bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole Genome Methylation Analysis of Nondysplastic Barrett Esophagus that Progresses to Invasive Cancer
Authors: Dilworth Mark P. , Nieto Tom , Stockton Jo D. , Whalley Celina M. , Tee Louise , James Jonathan D. , Noble Fergus , Underwood Tim J. , Hallissey Michael T. , Hejmadi Rahul , Trudgill Nigel , Tucker Olga , Beggs Andrew D. 
Published: January 2018

Objective:
To investigate differences in methylation between patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma and those who do not.

Background:
Identifying patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma remains a challenge. Previous studies have demonstrated the potential utility of epigenetic markers for identifying this group.

Methods:
A whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with nondysplastic Barrett esophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencing.

Results:
In all, 12 patients with “progressive” versus 12 with “nonprogressive” nondysplastic Barrett esophagus were analyzed via methylation array. Forty-four methylation markers were identified that may be able to discriminate between nondysplastic Barrett esophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumor suppressor OR3A4 (probe cg09890332) validated in a separate cohort of samples (median methylation in progressors 67.8% vs 96.7% in nonprogressors; P = 0.0001, z = 3.85, Wilcoxon rank-sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the 2 groups, but a global trend towards hypomethylation in the progressor group was observed.

Conclusion:
Hypomethylation of OR3A4 has the ability to risk stratify the patient with nondysplastic Barrett esophagus and may form the basis of a future surveillance program.
Too little too late: Hypotension and blood transfusion in the trauma bay are independent predictors of death in injured children
Authors: Leeper Christine M. , McKenna Christine , Gaines Barbara A. 
Published: January 2018

BACKGROUND
Hypotension is a late finding in pediatric shock despite significant blood loss; consequently, recognition of hemodynamic compromise can be delayed. We sought to describe the impact of late stage shock in children, indicated by hypotension or trauma bay blood transfusion, and quantify the association with poor outcome.

METHODS
Children age < 18 from the Pennsylvania Trauma Outcome Study registry (2000–2013) were included. Primary outcome was mortality. Demographics, transfusion volume, vitals and injury severity were recorded. Multivariable logistic regression modeling was performed, with multiple imputation sensitivity analysis for missing data (<8% for all variables).

RESULTS
Sixty-four thousand three hundred forty-four subjects were included with median (interquartile range) age, 9 years (4–15 years); 51% interfacility transfers; 2.0% mortality; 4.4% admission hypotension; and 1.6% trauma bay transfusion rate. Overall, 46% of hypotensive patients, 42% of transfused patients, and 63% both hypotensive and transfused died. Hypotension (odds ratio, 12.8; 95% confidence interval, 10.7–15.4; p < 0.001) and transfusion (odds ratio, 3.1; 95% confidence interval, 2.8–3.4; p < 0.001) significantly increased odds of death after controlling for injury severity, penetrating and child abuse mechanisms, admission Glasgow Coma Scale score, and age. Survival curves demonstrated worse survival for transfused patients in early (<24 hours), intermediate (1–5 days), and late (>5 days) periods (all p < 0.001).

CONCLUSION
Hypotension and trauma bay blood transfusion are poor prognostic indicators. These events should signal high acuity and prompt immediate and aggressive resuscitation. Earlier recognition of shock and appropriate interventions, including increased availability of blood products to prehospital providers, may facilitate timely hemostatic resuscitation, preventing circulatory collapse and secondary brain injury.

LEVEL OF EVIDENCE
Epidemiological, level III.
Cardiac Disorders in Patients With Leber Hereditary Optic Neuropathy
Authors: Orssaud Christophe 
Published: January 2018

Background:
Cardiac abnormalities have been described in patients with Leber hereditary optic neuropathy (LHON). Some are life-threatening because of the risk of ventricular fibrillation and sudden death. The purpose of our study was to better characterize the cardiac abnormalities in a large patient cohort with LHON.

Methods:
A retrospective study of the electrocardiogram (EKG) results performed on all patients with LHON evaluated at The Reference Center for Rare Diseases in Ophthalmology, Paris, France, from January 2015 to June 2017.

