bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchical processing of visual stimuli in nephropathic cystinosis
Authors: Sathappan Aakash , Trauner Doris
Published: January 2019

Previous studies have shown that individuals with cystinosis may exhibit difficulty with visuospatial tasks. Global and local (hierarchical) processing are specific types of visuospatial tasks mediated by the right and left parietal lobes respectively. The study objective was to determine whether individuals with cystinosis and carriers of the cystinosin gene mutation show deficits in global and/or local processing. The study included 48 children (32 controls, 16 cystinosis) and 56 adults (25 controls, 25 carriers, and 6 cystinosis). Participants were instructed to replicate 10 hierarchical stimuli to assess global‐local processing. The primary outcome measure was mean global and local performance on the hierarchical stimuli task between subgroups. Error subtypes were included to further assess each image. Compared to the control subgroups, adult and child cystinosis patients as well adult carriers demonstrated significant deficits in the global processing of a hierarchical stimulus against a background of unimpaired local processing. Child cystinosis patients performed significantly more poorly than controls on all error subtypes except local shape distortion. Adult cystinosis patients and carriers made significantly more global shape distortion errors than the controls. Our study shows that the cognitive profile documented in cystinosis patients and carriers includes significant difficulties with the global processing of an image. Results of the carrier population are important since they suggest that the cognitive impairments observed in patients cannot be attributed to symptomatic manifestations of the disease. Instead, the global processing deficits observed provide insight into the potential role of the cystinosin gene mutation on neurodevelopmental differences seen in these individuals.
A new metabolic disorder in human cationic amino acid transporter‐2 that mimics arginase 1 deficiency in newborn screening
Authors: Yahyaoui Raquel , Blasco‐Alonso Javier , Benito Carmen , Rodríguez‐García Enrique , Andrade Fernando , Aldámiz‐Echevarría Luis , Muñoz‐Hernández María C. , Vega Ana I. , Pérez‐Cerdá Celia , García‐Martín María L. , Pérez Belén
Published: January 2019

Purpose

We report a patient with a human cationic amino acid transporter 2 (CAT‐2) defect discovered due to a suspected arginase 1 deficiency observed in newborn screening (NBS).

Methods

A NBS sample was analyzed using tandem mass spectrometry. Screen results were confirmed by plasma and urine amino acid quantification. Molecular diagnosis was done using clinical exome sequencing. Dimethylated arginines were determined by HPLC and nitrate/nitrite levels by a colorimetric assay. The metabolomic profile was analyzed using 1D nuclear magnetic resonance spectroscopy.

Results

A Spanish boy of nonconsanguineous parents had high arginine levels in a NBS blood sample. Plasma and urinary cationic amino acids were high. Arginase enzyme activity in erythrocytes was normal and no pathogenic mutations were identified in the ARG1 gene. Massive parallel sequencing detected two loss‐of‐function mutations in the SLC7A2 gene. Currently, the child receives a protein‐controlled diet of 1.2 g/kg/day with protein‐and amino‐acid free infant formula, 30 g/day, and is asymptomatic.

Conclusion

We identified a novel defect in human CAT‐2 due to biallelic pathogenic variants in the SLC7A2 gene. The characteristic biochemical profile includes high plasma and urine arginine, ornithine, and lysine levels. NBS centers should know of this disorder since it can be detected in arginase 1 deficiency screening.
20-Hydroxy- and 20-carboxy-leukotriene (LT) B4 downregulate LTB4-mediated responses of human neutrophils and eosinophils
Authors: Archambault Anne-Sophie , Poirier Samuel , Lefebvre Julie-S , Robichaud Philippe-Pierre , Larose Marie-Chantal , Turcotte Caroline , Martin Cyril , Provost Véronique , Boudreau Luc H , McDonald Patrick P , Laviolette Michel , Surette Marc E , Flamand Nicolas
Published: January 2019

Leukotriene B4 (LTB4) plays a prominent role in innate immunity as it induces phagocyte recruitment, the release of antimicrobial effectors, and as it potentiates the ingestion and killing of pathogens. In humans, LTB4 has a short half-life and is rapidly metabolized by leukocytes, notably into 20-OH- and 20-COOH-LTB4 by neutrophils. Although these LTB4 metabolites bind to the BLT1 receptor with high affinity, they activate neutrophils to a much lower extent than LTB4. We thus postulated that LTB4 metabolites could dampen BLT1-mediated responses, therefore limiting the impact of LTB4 on human neutrophil functions. We found that 20-OH-LTB4 and 20-COOH-LTB4 inhibited all of the LTB4-mediated neutrophil responses we tested (migration, degranulation, leukotriene biosynthesis). The potencies of the different compounds at inhibiting LTB4-mediated responses were 20-OH-LTB4 = CP 105,696 (BLT1 antagonist) > > 20-COOH-LTB4 ≥ resolvin E1 (RVE1). In contrast, the fMLP- and IL-8-mediated responses we tested were not affected by the LTB4 metabolites or RVE1. 20-OH-LTB4 and 20-COOH-LTB4 also inhibited the LTB4-mediated migration of human eosinophils but not that induced by 5-KETE. Moreover, using 20-COOH-LTB4, LTB4, and LTB4-alkyne, we show that LTB4 is a chemotactic, rather than a chemokinetic factor for both human neutrophils and eosinophils. In conclusion, our data indicate that LTB4 metabolites and RVE1 act as natural inhibitors of LTB4-mediated responses. Thus, preventing LTB4 ω-oxidation might result in increased innate immunity and granulocyte functions.
Fast myocardial T1 mapping using shortened inversion recovery based schemes
Authors: Huang Li , Neji Radhouene , Nazir Muhummad Sohaib , Whitaker John , Reid Fiona , Bosio Filippo , Chiribiri Amedeo , Razavi Reza , Roujol Sébastien
Published: January 2019

Background

Myocardial T1 mapping shows promise for assessment of cardiomyopathies. Most myocardial T1 mapping techniques, such as modified Look–Locker inversion recovery (MOLLI), generate one T1 map per breath‐held acquisition (9–17 heartbeats), which prolongs multislice protocols and may be unsuitable for patients with breath‐holding difficulties.

