bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging exposures of developmental toxicants
Authors: Wolff Mary S. , Buckley Jessie P. , Engel Stephanie M. , McConnell Rob S. , Barr Dana B. 
Published: January 2017

Purpose of review
The purpose of this review is to identify emerging developmental toxicants that are understudied in children's health. Exposures may arise from new products designed to improve utility, to reduce toxicity, or to replace undesirable chemicals. Exposures to less-toxic chemicals may also be significant if they are very commonly used, thereby generating widespread exposure. Sources of exposure include the workplace, personal, home, and office products; food, water, and air.

Recent findings
We describe eight exposure categories that contain numerous potential developmental toxicants. References are discussed if reported in PubMed during the past decade at least 10 times more frequently than in 1990–2000. Examples included phthalates, phenols, sunscreens, pesticides, halogenated flame retardants, perfluoroalkyl coatings, nanoparticles, e-cigarettes, and dietary polyphenols. Replacements are often close structural homologs of their precursors. We suggest biomonitoring as preferred means of exposure assessment to emerging chemicals. Some existing analytic methods would require minimal modification to measure these exposures, but others require toxicokinetic and analytic investigation.

Summary
A deliberate strategy for biomonitoring of emerging replacement chemicals is warranted, especially in view of concerns regarding developmental toxicity. To prevent adverse health effects, it is important to characterize such exposures before they become widely disseminated.
Tobacco, e-cigarettes, and child health
Authors: Peterson Lisa A. , Hecht Stephen S. 
Published: January 2017

Purpose of the review
The availability of the Children's Health Exposure Assessment Resource funded by the National Institute of Environmental Health Sciences provides new opportunities for exploring the role of tobacco smoke exposure in causing harm to children.

Recent findings
Children of smokers are exposed to nicotine and other harmful tobacco smoke chemicals in utero as well as in their environment. This passive exposure to tobacco smoke has a variety of negative effects on children. In-utero exposure to tobacco smoke causes poor birth outcomes and influences lung, cardiovascular, and brain development, placing children at increased risk of a number of adverse health outcomes later in life, such as obesity, behavioral problems, and cardiovascular disease. Furthermore, most smokers start in their adolescence, an age of increased nicotine addiction risk. Biomarkers of tobacco exposure helps clarify the role tobacco chemicals play in influencing health both in childhood and beyond. Although electronic cigarettes (e-cigarettes) appear to be a nicotine delivery device of reduced harm, it appears to be a gateway to the use of combustible cigarette smoking in adolescents.

Summary
Pediatric researchers interested in elucidating the role of tobacco smoke exposure in adverse outcomes in children should incorporate biomarkers of tobacco exposure in their studies.
Does quality improvement work in neonatology improve clinical outcomes?
Authors: Ellsbury Dan L. , Clark Reese H. 
Published: January 2017

Purpose of review
Quality improvement initiatives in neonatology have been promoted as an important way of improving outcomes of newborns. The purpose of this review is to examine the effectiveness of recent quality improvement work in improving the outcomes of infants requiring neonatal intensive care.

Recent findings
Quality improvement collaboratives and single-center projects demonstrate improvement of clinical processes and outcomes in neonatology that impact both preterm and term infants. Declines in morbidities, resource use, and length of stay have been associated with reductions in healthcare costs.

Summary
Recent quality improvement work has shown evidence of improvement in clinical outcomes in neonatal intensive care patients. These improvements have important implications for the reduction of healthcare costs in this population.
Interleukin-6 and Interleukin-8 Levels Correlate With the Severity of Aplastic Anemia in Children
Authors: Gupta Vineeta , Kumar Sushil , Sonowal Rimjhim , Singh Surya K. 
Published: January 2017

Aim:
The aim of this study was to evaluate the levels of interleukin (IL)-6 and IL-8 in patients with aplastic anemia and its correlation with severity of the disease.

