bluuebunny/crossref_metadata_2025 huggingface dataset:
First records of polycyclic aromatic hydrocarbons and metals in sediments from a shallow lake in the Pampean–Patagonian region (Argentina)
Authors: Oliva Ana L. , La Colla Noelia S. , Arias Andrés H. , Botté Sandra E. , Perillo Gerardo M. E. , Piccolo M. Cintia
Published: April 2019

This study evaluated, for the first time, organic and metal contaminants in sediments from Argentinean saline lakes, specifically La Salada shallow lake, a small polymictic lake on the south border of the Pampean region. The concentration of 16 priority polycyclic aromatic hydrocarbons (PAHs) and 8 metals (Cd, Cu, Cr, Fe, Mn, Ni, Pb and Zn) was assessed and the ecotoxicological effects of these pollutants were examined. The total concentration of the 16 PAHs ranged from 12.55 to 10679.48ngg–1 dry weight, with a predominance of four-ringed PAHs. Molecular ratio analysis showed pyrolytic sources as the main source of PAHs. Among the metals, Mn, Fe and Zn had the highest concentrations in sediments. General metal levels revealed a multiplicity of point sources and rock weathering as their main source. Regarding the potential ecotoxicological effects, adverse effects may be expected from PAHs because several compounds exceeded the sediment quality guidelines threshold effect level and likely effect level. Conversely, metal levels were below levels specified in safety guidelines. These results are interpreted in an international context, providing information that addresses a gap in the pollution record of Argentinean lakes, and should have strong implications for future planning management.
Climate models can correctly simulate the continuum of global-average temperature variability
Authors: Zhu Feng , Emile-Geay Julien , McKay Nicholas P. , Hakim Gregory J. , Khider Deborah , Ault Toby R. , Steig Eric J. , Dee Sylvia , Kirchner James W.
Published: April 2019

Significance

Climate models are foundational to formulations of climate policy and must successfully reproduce key features of the climate system. The temporal spectrum of observed global surface temperature is one such critical benchmark. This spectrum is known to obey scaling laws connecting astronomical forcings, from orbital to annual scales. We provide evidence that the current hierarchy of climate models is capable of reproducing the increase in variance in global-mean temperature at low frequencies. We suggest that successful climate predictions at decadal-to-centennial horizons hinge critically on the accuracy of initial and boundary conditions, particularly for the deep ocean state.
Competitive binding predicts nonlinear responses of olfactory receptors to complex mixtures
Authors: Singh Vijay , Murphy Nicolle R. , Balasubramanian Vijay , Mainland Joel D.
Published: April 2019

In color vision, the quantitative rules for mixing lights to make a target color are well understood. By contrast, the rules for mixing odorants to make a target odor remain elusive. A solution to this problem in vision relied on characterizing receptor responses to different wavelengths of light and subsequently relating these responses to perception. In olfaction, experimentally measuring receptor responses to a representative set of complex mixtures is intractable due to the vast number of possibilities. To meet this challenge, we develop a biophysical model that predicts mammalian receptor responses to complex mixtures using responses to single odorants. The dominant nonlinearity in our model is competitive binding (CB): Only one odorant molecule can attach to a receptor binding site at a time. This simple framework predicts receptor responses to mixtures of up to 12 monomolecular odorants to within 15% of experimental observations and provides a powerful method for leveraging limited experimental data. Simple extensions of our model describe phenomena such as synergy, overshadowing, and inhibition. We demonstrate that the presence of such interactions can be identified via systematic deviations from the competitive-binding model.
Dating glacier ice of the last millennium by quantum technology
Authors: Feng Zhongyi , Bohleber Pascal , Ebser Sven , Ringena Lisa , Schmidt Maximilian , Kersting Arne , Hopkins Philip , Hoffmann Helene , Fischer Andrea , Aeschbach Werner , Oberthaler Markus K.
Published: April 2019

Significance

Alpine summit glaciers have a characteristic age range between 100 and 1,000 years. Reliable dating is the key to access this valuable environmental archive, including the Little Ice Age. Glacier ice contains past air and thus also the rare radioisotope
39
Ar, uniquely suitable as an age tracer for this time span. Only argon trap trace analysis (ArTTA), the adaptation of techniques from quantum optics to
39
Ar, enables small sample sizes necessary for the application to glacier ice. We present the first dating of glacier ice using less than 2 mL STP of argon from ∼5 kg of ice, finally opening the door for radioargon dating in glaciology.
Causal inference accounts for heading perception in the presence of object motion
Authors: Dokka Kalpana , Park Hyeshin , Jansen Michael , DeAngelis Gregory C. , Angelaki Dora E.
Published: April 2019

Significance

A moving observer faces an interpretational challenge when the visual scene contains independently moving objects. To correctly judge their direction of self-motion (heading), an observer must appropriately infer the causes of retinal image motion. We demonstrate that perception of object motion systematically influences heading judgments. When a moving object was erroneously perceived to be stationary in the world, heading judgments were significantly biased. On the contrary, when the object was correctly perceived to be moving, biases in heading estimates declined dramatically. Our results thus suggest that the brain makes inferences about sources of image motion using causal inference computations.
Electrically induced bacterial membrane-potential dynamics correspond to cellular proliferation capacity
Authors: Stratford James P. , Edwards Conor L. A. , Ghanshyam Manjari J. , Malyshev Dmitry , Delise Marco A. , Hayashi Yoshikatsu , Asally Munehiro
Published: April 2019

