bluuebunny/crossref_metadata_2025 huggingface dataset:
Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes
Authors: Zhao Lue Ping , Carlsson Annelie , Larsson Helena Elding , Forsander Gun , Ivarsson Sten A. , Kockum Ingrid , Ludvigsson Johnny , Marcus Claude , Persson Martina , Samuelsson Ulf , Örtqvist Eva , Pyo Chul‐Woo , Bolouri Hamid , Zhao Michael , Nelson Wyatt C. , Geraghty Daniel E. , Lernmark Åke ,   The Better Diabetes Diagnosis (BDD) Study Group
Published: July 2017

Aim

It is of interest to predict possible lifetime risk of type 1 diabetes (T1D) in young children for recruiting high‐risk subjects into longitudinal studies of effective prevention strategies.

Methods

Utilizing a case‐control study in Sweden, we applied a recently developed next generation targeted sequencing technology to genotype class II genes and applied an object‐oriented regression to build and validate a prediction model for T1D.

Results

In the training set, estimated risk scores were significantly different between patients and controls (P = 8.12 × 10−92), and the area under the curve (AUC) from the receiver operating characteristic (ROC) analysis was 0.917. Using the validation data set, we validated the result with AUC of 0.886. Combining both training and validation data resulted in a predictive model with AUC of 0.903. Further, we performed a “biological validation” by correlating risk scores with 6 islet autoantibodies, and found that the risk score was significantly correlated with IA‐2A (Z‐score = 3.628, P < 0.001). When applying this prediction model to the Swedish population, where the lifetime T1D risk ranges from 0.5% to 2%, we anticipate identifying approximately 20 000 high‐risk subjects after testing all newborns, and this calculation would identify approximately 80% of all patients expected to develop T1D in their lifetime.

Conclusion

Through both empirical and biological validation, we have established a prediction model for estimating lifetime T1D risk, using class II HLA. This prediction model should prove useful for future investigations to identify high‐risk subjects for prevention research in high‐risk populations.
Power of Orbitrap‐based LC‐high resolution‐MS/MS for comprehensive drug testing in urine with or without conjugate cleavage or using dried urine spots after on‐spot cleavage in comparison to established LC–MSn or GC–MS procedures
Authors: Michely Julian A. , Meyer Markus R. , Maurer Hans H.
Published: July 2017

Reliable, sensitive, and comprehensive urine screening procedures by gas chromatography–mass spectrometry (GC–MS) or liquid chromatography–mass spectrometry (LC–MS) with low or high resolution (HR) are of high importance for drug testing, adherence monitoring, or detection of toxic compounds. Besides conventional urine sampling, dried urine spots are of increasing interest. In the present study, the power of LC–HR–MS/MS was investigated for comprehensive drug testing in urine with or without conjugate cleavage or using dried urine spots after on‐spot cleavage in comparison to established LC–MSn or GC–MS procedures. Authentic human urine samples (n = 103) were split in 4 parts. One aliquot was prepared by precipitation (UP), one by UP with conjugate cleavage (UglucP), one spot on filter paper cards and prepared by on‐spot cleavage followed by liquid extraction (DUSglucE), and one worked‐up by acid hydrolysis, liquid–liquid extraction, and acetylation for GC–MS analysis. The 3 series of LC–HR–MS/MS results were compared among themselves, to corresponding published LC–MSn data, and to screening results obtained by conventional GC–MS. The reference libraries used for the 3 techniques contained over 4500 spectra of parent compounds and their metabolites. The number of all detected hits (770 drug intakes) was set to 100%. The LC–HR–MS/MS approach detected 80% of the hits after UP, 89% after UglucP, and 77% after DUSglucE, which meant over one‐third more hits in comparison to the corresponding published LC–MSn results with ≤49% detected hits. The GC–MS approach identified 56% of all detected hits. In conclusion, LC–HR–MS/MS provided the best screening results after conjugate cleavage and precipitation.
A translational neuroscience approach to body image disturbance and its remediation in anorexia nervosa
Authors: Feusner Jamie , Deshpande Rangaprakash , Strober Michael
Published: July 2017

Deviant perception of the body is a fundamental component of anorexia nervosa. Here we offer a potential mechanistic explanation that involves perturbations within the visual system and the brain circuits that modulate perceptual organization. Based on the model proposed, we also suggest a mechanistic strategy for altering neuronal activity in the visual system to normalize perception of the body, and set out a strategy for empirically testing its clinical application.
On the Reactivity of the Carba‐closo‐dodecaborate Anion with the Trityl Cation
Authors: Kleinsasser Jack F. , Fisher Steven P. , Tham Fook S. , Lavallo Vincent
Published: July 2017

In 1994 Reed and co‐workers reported a variety of trityl salts with various functionalized icosahedral carborane anions. However, it was mentioned that the parent carba‐closo‐dodecaborate anion [HCB11H11]– underwent an unidentified chemical reaction with the trityl cation as the ion pair formed in solution. In this communication, we have reexamined this reaction and identified the reaction as classical electrophilic substitution of a carborane B–H bond to afford new B‐arylated compounds, and not a carborane dimer as previously proposed. This is the first example of the electrophilic arylation of the [HCB11H11]– anion. The new arylated carborane anions are fully characterized by multinuclear NMR and IR spectroscopy, as well as single‐crystal X‐ray diffraction studies.
Synthesis, Characterization, and Selective Sr2+ Sensing Study of Copper(I)‐Bridged Calix[4]arene‐Based Binuclear Alkynylplatinum(II) Complexes
Authors: Chen Yu‐Zhe , Pan Dun , Chen Bin , Wang Ge‐Xia , Tung Chen‐Ho , Wu Li‐Zhu
Published: July 2017

