bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effective Fixation Level for Cosmetic Lateral Canthoplasty
Authors: Cho Young Kyoo , Suh Bo Ik , Park Kwang Min 
Published: March 2019

Background:
In previous reports of lateral canthoplasty, the components of the inferior retinaculum were mostly secured to the lateral orbital rim at a level around the pupil or superior limbus. However, that level is not adjustable in young patients who want to lengthen the short palpebral fissure for cosmetic purposes. Moreover, the anchoring method based on the palpebral portion can also be inconvenient and ineffective. Thus, the authors report an effective fixation level of the lateral orbital rim to lengthen and widen the lateral palpebral fissure.

Methods:
From June 2015 to August 2017, 202 women and 44 men underwent cosmetic lateral canthoplasty (mean age 28.4 ± 2.8 years old). The lower lid component of the lateral retinaculum was identified and selectively released through a small incision at the lateral commissure. Then, the released retinaculum was secured to the periosteum of the inner aspect of the lateral orbital wall. The fixation level corresponded to the most concave portion or immediately below the most concave point (1 to 2 mm below).

Results:
Cosmetic lateral canthoplasty was successfully performed in all cases. No severe complications were observed. There were some minor complications. In most cases, the lateral palpebral fissure was naturally reshaped into a wider and brighter contour. Almost all of the patients were satisfied with the results of the treatment.

Conclusions:
The anchoring procedure at the most concave portion of the lateral orbital rim, which corresponds to the level of the inferior edge of the limbus or medial epicanthus, consistently resulted in a brighter and wider shape of the lateral palpebral fissure. Fixation based on the bony portion, compared to palpebral portion, offers several advantages as follows: effective lengthening and widening the lateral palpebral fissure; ease of application; symmetry with consistent final results; and minimal occurrences of overcorrection and undercorrection.
Effect of Septoplasty On Voice Performance: Nasalance and Acoustic Study
Authors: Hernández-García Estefanía , Moro-Velazquez Laureano , González-Herranz Ramón , Lara Antonio , Godino-Llorente Juan Ignacio , Plaza Guillermo 
Published: March 2019

Background:
Septoplasty is a surgical technique for the correction of the nasal septum that may alter the vocal tract. The aim of our study is to assess whether this technique modifies nasalance and acoustic parameters, and their clinical implications in voice perception.

Methodology:
A prospective study was performed between January 2017 and June 2017 including 2 groups of patients: those undergoing septoplasty, and a control group. Subjective nasality questionnaire, objective nasalance with nasometer, and GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) assessment were statistically analysed. In addition, a recording of patients’ voices was made with a subsequent acoustic analysis. Samples were taken: pre-surgically, 2 weeks after surgery and after 3 months.

Results:
After septoplasty, a significant difference was observed in GRBAS, nasality questionnaire and nasometer nasalance, when compared with the control group. As for the acoustic analysis, no differences were observed in most parameters (F0, Jitter, Shimmer, HNR, NHR, Formants F1-F3), except for the antiF3 antiformant, which showed significant changes in all the vowels studied.

Conclusions:
Septoplasty can produce changes in the vocal tract, with an increase in initial nasalance but with subsequent normalization. Besides, minor changes were found in the acoustic analysis but with no clinical relevance.
Impact of Sleep Deprivation on Surgical Laparoscopic Performance in Novices: A Computer-based Crossover Study
Authors: Leu Svenja , Staerkle Ralph F. , Gaukel Stefan , Fink Lukas , Soll Christopher , Aasen Davis M. , Liechty Kenneth , Vitz Martina , Ramseier Leonhard E. , Vuille-dit-Bille Raphael N. 
Published: March 2019

Objective:
The 24-hour work shifts are newly permitted to first-year surgical residents in the United States. Whether surgery novices’ motor activity is affected by sleep deprivation is controversial.

