bluuebunny/crossref_metadata_2025 huggingface dataset:
n‐6 and n‐3 Fatty acids and their metabolites augment inhibitory action of doxorubicin on the proliferation of human neuroblastoma (IMR‐32) cells by enhancing lipid peroxidation and suppressing Ras, Myc, and Fos
Authors: Hari Anasuya Devi , Naidu Vegi G. M. , Das Undurti N.
Published: August 2018

Polyunsaturated fatty acids (PUFAs) have growth inhibitory action on tumor cells possibly, by augmenting free‐radical generation and accumulation of lipid peroxides. This study focused on PUFAs and their metabolites role on IMR‐32 cell proliferation with and without doxorubicin to elucidate their mechanism of action by employing cell viability assay (MTT), gene expression, and biochemical studies. All the PUFAs tested inhibited proliferation of IMR‐32 cells in vitro on theirown and boosted the growth suppressive action of doxorubicin. Surprisingly indomethacin enhanced while NDGA inhibited growth of IMR‐32 cells. Proinflammatory and anti‐inflammatory PUFA metabolites inhibited growth of IMR‐32 cells and enhanced growth inhibitory action of doxorubicin. AA, EPA alone, and in combination with doxorubicin inhibited expression of genes: NF‐kB, IkB, BCL‐2, BAX, cytochrome C, caspase9,3, p53, 5‐LOX, and enhanced levels of GPX. AA and EPA enhanced buildup of lipid peroxides and suppressed expression of Ras, Myc, and Fos. Based on these studies, it is proposed that accumulation of lipid peroxides seems to be the principle mechanism by which AA, EPA, and other PUFAs bring about their growth inhibitory action on tumor cells. © 2018 BioFactors, 44(4):387–401, 2018
A correlation research of Ki67 index, CT features, and risk stratification in gastrointestinal stromal tumor
Authors: Li Huali , Ren Gang , Cai Rong , Chen Jian , Wu Xiangru , Zhao Jianxi
Published: August 2018

Background and Objectives

Recurrence and metastasis are the most important factors affecting the quality of life and survival rate of patients with gastrointestinal stromal tumors (GISTs). Accurate preoperative determination of the malignant degree of GISTs and the development of a reasonable treatment plan can effectively reduce the recurrence rate. CT is currently considered the preferred imaging modality for initial assessment. Until now, there have only been a few studies investigating the relationship between CT features and recurrence of GISTs. However, the value of CT features in prognostic assessment is still unclear. In this study, we attempted to investigate the prognostic significance of CT features and the Ki67 index in GISTs.

Methods

We retrospectively analyzed the clinicopathological and imaging data for 151 patients with a histopathological diagnosis of GIST who had received contrast‐enhanced CT examination and surgical resection at XinHua Hospital from October 2008 to December 2015 or Sir Run Run Shaw Hospital in 2017. Then, we explored the correlation among CT features, the Ki67 index, and risk stratification of GISTs. The correlation among CT features, the Ki67 index, and risk stratification was mainly analyzed using the Spearman rank correlation.

Results

The incidence of high‐risk disease or metastasis was clearly higher in the group with Ki67 > 5% than that in the group with Ki67 ≤ 5% (P < 0.001). The Ki67 index was positively correlated with risk stratification (r = 0.558) or mitotic index (r = 0.619). CT imaging features including size, contour, and margin of the tumor were associated with the Ki67 index (r = 0.332, 0.333, and 0.302, respectively). The multivariate logistic regression analysis revealed that the tumor size [P = 0.043 Exp (B) = 1.150] and the presence of ulceration [P = 0.011, Exp (B) = 3.669] were effective variables in distinguishing between the groups with Ki67 ≤ 5% and >5%. The presence of necrosis or cystic degeneration, tumor contour, tumor margin, and pattern of enhancement were associated with risk stratification (r = 0.530, 0.501, 0.419, and 0.447, respectively).

