bluuebunny/crossref_metadata_2025 huggingface dataset:
Using ultrahigh-resolution mass spectrometry and toxicity identification techniques to characterize the toxicity of oil sands process-affected water: The case for classical naphthenic acids
Authors: Hughes Sarah A. , Mahaffey Ashley , Shore Bryon , Baker Josh , Kilgour Bruce , Brown Christine , Peru Kerry M. , Headley John V. , Bailey Howard C.
Published: June 2017

Previous assessments of oil sands process-affected water (OSPW) toxicity were hampered by lack of high-resolution analytical analysis, use of nonstandard toxicity methods, and variability between OSPW samples. We integrated ultrahigh-resolution mass spectrometry with a toxicity identification evaluation (TIE) approach to quantitatively identify the primary cause of acute toxicity of OSPW to rainbow trout (Oncorhynchus mykiss). The initial characterization of OSPW toxicity indicated that toxicity was associated with nonpolar organic compounds, and toxicant(s) were further isolated within a range of discrete methanol fractions that were then subjected to Orbitrap mass spectrometry to evaluate the contribution of naphthenic acid fraction compounds to toxicity. The results showed that toxicity was attributable to classical naphthenic acids, with the potency of individual compounds increasing as a function of carbon number. Notably, the mass of classical naphthenic acids present in OSPW was dominated by carbon numbers ≤16; however, toxicity was largely a function of classical naphthenic acids with ≥17 carbons. Additional experiments found that acute toxicity of the organic fraction was similar when tested at conductivities of 400 and 1800 μmhos/cm and that rainbow trout fry were more sensitive to the organic fraction than larval fathead minnows (Pimephales promelas). Collectively, the results will aid in developing treatment goals and targets for removal of OSPW toxicity in water return scenarios both during operations and on mine closure. Environ Toxicol Chem 2017;36:3148–3157. © 2017 SETAC

Abstract

The aquatic toxicity of oil sands process-affected water was isolated to the organic fraction using toxicity identification evaluation techniques. The organic fraction was then further fractionated into different percent methanol fractions and analyzed for toxicity and naphthenic acids using ultrahigh-resolution Orbitrap mass spectrometry to confirm the potency of naphthenic acid species and identify those responsible for toxicity.
The uppermost Carboniferous (Gzhelian)–Lower Permian (Asselian–Sakmarian) stratigraphy and smaller foraminifers of the Ozbak‐Kuh region (Tabas Block, east central Iran)
Authors: Yarahmadzahi Hamed , Vachard Daniel
Published: June 2017

The uppermost Carboniferous (Gzhelian)–Lower Permian (Asselian to Sakmarian) Anarak Group of the Zaladou section in central Iran is more than 180‐m thick and includes thick units of shale, calcareous sandstone, fusulinid limestone, sandy limestone, and dolomite. The Zaladou and Tigh‐e‐Madanu formations of this group were dated as Gzhelian to Sakmarian. A review of the smaller foraminifers of the Zaladou section is presented. Five foraminiferal subzones grouped in three biozones are proposed in this work: The first assemblage zone (I) is Gzhelian; the second zone (II) corresponds to the Gzhelian–Asselian boundary interval, and the third biozone (III) is Asselian in age. Biozone I is subdivided informally into two subzones: the Hemigordius spirilliniformis‐Bradyina cf. samarica subzone IA (probably early Gzhelian in age) and the Raphconilia modificata and Globivalvulina spp. subzone IB (middle to late Gzhelian); biozone II is the Nodosinelloides spp. zone; biozone III is subdivided informally into two subzones: IIIA with Pseudoacutella partoazari‐Bradyina lucida and IIIB with Planoendothyra persica n. sp.‐Rectogordius sp. The studied assemblages are correlated with those from the Carnic Alps (Austria–Italy), East European Platform of Russia, the Urals (Russia), Darvas (Uzbekistan), the northern and central Pamirs (Tajikistan), northern Iran (Alborz), northern Afghanistan, and other classical regions of the Tethyan realm. The genera Raphconilia and Planoendothyra are revised, and Planoendothyra persica n. sp. is described.
Geochemistry and zircon U–Pb–Hf isotopes of the granitoids of Qianjinchang pluton in the Xi Ujimqi, Inner Mongolia: Implications for petrogenesis and geodynamic setting
Authors: Wang Guosheng , Liu Changfeng , Pei Weixun , Zhou Zhiguang , Li Hongying , Wu Chen , Zhu Yan , Ye Baoying
Published: June 2017