Significance

Transmembrane voltage in bacteria plays a central role both in electrical signaling and cell proliferation. However, whether proliferation state influences the response to electrical signals was unknown. Combining fluorescence time-lapse microscopy with a bespoke device and mathematical modeling, we show that proliferative and inhibited cells respond in opposite directions to an identical electrical signal. The response differentiation can be seen within a minute after stimulation. Therefore, our findings offer an approach for rapid detection of proliferative bacteria at the single-cell level.
Topic prominence in L2 acquisition
Authors: Gong Zhiqi
Published: April 2019

This study investigated the topic-prominent characteristics of the interlanguage development of native speakers of Chinese learning English as a foreign language (EFL). Two groups of Chinese EFL learners – an intermediate group and an advanced group – were recruited to complete two production tasks: a written Chinese-to-English translation task and an oral story-retelling task. The findings showed that Chinese EFL learners at each proficiency level transferred Chinese topic-prominent structures to their target language production at a varying degree. The topic-prominent constructions in the learners’ production, based on a hierarchy of difficulty, were placed on two slightly different Gradation Zones, one for written production and the other for oral production. Gradation Zones were a generalized reflection of how discourse and pragmatic relations in topic-prominent Chinese were gradually reanalyzed as syntactic relations with the development of learners’ English proficiency level. There was a tendency for topic-prominent features to decrease and subject-prominent features to increase as EFL learners’ proficiency level progressed. It was also argued that sources of these topic-prominent properties in interlanguage were an interaction of factors, including degree of markedness, perceptual saliency, second language (L2) input, and language production task type.
Time Changes of the Brownian Motion: Poincaré Inequality, Heat Kernel Estimate and Protodistance
Authors: Kigami Jun
Published: April 2019

In this paper, time changes of the Brownian motions on generalized Sierpinski carpets including

n
n

-dimensional cube

[
0
,
1

]
n

[0, 1]^n

are studied. Intuitively time change corresponds to alteration to density of the medium where the heat flows. In case of the Brownian motion on

[
0
,
1

]
n

[0, 1]^n

, density of the medium is homogeneous and represented by the Lebesgue measure. Our study includes densities which are singular to the homogeneous one. We establish a rich class of measures called measures having weak exponential decay. This class contains measures which are singular to the homogeneous one such as Liouville measures on

[
0
,
1

]
2

[0, 1]^2

and self-similar measures. We are going to show the existence of time changed process and associated jointly continuous heat kernel for this class of measures. Furthermore, we obtain diagonal lower and upper estimates of the heat kernel as time tends to

0
0

. In particular, to express the principal part of the lower diagonal heat kernel estimate, we introduce “protodistance”associated with the density as a substitute of ordinary metric. If the density has the volume doubling property with respect to the Euclidean metric, the protodistance is shown to produce metrics under which upper off-diagonal sub-Gaussian heat kernel estimate and lower near diagonal heat kernel estimate will be shown.
A Dictionary of Contemporary World History
Authors: Riches Christopher , Palmowski Jan
Published: April 2019

‘Concise, current information … highly recommended’ – Choice, the magazine of the American Library Association

Over 2,800 entries

The authoritative dictionary provides informative and analytical entries on the most important people, organizations, events, movements, and ideas that have shaped the world we live in. Covering the period from 1900 to the present day, this fully revised and updated new edition presents a global perspective on recent history, with a wide range of new entries from Tony Abbott, the European migration crisis, and ISIS to Narendra Modi, Hassan Rouhani, and UKIP. All existing entries have been brought up to date. Handy tables include lists of office-holders for countries and organizations and winners of the Nobel Peace Prize.

This comprehensive reference resource will be invaluable to students of history, politics, and international relations as well as to journalists, policymakers, and general readers interested in the modern world.
Optimal Facelift Vector and its Relation to Zygomaticus Major Orientation
Authors: Jacono Andrew A , Bryant Lucas M , Alemi A Sean
Published: April 2019

Background

The vector of superficial musculoaponeurotic system (SMAS) redraping in rhytidectomy is often described in relation to the zygomaticus major muscle (ZMM), so that suspension prevents distortion of the mimetic musculature and a “facelifted appearance.” There are no data describing the true orientation of this muscle in the midface.

Objectives

The aim of this study was to define the vector of the ZMM relative to the Frankfort horizontal plane.

Methods

One hundred patients underwent deep plane rhytidectomy. As part of this procedure the tissues overlying the ZMM are elevated, allowing muscle orientation to be measured as an angle relative to the Frankfort horizontal plane.

Results

Data for 200 hemifaces were aggregated. The average ZMM angle was 59° (standard deviation, 6°; range, 41–72°) relative to the Frankfort horizontal plane, and showed a statistically significant pattern of change with advancing age, becoming more acute with increasing age below the age of 60 years and more obtuse with age over 60 years.