Purpose

To develop and characterize novel shortened inversion recovery based T1 mapping schemes of 2–5 heartbeats.

Study Type

Prospective.

Population/Phantom

Numerical simulations, agarose/NiCl2 phantom, 16 healthy volunteers, and 24 patients.

Field Strength/Sequence

1.5T/MOLLI.

Assessment

All shortened T1 mapping schemes were characterized and compared with a conventional MOLLI scheme (5‐(3)‐3) in terms of accuracy, precision, spatial variability, and repeatability.

Statistical Tests

Kruskal–Wallis, Wilcoxon rank sum tests, analysis of variance, Student's t‐tests, Bland–Altman analysis, and Pearson correlation analysis.

Results

All shortened schemes provided limited T1 time variations (≤2% for T1 times ≤1200 msec) and limited penalty of precision (by a factor of ~1.4–1.5) when compared with MOLLI in numerical simulations. In phantom, differences between all schemes in terms of accuracy, spatial variability, and repeatability did not reach statistical significance (P > 0.71). In healthy volunteers, there were no statistically significant differences between all schemes in terms of native T1 times and repeatability for myocardium (P = 0.21 and P = 0.87, respectively) and blood (P = 0.79 and P = 0.41, respectively). All shortened schemes led to a limited increase of spatial variability for native myocardial T1 mapping with respect to MOLLI (by a factor of 1.2) (P < 0.0001). In both healthy volunteers and patients, the two‐heartbeat scheme and MOLLI led to highly linearly correlated T1 times (correlation coefficients ≥0.83).

Data Conclusion

The proposed two‐heartbeat T1 mapping scheme yields a 5‐fold acceleration compared with MOLLI, with highly linearly correlated T1 times, no significant difference of repeatability, and limited spatial variability penalty at 1.5T. This approach may enable myocardial T1 mapping in patients with severe breath‐holding difficulties and reduce the examination time of multislice protocols.

Level of Evidence: 1

Technical Efficacy Stage: 3

J. Magn. Reson. Imaging 2019;50:641–654.
Intellectual property—The Foundation of Innovation: A scientist's guide to intellectual property
Authors: Poticha David , Duncan Mark W.
Published: January 2019

Increasingly, the activities of the practicing scientist inextricably intersect with the business world. Science is central to the development and delivery of many goods or services, and scientific discovery can directly, or indirectly, lead to substantial revenue generation. Scientists, however, have little training in the complex issues of intellectual property (IP), and often little understanding of their rights and obligations. Here, we define IP and disuss what it means to be an inventor or creator of IP. We define and differentiate between the primary forms of IP—trade secrets, copyright, trademarks, and patents—and discuss their implementation and implications for the practicing scientist.
Quantification of enantiomers by mass spectrometry based on chemical derivatization and spectral shape deformation quantitative theory
Authors: Zhu Yan‐Li , Peng Zu‐Bin , Chen Zeng‐Ping , Wang Ji‐Kai , Shi Cai‐Xia , Chen Yao , Yu Ru‐Qin
Published: January 2019

A facile mass spectrometric kinetic method for quantitative analysis of chiral compounds was developed by integrating mass spectrometry based on chemical derivatization and the spectral shape deformation quantitative theory. Chemical derivatization was employed to introduce diastereomeric environments to the chiral compounds of interest, resulting in different abundance distribution patterns of fragment ions of the derivatization products of enantiomers in mass spectrometry. The quantitative information of the chiral compounds of interest was extracted from complex mass spectral data by an advanced calibration model derived based on the spectral shape deformation quantitative theory. The performance of the proposed method was tested on the quantitative analysis of R‐propranolol in propranolol tablets. Experimental results demonstrated that it could achieve accurate and precise concentration ratio predictions for R‐propranolol with an average relative predictive error (ARPE) of about 4%, considerably better than the corresponding results of the mass spectrometric method based on chemical derivatization and the univariate ratiometric model (ARPE: about 12%). The limit of detection (LOD) and limit of quantification (LOQ) of the proposed method for the concentration ratio of R‐propranolol were estimated to be 1.5% and 6.0%, respectively. The proposed method is complementary to the existing methods designed for the quantification of enantiomers such as the Cooks kinetic method.
Comparison of ESI‐MS/MS and APCI‐MS methods for the quantification of folic acid analogs in C. elegans
Authors: Annibal Andrea , Tam Hannah , Latza Christian , Antebi Adam
Published: January 2019