We conducted zircon U–Pb dating and geochemical analyses for the Qianjinchang (QJC) pluton in the Xi Ujimqi, Northeast China, with an aim to determine their ages, petrogenesis, and sources. The QJC pluton consists of coarse/medium‐grained biotite monzogranite in the core and fine‐grained biotite granodiorite in the rim; those rocks intrude into quartz diorite but are intruded by minor intrusive phases, including small biotite syenogranite, diorite bodies, late diorite, granodiorite, granite, and pegmatite dykes. Our new laser ablation inductively coupled plasma mass spectrometry zircon U–Pb data indicate that the QJC composite pluton composed of 2 phases of magmatic activities, with the ages of 301~313 Ma for the quartz diorite, 283 ± 1 Ma for the biotite granodiorite, 280 ± 1 Ma for the biotite syenogranite, and 280 ± 2 Ma for the diorite dyke. Hf isotopic analyses for the quartz diorite sample show εHf(t) = 3.75 to 11.72, with 2‐stage Hf model age (TDM2) ranging 568–1,078 Ma. The biotite syenogranite sample also shows a depleted εHf(t) = 4.47 to 8.71, withTDM2ranging 745–1,015 Ma, suggesting the major involvement of juvenile crustal components. The various εHfvalues of the QJC pluton indicate a hybrid magma source of juvenile material with old crustal component, and theTDM2values increase from the Carboniferous to Permian, which suggests an increasing proportion of old continental material during this period. Petrological and geochemical characteristics of the biotite granodiorite and biotite monzogranite samples suggest that they are S‐type granites and derived from partial melting of the clay‐poor, plagioclase‐rich psammitic source, produced at low‐medium pressure. The biotite syenogranite sample belongs to alkaline and shoshonitic series and probably formed by a hybridization process between basaltic magma and old continental components. Combined with previous studies on the contemporaneous magma‐tectonic activities in the Xilinhot microcontinent, we suggest that the QJC pluton formed in a postcollisional setting.
The frontal assessment battery in clinical practice: a systematic review
Authors: Hurtado‐Pomares Miriam , Carmen Terol‐Cantero M. , Sánchez‐Pérez Alicia , Peral‐Gómez Paula , Valera‐Gran Desirée , Navarrete‐Muñoz Eva María
Published: June 2017

Background

The frontal assessment battery (FAB) is a brief tool designed to evaluate executive function. Some studies have particularly focused on assessing its applicability addressing two issues: first, on detecting the brain regions responsible for the FAB performance, and second, on determining its capability for differential diagnosis. Our aim was to summarize and analyze critically the studies that assessed the neuroanatomical correspondence and the differential diagnostic value of the FAB in several study populations suffering from different pathologies.

Methods

We completed a literature search in MEDLINE (via PubMed) database by using the term “frontal assessment battery” and the combination of this term with “applicability” or “use” or “usefulness”. The search was limited to articles in English or Spanish languages, published between 1 September 2000 and 30 September 2016, human studies, and journal articles.

Results

A total of 32 studies met inclusion criteria. Seventeen studies were aimed at identifying the brain regions or the neural substrates involved in executive functions measured by the FAB and 15 studies at verifying that the FAB was an appropriate tool for the differential diagnosis in neurological diseases.

Conclusion

Our study showed that the FAB may be an adequate assessment tool for executive function and may provide useful information for differential diagnosis in several diseases. Given that the FAB takes short time and is easy to administer, its usage may be of great interest as part of a full neuropsychological assessment in clinical settings. Copyright © 2017 John Wiley & Sons, Ltd.
The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis
Authors: Vagnildhaug Ola Magne , Blum David , Wilcock Andrew , Fayers Peter , Strasser Florian , Baracos Vickie E. , Hjermstad Marianne J. , Kaasa Stein , Laird Barry , Solheim Tora S. ,   for the European Palliative Care Cancer Symptom study group
Published: June 2017

Background

A body mass index (BMI) adjusted weight loss grading system (WLGS) is related to survival in patients with cancer. The aim of this study was to examine the applicability of the WLGS by confirming its prognostic validity, evaluating its relationship to cachexia domains, and exploring its ability to predict cachexia progression.

Methods

An international, prospective observational study of patients with incurable cancer was conducted. For each patient, weight loss grade was scored 0–4. Weight loss grade 0 represents a high BMI with limited weight loss, progressing through to weight loss grade 4 representing low BMI and a high degree of weight loss. Survival analyses were used to confirm prognostic validity. Analyses of variance were used to evaluate the relationship between the WLGS and cachexia domains [anorexia, dietary intake, Karnofsky performance status (KPS), and physical and emotional functioning]. Cox regression was used to evaluate if the addition of cachexia domains to the WLGS improved prognostic accuracy. Predictive ability of cachexia progression was assessed by estimating proportion of patients progressing to a more advanced weight loss grade.

Results

One thousand four hundred six patients were analysed (median age 66 years; 50% female, 63% KPS ≤ 70). The overall effect of the WLGS on survival was significant as expressed by change in −2 log likelihood (P < 0.001) and persisted after adjustment for age, sex, and cancer type and stage (P < 0.001). Median survival decreased across the weight loss grades ranging from 407 days (95% CI 312–502)—weight loss grade 0 to 119 days (95% CI 93–145)—weight loss grade 4. All cachexia domains significantly deteriorated with increasing weight loss grade, and deterioration was greatest for dietary intake, with a difference corresponding to 0.87 standard deviations between weight loss grades 0 and 4. The addition of KPS, anorexia, and physical and emotional functioning improved the prognostic accuracy of the WLGS. Likelihood of cachexia progression was greater in patients with weight loss grade 2 (39%) than that with weight loss grade 0 (19%) or 1 (22%).

