bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of DNA extraction from human urinary samples for mycobiome community profiling
Authors: Ackerman A. Lenore , Anger Jennifer Tash , Khalique Muhammad Umair , Ackerman James E , Tang Jie , Kim Jayoung , Underhill David M. , Freeman Michael R. ,   Multidisciplinary Approach to the Study of Pelvic Pain (MAPP)
Published: December 2018

Abstract

Introduction. Recent data suggest the urinary tract hosts a microbial community of varying composition, even in the absence of infection. Culture-independent methodologies, such as next-generation sequencing of conserved ribosomal DNA sequences, provide an expansive look at these communities, identifying both common commensals and fastidious organisms. A fundamental challenge has been the isolation of DNA representative of the entire resident microbial community, including fungi.

Materials and Methods. We evaluated multiple modifications of commonly-used DNA extraction procedures using standardized male and female urine samples, comparing resulting overall, fungal and bacterial DNA yields by quantitative PCR. After identifying protocol modifications that increased DNA yields (lyticase/lysozyme digestion, bead beating, boil/freeze cycles, proteinase K treatment, and carrier DNA use), all modifications were combined for systematic confirmation of optimal protocol conditions. This optimized protocol was tested against commercially available methodologies to compare overall and microbial DNA yields, community representation and diversity by next-generation sequencing (NGS).

Results. Overall and fungal-specific DNA yields from standardized urine samples demonstrated that microbial abundances differed significantly among the eight methods used. Methodologies that included multiple disruption steps, including enzymatic, mechanical, and thermal disruption and proteinase digestion, particularly in combination with small volume processing and pooling steps, provided more comprehensive representation of the range of bacterial and fungal species. Concentration of larger volume urine specimens at low speed centrifugation proved highly effective, increasing resulting DNA levels and providing greater microbial representation and diversity.

Conclusions. Alterations in the methodology of urine storage, preparation, and DNA processing improve microbial community profiling using culture-independent sequencing methods. Our optimized protocol for DNA extraction from urine samples provided improved fungal community representation. Use of this technique resulted in equivalent representation of the bacterial populations as well, making this a useful technique for the concurrent evaluation of bacterial and fungal populations by NGS.
Sparse functional data analysis accounts for missing information in single-cell epigenomics
Authors: Madrigal Pedro , Dai Xiongtao , Hadjipantelis Pantelis Z.
Published: December 2018

Single-cell epigenome assays produce sparsely sampled data, leading to coverage pooling across cells to increase resolution. Imputation of missing data using deep learning is available but requires intensive computation, and it has been applied only to DNA methylation obtained by single cell bisulfite sequencing. Here, sparsity in chromatin accessibility obtained by scNMT-seq is addressed using functional data analysis to fit sparsely sampled GpC coverage profiles of individual cells taking into account all the cells of the same cell-type or condition. For that, sparse functional principal component analysis (S-FPCA) is applied, and the principal components are used to estimate chromatin accessibility coverage in individual cells. This methodology can potentially be used with other single-cell assays with missing data such as scBS-seq, scNOME-seq, or scATAC-seq. The R package fdapace is available in CRAN, and R code used in this manuscript can be found at: http://github.com/pmb59/sparseSingleCell.
Perineuronal Nets in the Insula Regulate Aversion-Resistant Alcohol Drinking
Authors: Chen Hu , Lasek Amy W
Published: December 2018

One of the most pernicious characteristics of alcohol use disorder is the compulsion to drink despite negative consequences. The insular cortex (insula) controls decision-making under conditions of risk or conflict and regulates maladaptive behaviors in the context of addiction. Cortical activity is tightly controlled by fast-spiking inhibitory interneurons that are often enclosed by specialized extracellular matrix structures known as perineuronal nets, which regulate neuronal excitability and plasticity. Using a mouse model of compulsive drinking in which alcohol was adulterated with the bitter tastant quinine, we demonstrate that disrupting perineuronal nets in the insula rendered mice more sensitive to quinine-adulterated alcohol. Activation of the insula, as measured by c-fos expression, occurred during aversion-resistant drinking and was further enhanced by elimination of perineuronal nets. These results provide fundamental insight into neuroanatomical and cellular mechanisms that control compulsive drinking.
Single-particle reconstruction statistics: a diagnostic tool in solving biomolecular structures by cryo-EM
Authors: Heymann J. Bernard
Published: December 2018

In single-particle analysis (SPA), the aim is to obtain a 3D reconstruction of a biological molecule from 2D electron micrographs to the highest level of detail or resolution as possible. Current practice is to collect large volumes of data, hoping to reach high-resolution maps through sheer numbers. However, adding more particles from a specific data set eventually leads to diminishing improvements in resolution. Understanding what these resolution limits are and how to deal with them are important in optimization and automation of SPA. This study revisits the theory of 3D reconstruction and demonstrates how the associated statistics can provide a diagnostic tool to improve SPA. Small numbers of images already give sufficient information on micrograph quality and the amount of data required to reach high resolution. Such feedback allows the microscopist to improve sample-preparation and imaging parameters before committing to extensive data collection. Once a larger data set is available, a B factor can be determined describing the suppression of the signal owing to one or more causes, such as specimen movement, radiation damage, alignment inaccuracy and structural variation. Insight into the causes of signal suppression can then guide the user to consider appropriate actions to obtain better reconstructions.
catena-Poly[[[(acetato-κ2
O,O′)aquacadmium(II)]-μ-L-threoninato-κ3
N,O:O′] monohydrate]
Authors: Abila Jeba Queen M. , Bright K. C. , Mary Delphine S.
Published: December 2018