Materials and Methods:
IL-6 and IL-8 levels were measured in 40 patients with aplastic anemia in the age group of 4 to 14 years. A total of 40 healthy children served as controls. Quantitative estimation of IL-6 and IL-8 was performed using a solid-phase sandwich ELISA kit. Results were presented as IL-6 and IL-8 concentrations in pg/mL. Patients received immunosuppressive therapy per the British Committee for Standards in Haematology Guidelines 2009.

Results:
Mean age of the patients was 9.78±2.74 years. IL-6 level of patients was elevated compared with controls (193.48±352.3 vs. 4.58±3.39; P<0.001). IL-8 levels were also significantly elevated in patients compared with controls (15.58±18.0 vs. 1.85±0.95; P<0.001). IL levels were also assessed in relation to severity of the disease. Levels were the highest in patients with very severe aplastic anemia (724.33±519.42), followed by severe aplastic anemia (80.51±66.28 pg/mL), and non–severe aplastic anemia (6.01±1.89). Differences were statistically significant. A similar trend was also observed for IL-8 levels, where the levels were 41.02±24.23, 11.34±8.0, and 1.67±0.71 for very severe aplastic anemia, severe aplastic anemia, and non–severe aplastic anemia, respectively. The differences were again statistically significant. IL levels were also correlated with the treatment outcome. Responders had lower levels compared with nonresponders, but the difference was not statistically significant (186.36±322.45 vs. 198.74±368.10). Levels of ILs decreased in responders, but were not comparable with that of controls 6 months after therapy.

Conclusions:
High levels of IL-6 and IL-8 were observed in children with aplastic anemia. Increased levels showed correlation with disease severity and therefore appear to play an important role in aplastic anemia. However, levels had no significant correlation with the treatment outcome.
Pulmonary Nodule Size <5 mm Still Warrants Investigation in Patients With Osteosarcoma and Ewing Sarcoma
Authors: Kusma Jared , Young Cody , Yin Han , Stanek Joseph R. , Yeager Nicholas , Aldrink Jennifer H. 
Published: January 2017

Background:
Osteosarcoma (OS) and Ewing sarcoma (ES) have a high propensity to develop pulmonary metastases. Lung lesions with calcification, peripheral location, and size >5 mm are more likely to represent malignant metastases. We evaluated the incidence of malignancy in nodules 5 mm or less to potentially guide decisions between biopsy and observation.

Materials and Methods:
A retrospective review of patients <25 years of age with metastatic OS and ES treated at our institution between 2001 and 2014 who had undergone pulmonary nodule biopsy was performed. Computed tomographic scans were reviewed to evaluate nodule size and change over time.

Results:
Thirty-five patients (27 OS, 8 ES) met inclusion criteria. One hundred sixteen nodules were biopsied (97 OS, 19 ES). Nodule size at biopsy was not significantly different between the malignant (median, 6 mm, range, 1 to 79 mm) and benign (median, 3 mm, range, 1 to 21 mm) lesions (P=0.063). Size of pulmonary nodules <5 mm was not entirely predictive of benign status, with sensitivity estimate of 0.709 (95% confidence interval, 0.465-0.872; P=0.091) and specificity estimate of 0.776 (95% confidence interval, 0.324-0.962; P=0.219) for all nodules biopsied.

Conclusions:
Pulmonary nodules in patients with OS and ES <5 mm cannot be excluded from biopsy considerations.
Diabetes Complications and Depressive Symptoms: Prospective Results From the Montreal Diabetes Health and Well-Being Study
Authors: Deschênes Sonya S. , Burns Rachel J. , Pouwer Frans , Schmitz Norbert 
Published: January 2017

ABSTRACT

Objective
Prospective studies testing the potential impact of diabetes complications on depression are limited. The present study examined the longitudinal associations between diabetes complications and the risk and recurrence/persistence of depressive symptoms.

Methods
Data were from a prospective community cohort telephone survey of adults with diabetes (N = 1314). Diabetes complications and depressive symptoms were assessed via self-report (Diabetes Complications Index and Patient Health Questionnaire-9, respectively) at baseline and annually for 5 years. Statistical models adjusted for sociodemographic, lifestyle, and diabetes characteristics.

