bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro toxicity assessment of hydrogel patches obtained by cation‐induced cross‐linking of rod‐like cellulose nanocrystals
Authors: Meschini Stefania , Pellegrini Evelin , Maestri Cecilia Ada , Condello Maria , Bettotti Paolo , Condello Giancarlo , Scarpa Marina
Published: May 2019

With the purpose of designing active patches for photodynamic therapy of melanoma, transparent and soft hydrogel membranes (HMs) have been fabricated by cation‐induced gelation of rod‐like cellulose nanocrystals (CNCs) bearing negatively charged carboxylic groups. Na+, Ca2+, Mg2+ have been used as cross‐linkers of cellulose nanocrystal (CNC). The biosafety of this material and of its precursors has been evaluated in vitro in cell cultures. Morphological changes, cell organelles integrity, and cell survival with the tetrazolium salt reduction (MTT) assay were utilized as tests of cytotoxicity. Preliminary investigation was performed by addition of the hydrogel components to the cell culture medium and by incubations of the CNC‐HM in direct and indirect contact with a confluent monolayer of A375 melanoma cells. Direct contact assays suffered from interference of physical stress. Careful evaluation of cytotoxicity was obtained considering the overall picture provided by microscopy and biochemical tests performed with the CNC‐HM in indirect contact with two melanoma cell lines (A375, M14) and human fibroblasts. CNCs have been demonstrated to be a safe precursor material and CNC‐HMs have a good biocompatibility provided that the excess of cations, in particular of Ca2+ is removed. These results indicate that CNC and can be safely used to fabricate biomedical devices such as transparent hydrogel patches, although attention must be paid to the fabrication procedure.
Protective effect of gallic acid on apoptosis of sperm and in vitro fertilization in adult male mice treated with cyclophosphamide
Authors: Mehraban Zahra , Ghaffari Novin Marefat , Golmohammadi Mohammad Ghasem , Sagha Mohsen , Pouriran Khashayar , Nazarian Hamid
Published: May 2019

Background

Alteration of free radicals (reactive oxygen species) causes mammals' sperm damage. Gallic acid (GA) is known as an antioxidant which is effective against oxidative stress. The purpose of this study was to evaluate the antioxidant effects of GA on the sperm apoptosis and in vitro fertilization (IVF) in adult male mice treated with cyclophosphamide (CP).

Materials and Methods

Following a pilot study to find the dose responses of GA, 40 adult male naval medical research institute (NMRI) mice (32 ± 3 g) were divided into five groups (n = 8): control, sham (normal saline, NS: 0.2 mL per day), CP (15 mg kg–1 per week; intraperitoneal, IP), GA (12.5 mg kg
–1 per day; IP), and GA+CP. After the treatment, sperm parameters were analyzed. The apoptosis of sperm was measured by Annexin‐PI staining method followed by flow cytometry detection. Fertility was assessed by IVF method among the groups.

Results

The difference in sperm parameter and fertility rate between the control (% 80.05 ± 6.53) and cyclophosphomide groups (% 51.82 ± 10.78) was significant (P < .001) but GA plus CP (% 78.16 ± 5.71) restored the fertilization rate (P < .001).

Also, a remarkable increase was noted regarding apoptotic sperm in CP group vs the control group. The comparison in the five groups shows that GA cotreatment was significantly effective in reducing the apoptosis rate caused by cyclophosphamide (P < .05).

Conclusion

It was ultimately attained that GA has a potent antioxidant effect which could inhibit the detrimental effect of CP on the apoptosis and fertility rate of sperm in the mouse.
Effects of Ketoconazole, a CYP4F2 Inhibitor, and CYP4F2*3 Genetic Polymorphism on Pharmacokinetics of Vitamin K1
Authors: Park Jin‐Woo , Kim Kyoung‐Ah , Park Ji‐Young
Published: May 2019

The objective of this study was to evaluate whether cytochrome P450 (CYP)4F2 is involved in the exposure of vitamin K1 through a drug interaction study with ketoconazole, a CYP4F2 inhibitor, and a pharmacogenetic study with CYP4F2*3. Twenty‐one participants with different CYP4F2*3 polymorphisms were enrolled (8 for *1/*1, 7 for *1/*3, and 6 for *3/*3). All participants were treated twice daily for 5 days with 200 mg of ketoconazole or placebo. Finally, a single dose of 10 mg vitamin K1 was administered, plasma levels of vitamin K1 were measured, and its pharmacokinetics was assessed. Ketoconazole elevated the plasma levels of vitamin K1 and increased the average area under the concentration‐time curve (AUCinf) and peak concentration by 41% and 40%, respectively. CYP4F2*3 polymorphism also affected plasma levels of vitamin K1 and its pharmacokinetics in a gene dose–dependent manner. The average AUCinf value was 659.8 ng·h/mL for CYP4F2*1/*1, 878.1 ng·h/mL for CYP4F2*1/*3, and 1125.2 ng·h/mL for CYP4F2*3/*3 (P = .010). This study revealed that ketoconazole and CYP4F2*3 polymorphism substantially increased the exposure of vitamin K1 in humans. These findings provide a plausible explanation for variations in warfarin dose requirements resulting from interindividual variations in vitamin K1 exposure due to CYP4F2‐related drug interactions and genetic polymorphisms.
Anaerobic biodegradation and dewaterability of aerobic granular sludge
Authors: Jahn Lydia , Saracevic Ernis , Svardal Karl , Krampe Jörg
Published: May 2019

BACKGROUND

Although a growing number of full‐scale wastewater treatment plants have already been constructed and operated with aerobic granular sludge (AGS), only limited information is available about further post‐treatment, in particular about sludge stabilization and dewaterability. The aim of the present study was to investigate the biodegradation and methane yield of AGS by the use of anaerobic laboratory‐scale reactors operated under mesophilic conditions and hydraulic retention times of 25 and 40 days.

