bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatotoxicity of Statins as Determined by Serum Alanine Aminotransferase in a Pediatric Cohort With Dyslipidemia
Authors: Desai Nirav K. , Mendelson Michael M. , Baker Annette , Ryan Heather H. , Griggs Suzanne , Boghani Meera , Yellen Elizabeth , Buckley Lucy , Gillman Matthew W. , Zachariah Justin P. , Graham Dionne , Jonas Maureen M. , de Ferranti Sarah D. 
Published: October 2018

ABSTRACTObjective:The aim of the study was to evaluate the hepatotoxicity of statins, as determined by serum alanine aminotransferase (ALT), in children and adolescents with dyslipidemia in real‐world clinical practice.Study design:Clinical and laboratory data were prospectively collected between September 2010 and March 2014. We compared ALT levels between patients prescribed versus not prescribed 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase inhibitors (statins), and then compared ALT before and after initiation of statins.Results:Over the 3.5‐year observation period, there were 2704 ALT measurements among 943 patients. The mean age was 14 years; 54% were boys, 47% obese, and 208 patients were treated with statins. Median follow‐up after first ALT was 18 months. The mean (SD) ALT in statin and non‐statin users was 23 (20) U/L and 28 (28) U/L, respectively. In models adjusted for age, sex, and race, ALT was 2.1 U/L (95% CI 0.1 to 4.4; P = 0.04) lower among statin users, which was attenuated after adjustment for weight category. Patients started on statins during the observation period did not demonstrate an increase in ALT over time (ALT 0.9 U/L [95% confidence interval −5.2 to 3.4] increase per year; P = 0.7).Conclusions:In our study population, we did not observe a higher burden of ALT elevations among pediatric patients on statins as compared to those with dyslipidemia who are not on statins, supporting the hepatic safety of statin use in childhood.
Identifying Hesitation and Discomfort with Diagnosing Sepsis: Survey of a Pediatric Tertiary Care Center
Authors: Breuer Ryan K. , Hassinger Amanda B. 
Published: October 2018

Objective:
Pediatric sepsis remains a significant cause of morbidity and mortality despite the development of strategies proven to improve diagnosis and treatment. Specifically, early recognition and urgent therapy initiation are consistently associated with improved outcomes. However, providers bring these principles inconsistently to the bedside. The objective of this study was to describe practitioner knowledge of, and attitudes toward, sepsis as a means of identifying potentially modifiable factors delaying life-saving treatment. We hypothesized there would be difficulties with sepsis recognition and self-reported discomfort with making the diagnosis among all provider groups in a pediatric tertiary care center.

Methods:
Emergency department and inpatient pediatric physicians, nurses, and respiratory therapists in a single, freestanding children’s hospital received an electronic survey. Likert scales permitted anonymous self-reporting of comfort and diagnostic delays. Seven clinical vignettes assessed diagnostic knowledge. Independent sample t tests and Chi-square compared responses.

Results:
Three hundred two staff participated (73% response rate), 41% of whom had at least 10 years of clinical experience. One in 5 was uncomfortable alerting coworkers to a patient with suspected sepsis or septic shock, and almost half were uncomfortable doing so in cases of compensated shock. Every role self-reported diagnostic delays, including faculty physicians. On average, physicians answered a greater percentage of vignette questions correctly (66%), compared with nurses (58%; P = 0.013) and respiratory therapists (52%; P = 0.005).

Conclusions:
Sepsis knowledge deficits, provider discomfort, and diagnostic delays are prevalent within a tertiary care children’s hospital. Their presence and scale suggest areas for future research and targeted intervention.
Master regulators of genetic interaction networks mediating statin drug response inSaccharomyces cerevisiaevary with genetic background
Authors: Busby Bede P. , Niktab Eliatan , Roberts Christina A. , Coorey Namal V. , Sheridan Jeffrey P. , Senanayake Dinindu S. , Munkacsi Andrew B. , Atkinson Paul H. 
Published: October 2018

ABSTRACTDetermination of genetic interaction networks (GINs) surrounding drug targets identifies buffering genes and provides molecular insight into drug response in individuals. Here we used backcross methodology to createSaccharomyces cerevisiaedeletion libraries in three genetic backgrounds resistant to statins, which are additional to the statin-sensitive S288C deletion library that has provided much of what is known about GINs in eukaryotes. Whole genome sequencing and linkage group analysis confirmed the genomic authenticity of the new deletion libraries. Statin response was probed by drug-gene interactions with atorvastatin and cerivastatin treatments, as well as gene-gene interactions with the statin targetHMG1andHMG2genes or the sterol homeostaticARV1gene. The 20 GINs generated from these interactions were not conserved by function or topology across the four genetic backgrounds. Centrality measures and hierarchical agglomerative clustering identified master regulators that if removed collapsed the networks. Community structure distinguished a characteristic early secretory pathway pattern of gene usage in each genetic background. ER stress in statin-resistant backgrounds was buffered by protein folding genes, which was confirmed by reduced activation of the unfolded protein response in statin-resistant backgrounds relative to the statin-sensitive S288C background. These network analyses of new gene deletion libraries provide insight into the complexity of GINs underlying individual drug response.
Revealing S-layer Functions in the Hyperthermophilic Crenarchaeon Sulfolobus islandicus
Authors: Zhang Changyi , Wipfler Rebecca L. , Li Yuan , Wang Zhiyu , Hallett Emily N. , Whitaker Rachel J. 
Published: October 2018

