bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated With Revision Surgery After Internal Fixation of Hip Fractures
Authors: Sprague Sheila , Schemitsch Emil H. , Swiontkowski Marc , Della Rocca Gregory J. , Jeray Kyle J. , Liew Susan , Slobogean Gerard P. , Bzovsky Sofia , Heels-Ansdell Diane , Zhou Qi , Bhandari Mohit ,   on behalf of the FAITH Investigators
Published: April 2018

Background:
Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device.

Methods:
We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation.

Results:
Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25–2.50; P = 0.001], higher body mass index (for every 5-point increase) (HR 1.19, 95% CI 1.02–1.39; P = 0.027), displaced fracture (HR 2.16, 95% CI 1.44–3.23; P < 0.001), unacceptable quality of implant placement (HR 2.70, 95% CI 1.59–4.55; P < 0.001), and smokers treated with cancellous screws versus smokers treated with a sliding hip screw (HR 2.94, 95% CI 1.35–6.25; P = 0.006). Additionally, for every 10-year decrease in age, participants experienced an average increased risk of 39% for hardware removal.

Conclusions:
Results of this study may inform future research by identifying high-risk patients who may be better treated with arthroplasty and may benefit from adjuncts to care (HR 1.39, 95% CI 1.05–1.85; P = 0.020).

Level of Evidence:
Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Current Publication Rates of Abstracts Presented at the Orthopaedic Trauma Association Annual Meetings: 2005–2010
Authors: Lee Ryan , Mamidi Ishwarya S. , Gu Alex , Cohen Jordan S. , Probasco William , DeBritz James 
Published: April 2018

Objectives:
To evaluate the publication rate of abstracts presented at the 2005–2010 Orthopaedic Trauma Association (OTA) Annual Meetings.

Methods:
All abstracts from the 2005 to 2010 OTA meetings were identified through the OTA's official website. Each abstract was searched across PubMed and Google to determine its publication status. The overall publication rate of abstracts was determined, along with the first authors' sex, number of authors, time and journal of publication, and analyzed with statistical testing.

Results:
Of the 392 abstracts presented at the 2005–2010 OTA meetings, the overall publication rate was 66.3%, with an overall mean time to publication of 28.3 months. The Journal of Orthopaedic Trauma published 38.5% of published OTA abstracts, the most of any journal. The proportions of published OTA abstracts with female first authors exhibit increasing trends within the time period.

Conclusion:
The quality of research presented at OTA meetings is relatively high compared with other orthopaedic meetings, with 66.3% of OTA abstracts progressing to peer-reviewed publication. The publication rate of 2005–2010 OTA abstracts was greater than that of the 1990–1995 abstracts. The Journal of Orthopaedic Trauma remains the most frequent publisher of manuscripts presented as abstracts at OTA meetings. Although most abstracts are eventually published, the information presented at these meetings, like all scholarly work, should be critically evaluated as they have undergone a less robust peer-review process and may be modified in the future in preparation for publication.
Differentiating Usual Interstitial Pneumonia From Nonspecific Interstitial Pneumonia Using High-resolution Computed Tomography
Authors: Zhan Xi , Koelsch Tilman , Montner Steven M. , Zhu Allen , Vij Rekha , Swigris Jeffery J. , Chung Jonathan H. 
Published: April 2018

Purpose:
The purpose of this article was to determine whether a novel finding on coronal computed tomography (CT) can help differentiate usual interstitial pneumonia (UIP) from nonspecific interstitial pneumonia (NSIP) in order to obviate lung biopsy.

Materials and Methods:
Two chest radiologists, blinded to clinical data, reviewed 3 preselected coronal images from CT scans, performed within 1 year of surgical lung biopsy (SLB), from 51 patients with biopsy-proven UIP and 15 with biopsy-proven NSIP. The 198 (66×3) images were anonymized and randomized. The radiologists assessed each coronal image for the presence or absence of the straight-edge sign (SES) on both the right and left sides, anecdotally thought to be more common in NSIP than in UIP. The SES was defined as reticulation isolated to the lung bases with sharp demarcation in the craniocaudal plane and without substantial extension along the lateral margins of the lungs. A validation cohort from a second medical center was also evaluated to reassess our findings.