Three copper(I)‐bridged p‐tert‐butylcalix[4]arene‐tethered binuclear 6‐aryl‐2,2′‐bipyridine (C^N^N) alkynylplatinum(II) complexes were designed and synthesized. Their photophysical properties and sensing ability to strontium ions (Sr2+) were investigated in terms of UV/Vis absorption, emission, and 1H NMR spectroscopy and MS. The binuclear complex bearing aza[15]crown‐5 pendants exhibited a unique emission enhancement at ca. 750 nm toward Sr2+ ions, a result of altering the lowest excited state from the nonemissive ligand‐to‐ligand charge‐transfer state to the emissive metal–metal‐to‐ligand charge‐transfer state. A 1:1 sandwiched binding mode between Sr2+ and the two aza[15]crown‐5 moieties in the complex was proposed.
Structural and Electrochemical Properties of a Ruthenium–Diiron Dithiolene Complex
Authors: Sagawa Takuya , Tsukada Satoru , Yamamoto Kazuki , Gunji Takahiro
Published: July 2017

The ruthenium–diiron dithiolene complex [(η6‐C6Me6)Ru(CO)(µ‐CO)2Fe2(µ‐bdt)(CO)4] (2) (bdt = 1,2‐benzenedithiolate) was synthesized, and two crystallographic isomers, which depend on the recrystallization temperature, were isolated; specifically, 2 and its isomer (2′) were obtained at –30 °C and room temperature, respectively. A single crystal of 2 was converted to 2′ by leaving it in hexane at room temperature for one week. A single crystal of 2′ did not convert to 2 in hexane at –30 °C. However, 2 could be obtained by the recrystallization of 2′ from a mixed solvent of dichloromethane and hexane. These results indicate that 2 is the most stable form in solvent. The isomerization occurs because of the stability of the 2′ packing structure compared with that of 2. Additionally, 2 was found to act as a catalyst for proton reduction; catalytic proton reduction occurred at a potential of –2.1 V and 250 µA in acetic acid (50 equiv.).
Scalable Flow Synthesis of [6,6]‐Phenyl‐C61‐butyric Acid Methyl Ester (PCBM) using a Flow Photoreactor with a Sodium Lamp
Authors: Ueda Mitsuhiro , Imai Naoyuki , Yoshida Shunsuke , Yasuda Hiroshi , Fukuyama Takahide , Ryu Ilhyong
Published: July 2017

An efficient flow system was constructed for the synthesis of [6,6]‐phenyl‐C61‐butyric acid methyl ester (PCBM); the process involved flow [2+1] addition of C60 and subsequent flow photoisomerization of the resulting fulleroid to PCBM by using a flow photoreactor in combination with an Na lamp. With the present flow system, a scalable synthesis of PCBM (0.79 g/3.3 h) was achieved by continuous operation for 3.3 h.
Solvent‐Free Synthesis of Cyanoformamides from Carbamoyl Imidazoles
Authors: Nugent Jeremy , Campbell Sarah G. , Vo Yen , Schwartz Brett D.
Published: July 2017

A straightforward and solvent‐free synthesis of various secondary and tertiary cyanoformamides from carbamoyl imidazoles and TMSCN has been developed. Both cyclic and acyclic carbamoyl imidazoles react smoothly to form the relevant cyanoformamides in excellent yields, often within minutes.
Hydrodynamic lift forces on solutes in a tilted nanopillar array: A computer simulation study
Authors: Kabedev Aleksei , Ross‐Lonergan Mark , Lobaskin Vladimir
Published: July 2017

We study solute transport in a microfluidic channel, where the walls hold an array of tilted rigid nanopillars. By solving numerically the flow equations in the channel, we show that a combination of hydrodynamic effects with excluded volume interactions between the solute particles and the pillars leads to a hydrodynamic lift effect, which varies with the particle size, and depends in a strongly nonlinear fashion on the flow rate. We show that the lift force can be sufficiently strong to drive the solute accumulation or removal from the pillar region and can be switched to the opposite direction by variation of the shear rate or driving pressure. We also demonstrate that the nanopillar array can be used to selectively attract particles of certain size and enhance solute trapping at the surface.
Biosorption‐based dispersive liquid–liquid microextraction combined with polypyrrole‐coated magnetic nanoparticles as an effective sorbent for the extraction of ibuprofen from water samples using magnetic solid‐phase extraction
Authors: Haeri Seyed Ammar , Abbasi Shahryar , Sajjadifar Sami
Published: July 2017

In this paper, biosorption‐based dispersive liquid–liquid microextraction (BioDLLME) in combination with magnetic solid‐phase extraction (MSPE) has been developed as a sample pretreatment method with high enrichment factor for the sensitive determination of ibuprofen in water samples. At first, magnetic Fe3O4/polypyrrole nanoparticles were synthesized and employed as sorbent for the MSPE of ibuprofen. After the elution of the desired compound from the sorbent by using methanol, BioDLLME technique was performed on the obtained solution. After MSPE, the eluent of MSPE was used as the disperser solvent for BioDLLME, so that the extra preconcentration factor could be achieved. The properties of the prepared magnetic sorbent were characterized using field emission scanning electron microscopy, Fourier transform infrared spectroscopy and X‐ray diffraction methods. Experimental parameters affecting the extraction efficiency were studied and optimized. Under optimum conditions, the enrichment factor was 274. The linear dynamic range and limit of detection are 0.25–80 and 0.083 μg/L, respectively. The relative standard deviations for six replicate measurements are 3.82%.
The development and validation of EpiComet‐Chip, a modified high‐throughput comet assay for the assessment of DNA methylation status
Authors: Townsend Todd A. , Parrish Marcus C. , Engelward Bevin P. , Manjanatha Mugimane G.
Published: July 2017