Conclusions

The WLGS is related to survival, cachexia domains, and the likelihood of progression. Adding certain cachexia domains to the WLGS improves prognostic accuracy.
Synthesis, preclinical, and pharmacokinetic evaluation of a new zoledronate derivative as a promising antiosteoporotic candidate using radiolabeling technique
Authors: Motaleb H.A. , Ibrahim Ismail Taha , El‐Tawoosy M. , Mohamed M.I.
Published: June 2017

A novel zoledronic acid (ZL) derivative, 3‐(2‐ethyl‐4‐methyi‐1H‐imidazole‐1‐yl)‐1‐hydroxy‐1‐phosphonopropyl phosphonic acid (EMIHPBP), was synthesized, characterized, and successfully radiolabeled with 99mTc. The in vivo biodistribution of 99mTc‐EMIHPBP was investigated and compared with the previously reported zoledronate derivatives aiming to formulate a novel zoledronate derivative with a high‐potential uptake to bone as a promising antiosteoporotic candidate. To further evaluate the bone uptake efficiency, the pharmacokinetics of 99mTc‐EMIHPBP was investigated and showed that maximum concentration in bone (Cmax) was 31.60 ± 0.15%ID/gram after 60 minutes (tmax). Cumulative residence of 99mTc‐EMIHPBP in the bone [AUC (0−∞) (%ID∙min/gram bone)] was 3685.23, mean residence time was 384.354 minutes, and the calculated bone bioavailability was 15.831%. Finally, the time needed for half of the 99mTc‐EMIHPBP formulation to be eliminated from bone (t1/2) was 263.914 minutes. Excellent bone uptake can be obtained 1‐hour postinjection with high bone/blood ratio of 23.76 detected with gamma counter. The biodistribution and kinetic studies could recommend EMIHPBP as a promising antiosteoporotic candidate with high selectivity to the skeletal system and rapid clearance from soft tissues.
Pre‐ and post‐operative HBsAg levels may predict recurrence and survival after curative resection in patients with HBV‐associated hepatocellular carcinoma
Authors: Qiu Jing‐Feng , Ye Jia‐Zhou , Feng Xu‐Zhuo , Qi Ya‐Peng , Ma Liang , Yuan Wei‐Ping , Zhong Jian‐Hong , zhang Zhi‐Ming , Xiang Bang‐De , Li Le‐Qun
Published: June 2017

Purpose

To investigate pre‐ and post‐operative levels of HBsAg influence prognosis of patients with hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) after curative resection.

Methods

Medical records were retrospectively analyzed for 881 patients with HBV‐related HCC treated by curative resection. Patients were classified as having high or low serum HBsAg levels (≥200 or <200 ng/mL) pre‐ or post‐operatively.

Results

OS and RFS were better for patients with low pre‐operative serum levels of HBsAg than for those with high levels. Similarly, OS was better among patients with low post‐operative serum levels of HBsAg than among those with high levels. RFS, in contrast, was similar between these two groups. After generating propensity score‐matched pairs of patients, OS was higher in patients with falling post‐operative HBsAg levels than in those with rising levels. In contrast, RFS was similar between these two groups. Antiviral nucleoside analog therapy prolonged OS in patients with high pre‐operative HBsAg levels.

Conclusions

Low pre‐ and post‐operative levels of HBsAg may be associated with better long‐term survival in patients with HBV‐related HCC. Pre‐operative serum levels of HBsAg ≥200 ng/mL may identify patients more likely to benefit from antiviral treatment.
Predicting the evolutionary consequences of trophy hunting on a quantitative trait
Authors: Coulson Tim , Schindler Susanne , Traill Lochran , Kendall Bruce E.
Published: June 2017

Some ecologists suggest that trophy hunting (e.g., harvesting males with a desirable trait above a certain size) can lead to rapid phenotypic change, which has led to an ongoing discussion about evolutionary consequences of trophy hunting. Claims of rapid evolution come from the statistical analyses of data, with no examination of whether these results are theoretically plausible. We constructed simple quantitative genetic models to explore how a range of hunting scenarios affects the evolution of a trophy such as horn length. We show that trophy hunting does lead to trophy evolution defined as change in the mean breeding value of the trait. However, the fastest rates of phenotypic change attributable to trophy hunting via evolution that are theoretically possible under standard assumptions of quantitative genetics are 1–2 orders of magnitude slower than the fastest rates of phenotypic change reported from statistical analyses. Our work suggests a re‐evaluation of the likely evolutionary consequences of trophy hunting would be appropriate when setting policy. Our work does not consider the ethical or ecological consequences of trophy hunting. © 2017 The Wildlife Society.
Studies on sliding wear characteristics of aluminium LM25/silicon dioxide functionally graded composite and optimisation of parameters using response surface methodology
Authors: Bhatija K. A. , Radhika N.
Published: June 2017

This paper deals with the study of dry sliding wear of LM25/silicon dioxide (10 wt.%) functionally graded composite. The composite was fabricated using stir casting technique and the melt was poured into a horizontal centrifugal die rotating at 1200 min−1. After casting, the specimen (length 150 mm, external diameter 150 mm and internal diameter 130 mm) was subjected to microstructure and hardness tests at three different depths from the outer periphery (1 mm, 8 mm and 13 mm). The results of the respective tests revealed that the outer periphery of the specimen had higher particle concentration and hardness. Then, wear test was done on a pin‐on‐disc tribometer at room temperature with the experiments designed using response surface methodology and by taking specimens of size 8 x 8 x 15 mm such that the surface undergoing wear was at 1 mm from the outer periphery of the cast. The process variables of load (10 ‐ 40 N), velocity (1 ‐ 4 m/s) and sliding distance (400 ‐ 1200 m) were varied using a level 5 design and experiments were carried on for 20 different optimal combinations. From the regression equation generated for the wear response, it was found that load had maximum effect on the wear rate. The confirmation experiments proved that the regression model could serve well in predicting the wear rate for the given ranges of the continuous factors, for the given composite. Surface plots showed that the wear rate had an increasing trend with respect to load, which was the dominating continuous factor. Though the wear rate increased, severe delamination of the functionally graded composite was delayed. The optimum levels of the continuous factors to minimize the wear rate were found using response optimisation and found to be 10 N, 1.7576 m/s and 2000 m respectively. Scanning electron microscopy analysis of the worn surface of the specimens connected to the obtained trends and thus further validated the model developed. Thus, a functionally graded LM13 composite with silicon dioxid reinforcements is developed and a wear model to predict its wear rate under different process parameters is proposed with predictions of optimal performance conditions. This composite can increase life of components of wear applications in aerospace and automobile industry.
Fatigue assessment of cut edges in high strength steel – Influence of surface quality
Authors: Stenberg T. , Lindgren E. , Barsoum Z. , Barmicho I.
Published: June 2017