The title compound, {[Cd(C2H3O2)(C4H8NO3)(H2O)]·H2O}
n
, was synthesized from the reaction between L-threonine and cadmium acetate dihydrate. The complex consists of the CdII metal ion bonded to bidentate threonine and acetate anions, and one water molecule. The carboxylate group of L-threonine bridges two metal cations related by the crystallographic screw axis parallel to [010], to form a one-dimensional polymeric structure in the crystal. The asymmetric unit is completed by one lattice water molecule, which is involved in hydrogen bonds.
A Historical, Detailed Toolmark Examination from 1916
Authors: Springer Eliot , Dumitra Aurora
Published: December 2018

Marc Bischoff received his PhD from the University of Lausanne, Institute of Police Science and Criminology, and later became the head of the Institute. His final examination paper for his doctorate degree constitutes a toolmark analysis and comparison between a suspected axe and questioned cuttings of wood trunks. Bischoff uses the scientific method to test the hypothesis he formulated. Dated 1916, this report includes his notes, measurements, photomicrographs of the questioned toolmarks and the test impressions, detailed sketches, technical discussion, results, and conclusions. Recognizing the historical value of Bischoff's work, it seemed important to get it translated. Photocopies of Bischoff's original work were obtained. The case report, translated from French, is presented here along with a brief history of the Firearm and Toolmark Identification field and Bischoff's role in the beginning of this field. Bischoff's work stands as testimony to the long tradition of the field of forensic toolmark analysis.
Age estimation in a long‐lived seabird (Ardenna tenuirostris) using DNA methylation‐based biomarkers
Authors: De Paoli‐Iseppi Ricardo , Deagle Bruce E. , Polanowski Andrea M. , McMahon Clive R. , Dickinson Joanne L. , Hindell Mark A. , Jarman Simon N.
Published: December 2018

Age structure is a fundamental aspect of animal population biology. Age is strongly related to individual physiological condition, reproductive potential and mortality rate. Currently, there are no robust molecular methods for age estimation in birds. Instead, individuals must be ringed as chicks to establish known‐age populations, which is a labour‐intensive and expensive process. The estimation of chronological age using DNA methylation (DNAm) is emerging as a robust approach in mammals including humans, mice and some non‐model species. Here, we quantified DNAm in whole blood samples from a total of 71 known‐age Short‐tailed shearwaters (Ardenna tenuirostris) using digital restriction enzyme analysis of methylation (DREAM). The DREAM method measures DNAm levels at thousands of CpG dinucleotides throughout the genome. We identified seven CpG sites with DNAm levels that correlated with age. A model based on these relationships estimated age with a mean difference of 2.8 years to known age, based on validation estimates from models created by repeated sampling of training and validation data subsets. Longitudinal observation of individuals re‐sampled over 1 or 2 years generally showed an increase in estimated age (6/7 cases). For the first time, we have shown that epigenetic changes with age can be detected in a wild bird. This approach should be of broad interest to researchers studying age biomarkers in non‐model species and will allow identification of markers that can be assessed using targeted techniques for accurate age estimation in large population studies.
Increased expression and altered subcellular distribution of cathepsin B in microglia induce cognitive impairment through oxidative stress and inflammatory response in mice
Authors: Ni Junjun , Wu Zhou , Stoka Veronika , Meng Jie , Hayashi Yoshinori , Peters Christoph , Qing Hong , Turk Vito , Nakanishi Hiroshi
Published: December 2018

During normal aging, innate immunity progresses to a chronic state. However, how oxidative stress and chronic neuroinflammation arise during aging remains unclear. In this study, we found that genetic ablation of cathepsin B (CatB) in mice significantly reduced the generation of reactive oxygen species (ROS) and neuroinflammation and improved cognitive impairment during aging. In cultured microglia, pharmacological inhibition of CatB significantly reduced the generation of mitochondria‐derived ROS and proinflammatory mediators induced by L‐leucyl‐L‐leucine methyl ester (LLOMe), a lysosome‐destabilizing agent. In the CatB‐overexpressing microglia after treatment with LLOMe, which mimicked the aged microglia, CatB leaked in the cytosol is responsible for the degradation of the mitochondrial transcription factor A (TFAM), resulting in the increased generation of mitochondria‐derived ROS and proinflammatory mediators through impaired mtDNA biosynthesis. Furthermore, intralateral ventricle injection of LLOMe‐treated CatB‐overexpressing microglia induced cognitive impairment in middle‐aged mice. These results suggest that the increase and leakage of CatB in microglia during aging are responsible for the increased generation of mitochondria‐derived ROS and proinflammatory mediators, culminating in memory impairment.
The impact of vaping and regulatory environment on cigarette demand: behavioral economic perspective across four countries
Authors: Heckman Bryan W. , Fong Geoffrey T. , Borland Ron , Hitchman Sara , O’Connor Richard J. , Bickel Warren K. , Stein Jeffrey S. , Yong Hua‐Hie , Nahhas Georges J. , Pope Derek A. , Shang Ce , Cheng Kai‐Wen , Levy David T. , Cummings K. Michael
Published: December 2018