AbstractThe crystalline surface layer (S-layer), consisting of two glycoproteins SlaA and SlaB, is considered to be the exclusive component of the cell envelope outside of the cytoplasmic membrane in Sulfolobus species. Although biochemically and structurally characterized, the S-layer in vivo functions remain largely elusive in Archaea. Here, we investigate how the S-layer genes contribute to the S-layer architecture and affect cellular physiology in a crenarchaeal model, Sulfolobus islandicus M.16.4. Electron micrographs of mutant cells lacking slaA or both slaA and slaB confirm the absence of the outermost layer (SlaA), whereas cells with intact, partially, or completely detached SlaA are observed for the ∆slaB mutant. Importantly, we identify a novel S-layer-associated protein M164_1049, which does not functionally replace its homolog SlaB but likely assists SlaB to stabilize SlaA. Additionally, we find that mutants deficient in SlaA form large cell aggregates and the individual cell size varies significantly. The slaB gene deletion also causes noticeable cellular aggregation, but the size of those aggregates is smaller when compared to ∆slaA and ∆slaAB mutants. We further show the ∆slaA mutant cells exhibit more sensitivity to hyperosmotic stress but are not reduced to wild-type cell size. Finally, we demonstrate that the ∆slaA mutant contains aberrant chromosome copy numbers not seen in wild-type cells where the cell cycle is tightly regulated. Together these data suggest that the lack of slaA results in either cell fusion or irregularities in cell division. Our studies provide novel insights into the physiological and cellular functions of the S-layer in Archaea.SignificanceRediscovery of the ancient evolutionary relationship between archaea and eukaryotes has revitalized interest in archaeal cell biology. Key to understanding the archaeal cell is the S-layer which is ubiquitous in Archaea but whose in vivo function is unknown. In this study, we genetically dissect how the two well-known S-layer genes as well as a newly identified S-layer-associated-protein-encoding gene contribute to the S-layer architecture in a hyperthermophilic crenarchaeal model S. islandicus. We provide genetic evidence for the first time showing that the slaA gene is a key cell morphology determinant and may play a role in Sulfolobus cell division or cell fusion.
Mitochondria form contact sites with the nucleus to couple pro-survival retrograde response
Authors: Desai Radha , East Daniel A , Hardy Liana , Crosby James , Rigon Manuel , Faccenda Danilo , Alvarez María Soledad , Singh Aarti , Mainenti Marta , Hussey Laura Kuhlman , Bentham Robert , Szabadkai Gyorgy , Zappulli Valentina , Dhoot Gurtej , Romano Lisa E , Dong Xia , Coppens Isabelle , Hamacher-Brady Anne , Chapple J Paul , Abeti Rosella , Fleck Roland A. , Vizcay-Barrena Gema , Smith Kenneth , Campanella Michelangelo 
Published: October 2018

AbstractMitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as Mitochondrial Retrograde Response (MRR) and is induced by mitochondrial dysfunctions which perturb cell signalling. MRR results in the nuclear stabilization and activation of pro-survival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Here we demonstrate that MRR is facilitated by the formation of contact sites between mitochondria and the nucleus which establish microdomains of communication between the two organelles. The 18kD Translocator Protein (TSPO), which de-ubiquitylates and stabilizes the mitochondrial network preventing its mitophagy-mediated segregation, is required for this interaction. The tethering TSPO enacts is mediated by the complex formed with the Protein Kinase A via the A-kinase anchoring protein Acyl-CoA Binding Domain Containing 3 (ACBD3) and allows the redistribution of cholesterol which sustains the pro-survival response by blocking NF-kB de-acetylation. This work proposes a new paradigm in the mitochondrial retro-communication by revealing the existence of contact sites between mitochondrial and the nucleus and a signalling role for cholesterol.
Repair, resilience and asymmetric segregation of damage in the context of replicative ageing: it is a balancing act
Authors: Borgqvist Johannes , Welkenhuysen Niek , Cvijovic Marija 
Published: October 2018