DNA damage and alterations in global DNA methylation status are associated with multiple human diseases and are frequently correlated with clinically relevant information. Therefore, assessing DNA damage and epigenetic modifications, including DNA methylation, is critical for predicting human exposure risk of pharmacological and biological agents. We previously developed a higher‐throughput platform for the single cell gel electrophoresis (comet) assay, CometChip, to assess DNA damage and genotoxic potential. Here, we utilized the methylation‐dependent endonuclease, McrBC, to develop a modified alkaline comet assay, “EpiComet,” which allows single platform evaluation of genotoxicity and global DNA methylation [5‐methylcytosine (5‐mC)] status of single‐cell populations under user‐defined conditions. Further, we leveraged the CometChip platform to create an EpiComet‐Chip system capable of performing quantification across simultaneous exposure protocols to enable unprecedented speed and simplicity. This system detected global methylation alterations in response to exposures which included chemotherapeutic and environmental agents. Using EpiComet‐Chip on 63 matched samples, we correctly identified single‐sample hypermethylation (≥1.5‐fold) at 87% (20/23), hypomethylation (≥1.25‐fold) at 100% (9/9), with a 4% (2/54) false‐negative rate (FNR), and 10% (4/40) false‐positive rate (FPR). Using a more stringent threshold to define hypermethylation (≥1.75‐fold) allowed us to correctly identify 94% of hypermethylation (17/18), but increased our FPR to 16% (7/45). The successful application of this novel technology will aid hazard identification and risk characterization of FDA‐regulated products, while providing utility for investigating epigenetic modes of action of agents in target organs, as the assay is amenable to cultured cells or nucleated cells from any tissue. Environ. Mol. Mutagen. 58:508–521, 2017. © 2017 Wiley Periodicals, Inc.
NiNb2O6‐BaTiO3 Ceramics for Energy‐Storage Capacitors
Authors: Zeng Mengshi , Liu Jingsong , Yu Hongtao , Chao Mingming , Tang Bin , Zhang Shuren
Published: July 2017

NiNb2O6‐BaTiO3 ceramics were prepared using a solid‐state reaction method, and the effects of the addition of NiNb2O6 on the dielectric properties and energy‐storage characteristics of BaTiO3 were investigated systematically. We used XRD to show that the obtained NiNb2O6‐BaTiO3 ceramics possess a single perovskite structure. The addition of NiNb2O6 improves the energy density efficiency and leads to a decrease of the dielectric loss to less than 1 %. Moreover, optimum performances of the BaTiO3 ceramics can be achieved by the addition of 1.0 mol % NiNb2O6, at which content the obtained ceramic satisfies the X7R specification. The addition of NiNb2O6 stabilizes the crystalline lattice, which enhances the temperature stability of the dielectric properties accordingly.
Influence of the diffusor angle and a damper opening angle on the performance of a hydrokinetic turbine
Authors: Chica E. , Pérez F. , Rubio‐Clemente A.
Published: July 2017

Computational fluid dynamic (CFD) technique has been used to investigate the effect of the diffuser expansion angle on the power coefficient of a hydrokinetic turbine. The performance coefficient was compared to that of a conventional bare hydrokinetic turbine of 1 Hp (746 W) designed for a water velocity of 1.5 m s−1 with a tip speed ratio of 6.325; an attack and pitch angle of 5 and 0 degrees, respectively; a power coefficient of 0.4382; a drive train efficiency of 70% and a S822 airfoil profile. The CFD results showed that the extracted power of the hydrokinetic turbine with diffuser can be larger than the power extracted by a bare turbine with the same area. Nevertheless, the level of stress on the blade structure was also increased due to the hydrokinetic turbine with diffuser was exposed to a larger structural loading condition by the water flow.

Additionally, the numerical analysis of a damper located at the exit of the turbine diffuser was developed. It was observed that when the opening angle of the damper is between 0 and 20 degrees, an increase in the mass flow through the turbine blades is achieved, resulting in a slight increase in the power coefficient. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 824–831, 2018
A new model for predicting the global solar radiation
Authors: Kaplan Yusuf Alper
Published: July 2017

In recent years, there has been an increasing demand for renewable energy due to the population growth and decline in fossil energy resources as well as the developing technology. Solar energy is the most important renewable energy source and the global solar radiation is the primary variable for evaluating solar energy systems. The main subject of this study is to show that there is enough solar energy potential in Turkey with using global solar radiation data of chosen region where is between Adana and Mersin cities. The new solar radiation models of selected region were developed with determining Angstrom coefficients and obtained results of new developed models were compared some models in the literature. In this study, the global radiation model correlations which were developed for Turkey and some other countries were investigated for selected region. The compatibility of some models in literature were tested by determining the nearest model to measured data. In addition to that climate data of selected region, four different new models were developed and brought into the literature. The performance of these proposed models has been examined at different regions. To comparative the efficiency of all used models the following statistical indicators were used: the percentage of the relative error, mean percentage error, analysis of variance, mean absolute percentage error, the squared relative error, total relative standard error, and T‐statistic. The obtained results reveal that the new proposed models gives very appropriate results for solar radiation estimation in selected region. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 870–880, 2018
Epilepsy is associated with ventricular alterations following convulsive status epilepticus in children
Authors: Ali Wail , Bubolz Beth A. , Nguyen Linh , Castro Danny , Coss‐Bu Jorge , Quach Michael M. , Kennedy Curtis E. , Anderson Anne E. , Lai Yi‐Chen
Published: July 2017

Objective

Convulsive status epilepticus can exert profound cardiovascular effects in adults, including ventricular depolarization–repolarization abnormalities. Whether status epilepticus adversely affects ventricular electrical properties in children is less understood. Therefore, we sought to characterize ventricular alterations and the associated clinical factors in children following convulsive status epilepticus.