Results:
The absence of a bilateral SES yielded a sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 56.9%, 93.3%, 96.7%, and 38.9%, respectively, for UIP on SLB. The unilateral or bilateral absence of the SES yielded a sensitivity, specificity, PPV, and negative predictive value of 76.5%, 66.7%, 88.6%, and 45.5%, respectively, for UIP on SLB. For the 11 subjects with an overall CT pattern consistent with NSIP but a pathologic diagnosis of UIP, the SES was absent in 6 (54.5%) subjects. In the validation cohort, the SES was much more common in NSIP than in UIP (46.6% compared with 3.3%, respectively; P<0.001).

Conclusion:
The absence of the SES has a high PPV for biopsy-proven UIP. Bilateral absence of the SES has high specificity (93.3%) for biopsy-proven UIP. The SES may be useful for differentiating UIP from NSIP.
Bioinformatics challenges and perspectives when studying the effect of epigenetic modifications on alternative splicing
Authors: Pacini Clare , Koziol Magdalena J. 
Published: April 2018

It is widely known that epigenetic modifications are important in regulating transcription, but several have also been reported in alternative splicing. The regulation of pre-mRNA splicing is important to explain proteomic diversity and the misregulation of splicing has been implicated in many diseases. Here, we give a brief overview of the role of epigenetics in alternative splicing and disease. We then discuss the bioinformatics methods that can be used to model interactions between epigenetic marks and regulators of splicing. These models can be used to identify alternative splicing and epigenetic changes across different phenotypes.
This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
Molecular atlas of postnatal mouse heart development
Authors: Talman Virpi , Teppo Jaakko , Pöhö Päivi , Movahedi Parisa , Vaikkinen Anu , Karhu S. Tuuli , Trošt Kajetan , Suvitaival Tommi , Heikkonen Jukka , Pahikkala Tapio , Kotiaho Tapio , Kostiainen Risto , Varjosalo Markku , Ruskoaho Heikki 
Published: April 2018

AbstractRationaleMammals lose the ability to regenerate their hearts within one week after birth. During this regenerative window, cardiac energy metabolism shifts from glycolysis to fatty acid oxidation, and recent evidence suggests that metabolism may participate in controlling cardiomyocyte cell cycle. However, the molecular mechanisms mediating the loss of postnatal cardiac regeneration are not fully understood.ObjectiveThis study aims at providing an integrated resource of mRNA, protein and metabolite changes in the neonatal heart to identify metabolism-related mechanisms associated with the postnatal loss of regenerative capacity.Methods and ResultsMouse ventricular tissue samples taken on postnatal days 1, 4, 9 and 23 (P01, P04, P09 and P23, respectively) were analyzed with RNA sequencing (RNAseq) and global proteomics and metabolomics. Differential expression was observed for 8547 mRNAs and for 1199 of the 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Gene ontology analysis, KEGG pathway analysis and fuzzy c-means clustering were used to identify biological processes and metabolic pathways either up- or downregulated on all three levels. Among these were branched chain amino acid degradation (upregulated at P23) and production of free saturated and monounsaturated medium- to long-chain fatty acids (upregulated at P04 and P09; downregulated at P23). Moreover, the HMG-CoA synthase (HMGCS)-mediated mevalonate pathway and ketogenesis were transiently activated. Pharmacological inhibition of HMGCS in primary neonatal rat ventricular cardiomyocytes reduced the percentage of BrdU+ cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating cardiomyocyte cell cycle.ConclusionsThis is the first systems-level resource combining data from genome-wide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses of the mouse heart throughout the early postnatal period. This integrated multi-level data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies.
Inter-institutional variation in predictive value of the ThyroSeq v2 genomic classifier for cytologically indeterminate thyroid nodules
Authors: Marcadis Andrea R. , Valderrabano Pablo , Ho Allen S. , Tepe Justin , Swartzwelder Christina E. , Byrd Serena , Sacks Wendy L. , Untch Brian R. , Shaha Ashok R. , Xu Bin , Lin Oscar , Ghossein Ronald A. , Wong Richard J. , Marti Jennifer L. , Morris Luc G.T. 
Published: April 2018

