bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstetric anesthesia/analgesia does not affect disease course in multiple sclerosis: 10‐year retrospective cohort study
Authors: Harazim Hana , Štourač Pavel , Janků Petr , Zelinková Hana , Frank Kamil , Dufek Michal , Štourač Petr
Published: July 2018

Objectives

Multiple sclerosis (MS) often occurs in young women and the effect of obstetric anesthesia/analgesia on the disease is poorly understood. No previous study has investigated the course of the disease in women in labor in the Czech Republic. The aim of this study was to evaluate the occurrence or absence of relapses in the 6‐month postpartum period in MS parturients with and without obstetric anesthesia/analgesia.

Materials and Methods

We retrospectively studied all deliveries (n = 58,455) at the University Hospital Brno from 2004 to 2013 and identified those of the women with an ICD‐10 code G35 (MS) recorded anytime in their medical history (n = 428). We included only deliveries of women with confirmed diagnosis at the time of labor (n = 70). Statistical analysis was performed using the Fischer Exact Test.

Results

There were 70 deliveries of 65 women, including 45 vaginal deliveries and 25 Cesarean deliveries (16 under general anesthesia, 8 with epidural anesthesia and 1 with spinal anesthesia). Epidural obstetric analgesia was performed in 11 deliveries. There was no statistically significant difference in relapses between the vaginal delivery group (n = 15; 33%) and Cesarean section group (n = 10; 40%), p = 0.611.

Conclusion

Neither delivery mode (vaginal vs Caesarean) nor type of obstetric anesthesia/analgesia was found to have any impact on the course of MS at 6 months postpartum in women with this condition.
Interaction between glutathione S‐transferase M1‐null/present polymorphism and adjuvant chemotherapy influences the survival of breast cancer
Authors: Li Shuang , Lang Guan‐Tian , Zhang Ying‐Zhou , Yu Ke‐Da , Shao Zhi‐Ming , Zhang Qiang
Published: July 2018

Glutathione S‐transferase M (GSTM) family is concerned with oxidative stress, which is associated with breast carcinogenesis and chemotherapy response. The null polymorphism of GSTM1 gene results in a thorough absence of the enzyme function. Our study was to evaluate the association between GSTM1 null/present polymorphism and chemotherapy treatment outcome in breast cancer patients. A total of unrelated 714 patients with a histologically confirmed breast cancer were randomly selected from two independent cancer centers. Polymerase chain reaction was performed to analyze null/present genotypes of GSTM1 in our study. Our study found that the present genotype of GSTM1 was associated with a better relapse‐free survival (RFS) (P = .03) with adjusted hazard ratio (HR) [95% confidence interval (CI)] of 0.63 (95% CI: 0.42‐0.93). The present genotype of GSTM1 was significantly correlated with a better RFS compared with the null genotype in the nonchemotherapy group (HR = 0.17, 95% CI: 0.06‐0.50; P = 0.001), but no effect was observed in the chemotherapy group (HR = 0.81, 95% CI: 0.52‐1.26; P = 0.35). Moreover, the interaction between the GSTM1‐null/present genotype and adjuvant chemotherapy was significant (P = 0.04) in further analysis. Our study suggests that the GSTM1 polymorphism plays a complex role in influencing the chemotherapy response and breast cancer survival. It is suggested that the GSTM1‐present genotype might prevent progression in breast cancer patients. In the meanwhile, it could damage the benefit of adjuvant chemotherapy as well in certain ways.
In Situ Electrochemical Impedance Spectroscopy Measurements and their Interpretation for the Diagnostic of Metallic Cultural Heritage: A Review
Authors: Ramírez Barat Blanca , Cano Emilio
Published: July 2018

Protecting metallic cultural heritage from corrosion is a major challenge for metal conservators. Electrochemical techniques offer a great potential for monitoring the conservation condition of this type of heritage, providing a powerful tool for designing conservation strategies. For this reason, the application of techniques such as electrochemical impedance spectroscopy (EIS) has aroused increasing interest in recent years, although some difficulties in application and interpretation of the results still keep it from being routine practice. This Review aims to picture the state‐of‐the‐art of using electrochemical impedance spectroscopy (EIS) for the in situ monitoring of metallic cultural heritage, focusing on spectra interpretation and different approaches that have been proposed to perform field measurements since the 1990’s. In the first part of the Review, different cell designs based on the use of liquid or solid electrolytes for in situ measurements are reviewed. In the second part, a few general equivalent circuits are proposed as a basis for interpreting results on different metal surfaces after discussing different models proposed in literature. This overview intends to summarize and clarify the key points in the use of EIS, and encourage the use of this and other electrochemical techniques in the field of conservation science, for a better preservation of our cultural heritage.
Transient Secondary and Tertiary Structure Formation Kinetics in the Intrinsically Disordered State of α‐Synuclein from Atomistic Simulations
Authors: Graen Timo , Klement Reinhard , Grupi Asaf , Haas Elisha , Grubmüller Helmut
Published: July 2018