The influence of surface roughness on the fatigue strength in high strength steels and different cutting processes are studied. Fatigue testing is conducted on S700 and S960 material for different plate thicknesses cut in dog bone specimens using oxygen, plasma, laser and waterjet cutting. The surface roughness is measured for all specimens and residual stress measurements are carried out. Estimations of the fatigue strength are made based on the measured surface roughness and the ISO 9013:2002 standard for thermal cutting quality tolerances. The testing shows a 15–70 % increase in the fatigue strength compared to the estimation, proving a weak connection between the surface quality levels in ISO 9013:2002 and the fatigue test results. Different codes and design recommendations (IIW, EC3 and EN 13001) for fatigue strength of cut surfaces are compared with the fatigue test results which clearly shows an increased fatigue strength with enhanced quality and steel grades. However, the codes and design recommendations do not allow for any fatigue strength improvement with improved quality and increased yield strength.
Predicting the Enzymatic Hydrolysis Half‐lives of New Chemicals Using Support Vector Regression Models Based on Stepwise Feature Elimination
Authors: Shen Wanxiang , Xiao Tao , Chen Shangying , Liu Feng , Chen Yu Zong , Jiang Yuyang
Published: June 2017

The enzymatic hydrolysis of chemicals, which is important for in vitro drug metabolism assays, is an important indicator of drug stability profiles during drug discovery and development. Herein, we employed a stepwise feature elimination (SFE) method with nonlinear support vector machine regression (SVR) models to predict the in vitro half‐lives in human plasma/blood of various esters. The SVR model was developed using public databases and literature‐reported data on the half‐lives of esters in human plasma/blood. In particular, the SFE method was developed to prevent over fitting and under fitting in the nonlinear model, and it provided a novel and efficient method of realizing feature combinations and selections to enhance the prediction accuracy. Our final developed model with 24 features effectively predicted an external validation set using the time‐split method and presented reasonably good R2 values (0.6) and also predicted two completely independent validation datasets with R2 values of 0.62 and 0.54; thus, this model performed much better than other prediction models.
Energy‐based Neural Networks as a Tool for Harmony‐based Virtual Screening
Authors: Zhokhova Nelly I. , Baskin Igor I.
Published: June 2017

In Energy‐Based Neural Networks (EBNNs), relationships between variables are captured by means of a scalar function conventionally called “energy”. In this article, we introduce a procedure of “harmony search”, which looks for compounds providing the lowest energies for the EBNNs trained on active compounds. It can be considered as a special kind of similarity search that takes into account regularities in the structures of active compounds. In this paper, we show that harmony search can be used for performing virtual screening. The performance of the harmony search based on two types of EBNNs, the Hopfield Networks (HNs) and the Restricted Boltzmann Machines (RBMs), was compared with the performance of the similarity search based on Tanimoto coefficient with “data fusion”. The AUC measure for ROC curves and 1 %‐enrichment rates for 20 targets were used in the benchmarking. Five different scores were computed: the energy for HNs, the free energy and the reconstruction error for RBMs, the mean and the maximum values of Tanimoto coefficients. The performance of the harmony search was shown to be comparable or even superior (significantly for several targets) to the performance of the similarity search. Important advantages of using the harmony search for virtual screening are very high computational efficiency of prediction, the ability to reveal and take into account regularities in active structures, flexibility and interpretability of models, etc.
Nodal bound state of nonlinear problems involving the fractional Laplacian
Authors: Long Wei , Lv Longbo
Published: June 2017

This paper is concerned with the following nonlinear fractional Schrödinger equation

where ε>0 is a small parameter, V(x) is a positive function, 0<s<1, and
. Under some suitable conditions, we prove that for any positive integer k, one can construct a nonradial sign‐changing (nodal) solutions with exactly k maximum points and k minimum points near the local minimum point of V(x).
A fast multitarget inverse treatment planning strategy optimizing dosimetric measures for high‐dose‐rate (HDR) brachytherapy
Authors: Guthier Christian V. , Damato Antonio L. , Viswanathan Akila N. , Hesser Juergen W. , Cormack Robert A.
Published: June 2017

Purpose

In this study, we introduce a novel, fast, inverse treatment planning strategy for interstitial high‐dose‐rate (HDR) brachytherapy with multiple regions of interest solely based on dose‐volume‐histogram‐related dosimetric measures (DMs).

Methods

We present a new problem formulation of the objective function that approximates the indicator variables of the standard DM optimization problem with a smooth logistic function. This problem is optimized by standard gradient‐based methods. The proposed approach is then compared against state‐of‐the‐art optimization strategies.