Background and Aims

Government regulations of nicotine vaping products (NVP) have evolved rapidly during the past decade. The impact of NVP regulatory environment and vaping on cigarette demand is unknown. The current study aims to investigate whether or not respondents’ reported cigarette demand, as measured by a hypothetical cigarette purchase task, varies with (1) smoking status, (2) vaping status or (3) NVP regulatory environment (country used as proxy).

Design

Cross‐sectional survey data from wave 1 of the International Tobacco Control (ITC) Four Country Smoking and Vaping (4CV) Survey (2016).

Setting

Australia, Canada, England and the United States.

Participants

A total of 10 316 adult smokers.

Measurements

A hypothetical purchase task asked smokers to estimate how many cigarettes they would purchase for consumption in a single day across multiple cigarette prices. Responses were used to derive measures of cigarette demand. Overall sensitivity of cigarette consumption to price increases was quantified to index cigarette demand elasticity, whereas estimated consumption when cigarettes are free was used to index cigarette demand intensity.

Findings

A majority of the non‐daily smokers had previously smoked daily (72.3%); daily vapers were more likely to be former daily smokers (89.9%) compared to non‐daily vapers (70.1%) and non‐vapers (69.2%) (P < 0.001). The smoking status × vaping status interaction was significant for cigarette demand intensity (F = 4.93; P = 0.007) and elasticity (F = 7.30; P = 0.001): among non‐daily smokers, vapers reported greater intensity but lower elasticity (i.e. greater demand) relative to non‐vapers (Ps < 0.05). Among daily smokers, daily vapers reported greater intensity relative to non‐vapers (P = 0.005), but vaping status did not impact elasticity (Ps > 0.38). Intensity was higher in Australia compared with all other countries (Ps < 0.001), but elasticity did not vary by country (F = 2.15; P = 0.09).

Conclusions

In a hypothetical purchase task, non‐daily smokers showed lower price elasticity if they used e‐cigarettes than if they did not, while there was no clear difference in elasticity between e‐cigarette users and non‐users among daily smokers or according to regulatory environment of their country with regard to e‐cigarettes.
Expressions of miR‐525‐3p and its target geneSEMG1in the spermatozoa of patients with asthenozoospermia
Authors: Zhou Q.‐z. , Guo X.‐b. , Zhang W.‐s. , Zhou J.‐h. , Yang C. , Bian J. , Chen M.‐k. , Guo W.‐b. , Wang P. , Qi T. , Wang C.‐y. , Yang J.‐k. , Liu C.‐d.
Published: December 2018

Background

Semenogelin 1 (SEMG1) is an important secretory protein in spermatozoa involved in the formation of a gel matrix encasing ejaculated spermatozoa. Previous studies show that theSEMG1 gene is highly expressed in spermatozoa from patients with asthenozoospermia (AZS); however, the underlying molecular mechanisms are not yet clear.

Objectives

To study the molecular mechanism of high expression ofSEMG1 gene and its potential roles inAZS.

Materials and Methods

Western blot and real‐timePCRwere used to detect the expression levels ofSEMG1protein andmRNAin the ejaculated spermatozoa from normozoospermic males andAZSpatients. Bioinformatics analysis was used to predict miRNAs targeting forSEMG1 3′‐untranslated region detection of the expression levels of all the candidate miRNAs in ejaculatory spermatozoa inAZSpatients or normozoospermic volunteers. Luciferase reporter assays were performed to confirm it can directly bind toSEMG1. Correlation of miR‐525‐3p andSEMG1mRNAexpression with clinical sperm parameters were also analyzed. Finally, we conducted a follow‐up study of reproductive history about all the subjects.

Results

SEMG1mRNAand protein level were significantly higher inAZSpatients compared to that in normozoospermic volunteers (p < 0.001). Subsequently, microRNA‐525‐3p (miR‐525‐3p) which was predicted as a candidate regulator ofSEMG1was found lower expressed in ejaculatory spermatozoa inAZSpatients (p = 0.0074). Luciferase experiment revealed that microRNA‐525‐3p could directly targetSEMG13′‐untranslated region and suppress its expression. Importantly, our retrospective follow‐up study showed that both low miR‐525‐3p expression and highSEMG1 expression level was significantly associated with low progressive sperm motility, abnormal sperm morphology, and infertility.

