bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating mechanisms of plant‐mediated effects on herbivore persistence and occupancy across an ecoregion
Authors: Wilkening Jennifer L. , Cole Evan J. , Beever Erik A. 
Published: June 2019

AbstractContemporary climate change is rapidly creating one of the greatest challenges for management and conservation during the 21st century. Mountain ecosystems, which have a high degree of spatial heterogeneity and contain numerous habitat specialists, have been identified as particularly vulnerable. We used data from multiple years across sites spanning a >40 million ha ecoregion to test hypotheses regarding how community‐level characteristics of vegetation may affect a mammalian generalist herbivore, the American pika (Ochotona princeps). We examined patterns of pika persistence across sites in the hydrographic Great Basin, and occupancy within a subset of these sites. We used mixed‐effects logistic regression models to compare evidence in support of competing explanations for each pattern within an information–theoretic framework (using Akaike's information criterion). Models reflected four hypothesized classes of mechanisms related to nutritional ecology, ecosystem function, indirect indication of climatic effects, and (synergistic) combinations of these three classes. At the site level, models reflecting synergistic effects received the most support. At the within‐site level, support appeared to be split equally among hypotheses containing predictors related to either nutritional ecology or indirect climate effects. Well‐supported predictors included cover of invasive plant species, cover of more‐xeric plant species, species evenness, and proportion of graminoid species. Our results both (1) identify important aspects of vegetation communities that may influence herbivore distribution in mountainous areas across a large, diverse geographic region, and (2) contribute to an improved understanding of how mountain ecosystems may be affected by ongoing climate change, more broadly.
Using Confocal Microscopy to Estimate the Distribution of Natural Antioxidants in Poultry Meal and Extruded Kibbles
Authors: Ye Liyun , Pham‐Mondala Alessandra , Li Jian , Joseph Poulson , Nahas Roger , Michel‐Salaun Francoise 
Published: June 2019

With the increasing demand for natural ingredients from the pet food market, new sources of natural antioxidants have been identified. However, many of them have low solubility in the traditional oil‐based delivery systems. To improve their distribution in dry matrices, new carriers and processes have been developed. To evaluate the effect of new delivery systems, a confocal microscopy method is developed. Based on confocal images, an emulsion carrier improves the distribution of hydrophilic antioxidants in poultry meal. Shelf life study shows that it slows down the decomposition of some lipophilic antioxidants even though it does not improve the oxidative stability of poultry meal directly. In extruded kibbles, confocal images show that hydrophilic compounds distribute better when added into premix before extrusion, while lipophilic compounds distribute well no matter when they are added. Confocal microscopy is a great tool for evaluating the effect of new delivery systems on antioxidants’ distribution. The overall performance of the antioxidant needs to be further evaluated through a comprehensive oxidative stability study.Practical Applications: Results presented in this paper may help renderers and pet food scientists to understand the distribution, migration, and performance of natural antioxidants in poultry meal and extruded kibbles. The confocal microscopy method developed in this study can be used to evaluate other delivery systems and in other protein‐rich dry matrices. Even though the water‐in‐oil emulsion improves the distribution of hydrophilic antioxidants and keeps the good distribution of lipophilic antioxidants, antioxidants in oil carrier still has the best performance in poultry meal. This reminds us of the importance of comprehensive oxidative stability studies in evaluating antioxidants performance.Two proprietary carriers’ effect on antioxidants’ performance in poultry meal through confocal imaging and shelf life study are evaluated. The confocal imaging method has been also tentatively used to estimate the distribution of antioxidants when added before and after extrusion in kibbles.
Double‐hit lymphoma: So what?
Authors: Davies Andrew 
Published: June 2019

AbstractThe revised WHO classification moved all aggressive B‐cell lymphomas with a MYC translocation and a concurrent translocation of BCL2 and/or BCL6 into a single diagnostic category. These are the double‐ and triple‐hit lymphomas. These represent a group with typically a poor outcome to conventional therapy, and as a result, intensification of immunochemotherapy has been explored. The optimal approach is far from clear, and recent insight into the biology suggest that they may represent just a subgroup of molecular high‐grade B‐cell lymphomas that maybe identified by gene expression profiling. There are a number of novel therapeutic approaches under investigation.
New treatment options in hairy cell leukemia with focus on BRAF inhibitors
Authors: Falini Brunangelo , Tiacci Enrico 
Published: June 2019