ABSTRACTBackgroundThe ThyroSeq v2 next-generation sequencing assay (ThyroSeq) estimates the probability of malignancy in indeterminate thyroid nodules (ITN). Its diagnostic accuracy in different practice settings and patient populations is not well understood.MethodsWe analyzed 273 Bethesda III/IV ITN evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n=98 and 102), a multicenter healthcare system (n=60), and an academic medical center (n=13). The positive (PPV) and negative predictive values (NPV) of ThyroSeq, and distribution of final pathology were analyzed and compared to values predicted by Bayes Theorem.ResultsAcross 4 institutions, the PPV was 35% (22-43%), and NPV was 93% (88-100%). Predictive values correlated closely with Bayes Theorem estimates (r2=.84), although PPVs were lower than expected. RAS mutations were the most frequent molecular alteration. Among 84 RAS-mutated nodules, malignancy risk was variable (25%, range 10-37%), and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12-85%, NIFTP 5-46%).ConclusionsIn a multi-institutional analysis, ThyroSeq PPVs were variable and lower than expected. This is attributable to differences in the prevalence of malignancy, and variability in pathologist interpretations of non-invasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results.
Prot-SpaM: Fast alignment-free phylogeny reconstruction based on whole-proteome sequences
Authors: Leimeister Chris-Andre , Schellhorn Jendrik , Schöbel Svenja , Gerth Michael , Bleidorn Christoph , Morgenstern Burkhard 
Published: April 2018

AbstractWord-based or ‘alignment-free’ sequence comparison has become an active area of research in bioinformatics. While previous word-frequency approaches calculated rough measures of sequence similarity or dissimilarity, some new alignment-free methods are able to accurately estimate phylogenetic distances between genomic sequences. One of these approaches isFiltered Spaced Word Matches. Herein, we extend this approach to estimate evolutionary distances between complete or incomplete proteomes; our implementation of this approach is calledProt-SpaM. We compare the performance ofProt-SpaMto other alignment-free methods on simulated sequences and on various groups of eukaryotic and prokaryotic taxa.Prot-SpaMcan be used to calculate high-quality phylogenetic trees from whole-proteome sequences in a matter of seconds or minutes and often outperforms other alignment-free approaches. The source code of our software is available throughGithub:https://github.com/jschellh/ProtSpaM
High coverage genome sequencing and identification of genomic variants in Bengal tiger (Panthera tigris tigris)
Authors: Anuradha Reddy P , Kothandaraman Harish , Parvati Sai Arun P V , Challagandla Anil , Baghel Dushyant Singh 
Published: April 2018

AbstractBengal tiger (Panthera tigris tigris), one of six extant tiger subspecies, occurs solely in the Indian subcontinent. Although endangered and threatened by various extinction risks, this is the most populous tiger subspecies with the highest genetic diversity and strongest chance of survival in the wild. Availability of high quality genomic information on this animal will help us understand its ability to adapt to different habitats and environmental changes, in addition to comparative studies with other subspecies. Here we report high coverage sequencing of the Bengal tiger genome and its mapping to the Amur tiger genome in order to discover single nucleotide to large structural variants. A total of 345 Gb, roughly equivalent to 144X coverage of the genome, was generated from 1,149,381,669 raw read pairs. Further, 990,060,729 clean read pairs, again equivalent to 115X coverage, were retained from the raw read data and considered for comparative analysis with the Amur tiger genome. This alignment showed that 97.35% of the bases mapped at 5X depth, 97.26% at 10X and 90.44% at 50X depth. We identified a total of 3,601,882 single nucleotide variants, 948 structural variants, 56,649 copy number variants and 1,760,347 simple sequence repeats. We report the first high coverage genome sequence of Bengal tiger with an overview of its genomic variants when compared to the Amur tiger genome. Of the several variants identified, we further have to assess and validate variants potentially associated with the ability of the animal to adapt to environmental changes, disease susceptibility and other important biological phenomena.
Exploring the mechanistic link between corticosterone and insulinlike growth factor-1 in a wild passerine bird
Authors: Tóth Zsófia , Ouyang Jenny Q. , Lendvai Ádám Z. 
Published: April 2018