Discussion and Conclusion

The elevated expression ofSEMG1 and reduced expression of miR‐525‐3p are associated withAZSand male infertility. Our study provides a potential therapeutic target for the treatment of male infertility or for male contraception.
Maintenance rituximab or observation after frontline treatment with bendamustine‐rituximab for follicular lymphoma
Authors: Hill Brian T. , Nastoupil Loretta , Winter Allison M. , Becnel Melody R. , Cerhan James R. , Habermann Thomas M. , Link Brian K. , Maurer Matthew J. , Fakhri Bita , Reddy Prathima , Smith Stephen D. , Mukhija Dhruvika , Jagadeesh Deepa , Desai Amrita , Alderuccio Juan Pablo , Lossos Izidore S. , Mehra Pooja , Portell Craig A. , Goldman Max L. , Calzada Oscar , Cohen Jonathon B. , Hussain Mohammad J. , Ghosh Nilanjan , Caimi Paolo , Tiutan Timothy , Martin Peter , Kodali Abhigna , Evens Andrew M. , Kahl Brad S.
Published: December 2018

Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R‐CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.
Neural correlates of cue‐ and stress‐induced craving in gambling disorders: implications for transcranial magnetic stimulation interventions
Authors: Spagnolo Primavera A. , Gómez Pérez Luis J. , Terraneo Alberto , Gallimberti Luigi , Bonci Antonello
Published: December 2018

Gambling disorder (GD), currently considered a behavioral addiction, shows substantial similarities with substance use disorders (SUDs) in terms of neurobiology and phenomenology. These similarities have been recognized in the DSM‐5, although several relevant differences still exist in the diagnostic criteria, in particular, with regard to the role of cue‐ and stress‐ induced craving. Craving, recently included as a new criterion for SUDs diagnosis only, is a key construct also in the pathophysiology of GD. Furthermore, brain imaging studies indicate that similar alterations in cortico‐limbic‐striatal and prefrontal control circuits underlie the emergence of craving states in both disorders. This has important implications for the identification of neurobiologically based anti‐craving interventions, which may be used for both GD and SUDs. In this regard, a novel neuromodulation intervention, named repetitive transcranial magnetic stimulation (rTMS), is emerging as a promising treatment for craving in SUDs, and could potentially be effective also in treating gambling urges. Here, we review the clinical neurobiological research on GD, with a specific emphasis on the neural circuits implicated in cue‐ and stress‐craving, taking SUDs as the major comparative example. Furthermore, we describe the studies that have evaluated rTMS as a therapeutic tool for targeting and restoring the neural alterations underlying gambling urge. The manuscript concludes discussing some of the limitations of the current studies, and suggests directions for future rTMS research in GD.
Norms for standard neuropsychological tests from the French CONSTANCES cohort
Authors: Ouvrard C. , Berr C. , Meillon C. , Ribet C. , Goldberg M. , Zins M. , Amieva H.
Published: December 2018

Background and purpose

Neuropsychological testing plays a key role in various clinical contexts. Even though a substantial number of adults suffer neurological disorders such as early‐onset dementia, stroke, traumatic brain injury or multiple sclerosis, most normative data do not include persons below 65. The aim of this study was to produce updated norms for the Mini‐Mental State Examination, the Free and Cued Selective Reminding Test, the Trail Making Test, verbal fluency tasks and the Digit Symbol Substitution Test for middle‐aged and older adults.

Methods

The sample consisted of 51 879 participants aged 45–70 years from the CONSTANCES study. Norms are presented in percentiles stratified on age, education and gender.

Results

The results illustrated the effect of age in all tests considered. For tests involving speed processing, the impact of age was observed including in tight age range categories (5 years). The results also showed the well‐known effect of education and an effect of gender in tests involving verbal memory and speed processing.

Conclusions

The norms provided allow the variability of the cognitive performances of middle‐aged to older populations to be understood, with a high precision in age categories. The tests considered are broadly used in neuropsychological practice and should be helpful in a variety of clinical contexts.
Crystallization, microstructure and mechanical behavior of titanium doped barium fluormica glass‐ceramics
Authors: Mallik Amit , Saha Sumit
Published: December 2018

Crystallization, microstructure and mechanical behavior of TiO2 doped barium fluorphlogopite glass‐ceramics were systematically studied. TiO2 was used as a doper nucleant in the BaO·4MgO·Al2O3·6SiO2·2MgF2 glass system. Melting technique was adopted to prepare the glass samples which were analyzed by differential thermal analysis (DTA), X‐ray diffraction, scanning electron microscopy, and micro hardness indenter. The DTA study demonstrated that the crystallization exotherm of fluorphlogopite mica appeared in the temperature window of 886‐903°C. In this investigation, four glass samples were prepared using 2 (MA1), 4 (MA2), 6 (MA3), and 8 (MA4) wt% of TiO2. Glass transition (Tg) and peak crystallization (Tp) temperatures escalated with an increase in the TiO2 content from 2 (MA1) to 4 wt% (MA2). However, beyond this value, Tg and Tp decreased with a surge in TiO2 content from 6 (MA3) to 8 wt% (MA4). Nevertheless, with a gradual rise in the TiO2 content, the crystals of the glass‐ceramics became enlarged and subsequently exhibited mechanical properties, such as hardness, fracture toughness, and machinability. Therefore, in solid oxide fuel cell applications, TiO2 is a promising nucleating agent to generate fluorphlogopite mica‐based glass‐ceramics.
Does post‐anthesis heat stress affect plant phenology, physiology, grain yield and protein content of durum wheat in a semi‐arid Mediterranean environment?
Authors: Cosentino Salvatore L. , Sanzone Emanuele , Testa Giorgio , Patanè Cristina , Anastasi Umberto , Scordia Danilo
Published: December 2018