Methods

We conducted a 2‐year retrospective case–control study. Children between 1 month and 21 years of age were included if they were admitted to the pediatric intensive care unit with primary diagnosis of convulsive status epilepticus and had 12‐lead electrocardiogram (ECG) within 24 h of admission. Children with heart disease or ion channelopathy, or who were on vasoactive medications were excluded. Age‐matched control subjects had no history of seizures or epilepsy. The primary outcome was ventricular abnormalities represented by ST segment changes, abnormal T wave, QRS axis deviation, and corrected QT (QTc) interval prolongation. The secondary outcomes included QT/RR relationship, beat‐to‐beat QTc interval variability, ECG interval measurement between groups, and clinical factors associated with ECG abnormalities.

Results

Of 317 eligible children, 59 met the inclusion criteria. History of epilepsy was present in 31 children (epileptic) and absent in 28 children (nonepileptic). Compared with the control subjects (n = 31), the status epilepticus groups were more likely to have an abnormal ECG, with overall odds ratios of 3.8 and 7.0 for the nonepileptic and the epileptic groups, respectively. Simple linear regression analysis demonstrated that children with epilepsy exhibited impaired dependence and adaptation of the QT interval on heart rate. Beat‐to‐beat QTc interval variability, a marker of ventricular repolarization instability, was increased in children with epilepsy.

Significance

Convulsive status epilepticus can adversely affect ventricular electrical properties and stability in children, especially those with epilepsy. These findings suggest that children with epilepsy may be particularly vulnerable to seizure‐induced arrhythmias. Therefore, postictal cardiac surveillance may be warranted in this population.
Perturbation of fluvial sediment fluxes following the 2008 Wenchuan earthquake
Authors: Wang Wei , Godard Vincent , Liu‐Zeng Jing , Scherler Dirk , Xu Chong , Zhang Jinyu , Xie Kejia , Bellier Olivier , Ansberque Claire , de Sigoyer Julia ,   ASTER Team
Published: July 2017

Quantifying the removal of co‐seismic landslide material after a large‐magnitude earthquake is central to our understanding of geomorphic recovery from seismic events and the topographic evolution of tectonically active mountain ranges. In order to gain more insight into the fluvial erosion response to co‐seismic landslides, we focus on the sediment fluxes of rivers flowing through the rupture zone of the 2008 Mw 7.9 Wenchuan earthquake in the Longmen Shan of the eastern Tibetan Plateau. Over the post‐seismic period of 2008–2013, we annually collected river sediment samples (0.25–1 mm) at 19 locations and measured the concentration of cosmogenic 10Be in quartz. When compared with published pre‐earthquake data, the 10Be concentrations declined dramatically after the earthquake at all sampling sites, but with significant spatial differences in the amplitude of this decrease, and were starting to increase toward pre‐earthquake level in several basins over the 5‐year survey. Our analysis shows that the amplitude of 10Be decrease is controlled by the amount of landslides directly connected to the river network. Calculations based on 10Be mixing budgets indicate that the sediment flux of the 0.25–1 mm size fraction increased up to sixfold following the Wenchuan earthquake. Our results also suggest that fluvial erosion became supply limited shortly after the earthquake, and predict that it could take a few years to several decades for fluvial sediment fluxes to go back to pre‐earthquake characteristics, depending on catchment properties. We also estimate that it will take at least decades and possibly up to thousands of years to remove the co‐seismic landslide materials from the catchments in the Longmen Shan. Copyright © 2017 John Wiley & Sons, Ltd.
Geomorphic and hydraulic unit richness and complexity in a coastal plain river
Authors: Phillips Jonathan D.
Published: July 2017

Geomorphic and hydraulic units in river channels are closely linked to geodiversity and habitats, and thus to biodiversity. In a ~ 200 km reach of the lower Sabine River, in the northern Gulf of Mexico Coastal Plain, 72 different hydraulic units (HU) were identified in six geomorphic zones or river styles. Richness–area relationships indicate a linear or logarithmic increase of HUs, as opposed to the less steep power functions generally found in biogeographic species–area curves or in soil richness–area analyses. Different results are obtained when starting from the upstream or downstream end of the study area, indicating the importance of directionality in such analyses. These results show that HUs (and related habitats and biotopes) are both richer and more variable than a repeated sequence of units. The number of HUs inundated increases linearly with flow stage categories, indicating the importance of high within‐bank flows in maintaining and activating HUs. Aggregated HUs (AHUs) associated with similar geomorphic units are highly connected, both with respect to patterns of spatial adjacency and potential connectivity at similar flow levels. Spectral graph theory metrics applied to a graph representation of spatial adjacency shows a highly complex network with a high potential for rapid propagation of changes—and even more so for a graph based on flow connectivity. The flow connectivity graph shows far higher synchronization as indicated by algebraic connectivity. Thus suggests more rapid and coherent changes for processes driven by river flow, as opposed to phenomena driven by other factors between flow events. These findings have important implications for understanding relationships between geodiversity and habitat diversity, managing habitat and biodiversity, and linking the latter to instream flows. Copyright © 2017 John Wiley & Sons, Ltd.
Duration of life-cycle toxicity tests with the ostracod Heterocypris incongruens
Authors: Hiki Kyoshiro , Tobino Tomohiro , Nakajima Fumiyuki , Tsukahara Kenta
Published: July 2017