In the absence of a stable fold, transient secondary structure kinetics define the native state of the prototypical and pharmacologically relevant intrinsically disordered protein (IDP) α‐Synuclein (aS). Here, we investigate kinetics preventing ordering and possibly pathogenic β‐sheet aggregation. Interestingly, transient β‐sheets form frequently at sub μs time scales precisely at the positions observed in aS amyloid fibrils. The formation kinetics competes with rapid secondary structure dissociation rates, thus explaining the low secondary structure content. The fast secondary structure dissociation times are very similar to the dynamics of tertiary structure rearrangements. These findings suggest that the fast dissociation kinetics slows down conformational selection processes for aS aggregation, which may be a general mechanism controlling the aggregation kinetics of IDPs.
Does customer engagement in corporate social responsibility initiatives lead to customer citizenship behaviour? The mediating roles of customer‐company identification and affective commitment
Authors: Hur Won‐Moo , Kim Hanna , Kim Hyun Kyung
Published: July 2018

This study examines how customers' perceptions of corporate social responsibility (CSR) affect their customer citizenship behaviour and the mediated link through customer‐company identification and affective commitment. Working with a sample of 615 banking service customers in South Korea, structural equation modelling is employed to test the research hypotheses. The results of this study suggest that customers' perceptions of CSR are positively related to their customer citizenship behaviour. Second, customer‐company identification was found to mediate the positive relationship between customers' perceptions of CSR and customer citizenship behaviour. Third, customers' affective commitment towards their organization also mediated the positive relationship between customers' perceptions of CSR and customer citizenship behaviour. Finally, the relationship between customers' perceptions of CSR and customer citizenship behaviour is sequentially and partially mediated by customer‐company identification and affective commitment. The theoretical and managerial implications of the results and the limitations of the study are discussed, and future research directions are suggested.
Selective constraints in cold‐region wild boars may defuse the effects of small effective population size on molecular evolution of mitogenomes
Authors: Chen Jianhai , Ni Pan , Tran Thi Thuy Nhien , Kamaldinov Evgeniy Varisovich , Petukhov Valeriy Lavrentyevich , Han Jianlin , Liu Xiangdong , Šprem Nikica , Zhao Shuhong
Published: July 2018

Spatial range expansion during population colonization is characterized by demographic events that may have significant effects on the efficiency of natural selection. Population genetics suggests that genetic drift brought by small effective population size (Ne) may undermine the efficiency of selection, leading to a faster accumulation of nonsynonymous mutations. However, it is still unknown whether this effect might be balanced or even reversed by strong selective constraints. Here, we used wild boars and local domestic pigs from tropical (Vietnam) and subarctic region (Siberia) as animal model to evaluate the effects of functional constraints and genetic drift on shaping molecular evolution. The likelihood‐ratio test revealed that Siberian clade evolved significantly different from Vietnamese clades. Different datasets consistently showed that Siberian wild boars had lower Ka/Ks ratios than Vietnamese samples. The potential role of positive selection for branches with higher Ka/Ks was evaluated using branch‐site model comparison. No signal of positive selection was found for the higher Ka/Ks in Vietnamese clades, suggesting the interclade difference was mainly due to the reduction in Ka/Ks for Siberian samples. This conclusion was further confirmed by the result from a larger sample size, among which wild boars from northern Asia (subarctic and nearby region) had lower Ka/Ks than those from southern Asia (temperate and tropical region). The lower Ka/Ks might be due to either stronger functional constraints, which prevent nonsynonymous mutations from accumulating in subarctic wild boars, or larger Ne in Siberian wild boars, which can boost the efficacy of purifying selection to remove functional mutations. The latter possibility was further ruled out by the Bayesian skyline plot analysis, which revealed that historical Ne of Siberian wild boars was smaller than that of Vietnamese wild boars. Altogether, these results suggest stronger functional constraints acting on mitogenomes of subarctic wild boars, which may provide new insights into their local adaptation of cold resistance.
Tropical forest temperature thresholds for gross primary productivity
Authors: Pau Stephanie , Detto Matteo , Kim Youngil , Still Christopher J.
Published: July 2018

Tropical forests are hyper‐diverse and perform critical functions that regulate global climate, yet they are also threatened by rising temperatures. Canopy temperatures depart considerably from air temperatures, sometimes by as much as air temperatures are projected to increase by the end of this century; however, canopy temperatures are rarely measured or considered in climate change analyses. Our results from near‐continuous thermal imaging of a well‐studied tropical forest show that canopy temperatures reached a maximum of ~34°C, and exceeded maximum air temperatures by as much as 7°C. Comparing different canopy surfaces reveals that bark was the warmest, followed by a deciduous canopy, flowers, and coolest was an evergreen canopy. Differences among canopy surfaces were largest during afternoon hours, when the evergreen canopy cooled more rapidly than other canopy surfaces, presumably due to transpiration. Gross primary productivity (GPP), estimated from eddy covariance measurements, was more strongly associated with canopy temperatures than air temperatures or vapor pressure deficit. The rate of GPP increase with canopy temperatures slowed above ~28–29°C, but GPP continued to increase until ~31–32°C. Although future warming is projected to be greater in high‐latitude regions, we show that tropical forest productivity is highly sensitive to small changes in temperature. Important biophysical and physiological characteristics captured by canopy temperatures allow more accurate predictions of GPP compared to commonly used air temperatures. Results suggest that as air temperatures continue to warm with climate change, canopy temperatures will increase at a ~40% higher rate, with uncertain but potentially large impacts on tropical forest productivity.
Lipase‐Catalyzed Butanolysis of Echium Oil for the Selective Enrichment in Gamma‐Linolenic and Stearidonic Acids
Authors: Corzo‐Martínez Marta , López Eduardo , Vázquez Luis , Ortego Elena , Olaya Erika , Reglero Guillermo , Torres Carlos F.
Published: July 2018