Conclusions

Our findings suggest that the Ki67 index is an effective complementation in predicting the prognosis of GISTs, and CT features including size, contour, and margin of the tumor, presence of necrosis or cystic degeneration, and pattern of enhancement provide evidence to support the importance of preoperative assessment.
Simultaneously Enhancing Stability and Activity of Maghemite via Site‐Specific Ti(IV) Doping for NO Emission Control
Authors: Chen Junxiao , Qu Weiye , Chen Yaxin , Liu Xiaona , Jiang Xiaoming , Wang Hu , Zong Yuhao , Ma Zhen , Tang Xingfu
Published: August 2018

Maghemite (γ‐Fe2O3) is an environmentally benign catalyst for selective catalytic reduction (SCR) of NO with NH3, but its poor stability and low activity hamper its application in real NO emission control. Herein, we developed a stable Ti4+ doped γ‐Fe2O3 catalyst (Ti‐γ‐Fe2O3) by site‐specific Ti4+ doping at the octahedral sites rather than tetrahedral active sites (Fe3+Td), as substantiated by synchrotron room‐temperature X‐ray diffraction (SXRD) data. In situ SXRD and thermogravimetric analysis (TG) data demonstrate that Ti4+ cations occupying part of the octahedral sites lead to enhanced thermal stability of Ti‐γ‐Fe2O3 with respect to γ‐Fe2O3, thus enabling Ti‐γ‐Fe2O3 to stably operate at 400 °C under simulated normal SCR conditions. Fe L3‐edge and O K‐edge X‐ray absorption spectra show that the high‐valence Ti4+ doping lengthens the Fe3+Td‐O bonds, and activates the lattice oxygen species, thus improving the SCR activity. This work provides a feasible strategy for designing environmentally benign Fe2O3‐based SCR catalysts with significant stability and high catalytic activity.
Chemical and Physical Analysis of Different Ash Fractions from Small Biomass Boilers
Authors: Kronenberger Daniel , Groß Bodo
Published: August 2018

Due to the growing number of small biomass boilers in residential buildings, the ash amounts from these plants are increasing. In order to find a beneficial use for these ashes, chemical and physical analyses were carried out on different ash fractions of different boilers. The results enable a comparison of the used boilers and fuels. As a result, it was shown that the chemical composition and physical properties strongly depend on the type of the ash, the fuel, and the boiler. The main focus of the investigations was on assessing whether the ashes were to be classified as fertilizer or waste. Accordingly, the results of the analyses were compared with the respective limit values for these cases. In addition, further possible applications were evaluated with regard to their suitability, and related current problems were identified.
Biomass and Lipid Productivity of Neochloris oleoabundans for CO2 Biofixation and Biodiesel Application
Authors: Razzak Shaikh Abdur
Published: August 2018

Microalgae cultivation and its use is a promising approach for integrated CO2 biofixation and biodiesel production. Freshwater Neochloris oleoabundans was investigated for lipid content, biomass productivity, and lipid productivity under different temperatures, CO2 concentrations, and nitrogen‐to‐phosphorus (N/P) ratios in culture media. A rapid calorimetric method based on sulfo‐phospho‐vanillin was used for the quantification of the intracellular lipid content. The growth of N. oleoabundans was found to be highly temperature‐sensitive. Lipid contents were found to be dependent on the CO2 concentration. Changing the N/P ratio also caused the biomass growth and lipid productivity to change. The results confirmed the potential of N. oleoabundans for CO2 biofixation and biodiesel production.
Methanol Synthesis from Steel Mill Exhaust Gases: Challenges for the Industrial Cu/ZnO/Al2O3 Catalyst
Authors: Schittkowski Julian , Ruland Holger , Laudenschleger Daniel , Girod Kai , Kähler Kevin , Kaluza Stefan , Muhler Martin , Schlögl Robert
Published: August 2018

One of the major goals of current research on energy conversion is the mitigation of CO2 emission. A beneficial scenario for CO2 utilization is the catalytic conversion of industrial waste or process gases into valuable products. Within the cross‐industry approach of Carbon2Chem® the synthesis of methanol from steel mill exhaust gases is a promising way to close the carbon cycle based on additional sustainably produced H2. New catalyst requirements have to be met due to fluctuating feed gas composition and availability as well as gas separation and purification issues.
A Glycal Approach to the Synthesis of Pregnane Glycoside P57
Authors: Liu Chao , Ma Yuyong , Pei Chengfeng , Li Wei , Yu Biao
Published: August 2018