Increasing air temperature due to changing climate is projected to decrease the length of the growing season, hasten vegetative development and maturation, and ultimately affect yield of many C3 crops. Previous multilocation trials highlighted strong relationships between thermal trends in the interval “beginning of flowering‐end of grain filling” and grain yield, and protein content in durum wheat (Triticum turgidum subsp. durum (Desf.) Husn.). With the aim to confirm these relationships, nine durum wheat genotypes, including old (Capeiti 8, Senatore Cappelli and Trinakria) and modern (Amedeo, Arcangelo, Mongibello, Simeto, and Svevo) varieties and a Sicilian landrace (Russello) were grown at three different sites representing a climate gradient in Sicily, Italy. Moreover, the effect of post‐anthesis heat stress on these durum wheats was further investigated in two contrasting environments: open‐field (control—C) and greenhouse heat stress (HS). HS shortened the interval “beginning‐end of flowering” of 1.5 days across genotypes, and the “end of flowering‐beginning of grain filling” and maturation of 4.9 days, with a range of 1 day in Arcangelo to 11 days in Cappelli. Advances in main phenophases significantly decreased kernel weight (KW) and grain yield (GY), whereas grain protein content (PC) increased. As expected, a negative relationship was observed between GY and PC, while positive relationships were found for GY and grain‐filling duration (GFD), and GY and KW. Genotypes responded differently to heat stress, as evidenced by the net photosynthesis, transpiration rate, instantaneous water use efficiency and dry matter accumulation in kernels. Genotypes were ranked according to the heat susceptibility index (HSI): Amedeo, Arcangelo, Capeiti 8, Svevo and Trinakria resulted heat‐tolerant. These varieties were characterized by an early trigger of dry matter accumulation in kernels under HS (Amedeo, Arcangelo and Trinakria), or showed similar length of the GFD (Capeiti 8) between environments. The multilocation trial confirmed a negative relationship between maximum temperatures and grain yield, and a positive relationship between minimum temperatures and protein content during grain–filling periods. Research focusing on agronomic strategies, phenology and breeding for tolerance to heat stress is of strategic importance to cope with the detrimental effect of global warming in semi‐arid climates.
Awareness is still warranted for ARBs
Authors: Javaud N. , Fain O.
Published: December 2018

Click here to view the Original article by Dr. Rasmussen et al.
Risk of high‐grade malignancy in parotid gland tumors as classified by the Milan System for Reporting Salivary Gland Cytopathology
Authors: Park Woori , Bae Hyunsik , Park Min‐Hae , Hwang Na Young , Sohn Insuk , Cho Junhun , Jeong Han‐Sin
Published: December 2018

Background

The Milan System for Reporting Salivary Gland Cytopathology (Milan System) has previously shown its diagnostic utility by categorizing the seven cytology findings in salivary gland lesions. However, there has been lack of study about the risk of high‐grade malignancy in the cytology diagnosis based on the Milan System. Thus, we tried to identify the diagnostic ability of the Milan System for high‐grade malignancy and to suggest an improved diagnostic approach for preoperative estimation of high‐grade malignancy using the Milan System.

Methods

A total of 413 patients with parotid gland tumors, who had undergone surgical resection from 2011 to 2015 were included in the present study retrospectively. Cytopathology was reclassified according to the Milan System by two independent reviewers. The outcomes were risk of malignancy and risk of high‐grade malignancy. The diagnostic performance of the Milan System category [Malignant] for detecting high‐grade malignancy was calculated.

Results

The risk of malignancy was 83.3% and 100% in the Milan System categories [Suspicious for Malignancy] and [Malignant], respectively. Meanwhile, the risk of high‐grade malignancy was 16.7% and 55.9% in these two categories. Disease‐free survival of patients with high‐grade malignancy was significantly worse than those with low‐ and intermediate‐grade malignancy. Union combining the Milan System category [Malignant] with the presence of nodal metastasis suggested high‐grade malignancy with an acceptable diagnostic sensitivity (0.889‐0.963) and negative predictive value (0.900‐0.966).

Conclusions

The Milan System category [Malignant] with the presence of nodal metastasis suggested parotid gland tumors as high‐grade malignancy in a pretreatment setting.
Preparation, chemical characterization and determination of crocetin's pharmacokinetics after oral and intravenous administration of saffron (Crocus sativus L.) aqueous extract to C57/BL6J mice
Authors: Christodoulou Eirini , Grafakou Maria-Eleni , Skaltsa Eleni , Kadoglou Nikolaos , Kostomitsopoulos Nikolaos , Valsami Georgia
Published: December 2018

Objectives

To prepare a lyophilized saffron aqueous extract (SFE) and determine its chemical profile and serum and tissue pharmacokinetics after intravenous and oral administration to C57/Bl6J mice.