Results

All generated plans fulfilled prescribed DMs for all organs at risk. Compared to clinical practice, a statistically significant improvement in coverage of target structures was achieved. Simultaneously, DMs representing high‐dose regions were significantly reduced . The novel optimization strategies run‐time was (0.8 ± 0.3) s and thus outperformed the best competing strategies of the state of the art. In addition, the novel DM‐based approach was associated with a statistically significant increase in the number of active dwell positions and a decrease in the maximum dwell time.

Conclusions

The generated plans showed a clinically significant increase in target coverage with fewer hot spots, with an optimization time approximately three orders of magnitude shorter than manual optimization currently used in clinical practice. As optimization is solely based on DMs, intuitive, interactive, real‐time treatment planning, which motivated the adoption of manual optimization in our clinic, is possible.
Technical Note: A 3‐D rendering algorithm for electromechanical wave imaging of a beating heart
Authors: Nauleau Pierre , Melki Lea , Wan Elaine , Konofagou Elisa
Published: June 2017

Purpose

Arrhythmias can be treated by ablating the heart tissue in the regions of abnormal contraction. The current clinical standard provides electroanatomic 3‐D maps to visualize the electrical activation and locate the arrhythmogenic sources. However, the procedure is time‐consuming and invasive. Electromechanical wave imaging is an ultrasound‐based noninvasive technique that can provide 2‐D maps of the electromechanical activation of the heart. In order to fully visualize the complex 3‐D pattern of activation, several 2‐D views are acquired and processed separately. They are then manually registered with a 3‐D rendering software to generate a pseudo‐3‐D map. However, this last step is operator‐dependent and time‐consuming.

Methods

This paper presents a method to generate a full 3‐D map of the electromechanical activation using multiple 2‐D images. Two canine models were considered to illustrate the method: one in normal sinus rhythm and one paced from the lateral region of the heart. Four standard echographic views of each canine heart were acquired. Electromechanical wave imaging was applied to generate four 2‐D activation maps of the left ventricle. The radial positions and activation timings of the walls were automatically extracted from those maps. In each slice, from apex to base, these values were interpolated around the circumference to generate a full 3‐D map.

Results

In both cases, a 3‐D activation map and a cine‐loop of the propagation of the electromechanical wave were automatically generated. The 3‐D map showing the electromechanical activation timings overlaid on realistic anatomy assists with the visualization of the sources of earlier activation (which are potential arrhythmogenic sources). The earliest sources of activation corresponded to the expected ones: septum for the normal rhythm and lateral for the pacing case.

Conclusions

The proposed technique provides, automatically, a 3‐D electromechanical activation map with a realistic anatomy. This represents a step towards a noninvasive tool to efficiently localize arrhythmias in 3‐D.
Embryo‐maternal dialogue during pregnancy establishment and implantation in the pig
Authors: Waclawik Agnieszka , Kaczmarek Monika M. , Blitek Agnieszka , Kaczynski Piotr , Ziecik Adam J.
Published: June 2017

Porcine conceptuses secrete pregnancy‐recognition signals (estrogens, including estradiol‐17β) that inhibit luteolysis, thereby prolonging progesterone production by corpora lutea. The supportive mechanism by which the conceptus also inhibits luteolysis is by shifting endometrial prostaglandin (PG) synthesis to luteoprotective PGE2. Progesterone stimulates endometrial production of factors that are essential for conceptus development. Priming the uterus by progesterone and loss of progesterone receptors from the uterine epithelium by D1ay 10–12 after estrus are key for achieving endometrial receptivity for implantation. Conceptus implantation involves a series of events, many resembling the inflammatory reaction, that are greatly influenced by cytokines, growth factors, and prostaglandins. We herein present a novel, dual role for PGF2α in corpora lutea that depends on the acquisition of luteolytic sensitivity, based on the knowledge that PGF2α triggers pathways involved in luteolysis during the estrous cycle or/and may have an alternative function in maintaining progesterone synthesis during pregnancy. We also point out a new role for PGF2α that, together with PGE2, can act as embryonic signal mediators. PGF2α, which until recently was considered undesirable for promoting pregnancy, is now known to stimulate conceptus‐maternal interactions and angiogenesis in the endometrium. This function is in line with other important prostaglandin functions, such as stimulating adhesion of trophoblasts (PGE2, PGI2) as well as endometrial vascular functions and trophoblast cell proliferation (PGI2). Finally, microRNAs have emerged as important post‐transcriptional regulators of gene function, adding a new area of investigation that may enhance understanding of conceptus‐endometrial interactions.
U.S. Food and Drug Administration approval summary: Eltrombopag for the treatment of pediatric patients with chronic immune (idiopathic) thrombocytopenia
Authors: Ehrlich Lori A. , Kwitkowski Virginia E. , Reaman Gregory , Ko Chia‐Wen , Nie Lei , Pazdur Richard , Farrell Ann T.
Published: June 2017

The U.S. Food and Drug Administration (FDA) approved eltrombopag for pediatric patients with chronic immune (idiopathic) thrombocytopenia (ITP) ages ≥6 on June 11, 2015, and ages ≥1 on August 24, 2015. Approval was based on the FDA review of two randomized trials that included 159 pediatric patients with chronic ITP who had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This manuscript describes the basis for approval of these applications. The FDA concluded that eltrombopag has shown efficacy and a favorable benefit to risk profile for pediatric patients with chronic ITP.
Regular exercise improves the well‐being of parents of children with cancer
Authors: Halliday Gail C. , Miles Gordon C. P. , Marsh Julie A. , Kotecha Rishi S. , Alessandri Angela J.
Published: June 2017

Aim

Parents of children with cancer describe impaired physical and social functioning, sleep disturbance and poor mental health. Exercise‐related interventions impact positively on these quality of life domains, but have not been examined in this population. The aim of this longitudinal pilot study was to explore the feasibility of a 12‐week pedometer‐monitored walking intervention among parents of children with cancer, assessing adherence to a set activity target of 70,000 steps per week, and to explore the benefits of physical activity on mental and physical health.