Results:
Our series included 73 patients with LHON (9 women/64 men) with a mean age of 30.29 ± 14.48 years. Although only 1 patient had cardiac complaints, cardiac abnormalities were detected in 17 patients (23.2%): 9 patients had an excitation syndrome, 6 had atrioventricular block, and 2 had repolarization abnormalities. All patients harbored mtDNA point mutations 11778 or 3460.

Conclusions:
Cardiac abnormalities occur frequently enough in patients with LHON that a baseline EKG is warranted. However, further studies are needed to determine the true cardiac risk associated with specific LHON mtDNA mutations.
Optimal Intereye Difference Thresholds in Retinal Nerve Fiber Layer Thickness for Predicting a Unilateral Optic Nerve Lesion in Multiple Sclerosis
Authors: Nolan Rachel C. , Galetta Steven L. , Frohman Teresa C. , Frohman Elliot M. , Calabresi Peter A. , Castrillo-Viguera Carmen , Cadavid Diego , Balcer Laura J. 
Published: January 2018

Background:The optic nerve is a frequent site for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects thinning of the retinal nerve fiber layer (RNFL) in eyes of patients with MS and in those meeting criteria for clinically or radiologically isolated demyelinating syndromes. Current international diagnostic criteria for MS do not include the optic nerve as an imaging lesion site despite the high prevalence of acute optic neuritis (ON), or occult optic neuropathy, among early MS and clinically isolated syndrome patients; as well as most MS patients over the course of the disease. We sought to determine optimal thresholds for intereye difference in peripapillary RNFL thickness that are most predictive of a unilateral optic nerve lesion.Methods:We analyzed spectral domain OCT data of 31 healthy volunteers and 124 patients with MS at a single center as part of an ongoing collaborative investigation of visual outcomes. Intereye differences in peripapillary (360°) RNFL thickness were calculated as the absolute value of the difference. First, we determined the 95th percentile value of intereye difference for the healthy volunteers. This value was applied to the convenience sample group of MS patients as a validation cohort determining how well this threshold could distinguish patients with vs without a history of unilateral ON. The relation of intereye differences in peripapillary RNFL thickness to binocular low-contrast letter acuity scores was also examined.Results:Among healthy volunteer participants (n = 31), the 95th percentile value for intereye difference (upper boundary of expected for normal controls) was 6.0 μm. This value was applied to the convenience sample group of MS patients (n = 124, validation cohort). Positive predictive value, negative predictive value, sensitivity, and specificity for identifying MS patients with a history of unilateral ON were calculated for the 6-μm threshold value in a 2 × 2 table analysis with the application ofχ2tests (P< 0.0001). The 6-μm threshold was predictive of worse binocular low-contrast acuity scores at 2.5% (P= 0.03) and 1.25% (P= 0.002 by linear regression analyses). A receiver operating characteristic curve analysis demonstrated an optimal intereye difference threshold of 5 μm for identifying unilateral ON in the MS cohort.Conclusions:An intereye difference of 5–6 μm in RNFL thickness is a robust structural threshold for identifying the presence of a unilateral optic nerve lesion in MS.
Data mining and classification of polycystic ovaries in pelvic ultrasound reports
Authors: Cheng J. Jojo , Mahalingaiah Shruthi 
Published: January 2018

AbstractObjectivesTo develop and evaluate the performance of a rules-based classifier and a gradient boosted tree model for automatic feature extraction and classification of polycystic ovary morphology (PCOM) in pelvic ultrasoundsMethodsPelvic ultrasound reports from patients at Boston Medical Center between October 1, 2003 and December 12, 2016 were included for analysis, which resulted in 39,093 ultrasound reports from 25,535 unique women. Following the 2003 Rotterdam Consensus Criteria for polycystic ovary syndrome, 2000 randomly selected ultrasounds were manually labeled for PCOM status as present, absent, or unidentifiable. Half of the labeled data was used as a training set, and the other half was used as a test set.ResultsOn the test set of 1000 random US reports, the accuracy of rules-based classifier (RBC) was 97.6% (95% CI: 96.5%, 98.5%) and 96.1% (94.7%, 97.2%) for the gradient boosted tree model (GBT). Both models were more adept at identifying non-PCOM ultrasounds than either unidentifiable or PCOM ultrasounds. The two classifiers estimated prevalence of PCOM within our population’s ultrasounds to be about 44%, unidentifiable 32%, and PCOM 24%.ConclusionsAlthough accuracy measured on the test set and inter-rater agreement between the two classifiers (Cohen’s Kappa = 0.988) was high, a major limitation of our approach is that it uses the ultrasound report text as a proxy and does not directly count follicles from the ultrasound images themselves.
Cocaine Self-Administration and Time-dependent Decreases in Prelimbic Activity
Authors: Dennis Torry S. , Jhou Thomas C. , McGinty Jacqueline F. 
Published: January 2018