Conclusions

The native vector of the ZMM varies significantly between rhytidectomy patients as demonstrated by the high variance in this cohort. Assumptions about its orientation should not be made in rhytidectomy techniques that do not identify its course. Standard vectors of SMAS redraping, such as superior-lateral, vertically oblique, and purely vertical, should be reconsidered and a customized vector implemented in each case. Aging affects the orientation of the muscle, which can potentially be explained by soft tissue and bony changes at its attachments. This furthers the variability of the SMAS vector in each individual case.

Level of Evidence: 4
Continuous-state HMMs for modeling time-series single-cell RNA-Seq data
Authors: Lin Chieh , Bar-Joseph Ziv
Published: April 2019

Motivation

Methods for reconstructing developmental trajectories from time-series single-cell RNA-Seq (scRNA-Seq) data can be largely divided into two categories. The first, often referred to as pseudotime ordering methods are deterministic and rely on dimensionality reduction followed by an ordering step. The second learns a probabilistic branching model to represent the developmental process. While both types have been successful, each suffers from shortcomings that can impact their accuracy.

Results

We developed a new method based on continuous-state HMMs (CSHMMs) for representing and modeling time-series scRNA-Seq data. We define the CSHMM model and provide efficient learning and inference algorithms which allow the method to determine both the structure of the branching process and the assignment of cells to these branches. Analyzing several developmental single-cell datasets, we show that the CSHMM method accurately infers branching topology and correctly and continuously assign cells to paths, improving upon prior methods proposed for this task. Analysis of genes based on the continuous cell assignment identifies known and novel markers for different cell types.

Availability and implementation

Software and Supporting website: www.andrew.cmu.edu/user/chiehl1/CSHMM/

Supplementary information

Supplementary data are available at Bioinformatics online.
Dynamical important residue network (DIRN): network inference via conformational change
Authors: Li Quan , Luo Ray , Chen Hai-Feng
Published: April 2019

Motivation

Protein residue interaction network has emerged as a useful strategy to understand the complex relationship between protein structures and functions and how functions are regulated. In a residue interaction network, every residue is used to define a network node, adding noises in network post-analysis and increasing computational burden. In addition, dynamical information is often necessary in deciphering biological functions.

Results

We developed a robust and efficient protein residue interaction network method, termed dynamical important residue network, by combining both structural and dynamical information. A major departure from previous approaches is our attempt to identify important residues most important for functional regulation before a network is constructed, leading to a much simpler network with the important residues as its nodes. The important residues are identified by monitoring structural data from ensemble molecular dynamics simulations of proteins in different functional states. Our tests show that the new method performs well with overall higher sensitivity than existing approaches in identifying important residues and interactions in tested proteins, so it can be used in studies of protein functions to provide useful hypotheses in identifying key residues and interactions.

Supplementary information

Supplementary data are available at Bioinformatics online.
The lipid flippase subunit Cdc50 is required for antifungal drug resistance, endocytosis, hyphal development and virulence inCandida albicans
Authors: Xu Dayong , Zhang Xing , Zhang Biao , Zeng Xin , Mao Hongchen , Xu Haitao , Jiang Linghuo , Li Feng
Published: April 2019

Cdc50 is the non-catalytic subunit of the flippase that establishes phospholipid asymmetry in membranes and functions in vesicle-mediated trafficking in Saccharomyces cerevisiae. Here, we have identified the homologous gene CaCDC50 that encodes a protein of 396 amino acids with two conserved transmembrane domains in Candidaalbicans. Deletion of CaCDC50 results in C. albicans cells becoming sensitive to the antifungal drugs azoles, terbinafine and caspofungin, as well as to the membrane-perturbing agent sodium dodecyl sulfate. We also show that CaCDC50 is involved in both endocytosis and vacuolar function. CaCDC50 confers tolerance to high concentrations of cations, although it is not required for osmolar response. Moreover, deletion of CaCDC50 leads to severe defects in hyphal development of C. albicans cells and highly attenuated virulence in the mouse model of systemic infection. Therefore, CaCDC50 regulates cellular responses to antifungal drugs, cell membrane stress, endocytosis, filamentation and virulence in the human fungal pathogen C. albicans.
Social media and e-learning use among European exercise science students
Authors: Rigamonti L , Dolci A , Galetta F , Stefanelli C , Hughes M , Bartsch M , Seidelmeier I , Bonaventura K , Back D A
Published: April 2019

With the rise of digital technologies, electronic learning and communication tools are becoming a firm part of academia to promote knowledge of health sciences. This study sought to analyse the attitude of students regarding social media and digital learning for study purposes in sport and exercise science. A survey was carried out with a questionnaire (20 main items) in six sport science faculties, equally spread across Germany (G), Italy (I) and the United Kingdom (UK) between February and October 2017. The focus areas were students’ usage of social media (Facebook, Google+, Instagram, LinkedIn, Skype, Twitter, WhatsApp, YouTube) for academic purposes and their use of e-learning. Data were analysed by quantitative and qualitative methods. 229 students participated in the study (G: 68, I: 121, UK: 40). While YouTube was mostly used for receiving knowledge, WhatsApp and Facebook showed additional preferences for peer contacts for learning purposes and knowledge discussions. Preferred online data sources were PubMed (77%), free access journals (67%), YouTube (66%) and Wikipedia (63%). Often used digital learning materials were own universities’ PowerPoints (77%), scripts (59%) and scientific articles (53%). However, some preferences showed national differences. The evaluated participants showed an overall high use of social media and e-learning tools for their studies. Students would like more digital learning sources made available to them by their institutions. However, some differences in preferences of digital learning or communication tools may exist and this should be considered for international approaches to promote health knowledge among students.
A study of deep learning approaches for medication and adverse drug event extraction from clinical text
Authors: Wei Qiang , Ji Zongcheng , Li Zhiheng , Du Jingcheng , Wang Jingqi , Xu Jun , Xiang Yang , Tiryaki Firat , Wu Stephen , Zhang Yaoyun , Tao Cui , Xu Hua
Published: April 2019