Folic acid (FA) plays a vital role in central metabolism, including the one carbon cycle, nucleotide, and amino acid biosynthesis. The development of sensitive, accurate analytical methods to measure FA intermediates in tissues is critical to understand their biological roles in diverse physiological and pathological contexts. Here, we developed a highly sensitive method for the simultaneous quantification of FA intermediates in the nematode Caenorhabditis elegans as a model to dissect metabolic networks. The method was further validated by analyzing the worm folate pool upon RNAi knockdown of the dihydrofolate reductase gene dhfr‐1. Comparative mass spectrometry behavior of the FA analogs using two different ion sources, electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), revealed ESI‐MS/MS to be more sensitive, but APCI‐MS provided more detailed structure inferences, which can elucidate chemical investigation and synthesis of FA analogs. Finally, we report on the use of in vitro oxidation coupled with high‐resolution mass spectrometry as a tool to discover new endogenous FA derivatives in the nematode.
Distinct differences in rates of oxygen consumption and ATP synthesis of regionally isolated non‐synaptic mouse brain mitochondria
Authors: Andersen Jens V. , Jakobsen Emil , Waagepetersen Helle S. , Aldana Blanca I.
Published: January 2019

Brain mitochondrial dysfunction has been implicated in several neurodegenerative diseases. The distribution and efficiency of mitochondria display large heterogeneity throughout the regions of the brain. This may imply that the selective regional susceptibility of neurodegenerative diseases could be mediated through inherent differences in regional mitochondrial function. To investigate regional cerebral mitochondrial energetics, the rates of oxygen consumption and adenosine‐5′‐triphosphate (ATP) synthesis were assessed in isolated non‐synaptic mitochondria of the cerebral cortex, hippocampus, and striatum of the male mouse brain. Oxygen consumption rates were assessed using a Seahorse XFe96 analyzer and ATP synthesis rates were determined by an online luciferin‐luciferase coupled luminescence assay. Complex I‐ and complex II‐driven respiration and ATP synthesis, were investigated by applying pyruvate in combination with malate, or succinate, as respiratory substrates, respectively. Hippocampal mitochondria exhibited the lowest basal and adenosine‐5′‐diphosphate (ADP)‐stimulated rate of oxygen consumption when provided pyruvate and malate. However, hippocampal mitochondria also exhibited an increased proton leak and an elevated relative rate of oxygen consumption in response to the uncoupler carbonyl cyanide 4‐(trifluoromethoxy)phenylhydrazone (FCCP), showing a large capacity for uncoupled respiration in the presence of pyruvate. When the complex II‐linked substrate succinate was provided, striatal mitochondria exhibited the highest respiration and ATP synthesis rate, whereas hippocampal mitochondria had the lowest. However, the mitochondrial efficiency, determined as ATP produced/O2 consumed, was similar between the three regions. This study reveals inherent differences in regional mitochondrial energetics and may serve as a tool for further investigations of regional mitochondrial function in relation to neurodegenerative diseases.
An unusually late dislodged atrial lead catching externalized ICD‐lead conductor. A rare cause of simultaneous atrial and ICD lead over‐sensing
Authors: Kristensen Jens , Kronborg Mads Brix , Lukac Peter , Nielsen Jens Cosedis
Published: January 2019

Abstract
How well are the downscaled CMIP5 models able to reproduce the monsoon precipitation over seven homogeneous zones of India?
Authors: Das Lalu , Akhter Javed
Published: January 2019

Statistical downscaling through perfect prognosis (PP) method is widely utilized to bridge the gap between large‐scale global climate model (GCM) simulations and regional scale or local scale observed predictands. Present study has assessed the performances of PP‐based downscaled CMIP5 GCMs in simulating observed monsoon precipitation over seven homogeneous zones of India, namely, North Mountainous India (NMI), Northwest India (NWI), North Central India (NCI), Northeast India (NEI), West Peninsular India (WPI), East Peninsular India (EPI) and South Peninsular India (SPI). Firstly, PP models have been constructed through principal component regression (PCR) using large‐scale atmospheric predictors from National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis. Secondly, GCM predictors have been imposed on the PP models to downscale large scale GCM simulations at regional scale. Four performance metrics namely percent bias (PB), interquartile relative fractions (IRF), Perkins skill score (PS) and Kuiper metric (KM) have been considered to evaluate skills of downscaled GCMs in reproducing mean, variance, probability distribution function (PDF) and cumulative distribution functions (CDF) of observed precipitation, respectively. As per results of several metrics, PP models have performed relatively better over NCI and SPI zones. However, they have shown poor skills in reproducing the observed variance over all zones. Further to improve the performances of PP models, quantile mapping has been embedded to form hybrid (PPQM) models, which have shown superior skills over all the zones. In addition, PPQM models have also shown their applicability to provide more reliable added value information over sub‐regional scale compared to raw GCMs.
Effect of thermal conductivity of substrate on laser‐induced phase transition of MoTe2
Authors: Chen Zhirong , Nan Haiyan , Liu Zheng , Wang Xiaoya , Gu Xiaofeng , Xiao Shaoqing
Published: January 2019