ABSTRACTCocaine self-administration causes dephosphorylation of proteins in prelimbic (PL) cortex that mediate excitation-transcription coupling, suggesting that cocaine causes decreased activity in PL neurons. Thus, we used in vivo single-unit extracellular recordings in awake, behaving rats to measure activity in PL neurons before, during, and after cocaine self-administration on the first and last session day (range 12-14 days). On the last day, cocaine suppressed 52% of recorded neurons in the PL cortex when compared to a 20 min baseline, significantly more than the 23% of neurons suppressed on the first day of cocaine. There was no change in the percentage of neurons that were excited on the first vs. the last day of self-administration (14% vs. 13%, respectively). To determine whether the tonic inhibitory shift was induced by the behavior or by the drug itself, rats received a final session in which cocaine availability was delayed for the first 30 min or in which cocaine was administered non-contingently in the absence of levers or cues in a subset of rats. These manipulations indicated that cocaine was both necessary and sufficient to induce a downshift in PL neuronal activity. However, this activity decrease was not observed in rats that received only non-contingent cocaine for 12-14 days, indicating that contingency during self-administration training contributes to the cocaine-induced tonic downshift in PL activity. These data suggest that the session-by-session decrease in PL neuronal activity induced by cocaine is a reflection of learned drug-seeking behavior and, hence, reducing this inhibition may lessen cocaine addiction.
Honesty needs no cost: beneficial signals can be honest and evolutionarily stable
Authors: Számadó Szabolcs 
Published: January 2018

AbstractHow and why animals communicate honestly is a key issue in biology. The role of signal cost is strongly entrenched in the maintenance in honest signalling. The handicap principle claims that honest signals have to be costly at the equilibrium and this cost is a theoretical necessity. The handicap principle further claims that signalling is fundamentally different from any other adaptation because honest signalling would collapse in the absence of cost. Here I investigate this claim in simple action-response game where signals do not have any cost, instead they have benefits. I show that such beneficial signals can be honest and evolutionarily stable. These signals can be beneficial to both high and low-quality signallers independently of the receiver’s response, yet they can maintain honest signalling just as much as costly signals. Signal cost-at or out of equilibrium-is not a necessary condition of honesty. Benefit functions can maintain honest signalling as long as the marginal cost-loss of benefit-is high enough for potential cheaters.
Prospective control of movement in the basal ganglia
Authors: Lee David N. , Georgopoulos Apostolos P. , Pepping Gert-Jan 
Published: January 2018

AbstractNeural systems control purposeful movements both within an animal’s body (e.g., pumping blood) and in the environment (e.g., reaching). This is vital for all animals. The movement control functions of globus pallidus (GP), subthalamic nucleus (STN) and zona incerta (ZI) were analyzed in monkeys reaching for seen targets. Temporal profiles of their hand movements and the synchronized pattern of neuropower (rate of flow of electrochemical energy) through the basal ganglia were analyzed in terms of general tau theory of movement control (Lee et al., 2009), using the variable rho (=1/tau). The results suggest: (i) the neuroinformation for controlling movement is the relative-rate-of-change, rho, of neuropower in the nervous system; (ii) GP is involved in creating prescriptive rhos of neuropower to guide movements; (iii) STN is involved in registering perceptual rhos of neuropower to monitor the movement; (iv) ZI is involved in combining the prescriptive and perceptual rhos of neuropower to generate performatory rhos of neuropower to activate the muscles to produce the movement. Possible implications for Parkinson’s disease are discussed.
Reconciling S-LDSC and LDAK models and functional enrichment estimates
Authors: Gazal Steven , Marquez-Luna Carla , Finucane Hilary K. , Price Alkes L. 
Published: January 2018