Objective

This article presents our approaches to extraction of medications and associated adverse drug events (ADEs) from clinical documents, which is the second track of the 2018 National NLP Clinical Challenges (n2c2) shared task.

Materials and Methods

The clinical corpus used in this study was from the MIMIC-III database and the organizers annotated 303 documents for training and 202 for testing. Our system consists of 2 components: a named entity recognition (NER) and a relation classification (RC) component. For each component, we implemented deep learning-based approaches (eg, BI-LSTM-CRF) and compared them with traditional machine learning approaches, namely, conditional random fields for NER and support vector machines for RC, respectively. In addition, we developed a deep learning-based joint model that recognizes ADEs and their relations to medications in 1 step using a sequence labeling approach. To further improve the performance, we also investigated different ensemble approaches to generating optimal performance by combining outputs from multiple approaches.

Results

Our best-performing systems achieved F1 scores of 93.45% for NER, 96.30% for RC, and 89.05% for end-to-end evaluation, which ranked #2, #1, and #1 among all participants, respectively. Additional evaluations show that the deep learning-based approaches did outperform traditional machine learning algorithms in both NER and RC. The joint model that simultaneously recognizes ADEs and their relations to medications also achieved the best performance on RC, indicating its promise for relation extraction.

Conclusion

In this study, we developed deep learning approaches for extracting medications and their attributes such as ADEs, and demonstrated its superior performance compared with traditional machine learning algorithms, indicating its uses in broader NER and RC tasks in the medical domain.
Significant influence of lignin on axial elastic modulus of poplar wood at low microfibril angles under wet conditions
Authors: Özparpucu Merve , Gierlinger Notburga , Cesarino Igor , Burgert Ingo , Boerjan Wout , Rüggeberg Markus
Published: April 2019

Wood is extensively used as a construction material. Despite increasing knowledge of its mechanical properties, the contribution of the cell-wall matrix polymers to wood mechanics is still not well understood. Previous studies have shown that axial stiffness correlates with lignin content only for cellulose microfibril angles larger than around 20°, while no influence is found for smaller angles. Here, by analysing the wood of poplar with reduced lignin content due to down-regulation of CAFFEOYL SHIKIMATE ESTERASE, we show that lignin content also influences axial stiffness at smaller angles. Micro-tensile tests of the xylem revealed that axial stiffness was strongly reduced in the low-lignin transgenic lines. Strikingly, microfibril angles were around 15° for both wild-type and transgenic poplars, suggesting that cellulose orientation is not responsible for the observed changes in mechanical behavior. Multiple linear regression analysis showed that the decrease in stiffness was almost completely related to the variation in both density and lignin content. We suggest that the influence of lignin content on axial stiffness may gradually increase as a function of the microfibril angle. Our results may help in building up comprehensive models of the cell wall that can unravel the individual roles of the matrix polymers.
Transcript and metabolite changes during the early phase of abscisic acid-mediated induction of crassulacean acid metabolism in Talinum triangulare
Authors: Maleckova Eva , Brilhaus Dominik , Wrobel Thomas J , Weber Andreas P M
Published: April 2019

Crassulacean acid metabolism (CAM) has evolved as a water-saving strategy, and its engineering into crops offers an opportunity to improve their water use efficiency. This requires a comprehensive understanding of the regulation of the CAM pathway. Here, we use the facultative CAM species Talinum triangulare as a model in which CAM can be induced rapidly by exogenous abscisic acid. RNA sequencing and metabolite measurements were employed to analyse the changes underlying CAM induction and identify potential CAM regulators. Non-negative matrix factorization followed by k-means clustering identified an early CAM-specific cluster and a late one, which was specific for the early light phase. Enrichment analysis revealed abscisic acid metabolism, WRKY-regulated transcription, sugar and nutrient transport, and protein degradation in these clusters. Activation of the CAM pathway was supported by up-regulation of phosphoenolpyruvate carboxylase, cytosolic and chloroplastic malic enzymes, and several transport proteins, as well as by increased end-of-night titratable acidity and malate accumulation. The transcription factors HSFA2, NF-YA9, and JMJ27 were identified as candidate regulators of CAM induction. With this study we promote the model species T. triangulare, in which CAM can be induced in a controlled way, enabling further deciphering of CAM regulation.
Shearing-box simulations of MRI-driven turbulence in weakly collisional accretion discs
Authors: Kempski Philipp , Quataert Eliot , Squire Jonathan , Kunz Matthew W
Published: April 2019