Enzymatic butanolysis of Echium oil in the presence of lipases from Candida rugosa and Rhizopus oryzae has been studied. The effects of lipase immobilization, hydration of the reaction mixture and oil oxidation degree on lipase catalytic activity, fatty acid selectivity, and inactivation degree are evaluated. The utilization of butanol containing 2.5% (w/w) of water produces the highest catalytic activity of lipases in both powder and immobilized form; particularly of immobilized lipase from Rhizopus oryzae, which led to the complete conversion of triacylglycerols. The presence of 2.5% water also improves the biocatalyst stability, as the rate of immobilized lipase from Rhizopus oryzae inactivation (Kd = 0.0084 h−1) is much lower than in the absence of water (Kd = 0.0285 h−1). Stability of immobilized lipase from Rhizopus oryzae further increases when bleached oil is used (Kd = 0.0008 h−1). Then, fatty acid selectivity of immobilized lipase from Rhizopus oryzae is investigated by determining competitive factors for each fatty acid from Echium oil. Results indicates a very good activity, stability, and very important discrimination of this lipase against stearidonic and gamma‐linolenic acids which can be utilized for the efficient and selective oil enrichment in polyunsaturated fatty acids.

Practical Applications: This study describes an interesting methodology for the selective enrichment in polyunsaturated fatty acid from Echium oil utilizing intact triacylglycerols as starting material. This study also evaluates the lipase inactivation as a crucial tool for industrial application of this bioprocess. Finally the study describes the production of lower glycerides that can be used as precursors of structured bioactive lipids enriched in stearidonic and gamma‐linoleic acids.

Schematic representation of the simultaneous reactions that occur in the butanolysis reaction carried out. SAFA saturated fatty acid, MUFA monounsaturated fatty acid, PUFA polyunsaturated fatty acid, FABE fatty acid butyl ester, BUTOH Butanol.
Evaluation of battery modules state for electric vehicle using artificial neural network and experimental validation
Authors: Liang Xinyu , Bao Nengsheng , Zhang Jian , Garg Akhil , Wang Shuangxi
Published: July 2018

Abstract

This work undertakes research problem on prediction of state of battery modules used in electric vehicle. Past studies focussed extensively on the estimation of state of charge and state of health of a single cell/battery. However, the focus on the estimation of state of entire battery module is hardly studied. During the actual operation of electric vehicle, the environmental conditions (road slope and climate) and factors such as abnormal voltage and temperature conditions causes the deviations among the battery modules from its equilibrium state. As a result, its power efficiency and the life‐cycle decreases. One of the reasons of deviation is the defects in manufacturing of a battery module. For this purpose, the evaluation and estimation of state of battery modules is a priority to have information on which module among the given ones should be discharged first. Therefore, this study proposes the methodology for the evaluation of state of battery modules based on its current and temperature. Firstly, the rules are defined based on experiments to determine the priority for the discharge of each of the six modules. Dataset of 6000 samples obtained comprises of the 12 inputs (temperature and current) and 6 outputs (on‐off state of switch). Each output represents the priority of module to be discharged. To analyze this multi‐input multi‐output dataset, the popular artificial intelligence algorithm namely, artificial neural network with three training algorithms (Levenberg, Scaled conjugate and Bayesian regularization), using a number of neurons from 2 to 20 in the hidden layer is used. It was found that the model obtained using Levenberg algorithm performs the best.
Hourly to daily‐scale microtopographic fluctuations of supratidal sandstone
Authors: Yuan Runjie , Kennedy David M. , Stephenson Wayne J.
Published: July 2018

A traversing micro‐erosion meter (TMEM) was used to measure short‐term microtopographic changes on a supratidal rock surface at Marengo, Australia. In order to describe the characteristics of rock surface behaviour at different temporal scales, the TMEM site was monitored at 2‐hourly, daily and multiday (3.5 days) periods. The rock surface was highly dynamic at 2‐hourly scale, repeatedly falling and rising by up to 0.644 mm. Two‐hourly surface change was also characterised by spatial heterogeneity, with contraction and expansion occurring concurrently at centimetre scale across the rock surface. Two‐hourly microtopographic change was linked to the microclimate with significant relationships between surface movement and relative humidity (R2 = 0.27) and air temperature (R2 = 0.24). Expansion was observed across the rock surface when there was a fluctuation of 18% in relative humidity, and when cloudy the rock surface remained active during the day. Temporal variability in surface movement was also observed over a 24 h period with three distinct periods observed: falling (06:00–12:00), rising (12:00–20:00) and stable (20:00–06:00). The daily surface change underwent no net microtopographic change (no loss of material). In contrast, an overall contraction was observed at multiday scale. Rock surface behaviour in coastal environments is therefore complex with many cycles of expansion and contraction acting concurrently albeit at different temporal scales from hours to multiple days. © 2018 John Wiley & Sons, Ltd.
Stimulus contributions to operant resurgence
Authors: Nighbor Tyler D. , Kincaid Stephanie L. , O'Hearn Christopher M. , Lattal Kennon A.
Published: July 2018