Methods

Parents were provided with a pedometer and requested to achieve a daily step count of 10,000 steps per day for 12 weeks. Mood, well‐being and psychological distress were examined using validated questionnaires (Profile of Mood States 2nd edition [POMS‐2], Distress Thermometer for Parents [DT‐P] and Depression Anxiety Stress Scales [DASS‐42]) at baseline, midpoint (6 weeks) and endpoint (12 weeks) to identify changes in these domains with increased activity.

Results

Fifteen parents were recruited. The majority increased their counts during the first 4 weeks of the study and maintained this to week 8 (n = 12). Time‐dependent improvements were identified in the following psychometric test outcomes at week 12: DT‐P score (likelihood ratio test [LRT] P = 0.02), POMS‐2 total mood disturbance (LRT P = 0.03), fatigue inertia (LRT P = 0.009), tension anxiety (LRT P = 0.007) and vigour activity (LRT P = 0.001).

Conclusions

Mental health benefits of a pedometer‐based exercise intervention for parents of children with cancer were identified. Such programs should be included in a holistic approach to improve the psychological outcomes of parents whose children are receiving treatment for cancer.
Pencil beam scanned protons for the treatment of patients with Ewing sarcoma
Authors: Weber Damien C. , Murray Fritz R. , Correia Dora , Bolsi Alessandra , Frei‐Welte Martina , Pica Alessia , Lomax Antony J. , Schneider Ralf , Bachtiary Barbara
Published: June 2017

Background

Few data exist regarding the clinical outcome of patients with Ewing sarcoma (EWS) treated with pencil beam scanning proton therapy (PT). We report the outcome of children, adolescents and young adults (AYA) treated with PT at the Paul Scherrer Institute.

Materials

Thirty‐eight patients (median age, 9.9 years) received a median dose of 54.9 Gy(RBE) (where RBE is relative biologic effectiveness). Size of the tumor ranged from 1.7 to 24 cm. Most common primary site was axial/pelvic (n = 27; 71%). Four patients (11%) presented with metastases at diagnosis. Twenty (53%) patients had chemo‐PT only. Median follow‐up was 49.6 months (range, 9.2–131.7).

Results

The 5‐year actuarial rate of local control (LC), distant metastasis‐free survival (DMFS), and overall survival (OS) were 81.5%, 76.4%, and 83.0%, respectively. All local recurrences occurred in field and in patients with nonextremity primaries. Six patients died, all of tumor progression. Age < 10 years was a favorable factor of borderline significance for LC (P = 0.05) and OS (P = 0.05), but was significant for DMFS (P = 0.003). Tumor volume <200 ml was a significant prognostic factors for DMFS (P = 0.03), but not for OS (P = 0.07). Metastasis at diagnosis was a strong predictor of local failure (P = 0.003). Only two grade 3 late toxicities were observed. The 5‐year actuarial rate of grade 3 toxicity‐free survival was 90.9%.

Conclusions

These preliminary data suggest that the outcomes of children and AYA with EWS are good and PT was well tolerated with few late adverse events. The local and distant tumor control for older patients with large pre‐PT tumor volumes remains problematic.
Four‐membered cyclic peroxides: Carriers of chemical energy
Authors: Bastos Erick Leite , Farahani Pooria , Bechara Etelvino J.H. , Baader Wilhelm Josef
Published: June 2017

Four‐membered cyclic peroxides are high‐energy compounds often associated to cold light emission, but whose chemical and biological roles are still matters of debate. The often‐dangerous synthesis of 1,2‐dioxetanes, achieved around 50 years ago, has been mastered over the years to a point where some derivatives are commercially available. This fact does not imply that 1,2‐dioxetanes can be conveniently prepared in the gram scale or that the synthesis of analogous 1,2‐dioxetanones and the elusive 1,2‐dioxetanedione are simple. Important questions on the mechanism of chemiluminescence and bioluminescence reactions are under experimental and theoretical scrutiny. The available data have contributed to relate structural and medium effects to the quantum efficiency of these compounds to produce excited states. Consequently, such peroxides have been suggested to produce biologically relevant electronically excited species in vivo in the absence of light. The connection of this hypothesis with melanin‐mediated photodamage in the dark has renewed the interest in such cyclic peroxides. This review gives some insight on the synthesis, chemiluminescence mechanism, and biological relevance of 1,2‐dioxetanes, 1,2‐dioxetanones, and 1,2‐dioxetanedione and provides practical protocols for those interested in engaging this field.
Systematic review on the proteomic profile of Mycobacterium tuberculosis exposed to drugs
Authors: Campanerut‐Sá Paula Aline Zanetti , Ghiraldi‐Lopes Luciana Dias , Meneguello Jean Eduardo , Teixeira Jorge Juarez Vieira , Scodro Regiane Bertin de Lima , Siqueira Vera Lucia Dias , Svidzinski Terezinha Inez Estivalet , Pavan Fernando Rogério , Cardoso Rosilene Fressatti
Published: June 2017