Materials and Methods:
This study assesses sleep deprivation effects in computer-simulated laparoscopy in 20 surgical novices following 24 hours of sleep deprivation and after resting using a virtual-reality trainer. Participants were randomly assigned to perform simulator tests either well rested or sleep deprived first.

Results:
Of 3 different tasks performed, no significant differences in total time to complete the procedure and average speed of instruments were found. Instrument path length was longer following sleep deprivation (P=0.0435) in 1 of 3 tasks. Error rates (ie, noncauterized bleedings, perforations, etc.), as well as precision, and accuracy rates showed no difference. None of the assessed participants’ characteristics affected simulator performance.

Conclusions:
Twenty-four hours of sleep deprivation does not affect laparoscopic performance of surgical novices as assessed by computer-simulation.
SimRVSequences: an R package to simulate genetic sequence data for pedigrees
Authors: Nieuwoudt Christina , Brooks-Wilson Angela , Graham Jinko 
Published: March 2019

1AbstractSummaryFamily-based studies have several advantages over case-control studies for finding causal rare variants for a disease; these include increased power, smaller sample size requirements, and improved detection of sequencing errors. However, collecting suitable families and compiling their data is time-consuming and expensive. To evaluate methodology to identify causal rare variants in family-based studies, one can use simulated data. For this purpose we present the R package SimRVSequences. Users supply a sample of pedigrees and single-nucleotide variant data from a sample of unrelated individuals representing the pedigree founders. Users may also model genetic heterogeneity among families. For ease of use, SimRVSequences offers methods to import and format single-nucleotide variant data and pedigrees from existing software.Availability and ImplementationSimRVSequences is available as a library for R≥ 3.5.0 on the comprehensive R archive network.
Chronic unpredictable stress promotes cell-specific plasticity in prefrontal cortex D1 and D2 pyramidal neurons
Authors: Anderson EM , Gomez D , Caccamise A , McPhail D , Hearing M 
Published: March 2019

AbstractExposure to unpredictable environmental stress is widely recognized as a major determinant for risk and severity in neuropsychiatric disorders such as major depressive disorder, anxiety, schizophrenia, and PTSD. The ability of ostensibly unrelated disorders to give rise to seemingly similar psychiatric phenotypes highlights a need to identify circuit-level concepts that could unify diverse factors under a common pathophysiology. Although difficult to disentangle a causative effect of stress from other factors on medial prefrontal cortex (PFC) dysfunction, a wealth of data from humans and rodents demonstrates that the PFC is a key target of stress. The present study sought to identify a model of chronic unpredictable stress (CUS) which induces affective behaviors in C57BL6J mice and once established, measure spike firing and the ability to evoke an action potential in mPFC layer 5/6 pyramidal neurons. Adult male mice received 2 weeks of ‘less intense’ stress or 2 or 4 weeks of ‘more intense’ CUS followed by sucrose preference for assessment of anhedonia, elevated plus maze for assessment of anxiety and forced swim test for assessment of depressive-like behaviors. Our findings indicate that more intense CUS exposure results in increased anhedonia, anxiety, and depressive behaviors, while the less intense stress results in no measured behavioral phenotypes. Once a behavioral model was established, mice were euthanized approximately 21 days post-stress for whole-cell patch clamp recordings from layer 5/6 pyramidal neurons in the prelimbic (PrL) and infralimbic (IL) cortices. No significant differences were initially observed in intrinsic cell excitability in either region. However, post-hoc analysis and subsequent confirmation using transgenic mice expressing tdtomato or eGFP under control of dopamine D1- or D2-type receptor showed that D1-expressing pyramidal neurons (D1-PYR) in the PrL exhibit reduced thresholds to fire an action potential (increased excitability) but impaired firing capacity at more depolarized potentials, whereas D2-expressing pyramidal neurons showed an overall reduction in excitability and spike firing frequency. Examination of synaptic transmission showed that D1- and D2-PYR in exhibit differences in basal excitatory and inhibitory signaling under naïve conditions. In CUS mice, D1-PYR showed increased frequency of both miniature excitatory and inhibitory postsynaptic currents, whereas D2-PYR only showed a reduction in excitatory currents. These findings demonstrate that the intrinsic physiology and synaptic regulation of D1- and D2-PYR subpopulations differentially undergo stress-induced plasticity that may have functional implications for stress-related pathology, and that these adaptations may reflect unique differences in basal properties regulating output of these cells.
The role of insulators in transgene transvection inDrosophila
Authors: Piwko Pawel , Vitsaki Ilektra , Livadaras Ioannis , Delidakis Christos 
Published: March 2019