An acute sediment toxicity test using the ostracod Heterocypris incongruens is user friendly and has high sensitivity; however, a life-cycle test using this species has not been developed. The most challenging problem when developing a life-cycle test is that the egg development time varies greatly and is sometimes too long (> 150 d) to monitor. It is desirable to shorten the duration of life-cycle toxicity tests including the observation period of egg development while preserving the ecological relevance of the net reproductive rate (R0), an endpoint in the life-cycle test. Therefore, in the present study, we suggest a practical test duration for R0 using population growth rate (λ) as a measure of ecological relevance. We collected a range of life history characteristics of the ostracod by combining data from the literature and experimental results, constructed population matrix models, and calculated λ for 20 life history patterns. The results showed that a longer test period (> 150 d) did not increase the correlation coefficients between R0 and λ. Rather, a shorter test duration resulted in R0 being highly correlated with λ. Our results suggest that a life-cycle toxicity test using the ostracod can provide an ecologically relevant toxicity endpoint, even if the test is abandoned after approximately 50 d and unhatched eggs remain. Environ Toxicol Chem 2017;36:3443–3449. © 2017 SETAC
Characteristics of hepatic insulin‐sensitive nonalcoholic fatty liver disease
Authors: Shigiyama Fumika , Kumashiro Naoki , Furukawa Yasuhiko , Funayama Takashi , Takeno Kageumi , Wakui Noritaka , Ikehara Takashi , Nagai Hidenari , Taka Hikari , Fujimura Tsutomu , Uchino Hiroshi , Tamura Yoshifumi , Watada Hirotaka , Nemoto Tetsuo , Shiraga Nobuyuki , Sumino Yasukiyo , Hirose Takahisa
Published: July 2017

Nonalcoholic fatty liver disease (NAFLD) plays a crucial role in type 2 diabetes and hepatocellular carcinoma. The major underlying pathogenesis is hepatic insulin resistance. The aim of the present study was to characterize patients with NAFLD with paradoxically normal hepatic insulin sensitivity relative to patients with NAFLD with hepatic insulin resistance. We recruited 26 patients with NAFLD and divided them into three groups ranked by the level of hepatic insulin sensitivity (HIS; high‐HIS, mid‐HIS, low‐HIS), as assessed by the hyperinsulinemic‐euglycemic clamp studies using stable isotope. Hepatic insulin sensitivity of the high‐HIS group was identical to that of the non‐NAFLD lean control (clamped percent suppression of endogenous glucose production, 91.1% ± 5.2% versus 91.0% ± 8.5%, respectively) and was significantly higher than that of the low‐HIS group (66.6% ± 7.5%; P < 0.01). Adiposity (subcutaneous, visceral, intrahepatic, and muscular lipid content), hepatic histopathology, and expression levels of various genes by using liver biopsies, muscle, and adipose tissue insulin sensitivity, plasma metabolites by metabolomics analysis, putative biomarkers, and lifestyles were assessed and compared between the high‐HIS and low‐HIS groups. Among these, adipose tissue insulin sensitivity assessed by clamped percent suppression of free fatty acid, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites, such as citric acid and cis‐aconitic acid, were significantly higher in the high‐HIS group compared to the low‐HIS group. In contrast, there were no differences in adiposity, including intrahepatic lipid content assessed by proton magnetic resonance spectroscopy (28.3% ± 16.1% versus 20.4% ± 9.9%, respectively), hepatic histopathology, other putative biomarkers, and lifestyles. Conclusion: High levels of adipose tissue insulin sensitivity, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites are unique characteristics that define patients with hepatic insulin‐sensitive NAFLD regardless of intrahepatic lipid content. (Hepatology Communications 2017;1:634–647)
Effects of deltamethrin, dimethoate, and chlorpyrifos on survival and reproduction of the collembolan Folsomia candida and the predatory mite Hypoaspis aculeifer in two African and two European soils
Authors: Jaabiri Kamoun Ikram , Jegede Olukayode O , Owojori Olugbenga J , Bouzid Jalel , Gargouri Radhia , Römbke Jörg
Published: July 2017