AbstractHairy cell leukemia (HCL) responds initially very well to chemotherapy with purine analogues. However, up to 50% of patients relapse, often multiple times, and become progressively less sensitive to these myelotoxic and immune‐suppressive drugs. At progression, viable therapeutic strategies include addition of rituximab to purine analogues, and treatment with the anti‐CD22 immunotoxin moxetumomab pasudotox, which has been recently approved by the FDA in HCL patients after at least two prior therapies. Identification of the BRAF‐V600E kinase mutation as the genetic cause of HCL has opened the way, in the relapsed/refractory experimental setting, to targeted and non‐myelotoxic effective strategies that are based on inhibition of BRAF with vemurafenib, co‐inhibition of BRAF and its target MEK with dabrafenib and trametinib, and BRAF inhibition with vemurafenib combined with anti‐CD20 immunotherapy. In particular, vemurafenib plus rituximab is emerging as a short, safe, chemotherapy‐free regimen able to induce deep complete remissions in most HCL patients refractory to, or relapsed multiple times, after chemo(immuno)therapy.
Managing the toxicities of CAR T‐cell therapy
Authors: Neelapu Sattva S. 
Published: June 2019

AbstractChimeric antigen receptor (CAR) T‐cell therapy has the potential to revolutionize the management of B‐cell lymphomas and possibly other cancers. Two anti‐CD19 CAR T‐cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for the management of relapsed/refractory large B‐cell lymphoma after two lines of systemic therapy. Additional trials are ongoing to evaluate these and other CAR T products at earlier stages of the disease course as well as in other lymphomas. While the potential to induce durable remissions with a single CAR T‐cell infusion even in patients who are chemorefractory has generated much enthusiasm in the field, practitioners need to familiarize themselves with the unique toxicities associated with these therapies. This review will discuss the grading and management of the two most common toxicities, cytokine release syndrome (CRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS), observed acutely after this therapy. In addition, late toxicities including prolonged cytopenias and on‐target off‐tumor effects will be reviewed.
Malignant melanoma of the male urethra with increased 5‐S‐cysteinyldopa: A case report
Authors: Aoki Yusuke , Soma Takahiko , Nakamura Yuki , Fukui Naotaka , Sakai Yasuyuki , Kageyama Yukio 
Published: June 2019

IntroductionWe herein present a case of malignant melanoma of the male urethra with an increased serum 5‐S‐cysteinyldopa concentration.Case presentationA 77‐year‐old man visited our hospital complaining dysuria and a dark brown mass protruding from the external urethral meatus. His serum 5‐S‐cysteinyldopa concentration was elevated beyond the upper limit of the reference range. Biopsy of the tumor was performed, and the histological diagnosis was malignant melanoma. He underwent total penectomy, and the serum 5‐S‐cysteinyldopa concentration was normalized. He remained alive without evidence of locoregional recurrence or distant metastases for 6 months after surgery.ConclusionMalignant melanoma of the male urethra is uncommon. The prognosis is favorable if it is detected in its early stages. This case report suggests that measurement of the serum concentration of 5‐S‐cysteinyldopa, a melanin metabolite, is useful for early diagnosis of male urethral melanoma.
Linear array arrangement using composite right‐/left‐handed transmission lines for magnetic resonance imaging
Authors: Hernandez Daniel , Seo Jeung‐Hoon , Kim Kyoung‐Nam 
Published: June 2019