In two experiments, pigeons were exposed to a three‐phase resurgence procedure (train Response A; extinguish Response A and train Response B; extinguish Response B). In the first experiment, the stimuli associated with phases were different, resulting in a resurgence procedure combined with an ABC renewal procedure. Presenting the novel stimulus, C, during extinction of both responses in the third phase resulted in minimal resurgence. Subsequently, substituting the original training Stimulus A for Stimulus C resulted in resurgence with all pigeons. In the second experiment, resurgence with the same stimuli present in all three phases of the resurgence procedure (AAA) was compared concurrently with a resurgence procedure in which the ABC renewal procedure used in Experiment 1 was superimposed. Substantially more resurgence occurred with the AAA procedure compared to the ABC procedure. Although ABC renewal in combination with the resurgence procedure generated some resurgence, such recurrent responding was attenuated relative to that observed when the stimulus conditions were constant across phases. Combined with earlier research showing the enhancing effects of combining resurgence and ABA renewal procedures, the present results elaborate on how stimuli correlated with certain behavioral histories affect the course of operant resurgence.
Ethics and Sustainability in Global Contexts: Studying Engineering Student Perspectives Through Photoelicitation
Authors: Berdanier Catherine G. P. , Tang Xiaofeng , Cox Monica F.
Published: July 2018

Background

Ethical issues have become increasingly important in discussions of sustainability, an area involving ethical and sociotechnical decisions that engineers may not be prepared to consider. Recent literature on engineering ethics highlights the need to integrate social and environmental aspects of ethics into technical topics through culturally sensitive and community‐oriented approaches.

Purpose/Hypothesis

This paper explores the ethical reflections of U.S. doctoral engineering students after a two‐week experience studying electronics manufacturing in India. This authentic experience is essentially a lived case study, where the students' roles were to listen and engage with a broad range of stakeholders affiliated with the electronics industry.

Design/Method

This study used photoelicitation methods to elicit deep reflective interviews with the doctoral student participants, reporting the qualitative analysis of these interview transcripts.

Results

The concept of sustainability is typically seen as comprising the individual dimensions of economic, social, and environmental facets; however, the narratives of ethics and sustainability emerging from the interview data reported here point to the importance of the intersections among these aspects. Themes relating to safety and regulations, gender roles, and resources and waste emerged as manifestations of these intersections.

Conclusions

The graduate students demonstrated ethical reasoning skills related to regulations, gender roles, resources and waste, and their professional ethical responsibilities as they discussed the experiences of their trip. As students reflected on ethical tensions based on their experience, they demonstrated a deep commitment to engineering ethics, acknowledging their roles in fostering sustainability and committing to thinking about the distant stakeholders affected by engineering decisions.
Anabolic steroids and tendons: A review of their mechanical, structural, and biologic effects
Authors: Jones Ian A. , Togashi Ryan , Hatch George F. Rick , Weber Alexander E. , Vangsness C. Thomas
Published: July 2018

One of the suspected deleterious effects of androgenic‐anabolic steroids (AAS) is the increased risk for tendon rupture. However, investigations to date have produced inconsistent results and it is still unclear how AAS influence tendons. A systematic review of the literature was conducted to identify studies that have investigated the mechanical, structural, or biologic effects that AAS have on tendons. In total, 18 highly heterogeneous studies were identified. Small animal studies made up the vast majority of published research, and contradictory results were reported frequently. All of the included studies focused on the potential deleterious effects that AAS have on tendon, which is striking given the recent use of AAS in patients following tendon injury. Rather than providing strong evidence for or against the use of AAS, this review highlights the need for additional research. Future studies investigating the use of AAS as a possible treatment for tendon injury/pathology are supported by reports suggesting that AAS may counteract the irreparable structural/functional changes that occur in the musculotendinous unit following rotator cuff tears, as well as studies suggesting that the purported deleterious effects on tendon may be transient. Other possible areas for future research are discussed in the context of key findings that may have implications for the therapeutic application of AAS. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2830–2841, 2018.
p‐Coumaric acid improves oxidative and osmosis stress responses in Caenorhabditis elegans
Authors: Yue Yiren , Shen Peiyi , Xu Yuejia , Park Yeonhwa
Published: July 2018

BACKGROUND

Stress‐response pathways in Caenorhabditis elegans (C. elegans) were found to be closely related to human diseases and aging. Research on stress responses in C. elegans can therefore significantly facilitate understanding of related human diseases. p‐Coumaric acid is present in peanuts, carrots, and garlic, and exerts many biological effects, however, its responses to various environmental stressors remain unknown. Thus, in the current study, we employed C. elegans as the in vivo animal model to examine the function of p‐coumaric acid under various stressed conditions.

RESULTS

Treatment of C. elegans with p‐coumaric acid resulted in a significant reduction in the intercellular reactive oxygen species levels, which suggests the in vivo antioxidant capacity of p‐coumaric acid. Moreover, p‐coumaric acid significantly increased the worms' survival under oxidative and osmosis stressed conditions but had no effect under normal or heat‐stressed conditions. The increased oxidative resistance induced by p‐coumaric acid was mediated by skn‐1, an ortholog of the Nrf2 (nuclear factor erythroid 2‐related factor 2) transcriptional factor. Downregulation of the osmosis regulatory gene, osr‐1, might contribute to p‐coumaric acids' effect on increased resistance to high osmolarity.