We present a systematic shearing-box investigation of magnetorotational instability (MRI)-driven turbulence in a weakly collisional plasma by including the effects of an anisotropic pressure stress, i.e. anisotropic (Braginskii) viscosity. We constrain the pressure anisotropy (Δp) to lie within the stability bounds that would be otherwise imposed by kinetic microinstabilities. We explore a broad region of parameter space by considering different Reynolds numbers and magnetic-field configurations, including net vertical flux, net toroidal-vertical flux, and zero net flux. Remarkably, we find that the level of turbulence and angular-momentum transport are not greatly affected by large anisotropic viscosities: the Maxwell and Reynolds stresses do not differ much from the MHD result. Angular-momentum transport in Braginskii MHD still depends strongly on isotropic dissipation, e.g. the isotropic magnetic Prandtl number, even when the anisotropic viscosity is orders of magnitude larger than the isotropic diffusivities. Braginskii viscosity nevertheless changes the flow structure, rearranging the turbulence to largely counter the parallel rate of strain from the background shear. We also show that the volume-averaged pressure anisotropy and anisotropic viscous transport decrease with increasing isotropic Reynolds number (Re); e.g. in simulations with net vertical field, the ratio of anisotropic to Maxwell stress (αA/αM) decreases from ∼0.5 to ∼0.1 as we move from Re ∼ 103 to Re ∼ 104, while 〈4$\pi$Δp/B2〉 → 0. Anisotropic transport may thus become negligible at high Re. Anisotropic viscosity nevertheless becomes the dominant source of heating at large Re, accounting for ${\gtrsim } 50 {{\ \rm per\ cent}}$ of the plasma heating. We conclude by briefly discussing the implications of our results for radiatively inefficient accretion flows on to black holes.
SEanalysis: a web tool for super-enhancer associated regulatory analysis
Authors: Qian Feng-Cui , Li Xue-Cang , Guo Jin-Cheng , Zhao Jian-Mei , Li Yan-Yu , Tang Zhi-Dong , Zhou Li-Wei , Zhang Jian , Bai Xue-Feng , Jiang Yong , Pan Qi , Wang Qiu-Yu , Li En-Min , Li Chun-Quan , Xu Li-Yan , Lin De-Chen
Published: April 2019

Super-enhancers (SEs) have prominent roles in biological and pathological processes through their unique transcriptional regulatory capability. To date, several SE databases have been developed by us and others. However, these existing databases do not provide downstream or upstream regulatory analyses of SEs. Pathways, transcription factors (TFs), SEs, and SE-associated genes form complex regulatory networks. Therefore, we designed a novel web server, SEanalysis, which provides comprehensive SE-associated regulatory network analyses. SEanalysis characterizes SE-associated genes, TFs binding to target SEs, and their upstream pathways. The current version of SEanalysis contains more than 330 000 SEs from more than 540 types of cells/tissues, 5042 TF ChIP-seq data generated from these cells/tissues, DNA-binding sequence motifs for ∼700 human TFs and 2880 pathways from 10 databases. SEanalysis supports searching by either SEs, samples, TFs, pathways or genes. The complex regulatory networks formed by these factors can be interactively visualized. In addition, we developed a customizable genome browser containing >6000 customizable tracks for visualization. The server is freely available at http://licpathway.net/SEanalysis.
Molecular determinants of metazoan tricRNA biogenesis
Authors: Schmidt Casey A , Giusto Joseph D , Bao Alicia , Hopper Anita K , Matera A Gregory
Published: April 2019

Mature tRNAs are generated by multiple post-transcriptional processing steps, which can include intron removal. Recently, we discovered a new class of circular non-coding RNAs in metazoans, called tRNA intronic circular (tric)RNAs. To investigate the mechanism of tricRNA biogenesis, we generated constructs that replace native introns of human and fruit fly tRNA genes with the Broccoli fluorescent RNA aptamer. Using these reporters, we identified cis-acting elements required for tricRNA formation in vivo. Disrupting a conserved base pair in the anticodon-intron helix dramatically reduces tricRNA levels. Although the integrity of this base pair is necessary for proper splicing, it is not sufficient. In contrast, strengthening weak bases in the helix also interferes with splicing and tricRNA production. Furthermore, we identified trans-acting factors important for tricRNA biogenesis, including several known tRNA processing enzymes such as the RtcB ligase and components of the TSEN endonuclease complex. Depletion of these factors inhibits Drosophila tRNA intron circularization. Notably, RtcB is missing from fungal genomes and these organisms normally produce linear tRNA introns. Here, we show that in the presence of ectopic RtcB, yeast lacking the tRNA ligase Rlg1/Trl1 are converted into producing tricRNAs. In summary, our work characterizes the major players in eukaryotic tricRNA biogenesis.
TAGOOS: genome-wide supervised learning of non-coding loci associated to complex phenotypes
Authors: González Aitor , Artufel Marie , Rihet Pascal
Published: April 2019

Genome-wide association studies (GWAS) associate single nucleotide polymorphisms (SNPs) to complex phenotypes. Most human SNPs fall in non-coding regions and are likely regulatory SNPs, but linkage disequilibrium (LD) blocks make it difficult to distinguish functional SNPs. Therefore, putative functional SNPs are usually annotated with molecular markers of gene regulatory regions and prioritized with dedicated prediction tools. We integrated associated SNPs, LD blocks and regulatory features into a supervised model called TAGOOS (TAG SNP bOOSting) and computed scores genome-wide. The TAGOOS scores enriched and prioritized unseen associated SNPs with an odds ratio of 4.3 and 3.5 and an area under the curve (AUC) of 0.65 and 0.6 for intronic and intergenic regions, respectively. The TAGOOS score was correlated with the maximal significance of associated SNPs and expression quantitative trait loci (eQTLs) and with the number of biological samples annotated for key regulatory features. Analysis of loci and regions associated to cleft lip and human adult height phenotypes recovered known functional loci and predicted new functional loci enriched in transcriptions factors related to the phenotypes.