AbstractRecent work has highlighted the importance of accounting for linkage disequilibrium (LD)-dependent genetic architectures in analyses of heritability, motivating the development of the baseline-LD model used by stratified LD score regression (S-LDSC) and the LDAK model. Although both models include LD-dependent effects, they produce very different estimates of functional enrichment (with larger estimates using the baseline-LD model), leading to different interpretations of the functional architecture of complex traits. Here, we perform formal model comparisons and empirical analyses to reconcile these findings. First, by performing model comparisons using a likelihood approach, we determined that the baseline-LD model attains likelihoods across 16 UK Biobank traits that are substantially higher than the LDAK model. Second, we determined that S-LDSC using a combined model (unlike methods that use the LDAK or baseline-LD models) produces robust enrichment estimates in simulations under both the LDAK and baseline-LD models, validating the combined model as a gold standard. Third, in analyses of 16 UK Biobank traits, we determined that enrichment estimates obtained by S-LDSC using the combined model were nearly identical to those obtained by S-LDSC using the baseline-LD model (concordance correlation coefficient ρc = 0.99), but were larger than those obtained using LDAK (ρc = 0.54). Notably, LDAK enrichment estimates were much higher for a non-default version of LDAK that models SNPs in perfect LD differently by assigning non-zero weights to all SNPs. Our results support the use of the baseline-LD model and confirm the existence of functional annotations that are highly enriched for complex trait heritability.
Escherichia coliβ-clamp slows down DNA polymerase I dependent nick translation while accelerating ligation
Authors: Bhardwaj Amit , Ghose Debarghya , Thakur Krishan Gopal , Dutta Dipak 
Published: January 2018

AbstractThe nick translation property of DNA polymerase I (Pol I) ensures the maturation of Okazaki fragments by removing primer RNAs and facilitating ligation. However, prolonged nick translation traversing downstream DNA is an energy wasting futile process, as Pol I simultaneously polymerizes and depolymerizes at the nick sites utilizing energy-rich dNTPs. Using anin vitroassay system, we demonstrate that the β-clamp of theEscherichia colireplisome strongly inhibits nick translation on the DNA substrate. To do so, β-clamp inhibits the strand displacement activity of Pol I by interfering with the interaction between the finger subdomain of Pol I and the downstream primer-template junction. Conversely, β-clamp stimulates the 5’ exonuclease property of Pol I to cleave single nucleotides or shorter oligonucleotide flaps. This single nucleotide flap removal at high frequency increases the probability of ligation between the upstream and downstream DNA strands at an early phase, terminating nick translation. Besides β-clamp-mediated ligation helps DNA ligase to seal the nick promptly during the maturation of Okazaki fragments.
CozEa and CozEb play overlapping and essential roles in controlling cell division inStaphylococcus aureus
Authors: Stamsås Gro Anita , Myrbråten Ine Storaker , Straume Daniel , Salehian Zhian , Veening Jan-Willem , Håvarstein Leiv Sigve , Kjos Morten 
Published: January 2018

SummaryStaphylococcus aureusneeds to control the position and timing of cell division and cell wall synthesis to maintain its spherical shape. We identified two membrane proteins, named CozEa and CozEb, which together are important for proper cell division inS. aureus. CozEa and CozEb are homologs of the cell elongation regulator CozESpnofStreptococcus pneumoniae. WhilecozEaandcozEbwere not essential individually, the ΔcozEaΔcozEbdouble mutant was lethal. To study the functions ofcozEaandcozEb, we constructed a CRISPR interference (CRISPRi) system forS. aureus, allowing transcriptional knockdown of essential genes. CRISPRi knockdown ofcozEain the ΔcozEbstrain (and vice versa) causes cell morphological defects and aberrant nucleoid staining, showing thatcozEaandcozEbhave overlapping functions and are important for normal cell division. We found that CozEa and CozEb interact with the cell division protein EzrA, and that EzrA-GFP mislocalizes in the absence of CozEa and CozEb. Furthermore, the CozE-EzrA interaction is conserved inS. pneumoniae, and cell division is mislocalized incozESpn-depletedS. pneumoniaecells. Together, our results show that CozE proteins mediate control of cell division inS. aureusandS. pneumoniae, likely via interactions with key cell division proteins such as EzrA.
Sequence Alignment Through the Looking Glass
Authors: Appuswamy Raja , Fellay Jacques , Chaturvedi Nimisha 
Published: January 2018

