bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated With the Complexity of Facial Trauma
Authors: Pita Neto Ivo Cavalcante , Franco Jéferson Martins Pereira Lucena , Junior Júlio Leite de Araujo , Santana Milana Drumond Ramos , de Abreu Luiz Carlos , Bezerra Ítalla Maria Pinheiro , Soares Eduardo Costa Studart , de Alencar Gondim David Gomes , Rodrigues Luciano Miller Reis 
Published: April 2018

Introduction:
Facial fractures have their incidence, etiology, clinical presentation, and features influenced by variables such as economic, cultural, and demographic factors. A large number of these fractures require simple or more complex approaches, and it becomes important to understand their clinical and epidemiological profile and factors associated with the fracture event and surgical indication.

Objective:
The objective of this research is to analyze the clinical and epidemiological profile of surgical fractures and their associations with causal factors such as alcohol consumption, day of the incident, and nonuse of helmet for motorcycle accidents.

Method:
A retrospective study was conducted with collection of data from medical records of patients operated for facial fractures at the Hospital Regional of Cariri, state of Ceara, the Northeast of Brazil. Records from 2012 to 2014 were acquired highlighting sex, age, occupation, etiology, anatomical sites of fractures, and surgeries of varying complexities for single or multiple fractures. The day of the event, report or signs of alcohol consumption, and the use of helmets in motorcycle accidents were named associated factors.

Results:
As a result the authors had a total of 624 cases of surgical facial fractures. Out of these, 546 (87.5%) were male and the majority of them presented between 20 and 30 years of age (40.5%). It was also observed that as an etiological factor motorcycle accidents led to more cases of surgical facial fractures, with 357 cases (62.1%), followed by physical aggression with 72 cases (12.5%).

Conclusions:
It can be concluded that there is a high prevalence of surgical facial fractures in male patients between 20 and 30 years of age, caused by motorcycle accidents, and that there was a strong association between the consumption of alcohol, failure to wear a helmet, and the presence of surgical facial multiple fractures.
Primary and Secondary Stability of Single Short Implants
Authors: Alonso Fernando R. , Triches Diego F. , Mezzomo Luis A.M. , Teixeira Eduardo R. , Shinkai Rosemary S.A. 
Published: April 2018

Purpose:This prospective cohort study assessed the effect of bone quality on the primary and secondary stability of single short implants placed in the posterior region.Materials and Methods:A total of 39 short implants (4.1 × 6-mm long) were placed in the posterior region of the maxilla or mandible in 18 patients. Bone quality was classified into type I, II, III, or IV as assessed intrasurgically. Primary implant stability was measured with insertion torque, damping capacity (PTV values), and resonance frequency analysis (ISQ values). Secondary stability was measured by ISQ and PTV at abutment installation. Data were analyzed by using repeated-measures ANOVA and Tukey's test, Kruskall–Wallis test, and Spearman correlation tests.Results:Implants placed in bone type IV had significant lower insertion torque and ISQ values as well as higher PTV values than in bone types I to II (P< 0.05). The mean ISQ values were higher at abutment installation than at implant placement (P < 0.05), regardless the bone type. The assessment methods of implant stability showed a moderate correlation.Conclusions:Bone quality influences both the primary and secondary stability of single short implants in the posterior region.
Long-read whole genome sequencing and comparative analysis of six strains of the human pathogenOrientia tsutsugamushi
Authors: Batty Elizabeth M. , Chaemchuen Suwittra , Blacksell Stuart D. , Paris Daniel , Bowden Rory , Chan Caroline , Lachumanan Ramkumar , Day Nicholas , Donnelly Peter , Chen Swaine L. , Salje Jeanne 
Published: April 2018