The phase transition of molybdenum ditelluride (MoTe2) has aroused great interest for enormous potential application in two‐dimensional (2D) optoelectronic sensors and nonvolatile information storage. Many in situ synthesis such as chemical vapor deposition and tellurization of Mo as well as postgrowth methods including thermal and strain engineering have been reported to realize the 2H‐to‐1T′ phase transition in MoTe2. Laser irradiation as one of thermal engineering has been demonstrated to be efficient and convenient for phase transition in MoTe2 flakes, but the substrate effect especially the thermal conductivity of substrate has not been studied. In this work, we systematically investigate the effect of four substrates (SiO2, Si, PDMS, and GaAs) with different thermal conductivities on the laser‐induced phase transition of MoTe2. The evolutions of Raman spectra clearly reveal the phase transition from 2H to 1T′ phase in MoTe2 on four different substrates with the increase in laser power. The laser power required for the phase transition is proportional to the substrate thermal conductivity. The PDMS substrate with the lowest thermal conductivity of 0.35 W/MK requires the lowest laser power of 2 mW to complete the phase transition. We have also fabricated a micro pattern heterostructure through artificial manipulation of the laser beam. Our work may provide valuable insights on the laser‐induced phase transition in MoTe2 and be helpful for phase transition of other TMDs.
Antioxidative system in sweet potato rootis activated by low‐temperature storage
Authors: Wang Si‐Qi , Tang Jun , Hu Kang‐Di , Huang Zhong‐Qin , Yang Feng , Zhang Hui‐Yun , Hu Lan‐Ying , Li Yan‐Hong , Yao Gai‐Fang , Zhang Hua
Published: January 2019

BACKGROUND

Sweet potato is susceptible to chilling injury during low‐temperature storage. To explore the correlation between chilling injury and reactive oxygen species (ROS) metabolism, the content of ROS and the activities and gene expression of antioxidant enzymes were analyzed in the typical storage‐tolerant cultivar Xushu 32 and storage‐sensitive cultivar Yanshu 25.

RESULTS

The activities of antioxidant enzymes including ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were enhanced rapidly in the early period of storage in response to chilling stress. Thereafter, the content of ROS metabolites increased consistently due to gradual decrease in ROS scavenging enzymes. Storage‐tolerant cultivar Xushu 32 had higher antioxidant enzyme activities and gene expressions as well as higher content of antioxidant metabolites and lower content of ROS metabolites compared with storage‐sensitive cultivar Yanshu 25, suggesting that the capacity of ROS scavenging by antioxidant enzymes and antioxidants is highly associated with the tolerance of sweet potato to chilling stress.

CONCLUSION

These results indicated that the antioxidative system is activated in the storage root of sweet potato and the antioxidative capacity is positively associated with better storage performance in the storage‐tolerant cultivar. © 2019 Society of Chemical Industry
Somatosensory evoked potential: Preventing brachial plexus injury in transaxillary robotic surgery
Authors: Huang Shuo , Garstka Meghan E. , Murcy Mohammed A. , Bamford Jeremey A. , Kang Sang‐Wook , Randolph Gregory W. , Kandil Emad
Published: January 2019

Objectives/Hypothesis

The potential for brachial plexopathy due to arm positioning is a major concern regarding the robotic transaxillary approach. Intraoperative nerve monitoring via somatosensory evoked potential (SSEP) has been suggested to prevent such injury. In this study, we examined the use of SSEP in detecting imminent brachial plexus traction during robotic transaxillary thyroid and parathyroid surgery.

Study Design

Retrospective case series.

Methods

A analysis was performed for all patients undergoing robotic transaxillary surgery with continuous intraoperative SSEP monitoring at a North American institution between 2015 and 2017. A significant intraoperative SSEP change was defined as a decrease in signal amplitude of >50% or an increase in latency of >10% from baseline established during preoperative positioning.

Results

One hundred thirty‐seven robotic transaxillary surgeries using SSEP monitoring were performed on 123 patients. Seven patients (5.1%) developed significant changes, with an average SSEP amplitude reduction of 73% ± 12% recorded at the signals' nadir. Immediate arm repositioning resulted in recovery of signals and complete return to baseline parameters in 14.3 ± 9.2 minutes. There was no difference in age (40.4 ± 9.4 years vs. 44.5 ± 13.4 years; P = .31) or body mass index (27.3 ± 3.7 kg/m2 vs. 26.9 ± 6.1 kg/m2; P = .79) between cases with and without SSEP change. Operative time was shorter for patients with significant SSEP change (131.6 ± 14.7 minutes vs. 146.5 ± 46.7 minutes; P = .048). There were no postoperative positional brachial plexus injuries.

Conclusions

SSEP is a novel, safe, and reliable tool in detection of position‐related brachial plexus neuropathy. Intraoperative monitoring using SSEP can play a vital role in early recognition and prevention of injury during robotic transaxillary thyroid and parathyroid surgery.

Level of Evidence

4 Laryngoscope, 129:2663–2668, 2019
Validation of the Chinese Velopharyngeal Insufficiency Effects on Life Outcomes Instrument
Authors: Huang Hanyao , Chen Nan , Yin Heng , Skirko Jonathan R. , Guo Chunli , Ha Pin , Li Jingtao , Shi Bing
Published: January 2019

Objectives/Hypothesis

To translate the Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) instrument into Chinese and test its psychometric properties.

Study Design

Quality of life instrument translation and validation.

Methods

The original English version of the VELO instrument was translated into Mandarin, back‐translated, and adapted among the Chinese population, based on the standardized guidelines for the cross‐culture adaption process. Velopharyngeal insufficiency (VPI) patients were identified by a professional speech and language pathologist. Internal reliability of the VELO instrument was assessed by the Cronbach's α coefficient. Discriminant validity was tested by the Mann‐Whitney U test. Construct validity was assessed by factor analysis.

Results

A total of 113 patients with VPI and 72 parents of the patients were enrolled. The mean age of the VPI patients was 14.8 years. Internal reliability was excellent; Cronbach's α coefficients were 0.92 and 0.94 for VPI patients and their parents, respectively. The Chinese VELO discriminated well between the VPI group and the controls, with a mean (standard deviation) score that was significantly lower for the VPI group (74.8 [25.7]) than the control group (98.0 [15.9]) (P < .001). The total scores and scores in the emotional domain or perception domain showed differences between VPI patients and their parents. Similar to the original study, the factor loading after rotation followed hypothesized domains largely, in spite of items from several domains loaded on the same factor.