RESULTS

The methane yield of AGS was ca 260 mL gVSS−1 (volatile suspended solids) and thus slightly increased compared to that of suspended activated sludge (SAS; 240 mL gVSS−1). A clear difference between the methane yield was found for separated pure granules (500 μm), which was ca 50% higher compared to that for SAS. VSS removal of AGS during anaerobic degradation was ca 52%. Dewaterability of AGS after anaerobic digestion was slightly lower compared to SAS. Extracellular polymeric substance (EPS) extraction and fluorescence analysis showed tryptophan contents which were almost twice as high compared to the EPS extracted from SAS.

CONCLUSIONS

Overall, the anaerobic digestion of AGS was found to be a suitable stabilization strategy with the benefit of recovering energy in the form of methane. Further tests are needed to validate the decreased dewatering behaviour with full‐scale applications. The presented approach for tryptophan measurement allows the transfer of qualitative results from a fluorescence analysis into quantitative values and could be further adapted for identifying relevant EPS constituents. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Simultaneous separation, concentration and determination of trace fluoroquinolone antibiotics in environmental samples using a polymer aqueous two‐phase system coupled with HPLC
Authors: Sun Zhuo , Lu Yang , Zhu Lina , Liu Wei , Qu Yue , Lin Nan , Yu Ping
Published: May 2019

BACKGROUND

Fluoroquinolone antibiotics and their metabolites can accumulate in soil and water. Trace amounts of fluoroquinolone antibiotic residues in the environment necessitate the pretreatment of samples prior to analysis. In this work, a polyoxyethylene cetyl ether (POELE20)–NaH2PO4 aqueous two‐phase system (ATPS) was combined with high‐performance liquid chromatography (HPLC) to separate and determine trace quantities of ciprofloxacin (CIP), norfloxacin (NRF) and pefloxacin (PEF) in environmental samples.

RESULTS

Single‐factor, multi‐factor, reproducibility and accuracy experiments were performed. The extraction efficiencies and enrichment factors for the three antibiotics were above 90 and 13.8%, respectively, under optimal conditions. The recovery efficiency of CIP was 92.08–99.50%, with a relative standard deviation (RSD) of 0.60–6.34%, and the recovery efficiency of NRF and PEF was 93.40–99.30%, with RSD of 0.98–5.16%, when this method was applied to spiked water and soil samples. The RSDs of intra‐ and inter‐day analyses were 1.56–3.42 and 1.33–3.97%, respectively.

CONCLUSIONS

This study demonstrated that POELE20–NaH2PO4 ATPS coupled with HPLC was suitable for the simultaneous separation, concentration and determination of trace quantities of CIP, NRF and PEF in environmental samples. Moreover, this method can be applied for the determination of trace fluoroquinolone antibiotics in food samples. © 2019 Society of Chemical Industry
Modeling sports‐related mild traumatic brain injury in animals—A systematic review
Authors: Hiskens Matthew I. , Angoa‐Pérez Mariana , Schneiders Anthony G. , Vella Rebecca K. , Fenning Andrew S.
Published: May 2019

Sports‐related head trauma has emerged as an important public health issue, as mild traumatic brain injuries (mTBIs) may result in neurodegenerative disorders such as chronic traumatic encephalopathy (CTE). Research into mTBI and CTE pathophysiology are difficult to undertake in athletes, with observational trials and post‐mortem analysis the current mainstays. Thus, animal models play an important role in the study of mTBI, however, traditional animal models have focused on acute, severe injuries rather than the more typical mTBI's seen in sport injuries. Recently, a number of animal models have been developed that are both appropriately scaled and biomechanically relevant to the forces sustained by athletes. This review aimed to examine the literature for variables included in these animal models, and the resulting neurotrauma as evidenced by pathology and behavioral deficits. A systematic search of the literature was performed in multiple electronic databases. The inclusion criteria required mimicry of athlete mTBI conditions: freedom of head movement, lack of surgical alteration of the skull, and application of direct contact force. Studies were analyzed for variables including apparatus design features (impact force, change in animal head velocity, and kinetic energy transfer to the head), demonstrated pathology (phosphorylated tau, TDP‐43 aggregation, diffuse axonal injury, gliosis, cytokine inflammation response, and genetic integrity), and behavioral changes. These studies suggested that appropriate animal models can assist in understanding the pathological and functional outcomes of athlete mTBI, and could be used as a platform for future studies of diagnostic/prognostic markers and in the development of treatment interventions.
Raman mapping of 4‐MeV C and Si channeling implantation of 6H‐SiC
Authors: Flessa Aikaterini , Ntemou Eleni , Kokkoris Michael , Liarokapis Efthymios , Gloginjić Marko , Petrović Srdjan , Erich Marko , Fazinić Stjepko , Karlušić Marko , Tomić Kristina
Published: May 2019