Pregnane glycoside P57 is known as an active component of Hoodia gordonii, which has long been used as a diet with appetite suppressant property. Chemical synthesis of P57 demands installation of β‐cymarosyl linkage onto the steroid aglycone. The stereoselective formation of this special 2‐deoxy‐β‐glycosidic linkage has previously been proven to be difficult and thus a limiting step in the synthesis of P57 and its congeners. Herein, we report the glycosylation reactions with glycals as donors and TPHB (triphenylphosphine hydrobromide) as promoter and a convergent synthesis of P57 via a β‐selective glycosylation with a trisaccharide glycal donor.
Meltdown! Local Heating by Decaying Excited Host Positive Polarons Triggers Aggregation Quenching in Blue PhOLEDs
Authors: Setzer Tobias , Friederich Pascal , Meded Velimir , Wenzel Wolfgang , Lennartz Christian , Dreuw Andreas
Published: August 2018

Exciton‐polaron induced aggregation (EPIA) in organic host materials for blue Phosphorescent Organic Light Emitting Diodes (PhOLEDs) is driven by a non‐radiative decay of electronically excited positive polarons resulting in a local heating of the amourphous host matrix. The released heat triggers morphological changes, i. e. molecular aggregation between neighboring host molecules. The resulting aggregates, which our calculations identify as carbazolyl dimers, lead to decreased PhOLED efficiency. Statistical assessment of some host‐only morphologies reveals a structure‐dependent propensity for molecular aggregation corroborating the identified EPIA mechanism. Our findings provide a fresh look at established molecular design rules and will help to improve blue PhOLED host materials to enhance blue PhOLED device lifetimes.
Design, Synthesis and Photochemical Properties of a Phenalenone‐Based pH Sensor: Switchable pH Sensing in Four Detectable Channels
Authors: Mitra Amritaa , Bose Suranjana , Biswas Sachidulal , Bandyopadhyay Pinaki , Sarkar Arindam
Published: August 2018

The synthesis and pH‐sensing property of a novel phenalenone‐based compound, 9‐(4‐hydroxyphenylamino)‐1‐oxo‐phenalenone (HPAP), is reported. The newly synthesized compound is capable of functioning as a pH sensor in the region of pH 7 to 12. The sensor can be used as a colorimetric indicator in the transition from pH 10 to pH 11. The sensor is able to function in four detectable channels. All four channels (UV, emission, colorimetric/visible and photoluminescence) have been shown to be reversible, thus implying the reuse of this single‐molecule sensor and indicator for several experiments. Mechanistic investigations have been performed by UV, NMR and DFT studies which indicate that a photoinduced electron transfer (PET) based mechanism could be operative. Straightforward and cost‐effective application of the sensor in thin‐layer chromatography has also been established.
Pollinator activity and pollination success of Medicago sativa L. in a natural and a managed population
Authors: Chen Min , Zhao Xue‐Yong , Zuo Xiao‐An
Published: August 2018

Medicago sativa L. is an important cash crop in the arid region of northwest China. Pollinator activity is an essential aspect of pollination success, but the relationships between pollinator visitation rate and seed set still need further study of M. sativa. We investigated the following characteristics of M. sativa in natural and managed populations: floral traits, pollinator activity, and breeding system. Our results indicated the management could affect the number of flowers produced; however, there was no detectable effect on the seed set per flower. We found the percentage of seeds among pollinated flowers in the managed population was significantly higher than that in the natural population. Moreover, the increase in the proportion of pollinated flowers could significantly increase seed set per flower, and pollinator visitation rate was the important limiting factor for seed set in both populations. Andrena lebedevi Popov was found to be the most frequent pollinator in both populations. Outcrossing was dominant in the breeding system and insect pollination played an important role in outcrossing. Our study suggested that proper management (artificial selection) could promote pollination success of M. sativa.
Moose movement rates are altered by wolf presence in two ecosystems
Authors: Ditmer Mark A. , Fieberg John R. , Moen Ron A. , Windels Steve K. , Stapleton Seth P. , Harris Tara R.
Published: August 2018