Conclusions

The translated Chinese version of the VELO instrument demonstrated an acceptable reliability, discriminant validity, and construct validity. These psychometric properties suggested theoretical evidence for the further use of the VELO instrument among Chinese patients with VPI.

Level of Evidence

3b Laryngoscope, 129:E395–E401, 2019
The impact of sustainable land management on household crop production in the Blue Nile Basin, Ethiopia
Authors: Schmidt Emily , Tadesse Fanaye
Published: January 2019

Agricultural productivity in the highlands of Ethiopia is threatened by severe land degradation, resulting in significant reductions in agricultural GDP. In order to mitigate ongoing erosion and soil nutrient loss, the government of Ethiopia initiated a Sustainable Land Management Program (SLMP) targeting 177 micro‐watersheds in six regions of the Country. This study evaluates the impact of SLMP on the value of agricultural production across diverse agro‐ecological zones by using a panel survey from 2010 to 2014. Results suggest the need for long‐term engagement in SLM activities regardless of underlying biophysical endowments and environmental characteristics. The analysis finds that the SLMP is not associated with significant increases in household‐level agricultural value of production after 4 years of program participation regardless of agro‐ecological zone or landscape type. However, SLM investments and agricultural value of production increased significantly in both treatment and nontreatment areas between 2010 and 2014. Although data suggest positive trends in agricultural productivity and SLM activities during program years, past soil and water conservation programs in Ethiopia have failed to maintain momentum in rural communities after programs ceased funding. Given the results presented in this paper, SLM programs should place emphasis on SLM infrastructure maintenance over the medium to long term in order to reap sustainable effects of SLM on agricultural productivity in critical watersheds.
Open access mythbusting: Testing two prevailing assumptions about the effects of open access adoption
Authors: Pollock Dan , Michael Ann
Published: January 2019

This article looks at whether there is evidence to support two prevailing assumptions about open access (OA). These assumptions are: (1) fully OA journals are inherently of poorer quality than journals supported by other business models and (2) the OA business model, that is, paying for publication, is more ‘competitive’ than the subscription journal access business model. The assumptions have been discussed in contemporary industry venues, and we have encountered them in the course of their work advising scholarly communications organizations. Our objective was to apply data analytics techniques to see if these assumptions bore scrutiny. By combining citation‐based impact scores with data from publishers’ price lists, we were able to look for relationships between business model, price, and ‘quality’ across several thousands of journals. We found no evidence suggesting that OA journals suffer significant quality issues compared with non‐OA journals. Furthermore, authors do not appear to ‘shop around’ based on OA price.
The combination of minimally invasive electrochemical investigations and FTIR‐spectroscopy to analyze atmospheric corrosion product layers on zinc
Authors: Langklotz Ulrike , Babutzka Martin , Schneider Michael , Burkert Andreas
Published: January 2019

The present work describes the combination of electrochemical investigations by using a gel‐type electrolyte with Fourier‐transformed infrared spectroscopy to investigate partially extremely thin corrosion product films on titanium‐zinc. The gel pad method enables the determination of corrosion relevant parameters such as the potential and the linear polarization resistance without altering the corrosion product layers, which are extremely prone to re‐dissolution when freshly formed. Complementary infrared spectroscopy enables the determination of main compounds of even very thin surface layers of few tenth of nanometers with a certain lateral resolution. It was found that zinc forms mostly zinc carboxy‐hydroxides such as hydrozincite, under various exposure conditions. The protective properties of these hydrozincite layers depend on the structure of the corrosion product film rather than on its thickness. In mid‐term exposure tests, shallow corrosion pits were found even in the absence of corrosive agents such as chloride.
Supramolecular Gel Based on Crown‐Ether‐Appended Dynamic Covalent Macrocycles
Authors: Ge Yan , Gong Hanlin , Shang Jie , Jin Lin , Pan Tiezheng , Zhang Qiao , Dong Shengyi , Wang Yangxin , Qi Zhenhui
Published: January 2019

A new type of dynamic covalent macrocycle with self‐promoted supramolecular gelation behavior is developed. Under oxidative conditions, the dithiol compound containing a diamide alkyl linker with an odd number (7) of carbon chain and an appended crown ether shows a remarkable gelation ability in acetonitrile, without any template molecules. Due to the existence of crown ethers and disulfide bonds, the obtained gel shows a multiple stimuli‐responsiveness behavior. The mechanical properties and reversibility of the gel are investigated. Computational modeling suggests that the peripheral chain for diamide hydrogen bonding is responsible for the gelation process.
The endocytic membrane trafficking pathway plays a major role in the risk of Parkinson's disease
Authors: Bandres‐Ciga Sara , Saez‐Atienzar Sara , Bonet‐Ponce Luis , Billingsley Kimberley , Vitale Dan , Blauwendraat Cornelis , Gibbs Jesse Raphael , Pihlstrøm Lasse , Gan‐Or Ziv ,   The International Parkinson's Disease Genomics Consortium (IPDGC), Cookson Mark R. , Nalls Mike A. , Singleton Andrew B.
Published: January 2019

Background

PD is a complex polygenic disorder. In recent years, several genes from the endocytic membrane‐trafficking pathway have been suggested to contribute to disease etiology. However, a systematic analysis of pathway‐specific genetic risk factors is yet to be performed.