Indiscriminate use of pesticides is rampant in most parts of Africa, but only scanty ecotoxicological data exist for the protection of soil organisms—and these data were usually obtained under temperate conditions, including the use of Organisation for Economic Co-operation and Development (OECD) standard test protocols. In order to assess the effects of 3 commonly used pesticides (deltamethrin, dimethoate, chlorpyrifos) on soil fauna in Africa, noncontaminated natural soils were collected from Nigeria and Tunisia. In addition, 2 common test soils, OECD artificial soil and European (Landwirtschaftliche Untersichungs- und Forschungsanstalt [LUFA]) 2.3 soil, were used in OECD standard reproduction tests. Two microarthropod species, the springtail Folsomia candida and the predatory mite Hypoaspis aculeifer, were exposed in these 4 soils spiked individually with the 3 insecticides. Results show that the collembolan F. candida was more sensitive than the mite H. aculeifer for all 3 insecticides. The toxicity of each insecticide in the 4 soils differed, with few exceptions, by less than an order of magnitude. However, the pattern of toxicity was not consistent, that is, the lowest toxicity was often but not always found in OECD artificial soil. Soil- and pesticide-specific patterns of toxicity to F. candida and H. aculeifer might be related to the physicochemical properties of the soils and thus the availability of the 3 pesticides. Following the rules laid down in the European Union for the registration of pesticides and using standard European exposure scenarios, neither an acute nor a chronic risk of dimethoate and chlorpyrifos can be excluded (with few exceptions) in all 4 soils. Lower risks were identified for deltamethrin. For pesticide used in Africa, an environmental risk assessment based on data gained in tests with at least 1 additional natural field soil, preferably of African origin, should be performed using the same risk assessment principles as in the European Union. Integr Environ Assess Manag 2018;14:92–104. © 2017 SETAC

Key Points

Comparison of effects of 3 insecticides on 2 microarthropods in 2 temperate and 2 African soils. Folsomia candida was always more sensitive than Hypoaspis aculeifer for both endpoints. No consistent pattern of toxicity was found regarding the effects of the 3 insecticides in the 4 soils. Acute and chronic risks were identified for dimethoate and chlorpyrifos, but much less for deltamethrin.
Radical hysterectomy after radiotherapy for recurrent or persistent cervical cancer
Authors: Mabuchi Seiji , Kozasa Katsumi , Kimura Tadashi
Published: July 2017

Objective

To evaluate the safety and efficacy of radical hysterectomy after radiotherapy (RH‐AR) for recurrent or persistent cervical cancer.

Methods

The present retrospective study included patients who underwent RH‐AR for recurrent or persistent cervical cancer at Osaka University Hospital, Japan, between May 1, 2010 and September 30, 2016. Patient characteristics, intraoperative and postoperative adverse events, and surgical outcomes were investigated to identify patients at increased risk of recurrence or severe surgical adverse events.

Results

There were 31 patients scheduled for treatment with RH‐AR; one hysterectomy procedure was aborted. No intraoperative adverse events or treatment‐related deaths occurred, and 8 (27%) patients experienced severe postoperative adverse events. After a median 34 months of follow‐up, 13 (43%) patients had developed recurrent disease, predominantly at distant sites. The estimated 3‐year overall survival rate was 53.8%. Positive surgical margins, nodal metastasis, parametrial invasion, and no adjuvant treatment after RH‐AR were found to be predictors of increased risk of recurrence. No predictors of severe surgical adverse events were identified.

Conclusion

RH‐AR was a safe, curative treatment for patients with recurrent or persistent cervical cancer. However, considering the significant risk of surgical adverse events, RH‐AR should only be performed for a select group of patients.
Severe maternal morbidity and perinatal outcomes of multiple pregnancy in the Brazilian Network for the Surveillance of Severe Maternal Morbidity
Authors: Santana Danielly S. , Cecatti José G. , Haddad Samira M. , Parpinelli Mary A. , Costa Maria L. , Surita Fernanda G. , Sousa Maria H. ,   the Brazilian Network for the Surveillance of Severe Maternal Morbidity Study Group
Published: July 2017

Objective

To compare severe maternal complications (potentially life‐threatening conditions [PLTCs], maternal near miss [MNM], and maternal death) and perinatal outcomes between multiple and singleton pregnancies.

Methods

A secondary analysis was undertaken using data from the Brazilian Network for Surveillance of Severe Maternal Morbidity (prospective surveillance of morbidities in 27 Brazilian obstetric units between July 2009 and June 2010). Health indicators and criteria used for PLTCs and MNM were assessed. Adjusted prevalence ratios (PRadj) with 95% confidence intervals (CIs) were calculated for perinatal outcomes.

Results

Among 267 multiple pregnancies, 235 (88.0%) were affected by PLTCs, 25 (9.4%) by MNM, and 7 (2.6%) by maternal death; these prevalences did not differ from singleton pregnancies (n=7986). Management criteria for MNM were used almost twice as much in multiple pregnancies (PRadj 1.85, 95% CI 1.41–2.42). Preterm birth (PRadj 1.62, 95% CI 1.41–1.86), low birthweight (PRadj 1.73, 95% CI 1.45–2.06 for the first‐born vs singleton), any adverse perinatal outcome (PRadj 1.12, 95% CI 1.03–1.22 for the second‐ vs first‐born), and neonatal near miss (PRadj 1.37, 95% CI 1.13–1.67 for the second‐born vs singleton) were significantly associated with multiple pregnancy.

Conclusion

Among cases of severe maternal morbidity, perinatal but not maternal outcomes were poorer for multiple pregnancies than for singletons. Differentiated care is needed during pregnancy and childbirth.
Fracture Incidence and Characteristics in Young Adults Aged 18 to 49 Years: A Population-Based Study
Authors: Farr Joshua N , Melton L. Joseph , Achenbach Sara J , Atkinson Elizabeth J , Khosla Sundeep , Amin Shreyasee
Published: July 2017