Predators directly impact prey populations through lethal encounters, but understanding nonlethal, indirect effects is also critical because foraging animals often face trade‐offs between predator avoidance and energy intake. Quantifying these indirect effects can be difficult even when it is possible to monitor individuals that regularly interact. Our goal was to understand how movement and resource selection of a predator (wolves;Canis lupus) influence the movement behavior of a prey species (moose;Alces alces). We tested whether moose avoided areas with high predicted wolf resource use in two study areas with differing prey compositions, whether avoidance patterns varied seasonally, and whether daily activity budgets of moose and wolves aligned temporally. We deployed GPS collars on both species at two sites in northern Minnesota. We created seasonal resource selection functions (RSF) for wolves and modeled the relationship between moose first‐passage time (FPT), a method that discerns alterations in movement rates, and wolf RSF values. Larger FPT values suggest rest/foraging, whereas shorter FPT values indicate travel/fleeing. We found that the movements of moose and wolves peaked at similar times of day in both study areas. Moose FPTs were 45% lower in areas most selected for by wolves relative to those avoided. The relationship between wolf RSF and moose FPT was nonlinear and varied seasonally. Differences in FPT between low and high RSF values were greatest in winter (−82.1%) and spring (−57.6%) in northeastern Minnesota and similar for all seasons in the Voyageurs National Park ecosystem. In northeastern Minnesota, where moose comprise a larger percentage of wolf diet, the relationship between moose FPT and wolf RSF was more pronounced (ave. across seasons: −60.1%) than the Voyageurs National Park ecosystem (−30.4%). These findings highlight the role wolves can play in determining moose behavior, whereby moose spend less time in areas with higher predicted likelihood of wolf resource selection.
Alaskan brown bears (Ursus arctos) aggregate and display fidelity to foraging neighborhoods while preying on Pacific salmon along small streams
Authors: Wirsing Aaron J. , Quinn Thomas P. , Cunningham Curry J. , Adams Jennifer R. , Craig Apryle D. , Waits Lisette P.
Published: August 2018

The interaction between brown bears (Ursus arctos) and Pacific salmon (Oncorhynchus spp.) is important to the population dynamics of both species and a celebrated example of consumer‐mediated nutrient transport. Yet, much of the site‐specific information we have about the bears in this relationship comes from observations at a few highly visible but unrepresentative locations and a small number of radio‐telemetry studies. Consequently, our understanding of brown bear abundance and behavior at more cryptic locations where they commonly feed on salmon, including small spawning streams, remains limited. We employed a noninvasive genetic approach (barbed wire hair snares) over four summers (2012–2015) to document patterns of brown bear abundance and movement among six spawning streams for sockeye salmon, O. nerka, in southwestern Alaska. The streams were grouped into two trios on opposite sides of Lake Aleknagik. Thus, we predicted that most bears would forage within only one trio during the spawning season because of the energetic costs associated with swimming between them or traveling around the lake and show fidelity to particular trios across years because of the benefits of familiarity with local salmon dynamics and stream characteristics. Huggins closed‐capture models based on encounter histories from genotyped hair samples revealed that as many as 41 individuals visited single streams during the annual 6‐week sampling season. Bears also moved freely among trios of streams but rarely moved between these putative foraging neighborhoods, either during or between years. By implication, even small salmon spawning streams can serve as important resources for brown bears, and consistent use of stream neighborhoods by certain bears may play an important role in spatially structuring coastal bear populations. Our findings also underscore the efficacy of noninvasive hair snagging and genetic analysis for examining bear abundance and movements at relatively fine spatial and temporal scales.
Cattle select African savanna termite mound patches less when sharing habitat with wild herbivores
Authors: Odadi Wilfred O. , Charles Grace K. , Young Truman P.
Published: August 2018

African savanna termite mounds function as nutrient‐rich foraging hotspots for different herbivore species, but little is known about their effects on the interaction between domestic and wild herbivores. Understanding such effects is important for better management of these herbivore guilds in landscapes where they share habitats. Working in a central Kenyan savanna ecosystem, we compared selection of termite mound patches by cattle between areas cattle accessed exclusively and areas they shared with wild herbivores. Termite mound selection index was significantly lower in the shared areas than in areas cattle accessed exclusively. Furthermore, cattle used termite mounds in proportion to their availability when they were the only herbivores present, but used them less than their availability when they shared foraging areas with wild herbivores. These patterns were associated with reduced herbage cover on termite mounds in the shared foraging areas, partly indicating that cattle and wild herbivores compete for termite mound forage. However, reduced selection of termite mound patches was also reinforced by higher leafiness of Brachiaria lachnantha (the principal cattle diet forage species) off termite mounds in shared than in unshared areas. Taken together, these findings suggest that during wet periods, cattle can overcome competition for termite mounds by taking advantage of wildlife‐mediated increased forage leafiness in the matrix surrounding termite mounds. However, this advantage is likely to dissipate during dry periods when forage conditions deteriorate across the landscape and the importance of termite mounds as nutrient hotspots increases for both cattle and wild herbivores. Therefore, we suggest that those managing for both livestock production and wildlife conservation in such savanna landscapes should adopt grazing strategies that could lessen competition for forage on termite mounds, such as strategically decreasing stock numbers during dry periods.
Predicting the cover and richness of intertidal macroalgae in remote areas: a case study in the Antarctic Peninsula
Authors: Kotta Jonne , Valdivia Nelson , Kutser Tiit , Toming Kaire , Rätsep Merli , Orav‐Kotta Helen
Published: August 2018