CONCLUSION

Taken together, our results suggest that p‐coumaric acid, an antioxidant agent, ameliorated oxidative and osmosis stresses in C. elegans. © 2018 Society of Chemical Industry
Quantifying estuarine‐scale invertebrate larval connectivity: Methodological and ecological insights
Authors: Kroll Ian R. , Poray Abigail K. , Puckett Brandon J. , Eggleston David B. , Fodrie F. Joel
Published: July 2018

The early life history of many marine organisms includes a dispersive planktonic larval phase which allows for the exchange of individuals among subpopulations. Knowledge of the degree of exchange, or connectivity, is critical to understanding the abundance and distribution of marine populations. Here, we applied geochemical tagging to assess estuarine‐scale larval connectivity among subpopulations of the commercially and ecologically important eastern oyster, Crassostrea virginica. To generate an “atlas” of geochemical signatures associated with spawning sites and potential dispersal pathways from spawning sites, we outplanted recently spawned oyster larvae to stationary moorings and surface drifters, respectively. Using the atlases generated from both outplant methods, we predicted natal origin, and thus larval connectivity, for newly settled oysters (spat) during three field trials over two summers (June 2013, June 2014, and August 2014), within three regions (∼ 35 km × 15 km quadrants) of Pamlico Sound, North Carolina, U.S.A. Patterns of larval connectivity varied both between months and annually but were predominately directed south to north following wind patterns. Predicted self‐recruitment was variable, as up to 100% of spat in a given region displayed signatures consistent with natal origin within that same region. Predicted connectivity patterns varied significantly based on atlases generated from outplanting on stationary moorings vs. surface drifters. For example, drifter‐predicted connectivity followed biophysical larval dispersal models more closely than mooring‐predicted connectivity, while mooring‐predicted connectivity displayed a higher diversity in larval sources. Both connectivity models highlight the need for resource management strategies such as reserve networks to incorporate designs that account for inherent variability in dispersal pathways.
Increased light availability and nutrient cycling by fish provide resilience against reversing eutrophication in an agriculturally impacted reservoir
Authors: Kelly Patrick T. , González María J. , Renwick William H. , Vanni Michael J.
Published: July 2018

High external nutrient loads to lakes are a primary cause of eutrophication. As such, management activities in the watersheds of heavily impacted systems are commonly implemented to reduce nutrient supply to lakes with high phytoplankton biomass. Although management efforts are often successful, resilience against the reversal of eutrophication may be maintained by a variety of different drivers of phytoplankton biomass. These may include internal sources of nutrients, and increases in light availability with declining sediment loads. We used a 21‐yr dataset to examine the responses of Acton Lake, a eutrophic agriculturally impacted reservoir, to determine the relative strength of potential drivers of changes in phytoplankton biomass through time. We also identified sources of ecosystem resilience that allow the lake to remain eutrophic. Despite declining nutrient concentrations in inflow streams, chlorophyll increased in Acton Lake over approximately the first decade of our study, and remained relatively stable in the second decade. Time series modeling suggests two primary drivers of increased phytoplankton: (1) increased nutrient excretion by detritivorous fish (gizzard shad, Dorosoma cepedianum), and (2) declining sediment loads from the watershed that reduced phytoplankton light limitation. We also identify precipitation patterns and stream discharge as being possible sources of ecosystem resilience, contributing to high loads of nutrients even if concentrations in inflow streams have declined with better management. These results suggest a more comprehensive view of management efforts to reduce eutrophication may be necessary, incorporating interactions among internal nutrient sources, climate variation, and changes in light availability.
JAK3 mutations in Italian patients affected by SCID: New molecular aspects of a long‐known gene
Authors: Di Matteo Gigliola , Chiriaco Maria , Scarselli Alessia , Cifaldi Cristina , Livadiotti Susanna , Di Cesare Silvia , Ferradini Valentina , Aiuti Alessandro , Rossi Paolo , Finocchi Andrea , Cancrini Caterina
Published: July 2018

Background

Mutations in the Janus Kinase 3 (JAK3) gene cause an autosomal recessive form of severe combined immunodeficiency (SCID) usually characterized by the absence of both T and NK cells, but preserved numbers of B lymphocytes (T‐B+NK‐SCID). The detection of larger (>100 bp) genomic duplications or deletions can be more difficult to be detected by PCR‐based methods or standard NGS protocols, and a broad range of mutation detection techniques are necessary.

Methods

We report four unrelated Italian patients (two females and two males) with SCID phenotype. Protein expression, functional studies, molecular analysis by standard methods and NGS, and transcripts studies were performed to obtain a definitive diagnosis.

Results

Here, we describe four JAK3‐deficient patients from four unrelated families. The first patient is homozygous for the known c.1951 C>T mutation causing the amino acidic change p.R651W. The other two patients, originating from the same small Italian town, resulted compound heterozygotes for the same g.15410_16542del deletion and two different novel mutations, g.13319_13321delTTC and c.933T>G (p.F292V), respectively. The fourth patient was compound heterozygous for the novel mutations p.V599G and p.W709R. Defective STAT5 phosphorylation after IL2 or IL15 stimulation corroborated the mutation pathogenicity. Concerning g.15410_16542del mutation, probably due to an unequal homologous recombination between Alu elements of JAK3 gene, microsatellites analysis revealed that both unrelated Pt2 and Pt3 and their carrier family members shared the same haplotype. These data support the hypothesis of a founder effect for the g.15410_16542del mutation that might have inherited in both unrelated families from the same ancient progenitor.