AbstractRapid advances in sequencing technologies are producing genomic data on an unprecedented scale. The first, and often one of the most time consuming, step of genomic data analysis is sequence alignment, where sequenced reads must be aligned to a reference genome. Several years of research on alignment algorithms has led to the development of several state-of-the-art sequence aligners that can map tens of thousands of reads per second.In this work, we answer the question “How do sequence aligners utilize modern processors?” We examine four state-of-the-art aligners running on an Intel processor and identify that all aligners leave the processor substantially underutilized. We perform an in-depth microarchitectural analysis to explore the interaction between aligner software and processor hardware. We identify bottlenecks that lead to processor underutilization and discuss the implications of our analysis on next-generation sequence aligner design.
Balancing self/collective-interest: equity theory for prosocial consumption
Authors: M. Ross Spencer , Kapitan Sommer 
Published: January 2018

Purpose
This work aims to use equity theory to explore how consumers assess prosocial actions as part of a mental portfolio of purchases and behaviors in a broader marketplace, seeking balance in market exchanges. Conceptualizing marketing exchange as both an exchange of perceived value and a balance between self- and collective-interest allows for segmentation by consumer sensitivity to equity and sheds light on why prosocial consumption might occur.

Design/methodology/approach
Two studies validate and segment consumers via their equity sensitivity. Between-subject designs with samples of consumers and marketing managers validate an equity sensitivity index that segments how people balance self- and collective-interests in marketplace exchange and predicts prosocial consumption choices.

Findings
The results indicate that Entitled decision makers are more willing to exchange collective-interest for self-interest and emphasize choices that maximize lower prices for consumers or greater profits for firms in lieu of prosocial outcomes. Benevolent decision makers, however, are more willing to exchange self-interest for collective-interest and support prosocial outcomes.

Originality/value
This work moves beyond research that focuses on attitudes, values and situational factors, instead using equity theory to uncover broader marketplace motivations for prosocial consumption. The research reveals that a motivating force behind prosocial consumption is how much consumers perceive they have given to, and gotten, from, the marketplace. Segmenting the market according to how consumers balance gains and losses provides an alternate approach to studying prosocial consumption, as well as a practical approach to developing targeted marketing strategies.
Authentic leadership and work engagement: the mediating effect of practicing core values
Authors: Oh Jihye , Cho Daeyeon , Lim Doo Hun 
Published: January 2018

Purpose
The purpose of this paper is to investigate the mediating effect of practicing core values on the relationship between authentic leadership and work engagement in a Korean corporate environment.

Design/methodology/approach
Self-report data on authentic leadership, practicing core values, and work engagement were obtained from 281 employees of three major corporations in South Korea. Structural equation modeling was adopted to analyze the data.

Findings
The results revealed a direct and significant influence of authentic leadership on both practicing core values and work engagement. In addition, practicing core values was found to have a partial mediating effect on the relationship between authentic leadership and work engagement.

Research limitations/implications
This study revealed a three-factor model of authentic leadership compared to the four-factor model found in western cultural contexts. Similar findings are indicated for other Asian countries. A rigorous future study is warranted to validate the psychometric structure across different cultural settings. Harman’s single factor test was performed to address the common method variance issue.

Practical implications
Practicing core values functioned as a catalyst for developing authentic leaders. Therefore, it is necessary that organizational development practitioners perform developmental activities to purposefully facilitate practicing core values.

Originality/value
The study falls under the isolated or disregarded researched topic of the practicing core values in relation to authentic leadership and work engagement.