AbstractArray coils for magnetic resonance imaging have been used to improve field uniformity, improve signal‐to‐noise ratios, and increase imaging speed. Alternative radio frequency (RF) coils that use metamaterials, such as loop or microstrip coils, have recently been proposed and are expected to provide better performance than the traditional RF array coils. Transmission lines (TLs) based on metamaterials are known as composite right‐ and left‐handed (CRLH) TLs, which are artificially created by adding inductances and capacitances to a common TL. CRLH TLs have a zero‐order resonance mode, wherein wave propagation is independent of the TL's electrical length. Decoupling between array elements is important for obtaining the benefits of parallel imaging. In this study, we analyze the decoupling properties between two CRLH TLs. In addition, we design a linear array of four CRLH TLs to obtain a uniform magnetic (|B1|)‐field in the axial‐ and longitudinal‐direction at 7T for the corresponding frequency of 300 MHz.
Enhancement of Cr(VI) Ion Removal Using Nanochitosan Coated on Bituminous Activated Carbon
Authors: Chooaksorn Wanida , Nitisoravut Rachnarin , Polprasert Chongrak , Babel Sandhya , Laohhasurayotin Kritapas , Kangwansupamonkon Wiyong 
Published: June 2019

ABSTRACT: Bituminous activated carbon (AC) has been widely used as a sorbent for adsorption of non‐polar species, but its performance for removal of ionic species such as heavy metals has not been as efficient. In this study, AC was modified with chitosan nanoparticles (CN) using facile methods of dip coating and wet impregnation. The CN‐coated AC demonstrated an increase in Cr(VI) removal efficiency in both kinetics and adsorption capacity. The adsorption capacity of the CN‐coated AC (mg/g) was more than twice that of the uncoated AC (36.36 mg/g), or pure chitosan (32.57 mg/g). The sizes of the synthesized CN (160‐2,000 nm) can be controlled by varying the concentration of the chitosan/reagents used. The adsorption isotherms are better described using the Freundlich rather than the Langmuir model and are in agreement with the heterogeneity of the surfaces. Adsorption kinetics followed that of the pseudo‐second‐order kinetics, suggesting chemisorption as a rate limiting step.
Updated Population Pharmacokinetic Model of Cabozantinib Integrating Various Cancer Types Including Hepatocellular Carcinoma
Authors: Nguyen Linh , Chapel Sunny , Tran Benjamin Duy , Lacy Steven 
Published: June 2019

AbstractAn integrated population pharmacokinetic (PPK) model was used to evaluate the effects of liver dysfunction on the pharmacokinetics (PK) of cabozantinib in patients with hepatocellular carcinoma and to determine whether clinical dosage adjustment may be necessary in this population. An integrated PPK model previously developed in healthy volunteers and patients with various cancer types was updated with cabozantinib concentration data from hepatocellular carcinoma patients in phase 2 and 3 studies (total 2023; hepatocellular carcinoma 489 patients). Covariate effects of cancer type including hepatocellular carcinoma population and liver dysfunction per the National Cancer Institute Organ Dysfunction Working Group criteria were evaluated (normal 1425; mild liver dysfunction 558; moderate/severe liver dysfunction 15/1 patients). With hepatocellular carcinoma patients, PK parameter estimates and covariate effects were similar to the previous PPK model (2 compartments with first‐ and zero‐order absorption and first‐order elimination). Only medullary thyroid cancer had appreciable PK differences from healthy volunteers. PK parameter estimates were similar with and without addition of liver dysfunction covariates. Patients with mild liver dysfunction were predicted to have minimal differences in apparent clearance of cabozantinib relative to patients with normal liver function. Therefore, no initial cabozantinib dosage adjustment is recommended for cancer patients with mild liver dysfunction. The small sample size for patients with moderate and severe liver dysfunction limited dosing recommendations in these subpopulations. The results from this PPK analysis were different from those of the single‐dose hepatic impairment study in healthy volunteers and more reflective of exposure in cancer patients following daily cabozantinib dosing.
Qualitative analysis of smear layer treated with different etidronate concentrations: A scanning electron microscopy study
Authors: Emre Erik C. , Onur Orhan E. , Maden Murat 
Published: June 2019