AbstractAccumulation of damaged proteins is a hallmark of ageing, occurring in organisms ranging from bacteria and yeast to mammalian cells. During cell division in Saccharomyces cerevisiae, damaged proteins are retained within the mother cell, resulting in a new daughter cell with full replicative potential and an ageing mother with a reduced replicative lifespan (RLS). The cell-specific features determining the lifespan remain elusive. It has been suggested that the RLS is dependent on the ability of the cell to repair and retain pre-existing damage. To deepen the understanding of how these factors influence the life span of individual cells, we developed and experimentally validated a dynamic model of damage accumulation accounting for replicative ageing. The model includes five essential properties: cell growth, damage formation, damage repair, cell division and cell death, represented in a theoretical framework describing the conditions allowing for replicative ageing, starvation, immortality or clonal senescence. We introduce the resilience to damage, which can be interpreted as the difference in volume between an old and a young cell. We show that the capacity to retain damage deteriorates with high age, that asymmetric division allows for retention of damage, and that there is a trade-off between retention and the resilience property. Finally, we derive the maximal degree of asymmetry as a function of resilience, proposing that asymmetric cell division is beneficial with respect to replicative ageing as it increases the RLS of a given organism. The proposed model contributes to a deeper understanding of the ageing process in eukaryotic organisms.
A new universal pore measurement and clustering approach for surgical meshes
Authors: Brune Carolin , Vogt Sebastian , Peiper Christian , Brinker Klaus , Trzewik Jürgen 
Published: October 2018

AbstractThe pore structure and pore size is a crucial characteristic of surgical meshes. A huge amount of different approaches for mesh classification based on pore size or materials are available. It is difficult to use these classification methods because of the large variety in knitting structures and pore shapes. No agreement on an established method to measure the pore size is available despite the fact that the surgical community agrees that pore size and geometry are crucial factors for the result of a hernia repair. In this publication a new approach to characterize meshes based on their pore shape and pore size is presented. The pore size is defined by the largest inscribed circle within a mesh pore and the smallest circumscribed circle outside the pore, in addition to hence calculated values. This allows a characterization with regards to tissue ingrowth and bridging behavior. The measurements are made using the scientific image processing software ImageJ and additional customized software plug-in. Since the program ImageJ is public domain and the plug-ins are available, the measurements can be reproduced. Furthermore, the presented pore descriptions can also be used for manual pore size verification.
A new causality measure
Authors: Majumdar Kaushik , Dheer Puneet 
Published: October 2018

SummaryLet there are n i.i.d observations, each producing a two tuple of real values (xi, yi), i ∊ {1,……, n} giving rise to random variables X = (x1,…, xn) and Y = (y1,…, yn). What is the statistical significance of the hypothesis that an increase in the independent variable X is causing an increase (or decrease) to the dependent variable Y ?
Neutral component of the local interstellar medium
Authors: Konior Wojciech , Ratkiewicz Romana , Kotlarz Jan 
Published: October 2018

Purpose
This paper aims to review the current knowledge about the neutral component of the local interstellar medium (LISM), which due to the resonant charge exchange, photoionization and electron impact ionization processes has a profound impact on the heliosphere structure.

Design/methodology/approach
This work is based on the heliospheric literature review.

Findings
The summary of four major effects of neutral hydrogen atoms penetrating solar wind (SW), i.e. the disappearance of the complicated flow structure; the emergence of “hydrogen wall” in front of the heliopause (HP); decreasing distance of termination shock (TS), HP and bow shock (BS) layer from the Sun; and recently discovered by the Interstellar Boundary Explorer mission, a region of enhanced energetic neutral atom (ENA) emission seen in all sky maps as a ribbon.

Practical implications
In the context of constantly developing space technologies in aerospace engineering and prospective deep space missions, there is a need of general reviews about the interstellar space surroundings of the Sun and gathering the knowledge to help in theoretical, numerical and experimental investigations such as the optimization of the scientific equipment and spacecraft structure to work in specific conditions.

Originality/value
The survey encapsulate basic and relevant processes playing an important role in the physics of the nearest surroundings of the Sun and the latest results of numerical and experimental investigations focused on the neutral LISM component and its influence on the heliosphere, which is strongly desired in future works. Until now, not many of such reviews have been done.
A new jig-shape optimization method for the high aspect ratio wing
Authors: Yuan Zhe , Huo Shihui , Ren Jianting 
Published: October 2018

Purpose
Computational efficiency is always the major concern in aircraft design. The purpose of this research is to investigate an efficient jig-shape optimization design method. A new jig-shape optimization method is presented in the current study and its application on the high aspect ratio wing is discussed.

Design/methodology/approach
First, the effects of bending and torsion on aerodynamic distribution were discussed. The effect of bending deformation was equivalent to the change of attack angle through a new equivalent method. The equivalent attack angle showed a linear dependence on the quadratic function of bending. Then, a new jig-shape optimization method taking integrated structural deformation into account was proposed. The method was realized by four substeps: object decomposition, optimization design, inversion and evaluation.