In conclusion, we trained a supervised model based on associated SNPs to prioritize putative functional regions. The TAGOOS scores, annotations and UCSC genome tracks are available here: https://tagoos.readthedocs.io.
Balancing Operative Efficiency and Surgical Education: A Functional Neurosurgery Model
Authors: Rao Abigail J , Bullis Carli , Holste Katherine G , Teton Zoe , Burchiel Kim J , Raslan Ahmed M
Published: April 2019

BACKGROUND

Attending surgeons have dual obligations to deliver high-quality health care and train residents. In modern healthcare, lean principles are increasingly applied to processes preceding and following surgery. However, surgeons have limited data regarding variability and waste during any given operation.

OBJECTIVE

To measure variability and waste during the following key functional neurosurgery procedures: retrosigmoid craniectomy (microvascular decompression [MVD] and internal neurolysis) and deep brain stimulation (DBS). Additionally, we correlate variability with residents’ self-reported readiness for the surgical steps. The aim is to guide surgeons as they balance operative safety and efficiency with training obligations.

METHODS

For each operation (retrosigmoid craniectomy and DBS), a standard workflow, segmenting the operation into components, was defined. We observed a representative sample of operations, timing the components, with a focus on variability. To assess perceptions of safety and risk among surgeons of various training levels, a survey was administered. Survey results were correlated with operative variability, attempting to identify areas for increasing value without compromising trainee experience.

RESULTS

A sampling of each operation (n = 36) was observed during the study period. For MVD, craniectomy had the highest mean duration and standard deviation, whereas the MVD itself had the lowest mean duration and standard deviation. For DBS, the segments with largest standard deviation in duration were registration and electrode placement. For many steps of both procedures, there was a statistically significant relationship between increasing level of training and increasing perception of safety.

CONCLUSION

This proof-of-concept study introduces an educational and process-improvement tool that can be used to aid surgeons in increasing the efficiency of patient care.
Pathways to Independent Primary Care Clinical Practice: How Tall Is the Shortest Giant?
Authors: Dewan Mantosh J. , Norcini John J.
Published: April 2019

Patients can be treated by a physician, a nurse practitioner (NP), or a physician assistant (PA) despite marked differences in the education and training for these three professions. This natural experiment allows examination of a critical question: What is the minimum education and training required to practice primary care? In other words, how tall is the shortest giant? State licensing requirements, not educational bodies, legislate minimum training. The current minimum is 6 years, which includes 27.5 weeks of supervised clinical experience (SCE), for NPs. In comparison, PAs train for 6 years with 45 weeks of SCE, and physicians for at least 8 years with 110 weeks of SCE. Initial, flawed studies show equivalent patient outcomes among the professions. If rigorous follow-up studies confirm equivalence, the content and length of medical education for primary care physicians should be reconsidered. Unmatched medical school graduates, with 7 years of training and 65 weeks of SCE, more than the required minimum for NPs, deserve to practice independently. So do PAs. If equivalence is not confirmed, the minimum requirements for NPs and/or PAs should be raised, including considering a required residency (currently optional). Alternatively, the scope of practice for the three professions could be defined to reflect differences in training. There is an urgent need to set aside preconceived notions and turf battles, conduct rigorous independent studies, and generate meaningful data on practice patterns and patient outcomes. This should inform optimal training, scope of practice, and workforce development for each invaluable primary care clinical practitioner.
Use of the Online Discussion Board in Health Professions Education: Contributions, Challenges, and Considerations
Authors: Donlan Pamela
Published: April 2019

Online discussion boards offer opportunities for individualized and interactive learning in higher education and are frequently used in health professions education. This article investigates the ways in which discussion board activities foster cognitive and affective domain learning among health professions students and contribute to the professional competencies that are required of emerging clinicians. In addition, pedagogical challenges, including the need to develop sophisticated interpersonal affective domain skills, promote problem-based learning, and prepare students for standardized examinations, are addressed. Considerations for practice, which include the importance of specific teaching strategies such as the shaping of student and instructor roles, scaffolding, and online debates and role-playing, are discussed.
“Beyond the Boundaries of Care Dependence”
Authors: Piredda Michela , Candela Maria L. , Mastroianni Chiara , Marchetti Anna , D’Angelo Daniela , Lusignani Maura , De Marinis Maria G. , Matarese Maria
Published: April 2019

Background

Dependence is a common life experience and innate condition for human beings due to their bodily and relational essence, but in contemporary society, it has become a stressful condition. Care dependence is central to nursing, and patients with advanced cancer are often dependent on care. Understanding nurses’ perceptions of care dependence can contribute to awareness of the impact it has on nurses.