AbstractThe aim of this study was to examine the smear layer removal capacity of various etidronate treatments. Seventy‐eight roots were instrumented up to apical size X4 and randomly divided into five treatment groups and a positive control group (n = 13). Groups were as follows: irrigation with 5 ml of sterile saline (control) for 3 min, 5 ml of 17% ethylenediaminetetraacetic acid (EDTA) for 3 min, 5 ml of 9% A1‐hydroxyethylidene‐1,1‐bisphosphonate (HEBP) for 3 min, 5 ml of 18% HEBP for 3 min, irrigation with 5 ml of 1% sodium hypochlorite (NaOCl) + 9% HEBP for 3 min, and 5 ml of 2% NaOCl + 18% HEBP for 3 min. The roots were examined using a scanning electron microscope. The smear layer scores in the 2% NaOCl + 18% HEBP group were lower than those in the other treatment groups and the control group (p < .05). There were no significant differences among the treatment groups in the smear layer scores of the coronal and middle thirds. However, the smear layer scores in the 2% NaOCl + 18% HEBP treatment group were lower those in the 9% HEBP and 18% HEBP treatment groups in the apical third (p < .05). In the clinical setting, the recommended concentration of HEBP is 18%, and it should be used with an oxidizing agent to ensure optimum smear layer removal.
Embryonic and larval development of the northern pike: An emerging fish model system for evo‐devo research
Authors: Pospisilova Anna , Brejcha Jindřich , Miller Vojtech , Holcman Radek , Šanda Radek , Stundl Jan 
Published: June 2019

AbstractThe northern pike, Esox lucius, is one of the largest temperate freshwater apex predators with a characteristic morphology: an elongated body with pelvic, dorsal, and anal fins located at the rear as a functional feature to sprint predation. However, the typical pike character is its head, which is characterized by a long, flattened snout, a well‐armed mouth with numerous teeth, and large eyes characteristic of shallow water visual predators. Although the northern pike is becoming increasingly popular as a model system for ecology and evolutionary research, a detailed staging table has not yet been reported. In this study, we report the first comprehensive staging table for the northern pike, spanning from the one‐cell stage to the freely‐swimming juvenile stage. In addition to classical embryological descriptions, we use a DAPI staining to distinguish individual cells and embryonic structures during the early development. This dataset, in combination with the genomic and transcriptomic resources already available, serves as a foundation for in‐depth mechanistic studies dealing with development using this species.
A 5.5‐inch full HD foldable AMOLED display based on neutral‐plane splitting concept
Authors: Nishimura Masumi , Takebayashi Kisako , Hishinuma Masatomo , Yamaguchi Hajime , Murayama Akio 
Published: June 2019

AbstractSplitting of the mechanical neutral plane is a promising concept for foldable displays because it reduces the folding stress in each layer of the display. We verified the splitting concept experimentally and revealed a linear relation between the relative position of the neutral plane and the logarithm of the adhesive's elastic modulus. As the modulus decreased, the position of the neutral plane approached that of perfect splitting. On the basis of the neutral‐plane splitting concept, we developed 5.5‐inch full high‐definition foldable active matrix organic light‐emitting diode (AMOLED) displays, which endured 150 k inward folding cycles and 150 k outward folding cycles with folding radii of 3 and 5 mm, respectively. This study is expected to improve the flexibility of designing foldable AMOLED displays, enabling better balance of the portability versus practicality trade‐off in mobile displays.
Sheoak woodlands: a newly identified habitat for western ringtail possums
Authors: Bader Jordan C. , Van Helden Bronte E. , Close Paul G. , Speldewinde Peter C. , Comer Sarah J. 
Published: June 2019

ABSTRACTAlthough critically endangered western ringtail possums (Pseudocheirus occidentalis) have been recorded from a variety of vegetation types in southwestern Australia, the extent to which many of these vegetation types are occupied by the species remains unknown. We conducted spotlight surveys for western ringtail possums between March and April 2018 in Albany, southwestern Australia, to determine the species’ occupancy in 2 vegetation types. Using occupancy models, we demonstrated that sheoak (Allocasuarina fraseriana) woodlands, previously unrecognized as providing western ringtail possum habitat, support the species, although the median probability of their occupancy was lower than in marri (Corymbia calophylla) and eucalypt (Eucalyptus marginata and E. staeri) woodlands. Use of trees and other habitat components by western ringtail possums varied within and between vegetation types. Sheoak woodlands are likely critical for western ringtail possums and given the apparent flexibility in vegetation types used by the species, investigation of the potential value of other vegetation types for this species has conservation merit. © 2019 The Wildlife Society.
TET2 missense variants in human neoplasia. A proposal of structural and functional classification
Authors: Bussaglia Elena , Antón Rosa , Nomdedéu Josep F. , Fuentes‐Prior Pablo 
Published: June 2019

