we propose a radically different approach: we contend that the structure could, in principle, be reconstructed directly from the micrographs, without intermediate detection. As a result, even small molecules should be within reach for cryo-EM. To support this claim, we setup a simplified mathematical model and demonstrate how our autocorrelation analysis technique allows to go directly from the micrographs to the sought signals. This involves only one pass over the micrographs, which is desirable for large experiments. We show numerical results and discuss challenges that lay ahead to turn this proof-of-concept into a competitive alternative to state-of-the-art algorithms.
Layer-specific ultra-high field 7T fMRI showing that threat anticipation is mediated by the pulvinar input to the superficial layers of primary visual cortex (V1)
Authors: Koizumi Ai , Zhan Minye , Ban Hiroshi , Kida Ikuhiro , Martino Federico de , Gelder Beatrice de , Amano Kaoru 
Published: October 2018

AbstractThe perceptual system gives priority to threat-relevant signals with survival value. Its mechanism may not only include the processing initiated in the presence of threat signals but also in the mere anticipation of such signals. Here, we show that the pulvinar modulates activity in the early visual cortex (V1) specifically in threat anticipation. Using ultra-high-field 7T fMRI, we examined the layer-specific interaction between V1 and the pulvinar, while taking advantage of the fact that the directionality of such interaction is anatomically constrained in specific V1 layers. Only in anticipation of a fearful face target, but not of a control happy face target, was false perception of anticipated-yet-unpresented target face accompanied by stronger activity in the V1 superficial-cortical-depth (layers 1-3), which was preceded by pre-target-onset pulvinar activity. The pulvinar may contribute to the visual processing initiated in the anticipation of threat, and play an important role in anxiety.
The TPX-Like protein TPXL3, but not TPX2, is the primary activator of α Aurora kinases and is essential for embryogenesis in Arabidopsis
Authors: Boruc Joanna , Deng Xingguang , Mylle Evelien , Besbrugge Nienke , Durme Matthias Van , Demidov Dmitri , Tomaštíková Eva Dvořák , Tan Tong-Reen Connie , Vandorpe Michaël , Eeckhout Dominique , Beeckman Tom , Nowack Moritz , Jaeger Geert De , Lin Honghui , Liu Bo , Damme Daniël Van 
Published: October 2018

AbstractAurora kinases are key regulators of mitosis. Multicellular eukaryotes generally possess two functionally diverged types. In plants like Arabidopsis, these are termed α versus β Auroras. As the functional specification of Aurora kinases is determined by their specific interaction partners, we initiated interactomics analyses using both α Aurora kinases (AUR1 and AUR2). Proteomics results revealed the TPX2-Like proteins 2 and 3 (TPXL2/3) prominently associating with α Auroras, as did the conserved TPX2 to a lower degree. Like TPX2, TPXL2 and TPXL3 strongly activated AUR1 kinase but exhibited cell cycle-dependent localization differences on microtubule arrays. The separate functions of TPX2 and TPXL2/3 were also suggested by their different influences on AUR1 localization upon ectopic expressions. Furthermore, genetic analyses disclosed that TPXL3, but not TPX2 and TPXL2, acts non-redundantly to secure proper embryo development. In contrast to vertebrates, plants expanded the TPX2 family for both redundant and unique functions among its members.
Genomic insights into evolutionary journey of the porcine endogenous retroviruses
Authors: Chen Yicong , Chen Mingyue , Duan Xiaoyan , Cui Jie 
Published: October 2018

AbstractBackgroundXenotransplantation may overcome significant shortage of human allotransplant. Porcine organs are considered favorable for xenotransplantation duo to similar size and function to human organ. However, porcine endogenous retroviruses (PERVs) are potential infectious agents during xenotransplantation as they are able to infect and horizontally transfer among human cells. Furthermore, PERVs can be endogenized in pig genomes and are transmitted genetically in a Mendelian fashion. Here, we depict a complex evolutionary history of modern PERVs.ResultsWein silicomined 142 mammalian genomes and 14 pig genomes. This led to the documentation of 185 PERVs and a new viral cluster. Large-scale genomic alterations were found in most PERVs including many insertion-deletion events and which are suggestive of ancient origins, and pig genomes have been shaped by PERV-mediated genomic rearrangement during evolution. Notably, we found that lesser Egyptian jerboa and rock hyrax harbor ancestral PERV-related elements indicative of ancient cross-species transmission events from none-porcine species to pigs. A comprehensive analysis of these viral “fossils” suggested that recombination among none-porcine endogenous retroviruses led to the origination of PERVs.ConclusionFor the first time, using large scale genomic mining, we decipher a complex evolutionary history for the PERVs. These new findings help us to understand the past of PERVs which pose the potential risk in clinical trials of xenotransplantation and provide novel insights into the origin and evolution of a human-infecting pathogen.
Genetic and behavioural requirements for structural brain plasticity
Authors: Vousden Dulcie A , Friesen Alexander , Wen Xianglan , Qiu Lily R , O’Toole Nicholas , Darwin Benjamin C , Noakes Leigh Spencer , Grand Rylan Allemang , Diorio Josie , Frankland Paul W , Josselyn Sheena A , Nieman Brian J , Meaney Michael , Zhang Tie-Yuan , Lerch Jason P 
Published: October 2018