AbstractTransvection is the phenomenon where a transcriptional enhancer activates a promoter located on the homologous chromosome. It has been amply documented inDrosophilawhere homologues are closely paired in most, if not all, somatic nuclei, but it has been known to rarely occur in mammals as well. We have taken advantage of site-directed transgenesis to insert reporter constructs into the same genetic locus inDrosophilaand have evaluated their ability to engage in transvection by testing many heterozygous combinations. We find that transvection requires the presence of an insulator element on both homologues. Homotypictrans-interactions between four different insulators can support transvection: thegypsy insulator(GI),Wari, Fab-8and1A2;GIandFab-8are more effective thanWarior1A2. We show that in the presence of insulators, transvection displays the characteristics that have been previously described: it requires homologue pairing, but can happen at any of several loci in the genome; a solitary enhancer confronted with an enhancerless reporter is sufficient to drive transcription; it is weaker than the action of the same enhancer-promoter pair incisand it is further suppressed bycis-promoter competition. Though necessary, the presence of homotypic insulators is not sufficient for transvection; their position, number and orientation matters. A single GI adjacent to both enhancer and promoter is the optimal configuration. The addition of a heterologous insulator in one homolog can positively or negatively influence transvection strength. The local landscape of enhancers and promoters is also important, indicative of complex insulator-enhancer-promoter interactions.
Hierarchical clustering of gene-level association statistics reveals shared and differential genetic architecture among traits in the UK Biobank
Authors: McGuirl Melissa R. , Pattillo Smith Samuel , Sandstede Björn , Ramachandran Sohini 
Published: March 2019

AbstractGenome-wide association (GWA) studies have generally focused on a single phenotype of interest. Emerging biobanks that pair genotype data from thousands of individuals with phenotype data using medical records or surveys enable testing for genetic associations in each phenotype assayed. However, methods for characterizing shared genetic architecture among multiple traits are lagging behind. Here, we present a new method, Ward clustering to identify Internal Node branch length outliers using Gene Scores (WINGS), for characterizing shared and divergent genetic architecture among multiple phenotypes. The objective of WINGS (freely available athttps://github.com/ramachandran-lab/PEGASUS-WINGS) is to identify groups of phenotypes, or “clusters”, that share a core set of genes enriched for mutations in cases. We show in simulations that WINGS can reliably detect phenotype clusters across a range of percent shared architecture and number of phenotypes included. We then use the gene-level association test PEGASUS with WINGS to characterize shared genetic architecture among 87 case-control and seven quantitative phenotypes in 349,468 unrelated European-ancestry individuals from the UK Biobank. We identify 10 significant phenotype clusters that contain two to eight phenotypes. One significant cluster of seven immunological phenotypes is driven by seven genes; these genes have each been associated with two or more of those same phenotypes in past publications. WINGS offers a precise and efficient new application of Ward hierarchical clustering to generate hypotheses regarding shared genetic architecture among phenotypes in the biobank era.
Shifted distribution baselines: neglecting long-term biodiversity records risks overlooking potentially suitable habitat for conservation management
Authors: Monsarrat Sophie , Novellie Peter , Rushworth Ian , Kerley Graham 
Published: March 2019