Methods

Lyophilized SFE was prepared, characterized using semi-preparative HPLC and NMR analysis, and stability studies at room temperature, and was quantified for crocin content with an HPLC-PDA method. After intravenous and oral administration of SFE (60 mg/kg, reconstituted with water for injection) to C57/Bl6J mice, crocetin (derived from in vivo crocin hydrolysis) serum and tissue levels (unconjugated and total) were measured with an HPLC-PDA method and subjected to compartmental and non-compartmental PK analysis.

Key findings

Saffron aqueous extract was rich in all-trans-crocin (27.8 ± 0.1% w/w) and stable for more than 15 months. One-compartment PK model described crocetin's (unconjugated) kinetics after intravenous administration of SFE, while a first-order kinetic parameter described the rate of crocetin biotransformation to crocetin metabolite (conjugated). Α οne-compartment PK model with first-order absorption described crocetin and crocetin's metabolite kinetics after SFE oral administration. Relative oral bioavailability was calculated at 1.17 for total crocetin. Tissue NCA PK analysis revealed extensive crocetin distribution to liver and kidneys.

Conclusions

SFE is a stable lyophilized extract rich in all-trans-crocin. The PK study allowed the estimation of basic PK parameters and the bioavailability of SFE’s main bioactive component, crocetin, after peros administration.
Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide
Authors: Fong Tse‐Ling , Lee Brian T. , Tien Andy , Chang Mimi , Lim Carolina , Ahn Aiden , Bae Ho S.
Published: December 2018

Tenofovir alafenamide (TAF) is a novel prodrug that reduces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF in as early as 12 weeks. This was a prospective single‐arm open‐label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA <21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Hip and spine bone mineral density significantly increased from baseline to week 12 (+12.9% and +2.4%, respectively, P < 0.01). There were significant decreases in urinary beta‐2‐microglobulin to creatinine and retinol‐binding protein to creatinine ratios by week 12 (P < 0.01 for both). Mean estimated glomerular filtration rate (GFR) did not change. Tubular reabsorption of phosphate was decreased at week 24 (P < 0.05). In conclusion, CHB patients previously treated with TDF experienced significant improvement in bone density and some markers of renal tubular function and as early as 12 weeks after switching to TAF. Bone density changes associated with TDF may not be entirely related to renal handling of phosphate.
Rescue of Citrus sudden death‐associated virus in Nicotiana benthamiana plants from cloned cDNA: insights into mechanisms of expression of the three capsid proteins
Authors: Matsumura Emilyn E. , Coletta‐Filho Helvécio D. , Machado Marcos A. , Nouri Shahideh , Falk Bryce W.
Published: December 2018

Citrus sudden death‐associated virus (CSDaV) is a member of the genus Marafivirus in the family Tymoviridae, and has been associated with citrus sudden death (CSD) disease in Brazil. Difficulties in the purification of CSDaV from infected citrus plants have prevented progress in the investigation of the role of this virus in CSD and an understanding of its molecular biology. In this work, we have constructed a full‐length cDNA clone of CSDaV driven by the 35S promoter (35SRbz‐CSDaV). Agrobacterium tumefaciens‐mediated inoculation of 35SRbz‐CSDaV in Nicotiana benthamiana plants enabled a fast recovery of large amounts of virions from the agroinfiltrated leaves, which allowed a better molecular characterization of CSDaV. In vivo analyses of mutant versions of 35SRbz‐CSDaV revealed the expression strategies used by CSDaV for production of the capsid proteins (CPs). We showed that CSDaV virions contain three forms of CP, each of which is generated from the same coding sequence, but by different mechanisms. The major CPp21 is a product of direct translation by leaky scanning from the second start codon in the subgenomic RNA (sgRNA), whereas the minor CPs, p25 and p23, are produced by direct translation from the first start codon in the sgRNA and by trans‐proteolytic cleavage processing derived from the p25 precursor, respectively. Together, these findings contribute to advance our understanding of CSDaV genome expression strategies. In addition, the construction and characterization of the CSDaV infectious clone represent important steps towards the investigation of the role of this virus in CSD and of its use as a tool for citrus biotechnology.
Legumes—The art and science of environmentally sustainable agriculture
Authors: Foyer Christine H. , Nguyen Henry , Lam Hon‐Ming
Published: December 2018