A 6H‐SiC single crystal implanted in channeling mode by 4‐MeV C+3 and Si+3 ions at various doping levels has been examined by scanning electron microscopy (SEM) and micro‐Raman spectroscopy in order to study the lattice distortions inflicted by the impinging ions. C ions create zones of strongly damaged regions, parallel to the front face of the wafer with width increasing with the amount of doping. As expected, Si has induced considerably more lattice distortions than C, and more than one order of magnitude less doping induces apparently the same effect as C. Despite the large laser spot size compared with the boundaries of the distorted regions, micro‐Raman data provided results agreeing with the SEM pictures and the Monte Carlo calculations using the SRIM‐2013 software. From the evolution of the crystalline peaks in the Raman spectra obtained across the damaged area, one can conclude that the impinging ions do not accommodate as defects in the lattice but mostly displace the ions breaking the bonds and destroying the long range order. The spatial correlation model that takes into consideration the intensity variation at the laser spot and the anticipated from Monte Carlo calculations for the collision events can reproduce the trend of the strong transversal optical phonon width indicating nanocrystallites of a few nanometers size in the most damaged area.
Estimating hazard ratios from published Kaplan‐Meier survival curves: A methods validation study
Authors: Saluja Ronak , Cheng Sierra , delos Santos Keemo Althea , Chan Kelvin K.W.
Published: May 2019

Objective

Various statistical methods have been developed to estimate hazard ratios (HRs) from published Kaplan‐Meier (KM) curves for the purpose of performing meta‐analyses. The objective of this study was to determine the reliability, accuracy, and precision of four commonly used methods by Guyot, Williamson, Parmar, and Hoyle and Henley.

Design

Pivotal randomized controlled trials (RCTs) in oncology were identified from the pan‐Canadian Oncology Drug Review (pCODR) database (primary analysis) and the Food and Drug Administration's (FDA) drug approvals page (secondary analysis) between January 2012 and May 2016. Two reviewers independently reconstructed HRs using each method on KM curves extracted from each trial and compared them with reported HRs (gold standard). Bland‐Altman plots and summary statistics were calculated to assess accuracy and precision of these methods. Interrater reliability was assessed using intraclass correlation coefficient (ICC). These four methods were also applied to KM curves of different structures (ie, flat versus steep curves).

Results

A total of 118 KM curves (55 RCTs) and 77 KM curves (46 RCTs) were extracted from pCODR and FDA, respectively. In the primary analysis, the Guyot method was the most accurate with the lowest mean error (0.0094; 95% CI, −0.0012‐0.020). All four methods had excellent interrater reliability. The Guyot method showed the smallest bias and greatest precision on the Bland‐Altman plots. The Guyot method was consistently superior in both the secondary and all sensitivity analyses.

Conclusion

In the absence of reported HRs, we recommend that researchers consider the Guyot method to reconstruct HRs from KM curves when performing aggregate data meta‐analyses.
Quantifying indium with ion chromatography in hydro‐ and biohydrometallurgical leaching solutions
Authors: Ashworth Charlotte , Weller Christian , Frisch Gero
Published: May 2019

A methodology has been developed to chromatographically quantify indium in polymetallic (bio)hydrometallurgical processing solutions using the Dionex IonPac CS5A column and pyridine‐2,6‐dicarboxylic acid eluent. Cu(II) and In(III) could be separated by elevating the column temperature to 45°C. The comparatively low stability constant of the In‐eluent complex (log K2 = 3.8) required typical leaching samples to be diluted in the eluent rather than acid or water to overcome ligand competition between components of the sample solution and the eluent. The methodology was applied to leachates from (bio)hydrometallurgical processing of oxidic flue dust residues and sulfidic zinc ores, where both are promising candidates for the recovery of indium from low grade ores and metallurgical wastes. Indium, ferrous iron, ferric iron, copper, zinc, nickel, and manganese concentrations could be simultaneously quantified. The method was found suitable for samples containing at least 0.25 mg/L indium and an iron to indium ratio of up to 100:1.
A novel process for copper protection in the simulated industrial cooling water based on click synthesis and self‐assembling method
Authors: Li Jin , Zhang Daquan , Zhang Kai , Gao Lixin , Shi Cheng , Chen Donghui , Huang Manhong
Published: May 2019

The triazole inhibitor of 1‐(p‐tolylthio)‐1H‐1,2,3‐triazole‐4‐carboxylic acid (TTC) was synthesized via the Cu(I)‐catalyzed azide‐alkyne 1,3‐dipolar cycloaddition reaction. The self‐assembling method was performed to fabricate the self‐assembled film of TTC on the copper surface. The electrochemical measurement results indicate that the TTC film can efficiently protect the copper from corrosion in high concentrated industrial cooling water. The protection efficiency of TTC film for copper is 92.2%. Surface characterizations imply that the copper with TTC film after corrosion is covered with multiple protective layers. It probably contains Cu(I) and Cu(II) complexes mixed with nitrogenous compound, Cl− and SO42−. The result of quantum chemical calculation shows that the superior performance of TTC film is related to the adsorption of TTC molecules on copper surface horizontally. This kind of adsorption is mainly achieved via the adsorption centers of triazole ring and O atoms in TTC molecule.
Tannic Acid‐Inspired Star‐Like Macromolecules via Temporally Controlled Multi‐Step Potential Electrolysis
Authors: Zaborniak Izabela , Chmielarz Paweł , Wolski Karol , Grzes´ Gabriela , Isse Abdirisak A. , Gennaro Armando , Zapotoczny Szczepan , Sobkowiak Andrzej
Published: May 2019