ABSTRACTSetting appropriate conservation measures to halt the loss of biodiversity requires a good understanding of species’ habitat requirements and potential distribution. Recent (past few decades) ecological data are typically used to estimate and understand species’ ecological niche. However, historical local extinctions may have truncated species-environment relationships, resulting in a biased perception of species’ habitat preferences. This may result in incorrect assessments of the area potentially available for their conservation. Incorporating long-term (centuries-old) occurrence records with recent records may provide better information on species-environment relationships and improve the modeling and understanding of habitat suitability. We test whether neglecting long-term occurrence records leads to an underestimation of species’ historical niche and potential distribution and identify which species are more vulnerable to this effect. We compare outputs of species distribution models and niche hypervolumes built using recent records only with those built using both recent and long-term (post-1500) records, for a set of 34 large mammal species in South Africa. We find that, while using recent records only is adequate for some species, adding historical records in the analyses impacts estimates of the niche and habitat suitability for fourteen species (41%) in our dataset, and that this effect is significantly higher for carnivores. These results show that neglecting long-term biodiversity records in spatial analyses risks misunderstanding, and generally underestimating, species’ niche, which in turn may lead to ill-informed management decisions, with significant implications for the effectiveness of conservation efforts.
The nonlinear structure of linkage disequilibrium
Authors: Smith Reginald D. 
Published: March 2019

AbstractThe allele frequency dependence of the ranges of all measures of linkage disequilibrium is well-known. The maximum values of commonly used parameters such asr2andDvary depending on the allele frequencies at each locus. However, though this phenomenon is recognized and accounted for in many studies, the comprehensive mathematical framework underlying the limits of linkage disequilibrium measures at various frequency combinations is often heuristic or empirical. Here, it is demonstrated that underlying this behavior is the fundamental shift between linear and nonlinear dependence in the linkage disequilibrium structure between loci. The proportion of linear and nonlinear dependence can be estimated and it demonstrates how even the same values ofr2can have different implications for the nature of the overall dependence. One result of this is the value ofD′, when defined as only a positive number, has a minimum value of |r|. Understanding this dependence is crucial to making correct inferences about the relationships between two loci in linkage disequilibrium.
A Novel and Efficient Approach for Screening Cancer Cell Specific Monoclonal Antibodies
Authors: Pei Xin-Hui 
Published: March 2019

AbstractCancer cell specific antibodies are pivotal tools in developing new immunotherapies for treating cancers. However, acquirement of cancer cell specific antibodies is time-consuming and often arduous. To circumvent such a barrier, we developed a novel antibody-screening method that can be used to efficiently produce cancer cell specific antibodies by an ‘antibody filter’ mechanism. First, we used normal human cells to perform the immunization in mice and collected the antisera. Second, we used human cancer cells together with the antisera against normal human cells to immunize another batch of mice. Theoretically, the antisera were able to neutralize the antigens from normal human cells, and therefore specific antigens only expressed in cancer cells could take advantage of the immunization. Third, we screened positive clones that are specific for cancer cells but not normal cells. Using this conceptual method, we successfully obtained 11 monoclonal antibodies that are specific for a human liver cancer cells line (HepG2) but not for a normal human liver cell line (HH). In addition, these clones failed to recognize other human cancer cells originated from different tissues, further highlighting the specificity. Collectively, we provide a novel and effective approach for screening cancer cell specific monoclonal antibodies, which may significantly facilitate the development of new anti-cancer therapeutics.
Complex polymorphic genetic architecture underlies trans-regulatory variation among strains of Saccharomyces cerevisiae
Authors: Metzger Brian P. H. , Wittkopp Patricia J. 
Published: March 2019