Results
The number of diabetes complications at baseline was positively associated with a greater risk of elevated depressive symptoms, with the highest risk found for those with four to six complications at baseline (risk ratio = 2.73, 95% confidence interval = 1.64–4.56). Cerebrovascular disease was the complication most strongly associated with incident depressive symptoms (risk ratio = 2.22, 95% confidence interval = 1.59–3.10). Coronary artery disease, peripheral vascular disease, and neuropathy were also associated with the risk of depression, whereas foot problems and eye problems were not. In addition, a greater number of diabetes complications were associated with recurrent/persistent depression, though with a small effect size (Δr
2 = .02). A parallel process latent growth curve model indicated that increases in diabetes complications were associated with increases in depressive symptoms during the course of the follow-up period (β = .74, p < .001).

Conclusions
This study demonstrates the temporal relation between diabetes complications and depressive symptoms and underscores the psychological burden of diabetes complications by prospectively demonstrating the increased risk and recurrence of depressive symptoms associated with diabetes complications.
A Giant Tumefactive Virchow-Robin Space: A Rare Cause of a Homonymous Quadrantanopia
Authors: Rivet Alysse , Gauthier Anne-Sophie , Chatain Marion , Billon-Grand Romain , Thines Laurent , Delbosc Bernard 
Published: January 2017

Abstract:
A 53-year-old woman was found to have a left inferior homonymous quadrantanopia. Brain MRI disclosed a giant Virchow–Robin space compressing the right optic tract. After fenestration of this cystic lesion, most of the visual field loss resolved. Giant Virchow–Robin spaces may cause homonymous field defects which, with appropriate management, may improve.
Efferent Vision Therapy
Authors: Rucker Janet C. , Phillips Paul H. 
Published: January 2017

Background:
Traditional orthoptic therapy used by ophthalmologists, orthoptists, and optometrists is directed at improving visual acuity, ocular alignment, or both. For example, convergence exercises are used to treat convergence insufficiency (CI). However, other forms of “vision therapy” are directed at improving “visual processing and efficiency.” The therapeutic regimen often entails repetitive ocular motor tasks performed during multiple office visits with a behavioral optometrist. These ocular motor tasks are used to treat diverse conditions such as learning disabilities, poor reading ability, dyslexia, and attention-deficit hyperactivity disorder (ADHD). Evidence regarding the efficacy of therapy directed at ocular motility for the treatment of multiple conditions is reviewed.

Evidence Acquisition:
Review of literature.

Results:
Randomized, controlled, double-masked studies show that convergence exercises reduce symptoms and improve signs of CI in otherwise healthy patients. However, the most efficacious convergence tasks, and the optimal duration and frequency of these tasks, remain unknown. Patients with learning disabilities, poor reading ability, dyslexia, or ADHD do not consistently have unique ocular motor deficits. Patients who acquire ocular motor deficits do not develop these conditions. There are no randomized, controlled studies that show treatment consisting of repetitive ocular motor tasks improves learning disabilities, reading, dyslexia, or ADHD.

Conclusions:
Convergence exercises effectively treat CI in healthy patients. The optimal treatment regimen is unknown. There is insufficient evidence to recommend “vision therapy” for the treatment of learning disabilities, impaired reading, dyslexia, or ADHD.
Transcriptome-wide splicing quantification in single cells
Authors: Huang Yuanhua , Sanguinetti Guido 
Published: January 2017

AbstractSingle cell RNA-seq (scRNA-seq) has revolutionised our understanding of transcriptome variability, with profound implications both fundamental and translational. While scRNA-seq provides a comprehensive measurement of stochasticity in transcription, the limitations of the technology have prevented its application to dissect variability in RNA processing events such as splicing. Here we present BRIE (Bayesian Regression for Isoform Estimation), a Bayesian hierarchical model which resolves these problems by learning an informative prior distribution from sequence features. We show that BRIE yields reproducible estimates of exon inclusion ratios in single cells and provides an effective tool for differential isoform quantification between scRNA-seq data sets. BRIE therefore expands the scope of scRNA-seq experiments to probe the stochasticity of RNA-processing.
Nucleotide-dependent stiffness suggests role of interprotofilament bonds in microtubule assembly
Authors: Taute Katja M. , Florin Ernst-Ludwig 
Published: January 2017