Inspired by tea stains, a plant polyphenolic‐based macroinitiator is prepared for the first time by partial modification of tannic acid (TA) with 2‐bromoisobutyryl bromide. In accordance with the “grafting from” methodology, a naturally occurring star‐like polymer with a polar gallotannin core and a hydrophobic poly(n‐butyl acrylate) side arms is synthesized via a simplified electrochemically mediated ATRP (seATRP), utilizing multiple‐step potential electrolysis. To investigate the kinetics of the electrochemical catalytic process triggered by reduction of Cu(II) or Fe(III) catalytic complex in the presence of the multifunctional initiator, cyclic voltammetry measurements are conducted. The naturally derived tannin macromolecule shows narrow MWDs (Đ = 1.57). Moreover, solvolysis of the star polymer to cleave the side arms and characterize them indicates that all chains grow to the same length (homopolymers with Mw/Mn <1.17), which confirms the well‐controlled seATRP. The structure of the obtained TA‐based systems is characterized microscopically (AFM) and spectroscopically (1H NMR, FT‐IR). Atomic force microscopy measurements precisely determine the diameters of the obtained star polymers (19.7 ± 3.3 nm). These new star polymers may find biomedical applications as drug delivery systems and antifouling or antimicrobial coatings.
Extemporaneous Preparation of Injectable and Enzymatically Degradable 3D Cell Culture Matrices from an Animal‐Component‐Free Recombinant Protein Based on Human Collagen Type I
Authors: Kamata Hiroyuki , Ashikari‐Hada Satoko , Mori Yusuke , Azuma Akihiko , Hata Ken‐ichiro
Published: May 2019

Injectable hydrogels are considered important to realize safe and effective minimally invasive therapy. Although animal‐derived natural polymers are well studied, they typically lack injectability and fail to eliminate the potential risks of immunogenic reactions or unknown pathogen contamination. Despite extensive research activities to explore ideal injectable hydrogels, such state‐of‐the‐art technology remains inaccessible to non‐specialists. In this article, the design of a new injectable hydrogel platform that can be extemporaneously prepared from commercially available animal‐component‐free materials is described. The hydrogels can be prepared simply by mixing mutually reactive aqueous solutions without necessitating specialized knowledge or equipment. Their solidification time can be adjusted by choosing proper buffer conditions from immediate to an extended period of time, that is, few or several tens of minutes depending on the concentration of polymeric components, which not only provides injectability, but enables 3D encapsulation of cells. Mesenchymal stromal/stem cells can be encapsulated and cultured in the hydrogels at least for 2 weeks by traditional cell culture techniques, and retrieved by collagenase digestion with cell viability of approximately 80%. This hydrogel platform accelerates future cell‐related research activities.
High‐sensitivity detection and quantification of CHCl3 vapors in various gas environments based on the photoacoustic spectroscopy
Authors: Mohebbifar Mohammad Reza
Published: May 2019

In this study, the quality factor and cell constant vs acoustic resonator sizes in the first radial and longitudinal modes were calculated using our homemade simulation. Based on these simulations a photoacoustic (PA) spectroscopy system was designed, optimized, and finally fabricated as a high‐sensitivity gas sensor. The subsequent experiments have been done to online monitoring of the trichloromethane (CHCl3) vapors trace. The sensitivity of system for detection of CHCl3 vapors was measured 488 ppb. Corresponding PA signal for different concentrations of CHCl3 vapors is determined in the presence of N2, synthetic air, He, and Ar in various gas environments. It is shown that the effect of buffer gas and the relevant pressures are substantiated to achieve the minimum detectable concentration. In other words, using heavier gases at the same experimental conditions lead to detection of the lower concentrations. When the buffer gas of system was He, the lowest PA signal was recorded. This faint signal of He is due to vibrational‐translational processes of He, thermodynamic and acoustic properties of system such as cell constant, quality factor, speed of sound, thermal diffusion, thermal boundary layer, and viscous boundary layer for He. These properties for various buffer gases were calculated and discussed.
Parallel imaging and convolutional neural network combined fast MR image reconstruction: Applications in low‐latency accelerated real‐time imaging
Authors: Zhou Ziwu , Han Fei , Ghodrati Vahid , Gao Yu , Yin Wotao , Yang Yingli , Hu Peng
Published: May 2019

Purpose

To develop and evaluate a parallel imaging and convolutional neural network combined image reconstruction framework for low‐latency and high‐quality accelerated real‐time MR imaging.

Methods

Conventional Parallel Imaging reconstruction resolved as gradient descent steps was compacted as network layers and interleaved with convolutional layers in a general convolutional neural network. All parameters of the network were determined during the offline training process, and applied to unseen data once learned. The proposed network was first evaluated for real‐time cardiac imaging at 1.5 T and real‐time abdominal imaging at 0.35 T, using threefold to fivefold retrospective undersampling for cardiac imaging and threefold retrospective undersampling for abdominal imaging. Then, prospective undersampling with fourfold acceleration was performed on cardiac imaging to compare the proposed method with standard clinically available GRAPPA method and the state‐of‐the‐art L1‐ESPIRiT method.

Results

Both retrospective and prospective evaluations confirmed that the proposed network was able to images with a lower noise level and reduced aliasing artifacts in comparison with the single‐coil based and L1‐ESPIRiT reconstructions for cardiac imaging at 1.5 T, and the GRAPPA and L1‐ESPIRiT reconstructions for abdominal imaging at 0.35 T. Using the proposed method, each frame can be reconstructed in less than 100 ms, suggesting its clinical compatibility.