AbstractHeritable variation in gene expression is common within species. Much of this variation is due to genetic changes at loci other than the affected gene and is thus trans-acting. This trans-regulatory variation is often polygenic, with individual variants typically having small effects, making the genetic architecture of trans-regulatory variation challenging to study. Consequently, key questions about trans-regulatory variation remain, including how selection affects this variation and how trans-regulatory variants are distributed throughout the genome and within species. Here, we show that trans-regulatory variation affecting TDH3 promoter activity is common among strains of Saccharomyces cerevisiae. Comparing this variation to neutral models of trans-regulatory evolution based on empirical measures of mutational effects revealed that stabilizing selection has constrained this variation. Using a powerful quantitative trait locus (QTL) mapping method, we identified ∼100 loci altering expression between a reference strain and each of three genetically distinct strains. In all three cases, the non-reference strain alleles increased and decreased TDH3 promoter activity with similar frequencies, suggesting that stabilizing selection maintained many trans-acting variants with opposing effects. Loci altering expression were located throughout the genome, with many loci being strain specific and others being shared among multiple strains. These findings are consistent with theory showing stabilizing selection for quantitative traits can maintain many alleles with opposing effects, and the wide-spread distribution of QTL throughout the genome is consistent with the omnigenic model of complex trait variation. Furthermore, the prevalence of alleles with opposing effects might provide raw material for compensatory evolution and developmental systems drift.Significance statementGene expression varies among individuals in a population due to genetic differences in regulatory components. To determine how this variation is distributed within genomes and species, we used a powerful genetic mapping approach to examine multiple strains of Saccharomyces cerevisiae. Despite evidence of stabilizing selection maintaining gene expression levels among strains, we find hundreds of loci that affect expression of a single gene. These loci vary among strains and include similar frequencies of alleles that increase and decrease expression. As a result, each strain contains a unique set of compensatory alleles that lead to similar levels of gene expression among strains. This regulatory variation might form the basis for large scale regulatory rewiring observed between distantly related species.
Dynamics and Internal Control of Body Temperature in Response to Infectious Agents and Other Causal Factors
Authors: Schaper Charles D. 
Published: March 2019

AbstractThermoregulation is crucial to homeostasis, but the mechanisms of its dysfunction are still largely mysterious, including fever, which is generally the most disconcerting sign of a serious infection or disease. Theories on body temperature dynamics that aim to explain a fever, such as changes in an internal setpoint, have been proposed, but none can identify the fundamental molecular pathways that produce a fever. Here, potential molecular pathways resultant in fever are identified, modeled, and compared to experimental temperature response data. Based on recent developments made by this lab, which has shown that the pyrogen prostaglandin E2 (PGE2) possesses similar binding affinity as the hormone cortisol (CORT) at the critical ligand binding domain (LBD) of glucocorticoid receptors (GR); molecular modeling, mathematical modeling and a case study for validation is used to indicate that competitive inhibition of CORT by PGE2 as a fundamental reason for dysfunctional dynamics of body temperature, including fever. Comprised of a superposition of proportional and derivative terms of signals representing temperature receptors, CORT concentration, and PGE2 concentration, the internal temperature control model characterizes dynamics associated with the cardiovascular, immune, and neural systems in response to infectious agents, triggering events, and other causal factors. The model is validated by examination of the transient and spectral characteristics of a three-day case history involving temperature trajectories after physical activity protocols in response to a standard vaccination of pneumococcal and influenza species.
Genes essential for embryonic stem cells are associated with neurodevelopmental disorders
Authors: Shohat Shahar , Shifman Sagiv 
Published: March 2019

AbstractMouse embryonic stem cells (mESCs) are a key component in generating mouse models for human diseases and performing basic research on pluripotency, but how many genes are essential for mESCs is still unknown. We performed a genome-wide screen for essential genes in mESCs and compared it to human cells. We found that essential genes are enriched for basic cellular functions, are highly expressed in mESCs, and tend to lack paralog genes. Notably, we discovered that genes that are essential specifically in mESCs play a role in pathways associated with their pluripotent state. We show that 25% of human genes that are intolerant to loss-of-function mutations are essential in mouse or human ESCs and that the human phenotypes most significantly associated with essential genes are neurodevelopmental. Our results provide insights into essential genes in the mouse, the pathways which govern pluripotency, and suggest that many genes associated with neurodevelopmental disorders are essential at very early embryonic stages.