ABSTRACTMany eukaryotic cell functions depend on dynamic instability, meaning the nucleotide-driven assembly and disassembly of microtubules. Assembly requires the constituent tubulin dimers to bind the nucleotide GTP, and its subsequent hydrolysis to GDP induces disassembly. The underlying structural mechanisms, however, are not well understood. Here, we determine the strength of contacts in the microtubule lattice by combining high precision measurements of the bending stiffness of analogues of GTP and GDP microtubules with a recent theoretical model. While previous structural studies have focussed on how the curvature of the tubulin dimer is affected by nucleotide binding, we present evidence of a dramatic regulation of the lateral interactions between the parallel protofilaments that dimers form in the microtubule. We conclude that the shear coupling between neighboring protofilaments is at least two orders of magnitude stronger in the GTP state than in the GDP state, and discuss the implications for the microtubule assembly.
The Effects of Sex and Diet on Physiology and Liver Gene Expression in Diversity Outbred Mice
Authors: Gatti Daniel M. , Simecek Petr , Somes Lisa , Jeffrey Clifton T. , Vincent Matthew J. , Choi Kwangbom , Chen Xingyao , Churchill Gary A. , Svenson Karen L. 
Published: January 2017

ABSTRACTInter-individual variation in metabolic health and adiposity is driven by many factors. Diet composition and genetic background and the interactions between these two factors affect adiposity and related traits such as circulating cholesterol levels. In this study, we fed 850 Diversity Outbred mice, half females and half males, with either a standard chow diet or a high fat, high sucrose diet beginning at weaning and aged them to 26 weeks. We measured clinical chemistry and body composition at early and late time points during the study, and liver transcription at euthanasia. Males weighed more than females and mice on a high fat diet generally weighed more than those on chow. Many traits showed sex- or diet-specific changes as well as more complex sex by diet interactions. We mapped both the physiological and molecular traits and found that the genetic architecture of the physiological traits is complex, with many single locus associations potentially being driven by more than one polymorphism. For liver transcription, we find that local polymorphisms affect constitutive and sex-specific transcription, but that the response to diet is not affected by local polymorphisms. We identified two loci for circulating cholesterol levels. We performed mediation analysis by mapping the physiological traits, given liver transcript abundance and propose several genes that may be modifiers of the physiological traits. By including both physiological and molecular traits in our analyses, we have created deeper phenotypic profiles to identify additional significant contributors to complex metabolic outcomes such as polygenic obesity. We make the phenotype, liver transcript and genotype data publicly available as a resource for the research community.
Rps3/uS3 promotes mRNA binding at the 40S ribosome entry channel and stabilizes preinitiation complexes at start codons
Authors: Dong Jinsheng , Aitken Colin Echeverría , Thakur Anil , Shin Byung-Sik , Lorsch Jon R. , Hinnebusch Alan G. 
Published: January 2017