Conclusion

Different molecular techniques are still required to obtain a definitive diagnosis of AR‐SCID particularly in all cases in which a monoallelic mutation is found by standard mutation scanning methods.
Design and fabrication of starch‐nano clay composite films loaded with methyl orange and bromocresol green for determination of spoilage in milk package
Authors: Pirsa Sajad , Karimi Sani Iraj , Khodayvandi Sepideh
Published: July 2018

In this work, new composite film based on starch and nano clay particles was provided. The nano composite film was loaded by methyl orange (MO) and bromocresol green (BG) indicators. Two type films, including starch‐nano clay‐methyl orange (SCMO) and starch‐nano clay‐bromocresol green (SCBG) were provided. Some properties of provided films, including solubility in water, moisture uptake, water vapor permeability, FT‐IR, and scanning electron microscopy were studied. According to the results, MO and BG were loaded between starch and nano clay particles physically and clay particle size was between 40 and 100 nm. Finally, the SCMO and SCBG simultaneously were improvised in the milk bottle. According to the color change of indicators in the different pH (MO [3.1‐4.4] and BG [3.8‐5.4]), the fabricated films were used for determination of milk spoilage in a milk bottle. The best advantage of fabricated SCMO and SCBG films is that the indicators do not release into the milk by exposing with the milk. The milk pH is changed during the storage time (from 6.7 to the 4), and in the low pH, the milk is spoiled so the fabricated film smartly could show the spoilage of milk by color changing.
Noninvasive prenatal test for FGFR3‐related skeletal dysplasia based on next‐generation sequencing and plasma cell‐free DNA: Test performance analysis and feasibility exploration
Authors: Ren Yuan , Zhao Jia , Li Ruibing , Xie Yifan , Jiang Shufang , Zhou Honghui , Liu Hongtai , You Yanqin , Chen Fang , Wang Wei , Gao Ya , Meng Yuanguang , Lu Yanping
Published: July 2018

Objective

To explore the feasibility and accuracy of a noninvasive prenatal test for fibroblast growth factor receptor 3 (FGFR3)‐related skeletal dysplasia based on next‐generation sequencing (NGS) of plasma cell‐free DNA.

Method

Fragmented genome DNA (gDNA) of fetuses with achondroplasia (ACH) and thanatophoric dysplasia type I (TD I) was mixed with postdelivery maternal plasma cell‐free DNA to generate spiked samples of different modeled fetal fractions. Multiplex polymerase chain reaction was used to amplify the 19 FGFR3 loci, and the amplification products were then sequenced by NGS to detect the fetal mutant alleles. Then, maternal plasma samples of pregnant women carrying ACH (n = 4) and TD I fetuses (n = 2), as well as healthy controls (n = 15), were tested by NGS, and the test performance was evaluated.

Results

Fetal FGFR3 mutations were detected in all artificial mixtures with fetal gDNA concentrations above 3%. In clinical validation, our method identified all fetal FGFR3 mutant alleles from maternal plasma, with no false positive results. The sensitivity and specificity of our method were 100% (95% CI, 54.1%‐100%) and 100% (78.2%‐100%), respectively.

Conclusion

Our method had a favorable performance for noninvasively detecting fetal FGFR3 mutations in maternal plasma, highlighting its promising value in developing a noninvasive prenatal test for de novo and paternally inherited disorders.
A PASE Approach towards (Adamantyl‐1)‐, Alkyl‐ and (Het)Aryl‐Substituted [1, 2,4]triazolo[1, 5‐d][1, 2,4]triazines: A Sequence of Two Solvent‐Free Reactions Bearing Lower E‐Factors
Authors: Krinochkin Alexey P. , Kopchuk Dmitry S. , Giri Kousik , Shtaitz Yaroslav K. , Starnovskaya Ekaterina S. , Khalymbadzha Igor A. , Drokin Roman A. , Ulomsky Eugeny N. , Santra Sougata , Zyryanov Grigory V. , Rusinov Vladimir L. , Chupakhin Oleg N.
Published: July 2018

A Pot, Atom, Step Economic (PASE) approach is reported towards [1, 2,4]triazolo[1, 5‐d][1, 2,4]triazines, substituted with the azole ring with pharmacophore residues, such as 1‐adamantyl or 2‐furanyl moieties, naproxen residues, as well aliphatic and (het)aromatic substituents, starting from easily available 1,2,4‐triazine‐5‐carbonitriles and carboxylic acids hydrazides. This approach involves a sequence of two solvent‐free reactions accompanied by the Dimroth rearrangement on the last step. The structures of the final Dimroth rearrangement products were confirmed based on the DFT studies as well as the single crystal X‐ray analysis for the admantane‐substituted product. In addition, this method possesses lower E‐factors.
A High‐Performance Direct Methanol Fuel Cell Technology Enabled by Mediating High‐Concentration Methanol through a Graphene Aerogel
Authors: Liu Xiaoteng , Xi Jiabin , Xu Ben Bin , Fang Bo , Wang Yucheng , Bayati Maryam , Scott Keith , Gao Chao
Published: July 2018