Conclusion

The proposed Parallel Imaging and convolutional neural network combined reconstruction framework is a promising technique that allows low‐latency and high‐quality real‐time MR imaging.
Acentriolar microtubule organization centers and Ran‐mediated microtubule formation pathways are both required in porcine oocytes
Authors: Kim Yong‐Han , Lee In‐Won , Jo Yu‐Jin , Kim Nam‐Hyung , Namgoong Suk
Published: May 2019

Mammalian oocytes lack centrioles but can generate bipolar spindles using several different mechanisms. For example, mouse oocytes have acentriolar microtubule organization centers (MTOCs) that contain many components of the centrosome, and which initiate microtubule polymerization. On the contrary, human oocytes lack MTOCs and the Ran‐mediated mechanisms may be responsible for spindle assembly. Complete knowledge of the different mechanisms of spindle assembly is lacking in various mammalian oocytes. In this study, we demonstrate that both MTOC‐ and Ran‐mediated microtubule nucleation are required for functional meiotic metaphase I spindle generation in porcine oocytes. Acentriolar MTOC components, including Cep192 and pericentrin, were absent in the germinal vesicle and germinal vesicle breakdown stages. However, they start to colocalize to the spindle microtubules, but are absent in the meiotic spindle poles. Knockdown of Cep192 or inhibition of Polo‐like kinase 1 activity impaired the recruitment of Cep192 and pericentrin to the spindles, impaired microtubule assembly, and decreased the polar body extrusion rate. When the RanGTP gradient was perturbed by the expression of dominant negative or constitutively active Ran mutants, severe defects in microtubule nucleation and cytokinesis were observed, and the localization of MTOC materials in the spindles was abolished. These results demonstrate that the stepwise involvement of MTOC‐ and Ran‐mediated microtubule assembly is crucial for the formation of meiotic spindles in porcine oocytes, indicating the diversity of spindle formation mechanisms among mammalian oocytes.
Development of an ICF‐based questionnaire for urinary and/or fecal incontinence (ICF‐IAF): The female patients’ perspective using focus groups (subproject)
Authors: Gass Stephanie , Kuhn Manuel , Koenig Irene , Radlinger Lorenz , Koehler Barbara
Published: May 2019

Aims

The aim of this study was to identify the problems and resources of women with urinary or fecal incontinence based on the International Classification of Function and Health (ICF) framework and detecting the impact on the personal environment and quality of life. This study forms part of a project with an overall goal to enable standardized planning and evaluation of interventions in multi‐professional settings.

Methods

To answer the study question a mixed‐method sequential design with a priority to the quantitative approach was considered appropriate. Regarding methods, focus groups were chosen to collect data. Transcripts were analyzed with content analysis and identified concepts linked to the corresponding ICF categories by two different raters. Cohen's kappa was calculated for interrater reliability.

Results

Thirteen women with a mean age of 69.9 years were recruited. Four focus groups were conducted, whereas saturation was reached after two focus groups. Overall transcripts 99 defined ICF categories at second level could be linked (body functions = 31, body structures = 5, activities and participation = 33, and environmental factors = 30) whereas 4 categories were not sufficiently covered by the ICF (3 = personal factors, 1 = not covered).

Conclusions

This study has determined 103 resources and problems based on the ICF model of women with urinary and/or fecal incontinence. In spite of these results, it was shown that four concepts are not fully covered by the ICF framework. The current data highlight the importance of an extension of the ICF model, especially towards the personal factors of patients.
Contradiction between amide‐CEST signal and pH in breast cancer explained with metabolic MRI
Authors: Krikken Erwin , van der Kemp Wybe J.M. , Khlebnikov Vitaliy , van Dalen Thijs , Los Maartje , van Laarhoven Hanneke W.M. , Luijten Peter R. , van den Bosch Maurice A.A.J. , Klomp Dennis W.J. , Wijnen Jannie P.
Published: May 2019

Purpose

Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH.

Methods

In this study we combined APT MRI and 31P‐MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty‐two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi).

Results

While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo.

Conclusions

As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.
Design of Energetic Materials Based on Asymmetric Oxadiazole
Authors: Jin Xinghui , Xiao Menghui , Zhou Jianhua , Zhou Guowei , Hu Bingcheng
Published: May 2019

A new family of asymmetric oxadiazole based energetic compounds were designed. Their electronic structures, heats of formation, detonation properties and stabilities were investigated by density functional theory. The results show that all the designed compounds have high positive heats of formation ranging from 115.4 to 2122.2 kJ mol−1. −N− bridge/−N3 groups played an important role in improving heats of formation while −O− bridge/−NF2 group made more contributions to the densities of the designed compounds. Detonation properties show that some compounds have equal or higher detonation velocities than RDX, while some other have higher detonation pressures than RDX. All the designed compounds have better impact sensitivities than those of RDX and HMX and meet the criterion of thermal stability. Finally, some of the compounds were screened as the candidates of high energy density compounds with superior detonation properties and stabilities to that of HMX and their electronic properties were investigated.
A case of a sublingual dermoid cyst in a 6‐year‐old child
Authors: Miyamoto Isao , Endo‐Sakamoto Yosuke , Yamano Yukio , Kasamatsu Atsushi , Uzawa Katsuhiro , Tanzawa Hideki
Published: May 2019