Objective

The aim of this study was to explore palliative care nurses’ experiences and perceptions regarding patient dependence.

Methods

Sixteen nurses taking care of dependent patients in a palliative care center in Rome were interviewed. Giorgi’s descriptive phenomenological method was used.

Results

Nurses caring for dependent patients transcend the boundaries of dependence. Care dependence is an experience of powerlessness and regression. A patient’s life in dependence is precarious, as they have to overcome the daily limits of life. Taking care of dependent patients requires nurses to manage the unmanageable and to know and to embrace change from within in order to build positive relations of personal closeness and reciprocal self-giving.

Conclusions

Nurses should be aware that self-transcendence and the consequent positive relations could make the difference in the experience of care dependence and promote personal growth for both patient and nurse. Positive and transcending relationships can transform care dependence into the opportunity to find meaning and purpose in life.

Implications for Practice

The study highlights what nurses feel in caring for dependent patients. Understanding nurses’ perceptions is important to delineate a proper caring for dependent patients.
Giant Cell Lesions of the Maxillofacial Skeleton Express RANKL by RNA In Situ Hybridization Regardless of Histologic Pattern
Authors: Stagner Anna M. , Sajed Dipti P. , Nielsen G. Petur , Ebb David H. , Faquin William C. , Chebib Ivan , Rivera Miguel N. , Ting David T. , Resnick Cory M. , Peacock Zachary S. , Kaban Leonard B. , Deshpande Vikram
Published: April 2019

Maxillofacial central giant cell lesions (CGCLs) are often locally aggressive tumors in young patients that may be histologically very similar to or quite distinct when compared with giant cell tumors (GCTs) of long bones. It has been well established that GCTs express high levels of receptor activator of nuclear factor-kappa B ligand (RANKL) and are amenable to treatment with denosumab. To assess the predictive value of morphology, we evaluated CGCLs with GCT-like or non–GCT-like histology for RANKL expression by RNA in situ hybridization. Tumors were classified by clinical and radiographic criteria as aggressive or nonaggressive and histopathologically as resembling GCT or non–GCT-like. RNA in situ hybridization for RANKL mRNA was performed and scored semiquantitatively based on the magnification at which the signal was first detected. There were 17 patients (M:F=8:9) with a median age of 15 years. Nine patients were children under 18 years of age. In 10 patients, tumors were characterized as GCT-like and in 7, non–GCT-like; 6 occurred in the setting of a known associated syndrome. Of the sporadic tumors, 9/11 (82%) were classified as aggressive. Fifteen of 17 (88%) tumors strongly expressed RANKL (8/9 aggressive, 2/2 nonaggressive; 10/10 GCT-like and 5/7 non–GCT-like). Two patients with clinically aggressive CGCL, GCT-like histology and high tumor RANKL expression were identified as candidates for a trial of denosumab with notable clinical response. CGCLs demonstrate strong and diffuse RANKL mRNA expression in mononuclear stromal cells, regardless of histology or presence of an associated syndrome. Denosumab may be clinically beneficial in aggressive CGCLs.
Refinements in Otoplasty Surgery: Experience of 200 Consecutive Cases Using Cartilage-Sparing Technique
Authors: Mazeed Ahmed S. , Bulstrode Neil W.
Published: April 2019

Background:

Many techniques have been described to correct prominent ears, including cartilage-suturing, cartilage-scoring, and cartilage-breaking techniques. Understanding the topography and anatomy of the auricular cartilage is crucial for performing safe otoplasty with consistent results.

Methods:

Two hundred consecutive patients with prominent ears were operated on using a modified Mustardé and Furnas technique with some refinements and without performing any cartilage scoring or excision. Adequate dissection and exposure of cartilage and precise repositioning of the tail of helix (cauda helicis) are keys to correction of lobule prominence without the need for any adjunctive procedures such as skin excision from the back of the lobule or suture fixation of the lobular tissues to the concha, mastoid, or scalp. Detailed description of the technique and review of the complications are presented.

Results:

This suturing-only technique had a low complication rate. Hematoma occurred in two patients only. Skin necrosis and wound dehiscence were not reported in any patient. Suture extrusion was the most common complication and was easily managed, mostly in the clinic. Relapse of deformity needing surgical correction occurred in eight cases.

Conclusions:

The series demonstrates that most of the potential complications of otoplasty can be avoided and favorable results can be obtained by paying attention to the anatomical details of the deformity and the auricular cartilage anatomy. The described cartilage-sparing otoplasty procedure with the refinements outlined resulted in a reproducible natural correction, with a low risk profile, that can be applied to almost all prominent ears.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Deconstructing a Leader: An In-Depth Analysis of the Commonalities between Plastic Surgery Chiefs and Chairmen
Authors: Wenzinger Eric , Weinstein Brielle , Singh Robinder , Reid Christopher M. , Suliman Ahmed , Herrera Fernando A.
Published: April 2019

Background:

The authors sought to identify factors associated with current chiefs and chairpersons in academic plastic surgery to encourage and shape future leaders of tomorrow.

Methods:

Academic chairpersons in plastic surgery (n = 94) were identified through an Internet-based search of all Accreditation Council for Graduate Medical Education–accredited residency training programs during the year 2015. Sex, ethnicity, academic rank, board certification, time since certification, medical school attended, residency program attended, fellowships training, advanced degrees, obtaining leadership roles at trainee’s institution, and h-index were analyzed.