Objectives

To comprehensively study the role of the endocytic membrane‐trafficking pathway in the risk of PD.

Methods

Linkage disequilibrium score regression was used to estimate PD heritability explained by 252 genes involved in the endocytic membrane‐trafficking pathway including genome‐wide association studies data from 18,869 cases and 22,452 controls. We used pathway‐specific single‐nucleotide polymorphisms to construct a polygenic risk score reflecting the cumulative risk of common variants. To prioritize genes for follow‐up functional studies, summary‐data based Mendelian randomization analyses were applied to explore possible functional genomic associations with expression or methylation quantitative trait loci.

Results

The heritability estimate attributed to endocytic membrane‐trafficking pathway was 3.58% (standard error = 1.17). Excluding previously nominated PD endocytic membrane‐trafficking pathway genes, the missing heritability was 2.21% (standard error = 0.42). Random heritability simulations were estimated to be 1.44% (standard deviation = 0.54), indicating that the unbiased total heritability explained by the endocytic membrane‐trafficking pathway was 2.14%. Polygenic risk score based on endocytic membrane‐trafficking pathway showed a 1.25 times increase of PD risk per standard deviation of genetic risk. Finally, Mendelian randomization identified 11 endocytic membrane‐trafficking pathway genes showing functional consequence associated to PD risk.

Conclusions

We provide compelling genetic evidence that the endocytic membrane‐trafficking pathway plays a relevant role in disease etiology. Further research on this pathway is warranted given that critical effort should be made to identify potential avenues within this biological process suitable for therapeutic interventions. © 2019 International Parkinson and Movement Disorder Society
Association between the IL1R2 rs2072472 polymorphism and high‐altitude pulmonary edema risk
Authors: Jin Tianbo , Zhu Linhao , Bai Mei , He Xue , Wang Li , Yuan Dongya , Li Shanqu , He Yongjun
Published: January 2019

Aim

High‐altitude pulmonary edema (HAPE), as a multifactorial disease, is caused by stress failure and involves both environmental and genetic factors. Study shows that IL‐1 receptors can selectively decrease the oxygen arterial hypertension and influence the blood coagulation. So we evaluated whether genetic polymorphisms in IL1R1 and 1L1R2 genes are associated with the risk of HAPE in Chinese Han population.

Methods

Ten susceptible SNPs in the IL1R1 and IL1R2 genes were genotyped among 265 HAPE cases and 303 controls using the Agena MassARRAY platform. The associations of the SNP frequencies with HAPE were analyzed by chi‐square (χ2) test/Fisher's test. The genetic models were used to evaluate associations.

Results

In the allele model, we found that rs2072472 was significantly associated with a 0.73‐fold decreased risk of HAPE (OR = 0.73, 95% CI = 0.55–0.97, p = 0.033). In the genetic model analysis, the rs2072472 in IL1R2 gene was associated with a 0.32‐fold decreased risk of HAPE in the codominant model, 0.67‐fold decreased risk of HAPE in the dominant model, 0.36‐fold decreasing the risk of HAPE in the recessive model, and 0.66‐fold decreased risk of HAPE in the log‐additive model, respectively. We found three candidate SNPs (rs11674595, rs4851527, and rs719250) in the IL1R2 gene have shown strong linkage, and none of the haplotypes was significantly associated with risk of HAPE.

Conclusion

These findings suggested that IL1R2 polymorphisms may contribute to the protection of HAPE.
The prevalence of germline DICER1 pathogenic variation in cancer populations
Authors: Kim Jung , Schultz Kris Ann P. , Hill Dana Ashley , Stewart Douglas R.
Published: January 2019

Background

The DICER1 syndrome is an autosomal dominant tumor‐predisposition disorder associated with pleuropulmonary blastoma, a rare pediatric lung cancer. Somatic missense variation in “hotspot” codons in the RNaseIIIb domain (E1705, D1709, G1809, D1810, E1813) is observed in DICER1‐associated tumors. Previously, we found the prevalence of germline pathogenic DICER1 variation in the general population is 1:10,600. In this study, we investigated the prevalence of pathogenic DICER1 germline variation in The Cancer Genome Atlas (TCGA; 32 adult cancer types; 9,173 exomes) and the Therapeutically Applicable Research to Generate Effective Treatment (TARGET; two pediatric cancer types; 175 exomes) cohorts.

Methods

All datasets were annotated and binned into four categories: pathogenic, likely pathogenic, variant of unknown significance, or likely benign.

Results

The prevalence of DICER1 pathogenic variants was 1:4,600 in TCGA. A single participant with a uterine corpus endometrial carcinoma harbored two pathogenic germline DICER1 (hotspot and splice‐donor) variants, and a single participant with a rectal adenocarcinoma harbored a germline DICER1 stop‐gained variant. In the smaller TARGET dataset, we observed no pathogenic germline variants.