ABSTRACTThe eukaryotic 43S pre-initiation complex (PIC) bearing Met-tRNAiMetin a ternary complex (TC) with eIF2-GTP scans the mRNA leader for an AUG codon in favorable “Kozak” context. AUG recognition provokes rearrangement from an open PIC conformation with TC bound in a state not fully engaged with the P site (“POUT”) to a closed, arrested conformation with TC tightly bound in the “PIN” state. Yeast ribosomal protein Rps3/uS3 resides in the mRNA entry channel of the 40S subunit and contacts mRNA via conserved residues whose functional importance was unknown. We show that substitutions of these residues reduce bulk translation initiation and diminish initiation at near-cognate UUG start codons in yeast mutants in which UUG selection is abnormally high (Sui-), conferring the Ssu-phenotype. Two such Ssu-substitutions—R116D and R117D—also increase discrimination against an AUG codon in suboptimal Kozak context. Consistently, the Arg116 and Arg117 substitutions destabilize TC binding to 48S PICs reconstituted in vitro with mRNA harboring a UUG start codon, indicating destabilization of the closed PINstate with a UUG:anticodon mismatch. Using model mRNAs lacking contacts with either the mRNA entry or exit channels of the 40S subunit, we demonstrate that Arg116/Arg117 are crucial for stabilizing PIC:mRNA contacts at the entry channel, complementing the function of eIF3 at both entry and exit channels. The corresponding residues in bacterial uS3 promote the helicase activity of the elongating ribosome, suggesting that uS3 contacts with mRNA enhance multiple phases of translation across different domains of life.
A study into the ability of SPD to restore the buckling strength and modes of rib stiffened panels with simulated stress corrosion cracks
Authors: Jones Rhys , Matthews Neil , Peng Daren , Orchowski Nicholas 
Published: January 2017

Purpose
The purpose of this paper is to describe the results of a combined numerical and experimental study into the ability of supersonic particle deposition (SPD) to restore the load carrying capacity of rib stiffened wing planks with simulated stress corrosion cracking (SCC).

Design/methodology/approach
In this context the experimental results reveal that SCC can result in a dramatic reduction in the load carrying capacity of the structure and catastrophic failure via cracking that tears the length of the structure through buckling. A combined numerical and experimental study then reveals how this reduction, in the load carrying capacity can be overcome by using SPD.

Findings
This paper is the first to show that SPD can be used to restore the load carrying capacity of rib stiffened structures with SCC. It also shows that SPD repairs can be designed to have only a minimal effect on the local stiffness and hence on the load path. However, care should be taken to ensure that the design is such that premature failure of the SPD does not occur.

Originality/value
This is the first paper to show that a thin layer of SPD deposited 7,075 aluminium alloy powder on either side of the SCC-simulated stiffener has the potential to restore the load carrying capability of a rib stiffened structure. As such it represents an important first step into establishing the potential for SPD to restore the buckling strength of rib stiffened wing panels containing SCC.
Computational investigation of ballistic-impact behavior and penetration resistance of a nacre-like ceramic/polymer laminated composite
Authors: Grujicic Mica , Ramaswami S. , Snipes Jennifer 
Published: January 2017

Purpose
Nacre is a biological material constituting the innermost layer of the shells of gastropods and bivalves. It consists of polygonal tablets of aragonite, tessellated to form individual layers and having the adjacent layers as well as the tablets within a layer bonded by a biopolymer. Due to its highly complex hierarchical microstructure, nacre possesses an outstanding combination of mechanical properties, the properties which are far superior to the ones that are predicted using techniques such as the rule of mixtures. Given these properties, a composite armor the structure of which mimics that of nacre may have improved performance over a monolithic armor having a similar composition and an identical areal density. The paper aims to discuss these issues.

Design/methodology/approach
In the present work, an attempt is made to model a nacre-like composite armor consisting of B4C tablets and polyurea tablet/tablet interfaces. The armor is next tested with respect to impact by a solid right circular cylindrical (SRCC) rigid projectile, using a transient non-linear dynamics finite-element analysis. The ballistic-impact response and the penetration resistance of the armor are then compared with that of the B4C monolithic armor having an identical areal density. Furthermore, the effect of various nacre microstructural features (e.g. surface profiling, micron-scale asperities, mineral bridges between the overlapping tablets lying in adjacent layers, and B4C nano-crystallinity) on the ballistic-penetration resistance of the composite armor is investigated in order to identify an optimal nacre-like composite armor architecture having the largest penetration resistance.

Findings
The results obtained clearly show that a nacre-like armor possesses a superior penetration resistance relative to its monolithic counterpart, and that the nacre microstructural features considered play a critical role in the armor-penetration resistance.

Originality/value
The present work indicates that for a given choice of armor material, penetration resistance may be improved by choosing a structure resembling that of nacre.