Symbiotic nitrogen fixation, which is carried out by the legume‐rhizobia partnership, is a major source of nitrogen acquisition in natural ecosystems and in agriculture. The benefits to the plant gained through the rhizobial‐legume symbiosis can be further enhanced by associations of the legume with arbuscular mycorrhiza. The progressive engagement of the legume host with the rhizobial bacteria and mycorrhizal fungi requires an extensive exchange of signalling molecules. These signals alter the transcriptional profiles of the partners, guiding and enabling extensive microbial and fungal proliferation in the roots. Such interactions and associations are greatly influenced by environmental stresses, which also severely limit the productivity of legume crops. Part II of the Special Issue on Legumes provides new insights into the mechanisms that underpin sustainable symbiotic partnerships, as well as the effects of abiotic stresses, such as drought, waterlogging, and salinity on legume biology. The requirement for germplasm and new breeding methods is discussed as well as the future of legume production in the face of climate change.
Optimizing industrial‐scale coral reef restoration: comparing harvesting wild coral spawn slicks and transplanting gravid adult colonies
Authors: Doropoulos Christopher , Elzinga Jesper , ter Hofstede Remment , van Koningsveld Mark , Babcock Russell C.
Published: December 2018

Accelerating coral reef restoration is a global challenge that has been attempted around the world. Previous attempts show varying levels of success at localized scales, but comparisons of cost and benefits to evaluate large‐scale reef restoration approaches are lacking. Here, we compare two large‐scale restoration approaches: the harvesting, development, and release of wild coral spawn slicks onto a target reef, with the transplantation of gravid coral colonies to provide a seed population and local source of larvae. Comparisons incorporate the best available information on demographic rates to estimate population growth, beginning at embryo production to colony maturity 4 years following deployment. Cost‐effectiveness is considered in a coarse manner. The harvesting, development, and controlled release of coral spawn slicks is anticipated to achieve large‐scale restoration of coral communities with low‐impact technology at low cost per colony. Harvesting wild spawn slicks has the potential to (1) transport billions of larvae up to thousands of kilometers that (2) are relevant to coral restoration efforts at vast geographical scales while (3) benefitting from the use of technology with extremely low impact on wild populations and (4) retaining natural genetic and species diversity needed to enhance the resilience of restored communities. Transplanting colonies is most useful from reefs designated to be impacted by infrastructural development by providing an opportunity for transfer to high value zones, from dedicated nurseries, and for brooding species. Our contribution provides insights into critical elements of both concepts, and we highlight information gaps in parameter uncertainties.
Hierarchical Bayes small‐area estimation with an unknown link function
Authors: Sugasawa Shonosuke , Kubokawa Tatsuya , Rao J. N. K.
Published: December 2018

Area‐level unmatched sampling and linking models have been widely used as a model‐based method for producing reliable estimates of small‐area means. However, one practical difficulty is the specification of a link function. In this paper, we relax the assumption of a known link function by not specifying its form and estimating it from the data. A penalized‐spline method is adopted for estimating the link function, and a hierarchical Bayes method of estimating area means is developed using a Markov chain Monte Carlo method for posterior computations. Results of simulation studies comparing the proposed method with a conventional approach based on a known link function are presented. In addition, the proposed method is applied to data from the Survey of Family Income and Expenditure in Japan and poverty rates in Spanish provinces.
Children’s Digital Game Addiction and Opinions About Their Parents’ Playing Digital Games ( A Mixed Method Study)
Authors: Hazar Zekihan
Published: December 2018

The purpose of this research is to review the level of children's digital game playing addiction and to evaluate their opinions on the parents playing digital games. In the 2017-2018 academic year, the students of the Şehit Ramazan Konuş secondary school affiliated to the Niğde Provincial Directorate of National Education constitute the universe of the research. 246 students who were chosen according to the method of typical case sampling constituted the sampling of the research. "Mixed method research" has been adopted as a research model and "Explanatory Design" has been used as a mixed method research design.In this direction; the "Digital Game Addiction Scale for Children" developed by Hazar and Hazar was applied in 2017 in the quantitative part of the study. In the qualitative section, interviews were made with 14 participants, 7 females and 7 males, who had high level of addiction and who regularly played digital games, participated in the research voluntarily. The data were analyzed by content analysis and descriptive analysis.The data obtained for the study were analyzed primarily through the SPSS 24 packet program. According to the results of this analysis, participants were found to have statistically significant difference in gender, age, and parents’ playing and not playing digital games, while it was seen that there was no statistically significant difference. Whether they had a sportsman license, whether or not internet access was available at their residence, and parents' educational status variables In the qualitative analysis of the research, 8 themes and sub-themes related to this theme were formed.As a result; it is a striking result that the dependency of the participants with digital game playing parents and weak family relations is higher than the other participants. The high level of addiction of the participants with an athlete license is a noteworthy finding.
Preparation of UF4 by Carbochlorination of U3O8 and Solid-State Halogen Exchange Reaction
Authors: Guibaldo Cristina N. , De Micco Georgina , Bohé Ana E.
Published: December 2018