The authors present an overview about proteomics studies in Mycobacterium tuberculosis exposed to some anti‐tuberculosis drugs and new candidates, using two‐dimensional gel electrophoresis and mass spectrometry. To date, that the authors have knowledge, this is the first studies that was performed specifically in M. tuberculosis using systematic review on electronic literature conducted in three databases using the following search terms: tuberculosis OR mycobacterium tuberculosis, proteome OR proteomics, and mass spectrometry electrospray ionization OR matrix‐assisted laser desorption ionization OR two‐dimensional gel electrophoresis. By electronic search, 622 abstracts of the original articles published from November 2003 to March 2016 were selected. After the selection, four articles fulfill proposed criteria and were included in this study. The studies reported changes in the protein profile of M. tuberculosis after exposure to isoniazid, ethambutol, streptomycin, ofloxacin, moxifloxacin and two new drugs candidates, SQ109 and ATB107. In conclusion, the proteins changes were related to the synthesis of mycolic acids, cellular metabolism pathways, bacterial stress and starvation.
Quantitative proteome analysis of plasma microparticles for the characterization of HCV‐induced hepatic cirrhosis and hepatocellular carcinoma
Authors: Taleb Raghda Saad Zaghloul , Moez Pacint , Younan Doreen , Eisenacher Martin , Tenbusch Matthias , Sitek Barbara , Bracht Thilo
Published: June 2017

Purpose

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer‐related deaths worldwide. Cirrhosis induced by hepatitis‐C virus (HCV) infection is the most critical risk factor for HCC. However, the mechanism of HCV‐induced carcinogenesis is not fully understood. Plasma microparticles (PMP) contribute to numerous physiological and pathological processes and contain proteins whose composition correlates to the respective pathophysiological conditions.

Experimental design

We analyzed PMP from 22 HCV‐induced cirrhosis patients, 16 HCV‐positive HCC patients with underlying cirrhosis and 18 healthy controls. PMP were isolated using ultracentrifugation and analyzed via label‐free LC‐MS/MS.

Results

We identified 840 protein groups and quantified 507 proteins. 159 proteins were found differentially abundant between the three experimental groups. PMP in both disease entities displayed remarkable differences in the proteome composition compared to healthy controls. Conversely, the proteome difference between both diseases was minimal. GO analysis revealed that PMP isolated from both diseases were significantly enriched in proteins involved in complement activation, while endopeptidase activity was downregulated exclusively in HCC patients.

Conclusion

This study reports for the first time a quantitative proteome analysis for PMP from patients with HCV‐induced cirrhosis and HCC. Data are available via ProteomeXchange with identifier PXD005777.
New horizon for breast cancer biomarker discoveries: What might the liquid biopsy of nipple aspirate fluid hold?
Authors: Mannello Ferdinando
Published: June 2017

The existence of cellular, molecular and biochemical heterogeneity of human breast cancers reveals the intricacy of biomarkers complexity, stimulating studies on new approaches (like “liquid biopsies”) for the improvements in precision medicine. Breast cancer is recognized as a leading cause of morbidity and mortality worldwide with tumors significantly diverse and containing many types of cells showing different genetic and epigenetic profiles. In this field, the technology of liquid biopsy (applied to a fluid produced by breast gland, named nipple aspirate fluids, NAF) highlights the power of combining basic and clinical research. NAF is the mirror of the entire ductal/alveolar breast tree providing almost complete proteomic profile and a valuable source for biomarker discovery, in non‐invasive manner than tissue biopsies. The liquid biopsy technology using NAF may represent the outstanding breakthrough of proteomic cancer research revealing novel diagnostic and prognostic applications. In conjunction to metabolomic and degradome profiling, the use of NAF as liquid biopsy approach will improve the detection of changes in the cellular microenvironment of the breast tumors, understanding molecular and biochemical mechanisms which drive breast tumor initiation, maintenance and progression, and finally enhancing the development of novel drug targets and new treatment strategies.
Stoichiometric analysis of oligomeric states of three class‐A GPCRs, chemokine‐CXCR4, dopamine‐D2, and prostaglandin‐EP1 receptors, on living cells
Authors: Kawano Kenichi , Yagi Tetsuya , Fukada Nozomu , Yano Yoshiaki , Matsuzaki Katsumi
Published: June 2017

G‐protein‐coupled receptors (GPCRs) form the largest family of transmembrane receptors, and their oligomerization has been suggested to be related to their functions. Despite extensive studies, their oligomeric states are highly controversial. One of the reasons is the overestimation of oligomerization by conventional methods. We recently established a stoichiometric analysis method for precisely determining the oligomeric state of membrane proteins on living cells with the combined use of the coiled‐coil labeling method and a spectral imaging technique and showed that the prototypical class‐A GPCR β2‐adrenergic receptor (β2AR) did not form functional oligomers. In this study, we expanded our study to three well‐studied class‐A GPCRs: C‐X‐C chemokine receptor of stromal cell‐derived factor‐1α (CXCR4), dopamine receptor D2 short isotype (D2R), and prostaglandin E receptor subtype 1 (EP1R). We found that these receptors did not form constitutive homooligomers. The receptors exhibited calcium signaling upon agonist stimulation as monomers, although CXCR4 and EP1R gradually clustered after fast signaling. We conclude that homooligomerization is not necessary for the signal transductions of these four class‐A GPCRs. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
High‐resolution air–sea coupling impact on two heavy precipitation events in the Western Mediterranean
Authors: Rainaud R. , Brossier C. Lebeaupin , Ducrocq V. , Giordani H.
Published: June 2017

The Mediterranean Sea is an important source of heat and moisture for heavy precipitation events (HPEs). Moreover, the ocean mixed layer (OML) evolves rapidly under such intense events. Whereas short‐term numerical weather prediction systems generally use low‐resolution non‐evolving sea surface temperature (SST), the development of high‐resolution high‐frequency coupled system allows us to fully take into account the fine‐scale interactions between the low‐level atmosphere and the OML which occur during HPEs.