AbstractBackgroundOrientia tsutsugamushiis a clinically important but neglected obligate intracellular bacterial pathogen of the Rickettsiaceae family that causes the potentially life-threatening human disease scrub typhus. In contrast to the genome reduction seen in many obligate intracellular bacteria, early genetic studies ofOrientiahave revealed one of the most repetitive bacterial genomes sequenced to date. The dramatic expansion of mobile elements has hampered efforts to generate complete genome sequences using short read sequencing methodologies, and consequently there have been few studies of the comparative genomics of this neglected species.ResultsWe report new high-quality genomes ofOrientia tsutsugamushi,generated using PacBio single molecule long read sequencing, for six strains: Karp, Kato, Gilliam, TA686, UT76 and UT176. In comparative genomics analyses of these strains together with existing reference genomes from Ikeda and Boryong strains, we identify a relatively small core genome of 657 genes, grouped into core gene ‘islands’ and separated by repeat regions, and use the core genes to infer the first whole-genome phylogeny ofOrientia.ConclusionsComplete assemblies of multiple Orientia genomes verify initial suggestions that these are remarkable organisms. They have large genomes with widespread amplification of repeat elements and massive chromosomal rearrangements between strains. At the gene level, Orientia has a relatively small set of universally conserved genes, similar to other obligate intracellular bacteria, and the relative expansion in genome size can be accounted for by gene duplication and repeat amplification. Our study demonstrates the utility of long read sequencing to investigate complex bacterial genomes and characterise genomic variation.
Isolation and sequencing of AGO-bound RNAs reveals characteristics of mammalian stem-loop processing in vivo
Authors: Silverman Ian M. , Gosai Sager J. , Vrettos Nicholas , Foley Shawn W. , Berkowitz Nathan D. , Mourelatos Zissimos , Gregory Brian D. 
Published: April 2018

ABSTRACTMicroRNA precursors (pre-miRNAs) are short hairpin RNAs that are rapidly processed into mature microRNAs (miRNAs) in the cytoplasm. Due to their low abundance in cells, sequencing-based studies of pre-miRNAs have been limited. We successfully enriched for and deep sequenced pre-miRNAs in human cells by capturing these RNAs during their interaction with Argonaute (AGO) proteins. Using this approach, we detected > 350 pre-miRNAs in human cells and > 250 pre-miRNAs in a reanalysis of a similar study in mouse cells. We uncovered widespread trimming and non-templated additions to the 3’ ends of pre- and mature miRNAs. Additionally, we created an index for microRNA precursor processing efficiency. This analysis revealed a subset of pre-miRNAs that produce low levels of mature miRNAs despite abundant precursors, including an annotated miRNA in the 5’ UTR of the DiGeorge syndrome critical region 8 mRNA transcript. This led us to search for AGO-associated stem-loops originating from other mRNA species, which identified hundreds of putative pre-miRNAs derived from human and mouse mRNAs. In summary, we provide a wealth of information on mammalian pre-miRNAs, and identify novel microRNA and microRNA-like elements localized in mRNAs.
Machine-Learning prognostic models from the 2014-16 Ebola outbreak: data-harmonization challenges, validation strategies, and mHealth applications
Authors: Colubri Andres , Hartley Mary-Anne , Siakor Mathew , Wolfman Vanessa , Sesay Tom , Felix August , Levine Adam C. , Sabeti Pardis C. 
Published: April 2018

AbstractBackgroundWe created a family of prognostic models for Ebola virus disease from the largest dataset of EVD patients published to date. We incorporated these models into an app, “Ebola Care Guidelines”, that provides access to recommended, evidence-based supportive care guidelines and highlights the signs/symptoms with the largest contribution to prognosis.MethodsWe applied multivariate logistic regression on 470 patients admitted to five Ebola treatment units in Liberia and Sierra Leone during the 2014-16 outbreak. We validated the models with two independent datasets from Sierra Leone.FindingsViral load and age were the most important predictors of death. We generated a parsimonious model including viral load, age, body temperature, bleeding, jaundice, dyspnea, dysphagia, and referral time recorded at triage. We also constructed fallback models for when variables in the parsimonious model are unavailable. The performance of the parsimonious model approached the predictive power of observational wellness assessments by experienced health workers, with Area Under the Curve (AUC) ranging from 0.7 to 0.8 and overall accuracy of 64% to 74%.InterpretationMachine-learning models and mHealth tools have the potential for improving the standard of care in low-resource settings and emergency scenarios, but data incompleteness and lack of generalizable models are major obstacles. We showed how harmonization of multiple datasets yields prognostic models that can be validated across different cohorts. Similar performance between the parsimonious model and those incorporating expert wellness assessments suggests that clinically-guided machine learning approaches can recapitulate clinical expertise, and thus be useful when such expertise is unavailable. We also demonstrated with our guidelines app how integration of those models with mobile technologies enables deployable clinical management support tools that facilitate access to comprehensive bodies of medical knowledge.FundingHoward Hughes Medical Institute, US National Institutes of Health
The 100-plus Study of cognitively healthy centenarians: rationale, design and cohort description
Authors: Holstege Henne , Beker Nina , Dijkstra Tjitske , Pieterse Karlijn , Wemmenhove Elizabeth , Schouten Kimja , Thiessens Linette , Horsten Debbie , Rechtuijt Sterre , Sikkes Sietske , van Poppel Frans W.A. , Meijers-Heijboer Hanne , Hulsman Marc , Scheltens Philip 
Published: April 2018