AbstractBackgroundPhysiological regulators of life history trade-offs need to be responsive to sudden changes of resource availability. When homeostasis is challenged by unpredictable stressors, vertebrates respond through a set of physiological reactions, which can promote organismal survival. Glucocorticoids have been traditionally recognized as one of the main regulators of the physiological stress response, but the role of an evolutionarily more conserved pathway, the hypothalamic-pituitary-somatotropic (HPS) axis producing insulin-like growth factor-1 (IGF-1) has received much less attention. Although IGF-1 is known to affect several life history traits, little is known about its role in the physiological stress response and it has never been studied directly in adult wild animals.MethodsIn this study, we combined field observations with a controlled experiment to investigate how circulating levels of IGF-1 change in response to stress and whether this change is due to concomitant change in glucocorticoids in a free-living songbird, the bearded reedling Panurus biarmicus. We used a standard capture-restraint protocol in field observation, in which we took first and second (stress induced: 15 minutes later) samples. In a follow-up experiment, we used a minimally invasive oral corticosterone manipulation.ResultsWe showed that corticosterone levels significantly increased while IGF-1 levels significantly decreased during capture and handling stress. However, change in corticosterone levels were not related to change in IGF-1 levels. We found that experimentally elevated corticosterone levels did not affect IGF-1 levels.DiscussionOur results are the first to highlight that circulating IGF-1 levels are responsive to stress independently from glucocorticoids and suggest that the HPS axis is an autonomous physiological pathway that may play an important role as regulator of life-history decisions.
Separate the wheat from the chaff: genomic scan for local adaptation in the red coralCorallium rubrum
Authors: Pratlong M. , Haguenauer A. , Brener K. , Mitta G. , Toulza E. , Garrabou J. , Bensoussan N. , Pontarotti P. , Aurelle D. 
Published: April 2018

ABSTRACTGenomic data allow an in-depth and renewed study of local adaptation. The red coral (Corallium rubrum, Cnidaria) is a highly genetically structured species and a promising model for the study of adaptive processes along an environmental gradient. Here, we used RAD-Sequencing in order to study the vertical genetic structure of this species and to search for signals of local adaptation to depth and thermal regime in the red coral. Previous studies have shown different thermotolerance levels according to depth in this species which could correspond to genetic or environmental differences. We designed a sampling scheme with six pairs of ‘shallow vs deep’ populations distributed in three geographical regions as replicates. Our results showed significant differentiation among locations and among sites separated by around 20 m depth. The tests of association between genetics and environment allowed the identification of candidate loci under selection but with a potentially high rate of false positive. We discuss the methodological obstacles and biases encountered for the detection of selected loci in such a strongly genetically structured species. On this basis, we also discuss the significance of the candidate loci for local adaptation detected in each geographical region and the evolution of red coral populations along environmental gradients.A colony of red coral,Corallium rubrum, near Marseille. Photo: F. Zuberer / OSU Pythéas / CNRS
Field synopsis and systematic meta-analyses of genetic association studies in isolated dystonia
Authors: Ohlei Olena , Dobricic Valerija , Lohmann Katja , Klein Christine , Lill Christina , Bertram Lars 
Published: April 2018