Antarctica is an iconic region for scientific explorations as it is remote and a critical component of the global climate system. Recent climate change causes a dramatic retreat of ice in Antarctica with associated impacts to its coastal ecosystem. These anthropogenic impacts have a potential to increase habitat availability for Antarctic intertidal assemblages. Assessing the extent and ecological consequences of these changes requires us to develop accurate biotic baselines and quantitative predictive tools. In this study, we demonstrated that satellite‐based remote sensing, when used jointly with in situ ground‐truthing and machine learning algorithms, provides a powerful tool to predict the cover and richness of intertidal macroalgae. The salient finding was that the Sentinel‐based remote sensing described a significant proportion of variability in the cover and richness of Antarctic macroalgae. The highest performing models were for macroalgal richness and the cover of green algae as opposed to the model of brown and red algal cover. When expanding the geographical range of the ground‐truthing, even involving only a few sample points, it becomes possible to potentially map other Antarctic intertidal macroalgal habitats and monitor their dynamics. This is a significant milestone as logistical constraints are an integral part of the Antarctic expeditions. The method has also a potential in other remote coastal areas where extensive in situ mapping is not feasible.
No trade‐offs in interspecific interference ability and predation susceptibility in newt larvae
Authors: Hloušková Monika , Balogová Monika , Kršáková Veronika , Gvoždík Lumír
Published: August 2018

Coexistence of species with similar requirements is allowed, among others, through trade‐offs between competitive ability and other ecological traits. Although interspecific competition is based on two mechanisms, exploitation of resources and physical interference, trade‐off studies largely consider only species’ ability to exploit resources. Using a mesocosm experiment, we examined the trade‐off between interference competition ability and susceptibility to predation in larvae of two newt species, Ichthyosaura alpestris and Lissotriton vulgaris. In the presence of heterospecifics, L. vulgaris larvae slowed somatic growth and developmental rates, and experienced a higher frequency of injuries than in conspecific environments which suggests asymmetrical interspecific interference. During short‐term predation trials, L. vulgaris larvae suffered higher mortality than I. alpestris. Larvae of the smaller species, L. vulgaris, had both lower interference and antipredator performance than the larger I. alpestris, which suggests a lack of trade‐off between interference competition ability and predator susceptibility. We conclude that interference competition may produce a positive rather than negative relationship with predation susceptibility, which may contribute to the elimination of subordinate species from common habitats.
Legacy polychlorinated biphenyl contamination impairs male embryonic development in an elasmobranch with matrotrophic histotrophy, the round stingray (Urobatis halleri)
Authors: Lyons Kady , Wynne-Edwards Katherine E.
Published: August 2018

Anthropogenic chemical exposure can result in overall reductions in reproductive success. Using the round stingray (Urobatis halleri) as an elasmobranch model with internal gestation, we measured female fecundity and embryo growth from postovulation to near parturition to test the hypothesis that environmental polychlorinated biphenyl (PCB) contamination would impair reproductive success. Two sites were sampled from southern California, USA: the mainland site was exposed to legacy PCB contamination (with low exposure to other anthropogenic contaminants), and the offshore reference site at Catalina Island was a separate population with low anthropogenic influence. Contaminant-exposed embryos weighed less at each stage of development than reference embryos, while accumulating proportionately more liver mass over development. Furthermore, environmental contamination negatively affected male embryos more than female embryos. The present study is the first study to demonstrate a negative effect of contaminant exposure on elasmobranch embryo growth, with probable fitness costs later in life. Environ Toxicol Chem 2018;37:2904–2911. © 2018 SETAC
Encapsulation of Biosynthesized Nanosilver in Silica Composites for Sustainable Antimicrobial Functionality
Authors: Abou‐El‐Sherbini Khaled S. , Amer Mohey H. A. , Abdel‐Aziz Mohamed S. , Hamzawy Esmat M. A. , Sharmoukh Walid , Elnagar Mohamed M.
Published: August 2018