ABSTRACTRATIONALEAlthough the incidence of dementia increases exponentially with age, some individuals reach >100 years with fully retained cognitive abilities. To identify the characteristics associated with the escape or delay of cognitive decline, we initiated the 100-plus Study (www.100plus.nl).DESIGNThe 100-plus Study is an on-going prospective cohort study of Dutch centenarians who self-reported to be cognitively healthy, their first-degree family members and their respective partners. We collect demographics, life history, medical history, genealogy, neuropsychological data and blood samples. Centenarians are followed annually until death. PET-MRI scans and feces donation are optional. Almost 30% of the centenarians agreed to post-mortem brain donation.COHORT DESCRIPTIONTo date (September 2018), 332 centenarians were included in the study. We analyzed demographic statistics of the first 300 centenarians (25% males) included in the cohort. Centenarians came from higher socio-economic classes and had higher levels of education compared to their birth cohort; alcohol consumption of centenarians was similar, and most males smoked during their lifetime. At baseline, the centenarians had a median MMSE score of 25 points (IQR: 22.0-27.5); the large majority lived independently, retained hearing and vision abilities and was independently mobile. Mortality was associated with cognitive functioning: centenarians with a baseline MMSE score ≥26 and <26 points had a mortality percentage of respectively 17% and 42% per annual year in the second year after baseline (p=0.003). The cohort was 2.1-fold enriched with the neuroprotective APOE-ε2 allele relative to 60-80 year-old population controls (p=4.8×10-7), APOE-ε3 was unchanged and the APOE-ε4 allele was 2.3-fold depleted (p=6.3×10-7).CONCLUSIONSComprehensive characterization of the 100-plus cohort of cognitively healthy centenarians might reveal protective factors that explain the physiology of long-term preserved cognitive health.
The impact of endogenous retroviruses on nuclear organization and gene expression
Authors: Raviram Ramya , Rocha Pedro P , Luo Vincent M , Swanzey Emily , Miraldi Emily R , Chuong Edward B , Feschotte Cédric , Bonneau Richard , Skok Jane A 
Published: April 2018

AbstractBackgroundThe organization of chromatin in the nucleus plays an essential role in gene regulation. When considering the mammalian genome it is important to take into account that about half of the DNA is comprised of transposable elements. Given their repetitive nature, reads associated with these elements are generally discarded or randomly distributed among elements of the same type in genome-wide analyses. Thus, it is challenging to identify the activities and properties of individual transposons. As a result, we only have a partial understanding of how transposons contribute to chromatin folding and how they impact gene regulation.ResultsUsing adapted PCR and Capture-based chromosome conformation capture (3C) approaches, collectively called 4Tran, we take advantage of the repetitive nature of transposons to capture interactions from multiple copies of endogenous retrovirus (ERVs) in the human and mouse genomes. With 4Tran-PCR, reads are selectively mapped to unique regions in the genome. This enables the identification of TE interaction profiles for individual ERV families and integration events specific to particular genomes. With this approach we demonstrate that transposons engage in long-range intra-chromosomal interactions guided by the separation of chromosomes into A and B compartments as well as topologically associated domains (TADs). In contrast to 4Tran-PCR, Capture-4Tran can uniquely identify both ends of an interaction that involve retroviral repeat sequences, providing a powerful tool for uncovering the individual TE insertions that interact with, and potentially regulate target genes.Conclusions4Tran provides new insight into the manner in which transposons contribute to chromosome architecture and identifies target genes that transposable elements can potentially control.
Role of the default mode network in cognitive transitions
Authors: Smith Verity , Mitchell Daniel J , Duncan John 
Published: April 2018