AbstractBackground and objectivesDystonia is a genetically complex disease with both monogenic and polygenic causes. For the latter, numerous genetic associations studies have been performed with largely inconsistent results. The aim of this study was to perform a field synopsis including systematic meta-analyses of genetic association studies in isolated dystoniaMethodsFor the field synopsis we systematically screened and scrutinized the published literature using NCBI’s PubMed database. For genetic variants with sufficient information in at least two independent datasets, random-effects meta-analyses were performed, including meta-analyses stratified by ethnic descent and dystonia subtypes.ResultsA total of 3,575 articles were identified and scrutinized resulting in the inclusion of 42 independent publications allowing 134 meta-analyses on 45 variants across 17 genes. While our meta-analyses pinpointed several significant association signals with variants in TOR1A, DRD1, and ARSG, no single variant displayed compelling association with dystonia in the available data.ConclusionsOur study provides an up-to-date summary of the status of dystonia genetic association studies. Additional large-scale studies are needed to better understand the genetic causes of isolated dystonia.
The dynamics of ERK signaling in melanoma, and the response to BRAF or MEK inhibition, are cell cycle dependent
Authors: Simpson Chloe M. , Ferrari Nicola , Calvo Fernando , Bakal Chris 
Published: April 2018

AbstractActivating BRAF mutations drive melanoma tumorigenesis and metastasis by constitutively activating MEK and ERK, and small molecule inhibitors (SMIs) of BRAF or MEK have shown promise as melanoma therapeutics. However, the development of resistance to these inhibitors in both the short- and longterm is common; warranting investigation into how these SMIs influence ERK signaling dynamics. By quantitative single cell imaging of an ERK activity reporter in living cells, we describe both intra- and inter-cell heterogeneity in ERK activity in isogenic melanoma populations harboring a BRAFV600E mutation. This heterogeneity is largely due to a cell-cycle dependent bifurcation in ERK activation. Moreover, we show there are cell-cycle dependent responses in ERK activity following BRAF or MEK inhibition. Prior to, but not following, CDK4/6-mediated passage through the Restriction Point (RP) ERK activity is sensitive to BRAF and MEK inhibitors. In contrast, in cells that have passed the RP, ERK activity will remain elevated even in the presence of BRAF or MEK inhibition until mitosis. We propose that ERK activity in the presence of activating BRAF mutations is regulated by both positive and negative feedback loops that are engaged in cell-cycle dependent fashions. CDK4/6 inhibition sensitizes ERK activity to BRAF or MEK inhibition by preventing passage the transition from a BRAF/MEK dependent to independent state. Our results have implications for the use of MEK and BRAF inhibitors as melanoma therapeutics, and offer a rational basis for the use of these inhibitors in combination with CDK4/6 inhibition during cancer therapy.
Simulation of spontaneous G protein activation reveals a new intermediate driving GDP unbinding
Authors: Sun Xianqiang , Singh Sukrit , Blumer Kendall J. , Bowman Gregory R. 
Published: April 2018

AbstractActivation of heterotrimeric G proteins is a key step in many signaling cascades. However, a complete mechanism for this process, which requires allosteric communication between binding sites that are ~30 Å apart, remains elusive. We construct an atomically-detailed model of G protein activation by combining three powerful computational methods; metadynamics, Markov state models (MSMs), and CARDS analysis of correlated motions. We uncover a mechanism that is consistent with a wide variety of structural and biochemical data. Surprisingly, the rate-limiting step for GDP release correlates with tilting rather than translation of the GPCR-binding helix 5. β-Strands 1-3 and helix 1 emerge as hubs in the allosteric network that links conformational changes in the GPCR-binding site to disordering of the distal nucleotide-binding site and consequent GDP release. Our approach and insights provide foundations for understanding disease-implicated G protein mutants, illuminating slow events in allosteric networks, and examining unbinding processes with slow off-rates.