A facile methodology to fabricate graphene aerogel (GA), and its application in a direct methanol fuel cell (DMFC), is demonstrated for the first time. A new GADMFC design is proposed by using GA to replace two main components within the DMFC—the gas‐diffusion layer and the flow field plate. The results indicate a 24.95 mW cm−2 maximum power density of air polarization is obtained at 25 °C. The membrane electrolyte assembly has a 63.8% mass reduction compared to an ordinary one, which induced 3 times higher mass power density. Benefiting from its excellent organic solvent absorbency, the methanol crossover effect is dramatically suppressed while using 12 m methanol, therefore, a higher concentration or even pure methanol can be refilled into the fuel cell. Due to the excellent fuel‐storage function of the GA, the methanol cartridge and complicated fuel circulation system in the DMFC can be eliminated, which can reduce the manufacturing cost for DMFCs. It is expected this research will promote the application of GA in fuel‐cell applications, as well as shed light on the novel fuel‐cell technology to address future energy challenges.
Structural Diversity of Lithium, Sodium, and Potassium Complexes of N‐Mesityl‐P,P‐diphenylphosphoryl Amide
Authors: Al‐Shabatat Maha , Schüler Philipp , Krieck Sven , Görls Helmar , Westerhausen Matthias
Published: July 2018

Metalation of N‐mesityl‐P,P‐diphenylphosphinic amide Ph2P(=O)–N(H)Mes (1) with n‐butyllithium, sodium amide and potassium hydride yields the corresponding alkali metal N‐mesityl‐P,P‐diphenylphosphoryl amides of lithium (2), sodium (3), and potassium (4). The lithium complex 2 forms a dimer with an eight‐membered (Li–O–P–N)2 ring. The sodium derivative 3 crystallizes as a dinuclear centrosymmetric complex with a central Na2O2 ring. The potassium congener 4 precipitates as a tetranuclear compound with an inner K4O4 heterocubane cage. In these complexes the phosphoryl amido ligands act as bidentate Lewis bases and form strained four‐membered M–O–P–N rings. Due to this fact, the endocyclic M–O bonds of the M2O2 rings vary within a large range.
Assessing an Interactive Online Tool to Support Parents' Genomic Testing Decisions
Authors: Adam Shelin , Birch Patricia H. , Coe Rachel R. , Bansback Nick , Jones Adrian L. , Connolly Mary B. , Demos Michelle K. , Toyota Eric B. , Farrer Matthew J. , Friedman Jan M.
Published: July 2018

Clinical use of genome‐wide sequencing (GWS) requires pre‐test genetic counseling, but the availability of genetic counseling is limited. We developed an interactive online decision‐support tool, DECIDE, to make genetic counseling, patient education, and decision support more readily available. We performed a non‐inferiority trial comparing DECIDE to standard genetic counseling to assess the clinical value of DECIDE for pre‐GWS counseling. One hundred and six parents considering GWS for their children with epilepsy were randomized to conventional genetic counseling or DECIDE. Following the intervention, we measured parents' knowledge and empowerment and asked their opinions about using DECIDE. Both DECIDE and conventional genetic counseling significantly increased parents' knowledge, with no difference between groups. Empowerment also increased but by less than 2% in each group. Parents liked using DECIDE and found it useful; 81% would recommend it to others; 49% wished to use it along with a genetic counselor; 26% of parents preferred to see a genetic counselor; 7% preferred DECIDE alone; and 18% had no preference. DECIDE appears equivalent to genetic counseling at conveying information. In addition, it was highly acceptable to the majority of study participants, many of whom indicated that it was useful to their decision‐making. Use of DECIDE as a pre‐test tool may extend genetic counseling resources.
Association of cerebrospinal fluid α‐synuclein with total and phospho‐tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers
Authors: Vergallo Andrea , Bun René‐Sosata , Toschi Nicola , Baldacci Filippo , Zetterberg Henrik , Blennow Kaj , Cavedo Enrica , Lamari Foudil , Habert Marie‐Odile , Dubois Bruno , Floris Roberto , Garaci Francesco , Lista Simone , Hampel Harald ,   INSIGHT‐preAD study group,   for the lzheimer Precision Medicine Initiative (APMI)
Published: July 2018

Introduction

Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α‐synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α‐synuclein (α‐syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls.

Methods

The pathophysiological role of CSF α‐syn in asymptomatic subjects at risk of AD has not been explored. We performed a large‐scale cross‐sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT‐preAD).

Results

We found a positive association between CSF α‐syn concentrations and brain β‐amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α‐syn and both CSF t‐tau and p‐tau181 concentrations.

Discussion

Animal models presented evidence, indicating that α‐syn may synergistically and directly induce fibrillization of both tau and β‐amyloid. Our data indicate an association of CSF α‐syn with AD‐related pathophysiological mechanisms, during the preclinical phase of the disease.
The 2018 Revision to the Process of Care Model for Evaluation of Erectile Dysfunction
Authors: Mulhall John P. , Giraldi Annamaria , Hackett Geoff , Hellstrom Wayne J.G. , Jannini Emmanuele A. , Rubio-Aurioles Eusebio , Trost Landon , Hassan Tarek A.
Published: July 2018

Background

Erectile dysfunction (ED) is a common condition that may affect men of all ages; in 1999, a Process of Care Model was developed to provide clinicians with recommendations regarding the evaluation and management of ED.