Uranium tetrafluoride was synthesized using a novel method, which consists of a combination of carbochlorination reaction between a mixture of U3O8 and sucrose carbon with chlorine, and a solid-state halogen exchange reaction between the products of the carbochlorination reaction and sodium fluoride. The thermodynamic feasibility to produce the halogen exchange reaction between UCl4 and NaF was analyzed. Reactions are favorable in standard conditions, even at low temperature. We have prepared a mixture of UCl4 and UCl2O2 by U3O8 treatment in Cl2 atmosphere with presence of sucrose carbon at 900 °C. UCl4 and UCl2O2 were obtained as a condensed product, which was collected in a quartz capsule containing NaF. The capsules were sealed after several repeated stages of argon purges and mechanic vacuum. Subsequently, they were treated at 300–350 °C for 2 h. We obtained that when NaF is the limiting reagent, the solid product of the thermal treatment of the capsules consists in a mixture of UF4 and NaCl. Solid products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), fluorescence spectroscopy, and energy dispersive X-ray spectroscopy. Gaseous products were identified by Fourier-transform infrared spectroscopy.
Uncertainty Analysis and Experimental Design in the Monte Carlo Ray-Trace Environment
Authors: Yarahmadi Mehran , Robert Mahan J. , Priestley Kory J.
Published: December 2018

Despite the dominant role of the Monte Carlo ray-trace (MCRT) method in modern radiation heat transfer analysis, the contemporary literature remains surprisingly reticent on the uncertainty of results obtained using it. After first identifying the radiation distribution factor as a population proportion, standard statistical procedures are used to estimate its mean uncertainty, to a stated level of confidence, as a function of the number of surface elements making up the enclosure and the number of rays traced per surface element. This a priori statistical uncertainty is then shown to compare favorably with the observed variability in the distribution factors obtained in an actual MCRT-based analysis. Finally, a formal approach is demonstrated for estimating, to a prescribed level of confidence, the uncertainty in predicted heat transfer. This approach provides a basis for determining the minimum number of rays per surface element required to obtain the desired accuracy.
The Fluidyne engine
Authors: Romanelli Alejandro
Published: December 2018

The Fluidyne is a two-part hot-air engine which has the peculiarity that both its power piston and displacer are liquids. Both parts operate in tandem with the common working gas (air) transferring energy from the displacer to the piston side, from which work is extracted. We describe analytically the thermodynamics of the Fluidyne engine using the approach previously developed for the Stirling engine. We obtain explicit expressions for the amplitude of the power piston movement and for the working gas temperatures and pressure as functions of the engine parameters. We also study numerically the power and efficiency of the engine in terms of the phase shift between the motions of the piston and displacer.
Taking teachers' ideas seriously: Exploring the role of physics faculty in preparing teachers in the era of the Next Generation Science Standards
Authors: Robertson Amy D. , Seeley Lane , Wentink Orlala T. , Vokos Stamatis
Published: December 2018

The Next Generation Science Standards (NGSS) call for K-12 science instruction that centers on and substantively takes up students' science ideas. In this paper, we explore the question, “What role might physics faculties play in preparing teachers in the era of NGSS?,” as we also consider our field's adage that “most teachers tend to teach as they were taught.” In particular, we propose the importance of teacher education experiences that take teachers' own physics ideas seriously. We argue that physicists can play a critical role in this work by designing and facilitating teacher preparation and professional development that (1) elevates and maintains a focus on teachers' physics ideas and (2) collaboratively subjects teachers' ideas to the kinds of tests to which we subject our own ideas. We ground these considerations in two illustrative episodes from our local context: Focus on Energy professional development for elementary teachers. We highlight particular professional development instructor moves that take teachers' ideas seriously, and we discuss questions and implications that emerge from our analysis. Although the focus of our analysis is on taking teachers' ideas seriously, we suggest that most of our arguments also apply to taking students' ideas seriously in pre-college and university physics courses.
Fossils push back origin of key plant groups millions of years
Authors: Pennisi Elizabeth
Published: December 2018

Finds from Middle East point to the dry tropics as cradle for plant evolution 250 million years ago.
Next-generation wargames
Authors: Reddie Andrew W. , Goldblum Bethany L. , Lakkaraju Kiran , Reinhardt Jason , Nacht Michael , Epifanovskaya Laura
Published: December 2018

Technology enables new research designs, and more data
Temperament in preschool children with sickle cell anaemia
Authors: Downes Michelle , de Haan Michelle , O’Leary Tess , Telfer Paul T , Kirkham Fenella J
Published: December 2018

Aims

Few studies have investigated the potential impact of sickle cell anaemia (SCA) on temperament. The aim of the current study was to investigate temperament in preschool children with SCA and to establish the reliability of the Children’s Behaviour Questionnaire (CBQ) in this population.

Methods

The CBQ, a parent-report measure of temperament, was completed by parents of 21 preschool children with SCA and a control group of parents of typically developing children, matched for age, ethnicity and socioeconomic status.

Results

A significant difference between groups was identified for the dimension of negative affectivity only, with specific differences observed in the discomfort subdomain. Patients with a greater number of hospital admissions in the previous year were reported to have higher levels of discomfort.

Conclusions

Preschool children with SCA are reported to have higher rates of negative affectivity, particularly discomfort. Future research is required to investigate the potential influence of dysregulated negative emotions and discomfort on disease management and quality of life throughout childhood.