1AbstractHuman MRI studies show that experience can lead to changes in the volume of task-specific brain regions; however, the behavioural and molecular processes driving these changes remain poorly understood. Here, we used in-vivo mouse MRI and RNA sequencing to investigate the neuroanatomical and transcriptional changes induced by environmental enrichment, exercise, and social interaction. Additionally, we asked whether the volume changes require CREB, a transcription factor critical for memory formation and neuronal plasticity. Enrichment rapidly increased cortical and hippocampal volume, and these effects were not attributable to exercise or social interaction. Instead, they likely arise from learning and sensorimotor experience. Nevertheless, the volume changes were not attenuated in mice with memory impairments caused by loss of CREB, indicating that these effects are driven by processes distinct from this canonical learning and memory pathway. Finally, within brain regions that underwent volume changes, enrichment increased the expression of genes associated with axonogenesis, dendritic spine development, synapse structural plasticity, and neurogenesis, suggesting these processes underlie the volume changes detected with MRI.
Single-cell in situ transcriptomic map of astrocyte cortical layer diversity
Authors: Bayraktar Omer Ali , Bartels Theresa , Polioudakis Damon , Holmqvist Staffan , Haim Lucile Ben , Young Adam M.H. , Prakash Kirti , Brown Alexander , Paredes Mercedes F. , Kawaguchi Riki , Stockley John , Sabeur Khalida , Chang Sandra M. , Huang Eric , Hutchinson Peter , Ullian Erik M. , Geschwind Daniel H. , Coppola Giovanni , Rowitch David H. 
Published: October 2018

AbstractDuring organogenesis, patterns and gradients of gene expression underlie organization and diversified cell specification to generate complex tissue architecture. While the cerebral cortex is organized into six excitatory neuronal layers, it is unclear whether glial cells are diversified to mimic neuronal laminae or show distinct layering. To determine the molecular architecture of the mammalian cortex, we developed a high content pipeline that can quantify single-cell gene expression in situ. The Large-area Spatial Transcriptomic (LaST) map confirmed expected cortical neuron layer organization and also revealed a novel neuronal identity signature. Screening 46 candidate genes for astrocyte diversity across the cortex, we identified grey matter superficial, mid and deep astrocyte identities in gradient layer patterns that were distinct from neurons. Astrocyte layers formed in early postnatal cortex and mostly persisted in adult mouse and human cortex. Mutations that shifted neuronal post-mitotic identity or organization were sufficient to alter glial layering, indicating an instructive role for neuronal cues. In normal mouse cortex, astrocyte layer patterns showed area diversity between functionally distinct cortical regions. These findings indicate that excitatory neurons and astrocytes cells are organized into distinct lineage-associated laminae, which give rise to higher order neuroglial complexity of cortical architecture.
Structure of the large extracellular loop of FtsX and its interaction with the essential peptidoglycan hydrolase PcsB inStreptococcus pneumoniae
Authors: Rued Britta E. , Alcorlo Martín , Edmonds Katherine A. , Martínez-Caballero Siseth , Straume Daniel , Fu Yue , Bruce Kevin E. , Wu Hongwei , Håvarstein Leiv Sigve , Hermoso Juan A. , Winkler Malcolm E. , Giedroc David P. 
Published: October 2018

ABSTRACTStreptococcus pneumoniaeis a leading killer of infants and immunocompromised adults and has become increasingly resistant to major antibiotics. Therefore, the development of new antibiotic strategies is desperately needed. Targeting bacterial cell division is one such strategy, specifically targeting essential proteins for the synthesis and breakdown of peptidoglycan. One complex important to this process is FtsEX. FtsEX comprises an integral membrane protein (FtsX) and cytoplasmic ATPase (FtsE) that resembles an ATP-binding cassette (ABC) transporter. Here, we present NMR solution structural and crystallographic models of the large extracellular domain of FtsX, denoted ECL1. The structure of ECL1 reveals an upper extended β-hairpin and a lower α-helical lobe, each extending from a mixed α-β core. The helical lobe mediates a physical interaction with the peptidoglycan hydrolase PcsB, via the coiled-coil domain of PcsB (PcsB-CC). Characterization ofS. pneumoniaeD39 derived strains harboring mutations in the α-helical lobe shows that this subdomain is essential for cell viability and required for proper cell division ofS. pneumoniae.IMPORTANCEFtsX is a ubiquitous bacterial integral membrane protein involved in cell division that regulates the activity of peptidoglycan (PG) hydrolases. FtsX is representative of a large group of ABC3 superfamily proteins that function as “mechanotransmitters,” proteins that relay signals from inside to the outside of the cell. Here we present a structural characterization of the large extracellular loop (ECL1) of FtsX from the human opportunistic pathogenStreptococcus pneumoniae. We show a direct interaction between the peptidoglycan hydrolase PcsB and FtsX, and demonstrate that this interaction is essential for cell viability. As such, FtsX represents an attractive, conserved target for the development of new classes of antibiotics.