Dermoid cysts, which are lined by ectoderm elements, typically arise in skin, testicles, and ovaries. These cysts mostly occur during the second or third decade of life and rarely present in children. We describe a rare case of a dermoid cyst in a 6‐year‐old Japanese girl. Examination showed a smooth, well‐defined cystic swelling approximately 30 × 20 mm2 in the midline of the oral floor. The cyst was excised via the intraoral approach under general anesthesia. The histopathologic diagnosis of a dermoid cyst was made. The clinical outcome was satisfactory without postoperative complications during the 26‐month follow‐up period.
Evidence for BCR/ABL1‐positive T‐cell acute lymphoblastic leukemia arising in an early lymphoid progenitor cell
Authors: Ragg Susanne , Zehentner Barbara K. , Loken Michael R. , Croop James M.
Published: May 2019

BCR‐ABL1‐positive leukemias have historically been classified as either chronic myelogenous leukemia or Ph+ acute lymphoblastic leukemia. Recent analyses suggest there may be a wider range of subtypes. We report a patient with BCR‐ABL1 fusion positive T‐cell ALL with a previously undescribed cell distribution of the fusion gene. The examination of sorted cells by fluorescence in situ hybridization showed the BCR‐ABL1 fusion in the malignant T cells and a subpopulation of the nonmalignant B cells, but not nonmalignant T cells or myeloid or CD34+ progenitor cells providing evidence that the fusion may have occurred in an early lymphoid progenitor.
Robotic‐assisted laparoscopic management of renal tumors in children: Preliminary results
Authors: Blanc Thomas , Pio Luca , Clermidi Pauline , Muller Cecile , Orbach Daniel , Minard‐Colin Veronique , Harte Caroline , Meignan Pierre , Kohaut Jules , Heloury Yves , Sarnacki Sabine
Published: May 2019

Aim

We present the preliminary results of robotic‐assisted laparoscopic (RAL) total and partial nephrectomy for renal malignant tumors in children.

Methods

This is a prospective study of patients operated with RAL between December 2016 and September 2018. Patients with Wilms tumors were treated according to the SIOP‐2001 protocol. Patient and tumor characteristics, type of surgery, surgical‐related morbidity, and oncologic outcomes were recorded. Results were compared with a series of patients with similar age‐ and tumor‐related characteristics operated during the same period by an open surgical approach.

Results

Ten children underwent RAL nephrectomy with a mean age of five years (3.2–14.1 years). Total nephrectomy was done in six cases for Wilms tumor and in one case for renal sarcoma; three cases were converted. Complete removal of tumor without rupture was achieved in all cases. Postoperative course was uneventful, and patients were discharged between days 2 and 7. Neither recurrence nor medium‐term complications occurred. Nine patients are alive with a median follow‐up of 16 months (6–27 months) and one female died from complications of central nervous system metastases one year after surgery. When compared with the open surgical approach group, median tumor volume was smaller (P = 0.005), hospital stay was shorter (P = 0.01), and operative time was similar (P = 0.20).

Conclusions

RAL total and partial nephrectomy procedure for renal tumor in children may be an option in carefully selected cases. Indication should be discussed at tumor boards and surgery performed while adhering strictly to oncological surgical rules.
The sunken morphology of poly(lactic acid) stereocomplex spherulite
Authors: Liu Yanping , Zhang Mengnan , Wei Hanghang , Wang Zhen , Zeng Jun , Qian Li
Published: May 2019

The mechanical properties and microstructure of poly(lactic acid) (PLA) stereocomplex spherulite at the micrometric scale were investigated using nanoindentation and synchrotron radiation scanning X‐ray microdiffraction, which exhibits a new growth habit with more and more compact lamellae. Using atomic force microscopy and laser scanning confocal microscopy, a unique sunken morphology was found. Unbalanced surface stress and volume shrinkage are proposed as the main factors for the sunken morphology, which is also contributed by a novel growth regime driven by the hydrogen bonding between two PLA enantiomers. © 2019 Society of Chemical Industry
Cancer‐related cognitive impairment and associated factors in a sample of older male oral‐digestive cancer survivors
Authors: Regier Natalie G. , Naik Aanand D. , Mulligan Elizabeth A. , Nasreddine Ziad S. , Driver Jane A. , Sada Yvonne H.‐F. , Moye Jennifer
Published: May 2019

Objective

This study examines the demographic and clinical variables associated with cancer‐related cognitive impairment (CRCI) in a sample of older, male, oral‐digestive cancer survivors at VA Medical Centers in Boston and Houston.

Methods

A two‐time point, longitudinal design was used, with cognitive assessment conducted at 6 and 18 months post‐diagnosis. Using ANCOVA, the cognitive functioning of 88 older adults with head and neck, esophageal, gastric, or colorectal cancers was compared with that of 88 healthy controls. Paired t‐tests examined cognitive change over time in the cancer group. Hierarchical linear regression examined variables potentially associated with cognitive impairment at 18 months.

Results

Forty‐eight percent of cancer patients exhibited cognitive impairment 6 months post‐cancer diagnosis, and 40% at 18 months. Cancer survivors were impaired relative to controls on measures of sustained attention, memory, and verbal fluency at 18 months, controlling for age. Older age, low hemoglobin, and cancer‐related PTSD were associated with worse cognition at 18 months.