Although fractures in both the pediatric and, especially, the elderly populations have been extensively investigated, comparatively little attention has been given to the age group in between. Thus, we used the comprehensive (inpatient and outpatient) data resources of the Rochester Epidemiology Project to determine incidence rates for all fractures among young adult (age range, 18 to 49 years) residents of Olmsted County, Minnesota, in 2009 to 2011, and compared the distribution of fracture sites and causes in this young adult cohort with those for older residents aged 50 years or older. During the 3-year study period, 2482 Olmsted County residents aged 18 to 49 years experienced 1 or more fractures. There were 1730 fractures among 1447 men compared with 1164 among 1035 women, and the age-adjusted incidence of all fractures was 66% greater among the men (1882 [95% confidence interval 1793–1971] versus 1135 [95% CI 1069–1201] per 100,000 person-years; p < 0.001). Of all fractures, 80% resulted from severe trauma (eg, motor vehicle accidents) compared with 33% in Olmsted County residents age ≥50 years who sustained a fracture in 2009 to 2011. Younger residents (aged 18 to 49 years), when compared with older residents (aged ≥50 years), had a greater proportion of fractures of the hands and feet (40% versus 18%) with relatively few fractures observed at traditional osteoporotic fracture sites (14% versus 43%). Vertebral fractures were still more likely to be the result of moderate trauma than at other sites, especially in younger women. In conclusion, whereas pediatric and elderly populations often fracture from no more than moderate trauma, young adults, and more commonly men, suffer fractures primarily at non-osteoporotic sites due to more significant trauma. © 2017 American Society for Bone and Mineral Research.
Effect of Combination Folic Acid, Vitamin B6, and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial
Authors: Stone Katie L , Lui Li-Yung , Christen William G , Troen Aron M , Bauer Douglas C , Kado Deborah , Schambach Christopher , Cummings Steven R , Manson JoAnn E
Published: July 2017

Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12, B6, and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6, or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017 American Society for Bone and Mineral Research.
Overexpression of MiR-335-5p Promotes Bone Formation and Regeneration in Mice
Authors: Zhang Lan , Tang Yin , Zhu Xiaofang , Tu Tianchi , Sui Lei , Han Qianqian , Yu Liming , Meng Shu , Zheng Leilei , Valverde Paloma , Tang Jean , Murray Dana , Zhou Xuedong , Drissi Hicham , Dard Michel M , Tu Qisheng , Chen Jake
Published: July 2017

MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous study revealed high expression of miR-335-5p in osteoblasts and hypertrophic chondrocytes in mouse embryos and the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to investigate the effects of miR-335-5p constitutive overexpression on bone formation and regeneration in vivo. To that end, we generated a transgenic mouse line specifically overexpressing miR-335-5p in osteoblasts lineage by the osterix promoter and characterized its bone phenotype. Bone histomorphometry and μCT analysis revealed higher bone mass and increased parameters of bone formation in transgenic mice than in wild-type littermates. Increased bone mass in transgenic mice bones also correlated with enhanced expression of osteogenic differentiation markers. Upon osteogenic induction, bone marrow stromal cells (BMSCs) isolated from transgenic mice displayed higher mRNA expression of osteogenic markers than wild-type mice BMSCs cultures. Protein expression of Runx2 and Osx was also upregulated in BMSC cultures of transgenic mice upon osteogenic induction, whereas that of DKK1 was downregulated. Most important, BMSCs from transgenic mice were able to repair craniofacial bone defects as shown by μCT analysis, H&E staining, and osteocalcin (OCN) immunohistochemistry of newly formed bone in defects treated with BMSCs. Taken together, our results demonstrate constitutive overexpression of miR-335-5p driven by an osterix promoter in the osteoblast lineage induces osteogenic differentiation and bone formation in mice and support the potential application of miR-335-5p–modified BMSCs in craniofacial bone regeneration. © 2017 American Society for Bone and Mineral Research.
Differences in growth physiology and aggregation of Pichia pastoris cells between solid‐state and submerged fermentations under aerobic conditions
Authors: Lima‐Pérez Jorge , Rodríguez‐Gómez Divanery , Loera Octavio , Viniegra‐González Gustavo , López‐Pérez Marcos
Published: July 2017

BACKGROUND

Morphology and size of biofilms of Pichia pastoris under different culture conditions are key to understanding growth physiology in solid‐state fermentation (SSF) and differences relative to submerged fermentation (SmF). Two microscopic techniques were used to contrast these phenomena, comparing SSF on polyurethane foam and SmF, with three concentrations of glycerol as carbon source. Growth parameters such as specific growth rate, maintenance energy, and substrate consumption were also evaluated.

RESULTS

Higher specific growth rate and maximum growth were obtained in SSF at every glycerol concentration compared with that obtained in SmF. Maintenance energy was higher (33%) in SmF and was related to lower biomass production (66%) than that obtained in SSF. Besides, in SmF, as substrate concentration increased, oxygen availability decreased; such differences in oxygenation could explain differences in biofilm formation. Scanning electron microscopy revealed that P. pastoris produced a compact multilayered biofilm embedded in SSF when compared with SmF, where smaller aggregates were scarcely observed by confocal microscopy.

CONCLUSION

This is the first work where growth parameters of P. pastoris in SSF and SmF are related to biofilm observations, which will help to improve SSF systems for P. pastoris production and its industrial application. © 2017 Society of Chemical Industry
Selective biostimulation of cold‐ and salt‐tolerant hydrocarbon‐degrading Dietzia maris in petroleum‐contaminated sub‐Arctic soils with high salinity
Authors: Chang Wonjae , Akbari Ali , David Carolyn A , Ghoshal Subhasis
Published: July 2017

BACKGROUND

The dual tolerance of hydrocarbon‐degrading bacteria to low temperatures and salinity has not been extensively reported. This study identifies cold‐ and salt‐tolerant hydrocarbon degraders obtained from petroleum‐contaminated sub‐Arctic soils, with the objective of stimulating target populations and assessing hydrocarbon biodegradation in soils abruptly impacted by salinity.