Results:

Of the 94 chiefs and chairpersons, 96 percent were male and 81 percent obtained full professor status, and 98 percent were certified by the American Board of Plastic Surgery. Mean time since certification was 22 years (range, 7 to 45 years). Fifty-one percent graduated from 20 medical schools, whereas 42 percent graduated from only nine plastic surgery training programs. Fifty-six percent had pursued fellowship beyond their primary plastic surgery training. Eighteen percent had obtained advanced degrees. Twenty-nine percent of chiefs and chairpersons obtained leadership roles at the institution where they had completed plastic surgery training. The mean h-index was 17.6 (range, 1 to 63). Graduates of the nine most represented residency programs had a mean h-index of 21 versus 15 when compared with the remaining chief/chairpersons (p < 0.0062).

Conclusion:

Leaders in plastic surgery are more likely to be male, hold academic rank of professor, and have completed a fellowship after residency.
Acute Adverse Reactions to Nonionic Iodinated Contrast Media
Authors: Suh Young Joo , Yoon Soon Ho , Hong Hyunsook , Hahn Seokyung , Kang Dong-Yoon , Kang Hye-Ryun , Choi Young-Hun , Lee Whal
Published: April 2019

Objectives

We aimed to meta-analytically compare the incidence of acute adverse reactions (AARs) to nonionic iodinated contrast media (ICM) according to the type of ICM in patients who underwent radiologic examinations with administration of ICM via intravascular route.

Materials and Methods

A systematic literature search identified studies evaluating the incidence of AARs to 7 nonionic ICM (iobitridol, iohexol, iomeprol, iopamidol, iopromide, ioversol, and iodixanol) with extractable outcomes. These outcomes were pooled using a random-effects model, and the effect of ICM type on the incidence of overall and severe AARs was evaluated using meta-regression analysis.

Results

Thirty studies with 1,360,488 exposures to ICM were included. The pooled incidences of overall and severe AARs to nonionic ICM were 1.03% (95% confidence interval [CI], 0.81%–1.30%; I
2 = 0.99) and 0.0141% (95% CI, 0.0108%–0.0183%; I
2 = 0.56), respectively. Iomeprol had the highest overall AAR incidence (1.74%; 95% CI, 0.79%–3.76%; I
2 = 0.99), followed by iohexol (1.21%; 95% CI, 0.67%–2.17%; I
2 = 0.99), iopamidol (1.10%; 95% CI, 0.60%–2.03%; I
2 = 0.99), ioversol (0.88%; 95% CI, 0.43%–1.83%; I
2 = 0.96), iodixanol (0.85%; 95% CI, 0.36%–1.95%; I
2 = 0.99), iopromide (0.82%; 95% CI, 0.43%–1.55%; I
2 = 0.99), and iobitridol (0.77%; 95% CI, 0.36%–1.62%; I
2 = 0.99). Multivariable meta-regression analysis revealed that study design (P = 0.0014) and premedication (P = 0.0230) were statistically significant determinants affecting the incidence of overall AARs. Iodinated contrast media type did not affect the incidence of overall and severe AARs (P = 0.1453 and 0.4265, each).

Conclusions

The varying pooled incidences of overall and severe AARs to specific types of nonionic ICM do not remain as significant after adjusting confounders. Our results may support nonrestriction of certain types of nonionic ICM in the context of AAR avoidance.
Evaluating the Quality and Readability of Online Resources for Labiaplasty
Authors: Pandya Lopa K. , Hudson Catherine O. , Lynch Courtney D. , Nekkanti Silpa , Smith Pamela E. , Hundley Andrew F.
Published: April 2019

Objectives

The aim of this study was to evaluate the quality, readability, and accuracy of Web-based information regarding labiaplasty and to characterize the types of Web sites providing this information.

Methods

Investigators used 3 major search engines to query the internet using the search terms labiaplasty, labia reduction, and vaginal rejuvenation. Two validated tools were used to evaluate Web sites: the JAMA benchmark tool and the DISCERN instrument. Three physicians independently reviewed each Web site. Interrater agreement was assessed, and reviewer scores were averaged. Flesch-Kincaid reading ease and Flesch-Kincaid grade level of each site were assessed. Data were analyzed using Stata 14.0 (College Station, TX).

Results

Of the 112 Web sites reviewed, 100 Web sites were from North America, 9 from Europe, 2 from Australia, and 1 from Asia. The median score using the JAMA tool was 1.0 (0.33–4.0), indicating low accountability, whereas the median score using the DISCERN tool was 28 (18.7–77) of 80 with higher scores indicating higher quality. Cohen’s weighted κ statistic (0.81) demonstrated near perfect agreement among reviewers for DISCERN scores. The median reading level was 11.9 (6.4–19.5). A majority of the Web sites (92) were for-profit businesses or blogs.

Conclusions

The internet enables patients to research sensitive topics and seek answers without worry of social stigma. Online health-related information is a widely used yet poorly studied source of medical information. The majority of Web sites reviewed lack balanced, evidence-based information. Given the wide variation in the quality of information, physicians should guide patients to reputable online resources.