Conclusions

CRCI is more frequent in older adults than reported in studies of younger adults and may be more frequent in men. Potential areas of intervention for CRCI include psychotherapy for cancer‐related PTSD, treatment of anemia, and awareness of particularly vulnerable cognitive domains such as sustained attention, memory, and verbal fluency.
New Insights on the Compatibility of Nitrocellulose with Aniline‐Based Compounds
Authors: Trache Djalal , Tarchoun Ahmed Fouzi , Chelouche Salim , Khimeche Kamel
Published: May 2019

In this paper, the compatibility of nitrocellulose (NC) with some aniline‐based stabilizers was studied in order to detect any interaction between these materials. Both thermal techniques [differential scanning calorimetry (DSC) and vacuum stability test (VST)], and supplementary non‐thermal techniques [Fourier transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD) and densimetry] were used. The thermal and non‐thermal measurements showed that NC was highly compatible with N‐(2‐methoxyethyl)‐p‐nitroaniline (MENA) and diphenylamine (DPA), while a degree of incompatibility is indicated for N‐(2‐acetoxymethyl)‐p‐nitroaniline (ANA). The compatibility of the different mixtures was further probed by the kinetic investigation, and the activation energy and the pre‐exponential factors were computed. A detailed discussion and comparison of the compatibility results from all the methods are made.
Targeting prostate cancer cells with enzalutamide‐HDAC inhibitor hybrid drug 2‐75
Authors: Hu Wen‐Yang , Xu Liping , Chen Bailing , Ou Siyu , Muzzarelli Kendall M. , Hu Dan‐Ping , Li Ye , Yang Zhe , Vander Griend Donald J. , Prins Gail S. , Qin Zhihui
Published: May 2019

Background

The progression of castration‐resistant prostate cancer (CRPC) still relies on the function of androgen receptor (AR), achieved by evolving mechanisms to reactivate AR signaling under hormonal therapy. Histone deacetylase inhibitors (HDACis) disrupt cytoplasmic AR chaperone heat shock protein 90 (Hsp90) via HDAC6 inhibition, leading to AR degradation and growth suppression of prostate cancer (PCa) cells. However, current HDACis are not effective in clinical trials treating CRPC.

Methods

We designed hybrid molecules containing partial chemical scaffolds of AR antagonist enzalutamide (Enz) and HDACi suberoylanilide hydroxamic acid (SAHA) as new anti‐PCa agents. We previously demonstrated that Enz‐HDACi hybrid drug 2‐75 targets both AR and Hsp90, which inhibits the growth of Enz‐resistant C4‐2 cells. In the current study, we further investigate the molecular and cellular actions of 2‐75 and test its anti‐PCa effects in vivo.

Results

Compared with Enz, 2‐75 had greater AR antagonistic effects by decreasing the stability, transcriptional activity, and nuclear translocation of intracellular AR. In addition to inhibition of full‐length AR (FL AR), 2‐75 downregulated the AR‐V7 variant in multiple PCa cell lines. Mechanistic studies indicated that the AR affinity of 2‐75 retains the drug in the cytoplasm of AR + PCa cells and further directs 2‐75 to the AR‐associated protein complex, which permits localized effects on AR‐associated Hsp90. Further, unlike pan‐HDACi SAHA, the cytoplasm‐retaining property allows 2‐75 to significantly inhibit cytoplasmic HDAC6 with limited impact on nuclear HDACs. These selective cytoplasmic actions of 2‐75 overcome the unfavorable resistance and toxicity properties associated with classical AR antagonists, HDACis, and Hsp90 inhibitors. Finally, 2‐75 showed greater antitumor activities than Enz in vivo on SQ xenografts derived from LNCaP cells.

Conclusions

Novel therapeutic strategy using newly designed 2‐75 and related AR antagonist‐HDACi hybrid drugs has great potential for effective treatment of CRPC.
Prediction of quaternary structure by analysis of hot spot residues in protein‐protein interfaces: the case of anthranilate phosphoribosyltransferases
Authors: Schlee Sandra , Straub Kristina , Schwab Thomas , Kinateder Thomas , Merkl Rainer , Sterner Reinhard
Published: May 2019

It is an important goal of computational biology to correctly predict the association state of a protein based on its amino acid sequence and the structures of known homologues. We have pursued this goal on the example of anthranilate phosphoribosyltransferase (AnPRT), an enzyme that is involved in the biosynthesis of the amino acid tryptophan. Firstly, known crystal structures of naturally occurring homodimeric AnPRTs were analyzed using the Protein Interfaces, Surfaces, and Assemblies (PISA) service of the European Bioinformatics Institute (EBI). This led to the identification of two hydrophobic “hot spot” amino acids in the protein‐protein interface that were predicted to be essential for self‐association. Next, in a comprehensive multiple sequence alignment (MSA), naturally occurring AnPRT variants with hydrophilic or charged amino acids in place of hydrophobic residues in the two hot spot positions were identified. Representative variants were characterized in terms of thermal stability, enzymatic activity, and quaternary structure. We found that AnPRT variants with charged residues in both hot spot positions exist exclusively as monomers in solution. Variants with hydrophilic amino acids in one hot spot position occur in both forms, monomer and dimer. The results of the present study provide a detailed characterization of the determinants of the AnPRT monomer‐dimer equilibrium and show that analysis of hot spots in combination with MSAs can be a valuable tool in prediction of protein quaternary structures.
Leucine‐rich repeat kinase 2 (LRRK2) inhibitors differentially modulate glutamate release and Serine935 LRRK2 phosphorylation in striatal and cerebrocortical synaptosomes
Authors: Mercatelli Daniela , Bolognesi Paolo , Frassineti Martina , Pisanò Clarissa A. , Longo Francesco , Shimshek Derya R. , Morari Michele
Published: May 2019