ABSTRACTA frequently repeated finding is that the default mode network (DMN) shows activation decreases during externally-focused tasks. This finding has led to an emphasis in DMN research on internally-focused self-relevant thought processes. A recent study, in contrast, implicates the DMN in substantial externally-focused task switches. Using functional magnetic resonance imaging, we scanned 24 participants performing a task switch experiment. Whilst replicating previous DMN task switch effects, we also found large DMN increases for brief rests as well as task restarts after rest. Our findings are difficult to explain using theories strictly linked to internal or self-directed cognition. In line with principal results from the literature, we suggest that the DMN encodes scene, episode or context, by integrating spatial, self-referential and temporal information. Context representations are strong at rest, but re-reference to context also occurs at major cognitive transitions.
Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis
Authors: Kim Soo-Hyun , Redvers Richard P. , Chi Lap Hing , Ling Xiawei , Lucke Andrew J. , Reid Robert C. , Fairlie David P. , Baptista Moreno Martin Ana Carolina , Anderson Robin L. , Denoyer Delphine , Pouliot Normand 
Published: April 2018

ABSTRACTBreast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours. By immunohistochemistry, 4T1Br4 tumours and brain metastases display a triple negative phenotype, consistent with the high propensity of this breast cancer subtype to spread to brain.In vitroassays indicate that 4T1Br4 cells have an enhanced ability to adhere to or migrate across a brain-derived endothelial monolayer and greater invasive response to brain-derived soluble factors compared to 4T1 cells. These properties are likely to contribute to the brain-selectivity of 4T1Br4 tumours. Expression profiling and gene set enrichment analyses demonstrate the clinical relevance of the 4T1Br4 model at the transcriptomic level. Pathway analyses implicate tumour-intrinsic immune regulation and vascular interactions in successful brain colonisation, revealing potential therapeutic targets. Evaluation of two histone deacetylase inhibitors, SB939 and 1179.4b, shows partial efficacy against 4T1Br4 metastasis to brain and other sitesin vivoand potent radio-sensitising propertiesin vitro. The 4T1Br4 model provides a clinically relevant tool for mechanistic studies and to evaluate novel therapies against brain metastasis.SUMMARY STATEMENTWe introduce a new syngeneic mouse model of spontaneous breast cancer brain metastasis, demonstrate its phenotypic, functional and transcriptomic relevance to human TNBC brain metastasis and test novel therapies.
Connectivity Patterns in Cognitive Control Networks Predict Naturalistic Multitasking Ability
Authors: Wen Tanya , Liu De-Cyuan , Hsieh Shulan 
Published: April 2018

AbstractMultitasking is a fundamental aspect of everyday life activities. To achieve a complex, multi-component goal, the tasks must be subdivided into sub-tasks and component steps, a critical function of prefrontal networks. The prefrontal cortex is considered to be organized in a cascade of executive processes from the sensorimotor to anterior prefrontal cortex, which includes execution of specific goal-directed action, to encoding and maintaining task rules, and finally monitoring distal goals. In the current study, we used a virtual multitasking paradigm to tap into real-world performance and relate it to each individual’s resting-state functional connectivity in fMRI. While did not find any correlation between global connectivity of any of the major networks with multitasking ability, global connectivity of the lateral prefrontal cortex (LPFC) was predictive of EVET score. Further analysis showed that multivariate connectivity patterns within the sensorimotor network (SMN), and between-network connectivity of the frontopartietal network (FPN) and dorsal attention network (DAN), predicted individual multitasking ability and could be generalized to novel individuals. Together, these results support previous research that prefrontal networks underlie multitasking abilities and show that connectivity patterns in the cascade of prefrontal networks may explain individual differences in performance.
New tools for carbohydrate sulphation analysis: Heparan Sulphate 2-O-sulphotranserase (HS2ST) is a target for small molecule protein kinase inhibitors
Authors: Byrne Dominic P , Li Yong , Ramakrishnan Krithika , Barsukov Igor L , Yates Edwin A , Eyers Claire E , Papy-Garcia Dulcé , Chantepie Sandrine , Pagadala Vijayakanth , Liu Jian , Wells Carrow , Drewry David H , Zuercher William J , Berry Neil G , Fernig David G , Eyers Patrick A 
Published: April 2018