The aim of this study is to investigate the impact of fine‐scale air–sea interactions and coupled processes involved during the HPEs which occurred during 12–15 October 2012 (IOP13) and 26–28 October 2012 (IOP16a/b) of the HyMeX first field campaign. For that purpose, the high‐resolution coupled system AROME‐NEMO WMED was developed. This system is based on the 2.5 km‐resolution non‐hydrostatic convection‐permitting atmospheric model AROME‐WMED and the 1/36°‐resolution NEMO‐WMED36 ocean model. The coupling frequency is 1 h. To distinguish the effects due to the change in the initial SST field from that due to the interactive 3D ocean, the coupled run is compared to two AROME‐WMED atmosphere‐only experiments with no SST evolution during the 48 h forecast cycles—one using the AROME‐WMED SST analysis, the second using the SST field of the coupled experiment each day at 0000 UTC. The results of the three experiments re‐assert that the SST initial condition strongly influences the HPE forecast, in terms of intensity and location. With water budget analyses, the significant impact of the ocean interactive evolution on the surface evaporation water supply for HPEs is also highlighted. In cases of strong and intense air–sea exchanges, as in the mistral event of IOP16b, the coupling reproduces the intense and rapid surface cooling and demonstrates the importance of representing the ocean turbulent mixing with entrainment at the OML base.
Selective separation of strontium by multitopic ion‐pair receptor: A DFT exploration
Authors: Sadhu Biswajit , Sundararajan Mahesh , Pillai Anilkumar , Singh Rajvir , Bandyopadhyay Tusar
Published: June 2017

Selective extraction of a radionuclide in the presence of other interfering ions is one of the vital steps in the back‐end‐of‐the‐nuclear fuel cycle. The presence of interfering cations (such as Ca2+) in the radioactive waste and involvement of multiple separation steps are known to be bottlenecks in the efficient Sr2+ extraction. Here, using free energy corrected density functional theory, we have proposed a two‐step Sr2+ extraction methodology in nitrate media in the presence of interfering Ca2+ ion using a multitopic ion‐pair receptor, which was earlier reported to be strongly selective for K+ (Kim et al. J. Am. Chem. Soc. 2012, 134, 1782–1792). To depict the correct free energy trend in the proposed extraction processes, the most probable binding mode of the metal (Sr2+, Ca2+, and K+) nitrates in the host are identified. In excellent agreement with the previously reported experiment, Crown/Pyrrole (C/P) binding is noted to be the most preferable mode for KNO3, where K+ and
occupied the Crown (C) and Pyrrole (P) site, respectively. However, the divalent metal ions (Ca2+ and Sr2+) are noted to marginally prefer Crown/Crown‐Pyrrole (C/CP) mode, in which metal reside at the C site while two nitrates occupy the P site and also simultaneously bind at the outer sphere of C site to coordinate with the metal via monodentate motif. Based on the free energy of extraction, we predict that the selective separation of chemically alike Ca2+/Sr2+ pair is indeed achievable using this receptor. We propose that once [Sr(NO3)2] is extracted in organic media, the receptor's high affinity toward K+ in nitrate media can be used to back strip Sr2+ to the aqueous phase.
A review of camera trapping for conservation behaviour research
Authors: Caravaggi Anthony , Banks Peter B. , Burton A Cole , Finlay Caroline M. V. , Haswell Peter M. , Hayward Matt W. , Rowcliffe Marcus J. , Wood Mike D.
Published: June 2017

An understanding of animal behaviour is important if conservation initiatives are to be effective. However, quantifying the behaviour of wild animals presents significant challenges. Remote‐sensing camera traps are becoming increasingly popular survey instruments that have been used to non‐invasively study a variety of animal behaviours, yielding key insights into behavioural repertoires. They are well suited to ethological studies and provide considerable opportunities for generating conservation‐relevant behavioural data if novel and robust methodological and analytical solutions can be developed. This paper reviews the current state of camera‐trap‐based ethological studies, describes new and emerging directions in camera‐based conservation behaviour, and highlights a number of limitations and considerations of particular relevance for camera‐based studies. Three promising areas of study are discussed: (1) documenting anthropogenic impacts on behaviour; (2) incorporating behavioural responses into management planning and (3) using behavioural indicators such as giving up densities and daily activity patterns. We emphasize the importance of reporting methodological details, utilizing emerging camera trap metadata standards and central data repositories for facilitating reproducibility, comparison and synthesis across studies. Behavioural studies using camera traps are in their infancy; the full potential of the technology is as yet unrealized. Researchers are encouraged to embrace conservation‐driven hypotheses in order to meet future challenges and improve the efficacy of conservation and management processes.