Mutations in leucine‐rich repeat kinase 2 (LRRK2) gene have been pathogenically linked to Parkinson's disease, and pharmacological inhibition of LRRK2 is being pursued to tackle nigro‐striatal dopaminergic neurodegeneration. However, LRRK2 kinase inhibitors may have manifold actions, affecting not only pathological mechanisms in dopaminergic neurons but also physiological functions in nondopaminergic neurons. Therefore, we investigated whether LRRK2 kinase inhibitors differentially modulate dopamine and glutamate release from the mouse striatum and cerebral cortex. Spontaneous and KCl‐evoked [3H]‐dopamine and glutamate release from superfused synaptosomes obtained from wild‐type and LRRK2 knock‐out, kinase‐dead or G2019S knock‐in mice was measured. Two structurally unrelated inhibitors, LRRK2‐IN‐1 and GSK2578215A, were tested. LRRK2, phosphoSerine1292 and phosphoSerine935 LRRK2 levels were measured in all genotypes, and target engagement was evaluated by monitoring phosphoSerine935 LRRK2. LRRK2‐IN‐1 inhibited striatal glutamate but not dopamine release; GSK2578215A inhibited striatal dopamine and cortical glutamate but enhanced striatal glutamate release. LRRK2‐IN‐1 reduced striatal and cortical phosphoSerine935 levels whereas GSK2578215A inhibited only the former. Neither LRRK2 inhibitor affected neurotransmitter release in LRRK2 knock‐out and kinase‐dead mice; however, they facilitated dopamine without affecting striatal glutamate in G2019S knock‐in mice. GSK2578215A inhibited cortical glutamate release in G2019S knock‐in mice. We conclude that LRRK2‐IN‐1 and GSK2578215A modulate exocytosis by blocking LRRK2 kinase activity, although their effects vary depending on the nerve terminal examined. The G2019S mutation unravels a dopamine‐promoting action of LRRK2 inhibitors while blunting their effects on glutamate release, which highlights their positive potential for the treatment of PD, especially of LRRK2 mutation carriers.
Left‐behind villages, left‐behind children: Migration and the cognitive achievement of rural children in China
Authors: Xie Wubin , Sandberg John , Huang Cheng , Uretsky Elanah
Published: May 2019

Although the potential effects of migration on the cognitive development of children in origin communities reflect both household‐ and community‐level processes, few studies have examined how community‐level migration affects child cognitive development. By applying multilevel methods to nationally representative data of 2,248 children from 427 villages in China, we examine whether village migration intensity influences child cognitive ability and if so, what accounts for this influence. The findings suggest lower cognitive achievement in communities that experience high migration intensity. Living in a community with a large proportion of people who have migrated away from the community is associated with a 3.57‐unit decrease in verbal scores and a 1.54‐unit decrease in maths scores, which is equivalent to missing 1.67 and 0.87 years of schooling, respectively. A possible explanation for this effect is the change in demographic composition such that communities are depleted of better educated adults.
Estimations of Low Temperature Dislocation Mobility in GaN
Authors: Orlov Valeri I. , Vergeles Pavel S. , Yakimov Eugene B. , Li Xingji , Yang Jianqun , Lv Gang , Dong Shangli
Published: May 2019

The size of dislocation rosettes introduced by indentation in the temperature range from 300 to 773 K are studied. The dislocation velocity and its temperature dependence are estimated. It is shown that the activation energy of dislocation movement at temperatures lower than 773 K does not exceed 1 eV.
Composite antidisturbance control for nonlinear systems via nonlinear disturbance observer and dissipative control
Authors: Qi Shengbo , Wang Hong‐Du , Wu Huai‐Ning , Guo Lei
Published: May 2019

This paper investigates the design problem of composite antidisturbance control for a class of nonlinear systems with multiple disturbances. First, a novel nonlinear disturbance observer‐based control scheme is constructed to estimate and compensate the disturbance modeled by the nonlinear exosystem. Then, by combining the dissipative control theory, a linear matrix inequality‐based design method of composite antidisturbance control is developed such that the augmented system is exponentially stable in the absence of unmodeled disturbances, and is dissipative in the presence of unmodeled disturbances. In this case, the original closed‐loop system is exponentially stable in the presence of modeled disturbances. Subsequently, two special cases of composite antidisturbance control are derived with H∞ performance and passivity, respectively. Finally, the proposed method is applied to control A4D aircraft to show its effectiveness.
Multiple Pathways by Which Compounding Morphological Awareness Is Related to Reading Comprehension: Evidence From Chinese Second Graders
Authors: Kim Young‐Suk Grace , Guo Qian , Liu Yan , Peng Yan , Yang Li
Published: May 2019

Morphological awareness, or the knowledge and awareness of morphemes and morphological structures in a language, has been shown to be important to reading. The authors investigated multiple pathways by which compounding morphological awareness is related to reading comprehension: indirect pathways via vocabulary, word reading, and listening comprehension, as well as a direct relation. This question was addressed using data from 325 Chinese (Mandarin)‐speaking second graders. The authors tested alternative structural equation models that compared variations of direct and indirect relations. Results revealed that the two predictors according to the simple view of reading, word reading and listening comprehension, explained 80% of the variance in reading comprehension. Importantly, compounding morphological awareness was directly related to reading comprehension, as well as indirectly via vocabulary, word reading, and listening comprehension. Together, they explained 87% of the total variance in reading comprehension. Moreover, the total effect of compounding morphological awareness on reading comprehension, after accounting for the direct effect (0.18) and indirect effects (0.32) via multiple pathways, was substantial (0.49 standardized regression weight). These results add to growing evidence on the important role of morphological awareness in reading comprehension and highlight the multiple ways that morphological awareness makes a contribution to reading comprehension in Chinese.