Conclusion

This is the largest comprehensive analysis of DICER1 pathogenic variation in adult and pediatric cancer populations using publicly available data. The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation.
Admissible equivalence transformations for linearization of nonlinear wave type equations
Authors: Özer Saadet
Published: January 2019

In the present paper, we consider a general family of two‐dimensional wave equations, which represents a great variety of linear and nonlinear equations within the framework of the transformations of equivalence groups. We have investigated the existence problem of point transformations that lead mappings between linear and nonlinear members of particular families and determined the structure of the nonlinear terms of linearizable equations. We have also given examples about some equivalence transformations between linear and nonlinear equations and obtained exact solutions of nonlinear equations via the linear ones.
Modeling of Coesterification Process for Biodegradable Poly(Butylene Succinate‐co‐Butylene Terephthalate) Copolyesters
Authors: Liu Tianqi , Gu Xueping , Li Naixiang , Wu Linbo , Wang Jiajun , Feng Lianfang
Published: January 2019

Comprehensive mathematical model based on the kinetics and thermodynamic equations is developed to examine a coesterification concept of biodegradable aliphatic‐aromatic copolyesters, poly(butylene succinate‐co‐butylene terephthalate) (PBST). The simulation results for batch process are validated with pilot experimental data. The continuous process is further studied to figure out the coesterification performance of succinic acid (SA) and terephthalic acid (TPA) with different reaction activities and thermodynamic properties in terms of reaction efficiency, small molecular evaporation and product quality. There is a compromise between the operating conditions of the two systems of SA/1,4‐butanediol (BDO) and TPA/BDO. Proper pressure reduction is beneficial to reaction efficiency and product quality. The way to increase reaction efficiency by raising temperature is limited due to the serious evaporation of reactants. Influenced by the solid–liquid equilibrium and the slow reaction rate of TPA, the esterification of acid needs sufficient residence time to complete.
Parameter map error due to normal noise and aliasing artifacts in MR fingerprinting
Authors: Kara Danielle , Fan Mingdong , Hamilton Jesse , Griswold Mark , Seiberlich Nicole , Brown Robert
Published: January 2019

Purpose

To introduce a quantitative tool that enables rapid forecasting of T1 and T2 parameter map errors due to normal and aliasing noise as a function of the MR fingerprinting (MRF) sequence, which can be used in sequence optimization.

Theory and Methods

The variances of normal noise and aliasing artifacts in the collected signal are related to the variances in T1 and T2 maps through derived quality factors. This analytical result is tested against the results of a Monte‐Carlo approach for analyzing MRF sequence encoding capability in the presence of aliasing noise, and verified with phantom experiments at 3 T. To further show the utility of our approach, our quality factors are used to find efficient MRF sequences for fewer repetitions.

Results

Experimental results verify the ability of our quality factors to rapidly assess the efficiency of an MRF sequence in the presence of both normal and aliasing noise. Quality factor assessment of MRF sequences is in agreement with the results of a Monte‐Carlo approach. Analysis of MRF parameter map errors from phantom experiments is consistent with the derived quality factors, with T1 (T2) data yielding goodness of fit R2 ≥ 0.92 (0.80). In phantom and in vivo experiments, the efficient pulse sequence, determined through quality factor maximization, led to comparable or improved accuracy and precision relative to a longer sequence, demonstrating quality factor utility in MRF sequence design.

Conclusion

The here introduced quality factor framework allows for rapid analysis and optimization of MRF sequence design through T1 and T2 error forecasting.
A cohesive XFEM model for simulating fatigue crack growth under mixed‐mode loading and overloading
Authors: Dekker R. , van der Meer F.P. , Maljaars J. , Sluys L.J.
Published: January 2019

Structures are subjected to cyclic loads that can vary in direction and magnitude, causing constant amplitude mode I simulations to be too simplistic. This study presents a new approach for fatigue crack propagation in ductile materials that can capture mixed‐mode loading and overloading. The extended finite element method is used to deal with arbitrary crack paths. Furthermore, adaptive meshing is applied to minimize computation time. A fracture process zone ahead of the physical crack tip is represented by means of cohesive tractions from which the energy release rate, and thus the stress intensity factor can be extracted for an elastic‐plastic material. The approach is therefore compatible with the Paris equation, which is an empirical relation to compute the fatigue crack growth rate. Two different models to compute the cohesive tractions are compared. First, a cohesive zone model with a static cohesive law is used. The second model is based on the interfacial thick level set method in which tractions follow from a given damage profile. Both models show good agreement with a mode I analytical relation and a mixed‐mode experiment. Furthermore, it is shown that the presented models can capture crack growth retardation as a result of an overload.
The crowding‐out effect within government funding: Implications for within‐source diversification
Authors: Zhao Jianzhi , Lu Jiahuan
Published: January 2019

The benefits and risks of revenue diversification lead scholars to propose within‐source diversification as a possible compromise. Although this revenue strategy sounds promising, no scholarly attention has been devoted to empirically examining it. This study explores within‐source diversification across government funding, specifically whether nonprofit receipt of support from a major government funder affects support from other government funders. Using a panel dataset of U.S.‐based international development nonprofits from 1995 to 2014, we find that nonprofits with more funding from the major funder are associated with significantly less funding from other funders. This crowding‐out effect weakens as organization size grows. The findings imply that the within‐source diversification strategy might be more desirable for larger organizations with the capacity to manage multiple funding relationships.
Rapid Assessment of Reward‐Related Eating: The RED‐X5
Authors: Vainik Uku , Eun Han Jung , Epel Elissa S. , Janet Tomiyama A. , Dagher Alain , Mason Ashley E.
Published: January 2019

Objective

The prevalence of obesity has created a plethora of questionnaires characterizing psychological aspects of eating behavior, such as reward‐related eating (RRE). The Reward‐based Eating Drive questionnaires (RED‐9, RED‐13) broadly and deeply assess the RRE construct. However, large‐sample research designs require shorter questionnaires that capture RRE quickly and precisely. This study sought to develop a brief, reliable, and valid version of the RED questionnaire.