Findings
After the new jig-shape optimization design, both aerodynamic distribution and structural configuration have satisfactory results. Meanwhile, the method takes both bending and torsion deformation into account.

Practical implications
The new jig-shape optimization method can be well used for the high aspect ratio wing.

Originality/value
The new method is an innovation based on the traditional single parameter design method. It is suitable for engineering application.
Uncertain evaluation of crashworthiness of thin-walled composite structures
Authors: Xie Jiang , Mou Haolei , Su Xuan , Feng Zhenyu 
Published: October 2018

Purpose
This paper aims to present an evaluation method for energy-absorption characteristics of thin-walled composite structures with random uncertain parameters.

Design/methodology/approach
The mechanical properties of T700/3234 are obtained by material performance tests and energy-absorption results are obtained by quasi-static crushing tests of thin-walled composite circular tubes. The indicators of triggering specific load (TSL) and specific energy absorption (SEA) are introduced and calculated to determine the energy-absorption characteristics and validate the probability finite element analysis model. The uncertainty in the parameters contain the machining tolerance for the thickness and inner diameter of composite circular tubes and are associated with the composite material system. The Plackett–Burman method is used to choose the measurement parameters. Then, the response surface method is used to build a second-order function of random uncertain parameters versus TSL/SEA, and the Monte Carlo method is finally used to obtain the probabilities of TSL and SEA.

Findings
The finite element models can accurately simulate the initial peak load, load-displacement curve and SEA value. The random uncertain parameter method can be used to evaluate the energy-absorption characteristics of thin-walled composite circular tubes.

Practical implications
The presented evaluation method for energy-absorption characteristics of thin-walled composite structures is an approach that considers uncertain parameters to increase the simulation accuracy and decrease the computational burden.

Originality/value
This methodology considers uncertain parameters in evaluating the energy-absorption characteristics of thin-walled composite structures, and this methodology can be applied to other thin-walled composite structures.
Proof-of-concept analysis of a supplemental solar power system for aircraft
Authors: Liscouet-Hanke Susan , Shafiei Arash , Lopes Luiz , Williamson Sheldon 
Published: October 2018

Purpose
This paper aims to analyze the viability of a solar power system as a supplemental power source for commercial and business aircraft.

Design/methodology/approach
First, a model is established to estimate the potential available power from suitable aircraft surfaces for various meteorological conditions, ground and flight mission characteristics. A proposed aircraft system architecture and an associated parametric conceptual sizing model are presented. This supplemental solar power system sizing model is integrated into an aircraft multidisciplinary design optimization environment to evaluate the aircraft-level impact on mission fuel burn. A parametric study for a business jet aircraft is performed to analyze various solar cell types and power densities for converters. Trade-off studies are performed between efficiency and weight.

Findings
Considering today’s efficiency and power-to-weight ratio of the system components, overall fuel burn reduction can be achieved. Therefore, the technology development work can start now to target short to mid-term applications. In addition, promising system integration scenarios are identified, such as the use of solar power for autonomous operation of the air conditioning system on ground, which yield potential further benefit. In conclusion, a supplemental solar power system seems a promising candidate for more efficient aircraft operation.

Originality/value
The presented novel supplemental solar power system architecture concept and its foreseen aircraft integration show potential benefits for near term applications. The results show that the break even for this technology is already reached and therefore build the foundation to further investigate the technology integration challenges. Clear directions for future research and development are outlined enabling the advancement of the technology readiness level.
Variable-fidelity shape optimization of dual-rotor wind turbines
Authors: Thelen Andrew , Leifsson Leifur , Sharma Anupam , Koziel Slawomir 
Published: October 2018

Purpose
Dual-rotor wind turbines (DRWTs) are a novel type of wind turbines that can capture more power than their single-rotor counterparts. Because their surrounding flow fields are complex, evaluating a DRWT design requires accurate predictive simulations, which incur high computational costs. Currently, there does not exist a design optimization framework for DRWTs. Since the design optimization of DRWTs requires numerous model evaluations, the purpose of this paper is to identify computationally efficient design approaches.

Design/methodology/approach
Several algorithms are compared for the design optimization of DRWTs. The algorithms vary widely in approaches and include a direct derivative-free method, as well as three surrogate-based optimization methods, two approximation-based approaches and one variable-fidelity approach with coarse discretization low-fidelity models.

Findings
The proposed variable-fidelity method required significantly lower computational cost than the derivative-free and approximation-based methods. Large computational savings come from using the time-consuming high-fidelity simulations sparingly and performing the majority of the design space search using the fast variable-fidelity models.

Originality/value
Due the complex simulations and the large number of designable parameters, the design of DRWTs require the use of numerical optimization algorithms. This work presents a novel and efficient design optimization framework for DRWTs using computationally intensive simulations and variable-fidelity optimization techniques.