RESULTS

Halotolerant Dietzia and Arthrobacter bacteria were isolated from the soils. Dietzia maris strain NWWC4 can grow in the absence and presence of NaCl (≤12.5% w/v), adheres to hydrocarbons, and produces biosurfactant. The nutrient conditions preferred by strain NWWC4 were characterized to stimulate halotolerant hydrocarbon degraders related to strain NWWC4. In soil‐slurry microcosms with the selected nutrient, Terminal Restriction Fragment Length Polymorphism indicated the dominance of alkB‐gene‐harboring NWWC4 relatives. Radiolabeled 14C‐hexadecane mineralization in high‐salinity soil‐slurry microcosms (29 ± 0.33% 14CO2 production) was strikingly comparable with that in non‐saline conditions (35 ± 0.84% 14CO2 production). In nutrient‐amended, Arctic‐diesel‐spiked soil microcosms subjected to dual stresses (10 °C and 5% NaCl, w/v), hydrocarbon removal in the diesel range (C10–C21) was 21 ± 8% after 18 days and was comparable with the removal achieved under non‐saline conditions (37 ± 6% removal).

CONCLUSION

This study reports the unique versatility of cold‐adapted and salt‐tolerant Dietzia maris capable of degrading hydrocarbons in highly saline and non‐saline conditions. © 2017 Society of Chemical Industry
Radiosynthesis of 1‐iodo‐2‐[11C]methylpropane and 2‐methyl‐1‐[11C]propanol and its application for alkylation reactions and C―C bond formation
Authors: Rotteveel Lonneke , Poot Alex J. , Funke Uta , Pekošak Aleksandra , Filp Ulrike , Lammertsma Adriaan A. , Windhorst Albert D.
Published: July 2017

The multitude of biologically active compounds requires the availability of a broad spectrum of radiolabeled synthons for the development of positron emission tomography (PET) tracers. The aim of this study was to synthesize 1‐iodo‐2‐[11C]methylpropane and 2‐methyl‐1‐[11C]propanol and investigate the use of these reagents in further radiosynthesis reactions. 2‐Methyl‐1‐[11C]propanol was obtained with an average radiochemical yield of 46 ± 6% d.c. and used with fluorobenzene as starting material. High conversion rates of 85 ± 4% d.c. could be observed with HPLC, but large precursor amounts (32 mg, 333 μmol) were needed. 1‐Iodo‐2‐[11C]methylpropane was synthesized with a radiochemical yield of 25 ± 7% d.c. and with a radiochemical purity of 78 ± 7% d.c. The labelling agent 1‐iodo‐2‐[11C]methylpropane was coupled to thiophenol, phenol and phenylmagnesium bromide. Average radiochemical conversions of 83% d.c. for thiophenol, 40% d.c. for phenol, and 60% d.c. for phenylmagnesium bromide were obtained. In addition, [11C]2‐methyl‐1‐propyl phenyl sulphide was isolated with a radiochemical yield of 5 ± 1% d.c. and a molar activity of 346 ± 113 GBq/μmol at the end of synthesis. Altogether, the syntheses of 1‐iodo‐2‐[11C]methylpropane and 2‐methyl‐1‐[11C]propanol were achieved and applied as proof of their applicability.
Plan quality and delivery time comparisons between volumetric modulated arc therapy and intensity modulated radiation therapy for scalp angiosarcoma: A planning study
Authors: Kai Yudai , Toya Ryo , Saito Tetsuo , Kuraoka Akiko , Shimohigashi Yoshinobu , Nakaguchi Yuji , Maruyama Masato , Murakami Ryuji , Yamashita Yasuyuki , Oya Natsuo
Published: July 2017

Introduction

Due to its spherical surface, scalp angiosarcoma requires careful consideration for radiation therapy planning and dose delivery. Herein, we investigated whether volumetric modulated arc therapy (VMAT) is superior to intensity modulated radiation therapy (IMRT) in terms of the plan quality and delivery time.

Methods

Three different coplanar treatment plans were created for four patients, comprising a two‐arc VMAT plan as well as 5‐field and 9‐field IMRT plans with 6 MV beams. The X‐ray Voxel Monte Carlo algorithm was employed for dose calculation. A radiation therapy dose of 60 Gy was prescribed to the planning target volume (PTV) in 30 fractions. The homogeneity indexes (HIs) and conformity indexes (CIs) of the PTV, organs at risk (OARs) doses and delivery times were calculated and compared.

Results

For the VMAT, 5‐field and 9‐field IMRT plans, the mean HIs were 0.14, 0.16 and 0.15; CIs100% were 0.63, 0.61 and 0.64; CIs98% were 0.72, 0.66 and 0.70 and CIs95% were 0.74, 0.67 and 0.71 respectively. All mean dose parameters of the VMAT and 9‐field IMRT plans for the brain were equal to or lower than those of the 5‐field IMRT plan. For the 5‐field IMRT plan, the dose constraints for the left lens were not satisfied in two patients. The mean delivery times were 3.3, 11.1 and 14.7 min for the VMAT, 5‐field and 9‐field IMRT plans respectively.

Conclusion

The VMAT plan quality is comparable to that of 9‐field IMRT, with a reduced delivery time. Therefore, VMAT represents a valuable, sophisticated irradiation technique for treating scalp angiosarcoma.