Methods

All‐subset correlation was used to find a subset that maximally associated with the full RED‐13 in two separate samples. Results were validated in a third independent sample. Internal consistency, test‐retest reliability, and ability to explain variance in external outcomes were also assessed.

Results

A five‐item questionnaire (RED‐X5) correlated strongly with RED‐13 in the independent sample (r = 0.95). RED‐X5 demonstrated high internal consistency (omega total ≥ 0.80) and 6‐month test‐retest reliability (r = 0.72). RED‐X5 accurately reproduced known associations between RED‐13 and BMI, diabetes status, and craving for sweet and savory foods. As a novel finding, RED questionnaires predicted laboratory intake of chips.

Conclusions

RED‐X5 is a short, reliable, and valid measure of the RRE construct and can be readily implemented in large‐sample research designs in which questionnaire space is limited.
Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity
Authors: Srivastava Gitanjali , Fox Claudia K. , Kelly Aaron S. , Jastreboff Ania M. , Browne Allen F. , Browne Nancy T. , Pratt Janey S. A. , Bolling Christopher , Michalsky Marc P. , Cook Stephen , Lenders Carine M. , Apovian Caroline M.
Published: January 2019

A growing number of youth suffer from obesity and in particular severe obesity for which intensive lifestyle intervention does not adequately reduce excess adiposity. A treatment gap exists wherein effective treatment options for an adolescent with severe obesity include intensive lifestyle modification or metabolic and bariatric surgery while the application of obesity pharmacotherapy remains largely underutilized. These youth often present with numerous obesity‐related comorbid diseases, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, musculoskeletal problems, and psychosocial issues such as depression, anxiety, and social stigmatization. Current pediatric obesity treatment algorithms for pediatric primary care providers focus primarily on intensive lifestyle intervention with escalation of treatment intensity through four stages of intervention. Although a recent surge in the number of Food and Drug Administration‐approved medications for obesity treatment has emerged in adults, pharmacotherapy options for youth remain limited. Recognizing treatment and knowledge gaps related to pharmacological agents and the urgent need for more effective treatment strategies in this population, discussed here are the efficacy, safety, and clinical application of obesity pharmacotherapy in youth with obesity based on current literature. Legal ramifications, informed consent regulations, and appropriate off‐label use of these medications in pediatrics are included, focusing on prescribing practices and prescriber limits.
Illustration of Measurement Error Models for Reducing Bias in Nutrition and Obesity Research Using 2‐D Body Composition Data
Authors: Murillo Anarina L. , Affuso Olivia , Peterson Courtney M. , Li Peng , Wiener Howard W. , Tekwe Carmen D. , Allison David B.
Published: January 2019

Objective

This study aimed to illustrate the use and value of measurement error models for reducing bias when evaluating associations between body fat and having type 2 diabetes (T2D) or being physically active.

Methods

Logistic regression models were used to evaluate T2D and physical activity among adults aged 19 to 80 years from the Photobody Study (n = 558). Self‐reported T2D and physical activity were categorized as “yes” or “no.” Body fat measured by two‐dimensional photographs was adjusted for bias using dual‐energy x‐ray absorptiometry scans as a reference. Three approaches were applied: regression calibration (RC), simulation extrapolation (SIMEX), and multiple imputation (MI).

Results

Unadjusted two‐dimensional measures of body fat had upward biases of 30% and 233% for physical activity and T2D, respectively. For the physical activity model, RC‐adjusted values had a 13% upward bias, whereas MI and SIMEX decreased the bias to 9% and 91%, respectively. For the T2D model, MI reduced the bias to 0%, whereas RC and SIMEX increased the upward bias to > 300%.

Conclusions

Of three statistical approaches to reducing bias due to measurement errors, MI performed best in comparison to RC and SIMEX. Measurement error methods can improve the reliability of analyses that look for relations between body fat measures and health outcomes.
Early weight loss in a standalone mHealth intervention predicting treatment success
Authors: Patel M. L. , Hopkins C. M. , Bennett G. G.
Published: January 2019

Objective

Early weight loss is a strong predictor of longer‐term and clinically meaningful weight loss but has not been studied in the context of mobile health (‘mHealth’) interventions.

Methods

GoalTracker was a randomized trial among adults (21–65 years) with overweight or obesity comparing three 12‐week standalone mHealth interventions for weight loss. All arms received a free commercial mobile app (MyFitnessPal) for daily self‐monitoring of diet and/or weight and a goal to lose 5% of weight by 3 months. Collapsing across arms, this analysis examined participants with a 1‐month weight (n = 84), categorizing them as either early responders (≥2% weight loss at 1 month) or early non‐responders (<2% weight loss at 1 month).

Results

Early responders – 36% of participants – had greater per cent weight change at 3 months (−5.93% [95% confidence interval: −6.82%, −5.03%]) than early non‐responders (−1.45% [−2.15%, −0.75%]), which was sustained at 6 months (−5.91% [−7.33%, −4.48%] vs. −1.28% [−2.37%, −0.19%]; ps < 0.0001). Over half (57%) of early responders achieved ≥5% weight loss at 3 months vs. 11% of early non‐responders. At 4 weeks, self‐monitoring frequency (weight/diet) was significantly greater among early responders, which continued across 12 weeks.

Conclusion

Responding early to an mHealth treatment is associated with higher engagement and greater likelihood of achieving clinically meaningful weight loss.