ABSTRACTSulphation of carbohydrate residues occurs on a variety of glycans destined for secretion, and this modification is essential for efficient matrix-based signal transduction. Heparan sulphate (HS) glycosaminoglycans control physiological functions ranging from blood coagulation to cell proliferation. HS biosynthesis involves membrane-bound Golgi sulphotransferases, including heparan sulphate 2-O-sulphotransferase (HS2ST), which transfers sulphate from the co-factor PAPS (3’-phosphoadenosine 5’-phosphosulphate) to the 2-Oposition of α-L-iduronate in the maturing oligosaccharide chain. The current lack of simple non-radioactive enzyme assays that can be used to quantify the levels of carbohydrate sulphation hampers kinetic analysis of this process and the discovery of HS2ST inhibitors. In this paper, we describe a new procedure for thermal shift analysis of purified HS2ST. Using this approach, we quantify HS2ST-catalyzed oligosaccharide sulphation using a novel synthetic fluorescent substrate and screen the Published Kinase Inhibitor Set (PKIS), to evaluate compounds that inhibit catalysis. We report the susceptibility of HS2ST to a variety of cell permeable compoundsin vitro, including polyanionic polar molecules, the protein kinase inhibitor rottlerin and oxindole-based RAF kinase inhibitors. In a related study, published back-to-back with this article, we demonstrate that Tyrosyl Protein Sulpho Tranferases (TPSTs) are also inhibited by a variety of protein kinase inhibitors. We propose that appropriately validated small molecule compounds could become new tools for rapid inhibition of glycan (and protein) sulphation in cells, and that protein kinase inhibitors might be repurposed or redesigned for the specific inhibition of HS2ST.SUMMARY STATEMENTWe report that HS2ST, which is a PAPS-dependent glycan sulphotransferase, can be assayed using a variety of novel biochemical procedures, including a non-radioactive enzyme-based assay that detects glycan substrate sulphation in real time. HS2ST activity can be inhibited by different classes of compounds, including known protein kinase inhibitors, suggesting new approaches to evaluate the roles of HS2ST-dependent sulphation with small molecules in cells.
Cluster Failure Revisited: Impact of First Level Design and Data Quality on Cluster False Positive Rates
Authors: Eklund Anders , Knutsson Hans , Nichols Thomas E. 
Published: April 2018

AbstractMethodological research rarely generates a broad interest, yet our work on the validity of cluster inference methods for functional magnetic resonance imaging (fMRI) created intense discussion on both the minutia of our approach and its implications for the discipline. In the present work, we take on various critiques of our work and further explore the limitations of our original work. We address issues about the particular event-related designs we used, considering multiple event types and randomisation of events between subjects. We consider the lack of validity found with onesample permutation (sign ipping) tests, investigating a number of approaches to improve the false positive control of this widely used procedure. We found that the combination of a two-sided test and cleaning the data using ICA FIX resulted in nominal false positive rates for all datasets, meaning that data cleaning is not only important for resting state fMRI, but also for task fMRI. Finally, we discuss the implications of our work on the fMRI literature as a whole, estimating that at least 10% of the fMRI studies have used the most problematic cluster inference method (P = 0.01 cluster defining threshold), and how individual studies can be interpreted in light of our findings. These additional results underscore our original conclusions, on the importance of data sharing and thorough evaluation of statistical methods on realistic null data.