Aim

To reflect the evolution of the study of ED since 1999, this update to the process of care model presents health care providers with a tool kit to facilitate patient interactions, comprehensive evaluation, and counseling for ED.

Methods

A cross-disciplinary panel of international experts met to propose updates to the 1999 process of care model from a global perspective. The updated model was designed to be evidence-based, data-driven, and accessible to a wide range of health care providers.

Outcomes

This article summarizes the resulting discussion of the expert meeting and focuses on ED evaluation. The management of ED is discussed in an article by Muhall et al (J Sex Med 2018;15:1280-1292).

Results

A comprehensive approach to the evaluation of ED is warranted because ED may involve both psychological and organic components. The updated process of care model for evaluation was divided into core and optional components and now focuses on the combination of first-line pharmacotherapy and counseling in consideration of patient sexual dynamics.

Clinical Implications

Patient evaluation for ED should encompass a variety of aspects, including medical history, sexual history, physical examination, psychological evaluation, laboratory testing, and possibly adjunctive testing.

Strengths & Limitations

This update draws on author expertise and experience to provide multi-faceted guidance for the evaluation of ED in a modern context. Although a limited number of contributors provided input on the update, these experts represent diverse fields that encounter patients with ED. Additionally, no meta-analyses were performed to further support the ED evaluation guidelines presented.

Conclusion

Comprehensive evaluation of ED affords health care providers an opportunity to address medical, psychological/psycho-social, and sexual issues associated with ED, with the ultimate goal being effective management and possibly resolution of ED. While some or all techniques described in the updated model may be needed for each patient, evaluation should in all cases be thorough.
Profiting from collaborative innovation practices: Identifying organizational success factors along the process
Authors: Anzola-Román Paula , Bayona-Sáez Cristina , García-Marco Teresa
Published: July 2018

Research on innovation management has pointed out that the capitalization of collaborative innovation practices is influenced by firms’ internal context. This paper aims to answer the following question: which organizational factors help to overcome the challenges that firms face in the different phases of the collaborative innovation process? For this purpose, previous literature is revised and three case studies are analyzed by means of applying a framework that structures the collaborative innovation process in three areas of relevance (i.e., development, integration and commercialization of the innovation). The results of the analysis inform the proposal of a theoretical framework that identifies the organizational context factors that determine the success or failure of collaborative innovation practices in each of the stages of the process.
On perpetuities with gamma-like tails
Authors: Buraczewski Dariusz , Dyszewski Piotr , Iksanov Alexander , Marynych Alexander
Published: July 2018

An infinite convergent sum of independent and identically distributed random variables discounted by a multiplicative random walk is called perpetuity, because of a possible actuarial application. We provide three disjoint groups of sufficient conditions which ensure that the right tail of a perpetuity ℙ{X > x} is asymptotic to axce-bx as x → ∞ for some a, b > 0, and c ∈ ℝ. Our results complement those of Denisov and Zwart (2007). As an auxiliary tool we provide criteria for the finiteness of the one-sided exponential moments of perpetuities. We give several examples in which the distributions of perpetuities are explicitly identified.
On unimodality of the lifetime distribution of coherent systems with failure-dependent component lifetimes
Authors: Bieniek M. , Burkschat M.
Published: July 2018

We study the conditions for unimodality of the lifetime distribution of a coherent system when the ordered component lifetimes in the system are described by generalized order statistics. Results for systems with independent and identically distributed lifetimes of components are included in this setting. The findings are illustrated with some examples for different types of systems. In particular, coherent systems with strictly bimodal density functions are presented in the case of independent standard uniform distributed lifetimes of components. Furthermore, we use the results to derive a sharp upper bound on the expected system lifetime in terms of the mean and the standard deviation of the underlying distribution.
Effects of soil temperature and tidal condition on variation in carbon dioxide flux from soil sediment in a subtropical mangrove forest
Authors: Tomotsune Mitsutoshi , Yoshitake Shinpei , Iimura Yasuo , Kida Morimaru , Fujitake Nobuhide , Koizumi Hiroshi , Ohtsuka Toshiyuki
Published: July 2018

The variation in CO2 flux from the forest floor is important in understanding the role of mangrove forests as a carbon sink. To clarify the effects of soil temperature and tidal conditions on variation in CO2 flux, sediment–atmosphere CO2 fluxes were measured between June 2012 and May 2013. We used the closed chamber method for two plots, with a 0.5 m difference in elevation (B, high elevation; R-B, low elevation), in a mangrove forest in south-western Japan. CO2 fluxes were highest in the warm season and showed a weak positive correlation with soil temperature in both forests. Estimated monthly CO2 flux showed moderate seasonal variation in accordance with the exposure duration of the soil surface under tidal fluctuation. Additionally, measured CO2 flux and soil temperature were slightly higher in the R-B plot than the B plot, although estimated annual CO2 flux was higher in the B plot than the R-B plot due to different exposure durations. These results suggest that variation in the exposure duration of the forest floor, which changes seasonally and microgeographically, is important in evaluating the annual CO2 flux at a local scale and understanding the role of mangrove ecosystems as regulators of atmospheric CO2.