AbstractBackgroundThe human TET2 gene plays a pivotal role in the epigenetic regulation of normal and malignant hematopoiesis. Somatic TET2 mutations have been repeatedly identified in age‐related clonal hematopoiesis and in myeloid neoplasms ranging from acute myeloid leukemia (AML) to myeloproliferative neoplasms. However, there have been no attempts to systematically explore the structural and functional consequences of the hundreds of TET2 missense variants reported to date.MethodsWe have sequenced the TET2 gene in 189 Spanish AML patients using Sanger sequencing and NGS protocols. Next, we performed a thorough bioinformatics analysis of TET2 protein and of the expected impact of all reported TET2 missense variants on protein structure and function, exploiting available structure‐and‐function information as well as 3D structure prediction tools.ResultsWe have identified 38 TET2 allelic variants in the studied patients, including two frequent SNPs: p.G355D (10 cases) and p.I1762V (28 cases). Four of the detected mutations are reported here for the first time: c.122C>T (p.P41L), c.4535C>G (p.A1512G), c.4760A>G (p.D1587G), and c.5087A>T (p.Y1696F). We predict a complex multidomain architecture for the noncatalytic regions of TET2, and in particular the presence of well‐conserved α+β globular domains immediately preceding and following the actual catalytic unit. Further, we provide a rigorous interpretation of over 430 missense SNVs that affect the TET2 catalytic domain, and we hypothesize explanations for ~700 additional variants found within the regulatory regions of the protein. Finally, we propose a systematic classification of all missense mutants and SNPs reported to date into three major categories (severe, moderate, and mild), based on their predicted structural and functional impact.ConclusionsThe proposed classification of missense TET2 variants would help to assess their clinical impact on human neoplasia and may guide future structure‐and‐function investigations of TET family members.
Value of p‐Value
Authors: Golbraikh Alexander 
Published: June 2019

AbstractThe goal of this manuscript is to discuss important aspects of external validation of classification and category Quantitative Structure – Activity/Property/Toxicity Relationship QS/A/P/T/R models that to the best of author's knowledge are not addressed in publications. Statistical significance (in terms of p‐value) and accuracy of prediction (in terms of Correct Classification Rate (CCR)) of external validation set compounds are among most important characteristics of the models. We assert that in most cases the models built for classification or category response variable should be statistically significant and predictive for each class or category. We show that three thresholds of the number of compounds in each class or category of the external validation sets should be satisfied. 1) The p‐value criterion can never be satisfied, if the number of compounds is below the first threshold. 2) If the number of compounds is between the first and the second thresholds, p‐value criterion should be used. 3) If it is higher than the third threshold, classification or category accuracy criterion should be used. 4) If the number of compounds is between second and third thresholds, either one or the other criterion should be used depending on the value of p‐value. 5) When the number of compounds in the class approaches infinity, the maximum relative error of prediction approaches the relative expected error. The results are of interest in other areas of multidimensional data analysis.
Novel Electrotopological Atomic Descriptors for the Prediction of Xenobiotic Cytochrome P450 Reactions
Authors: Kaitoh Kazuma , Kotera Masaaki , Funatsu Kimito 
Published: June 2019

AbstractCytochrome P450 (CYP) is an enzyme family that plays a crucial role in metabolism, mainly metabolizing xenobiotics to produce non‐toxic structures, however, some metabolized products can cause hepatotoxicity. Hence, predicting the structures of CYP products is an important task in designing non‐hepatotoxic drugs. Here, we have developed novel atomic descriptors to predict the sites of metabolism (SoM) in CYP substrates. We proposed descriptors that describe topological and electrostatic characteristics of CYP substrates using Gasteiger charge. The proposed descriptors were applied to CYP3A4 data analysis as a case study. As a result of the descriptor selection, we obtained a gradient boosting decision tree‐based SoM classification model that used 139 existing descriptors and the proposed 45 descriptors, and the model performed well in terms of the Matthews correlation coefficient. We also developed a structure converter to predict CYP products. This converter correctly generated 51 structural formulas of experimentally observed CYP3A4 products according to a manual evaluation.