Silver nanoparticles (AgNPs) have become known as a broad‐spectrum antimicrobial agent. The antimicrobial activity of AgNPs is dependent on the particle size and the dispersion status. In this study, a simple and effective approach is developed for sequestering the biosynthesized AgNPs in silica composites during the gel formation of MCM‐41. Composites with different Ag concentrations of 0.034% (Ag1@MCM‐41), 0.151% (Ag2@MCM‐41), and 0.369% (Ag3@MCM‐41) are synthesized and then heated at 400 °C to produce Ag1@MCM‐41H, Ag2@MCM‐41H, and Ag3@MCM‐41H, respectively. The samples are characterized by flame atomic absorption spectrometry, Fourier‐transform infrared spectroscopy, X‐ray diffraction, N2 physisorption, scanning electron microscopy, transmission electron microscopy, and thermogravimetric analysis. The AgNPs are confirmed to be highly dispersed in the amorphous silica framework. The antimicrobial activity of the AgNP–silica samples is investigated against Staphylococcus aureus, Escherichia coli, and Candida albicans using the cup–plate and the plate‐count techniques. The results show an excellent antimicrobial effect of these samples against the studied microorganisms. Importantly, the AgNP–silica samples are found to be stable up to 58 months under ambient conditions. These stable and powerful antimicrobial composites provide a more practical and effective strategy for combating biomedical pathogens and public health threats.
Relationship Among Fatty Liver, Specific and Multiple‐Site Atherosclerosis, and 10‐Year Framingham Score
Authors: Pais Raluca , Redheuil Alban , Cluzel Philippe , Ratziu Vlad , Giral Philippe
Published: August 2018

Despite a well‐documented increase in the prevalence of subclinical atherosclerosis in patients with steatosis, the relationship among steatosis and atherosclerosis, specific atherosclerotic sites, multiple‐site atherosclerosis, and cardiovascular risk prediction is incompletely understood. We studied the relationship among steatosis, atherosclerosis site, multiple‐site atherosclerosis, coronary artery calcification (CAC), and 10‐year Framingham Risk Score (FRS) in 2,554 patients with one or more cardiovascular risk factors (CVRF), free of cardiovascular events and other chronic liver diseases, and drinking less than 50 g alcohol/day. All patients underwent arterial ultrasound (carotid [CP] and femoral [FP] plaques defined as intima‐media thickness (IMT) > 1.5 mm), coronary computed tomography scan (severe CAC if ≥ 100), 10‐year FRS calculation, and steatosis detection by the fatty liver index (FLI, present if score ≥ 60). Patients with steatosis (36% of total) had higher prevalence of CP (50% versus 45%, P = 0.004) and higher CAC (181 ± 423 versus 114 ± 284, P < 0.001) but similar prevalence of FP (53% versus 50%, P = 0.099) than patients without steatosis. Steatosis was associated with carotid IMT and CAC, but not with FP, independent of age, diabetes, hypertension, and tobacco use (P < 0.001). Fifty‐three percent of patients had at least 2‐site atherosclerosis and steatosis was associated with at least 2‐site atherosclerosis independent of age and CVRF (odds ratio = 1.21, 95% confidence interval 1.01‐1.45, P = 0.035). Sixty‐four percent of patients with steatosis had a FRS score of 10% or more. FLI was associated with FRS beyond the CVRF or the number of atherosclerosis sites (P < 0.001). Adding FLI to CVRF predicted an FRS greater than or equal to 10% better than CVRF alone (area under the receiver operating characteristic curve = 0.848 versus 0.768, P < 0.001). Conclusion: Steatosis is associated with carotid and coronary, but not femoral atherosclerosis, and with cardiovascular mortality risk. The multiple‐site involvement and quantitative tonic relationship could reinforce the prediction of cardiovascular mortality or events over classical CVRF or imaging‐based detection of atherosclerosis.
The NACSTOP Trial: A Multicenter, Cluster‐Controlled Trial of Early Cessation of Acetylcysteine in Acetaminophen Overdose
Authors: Wong Anselm , McNulty Richard , Taylor David , Sivilotti Marco , Greene Shaun , Gunja Naren , Koutsogiannis Zeff , Graudins Andis
Published: August 2018

Historically, intravenous acetylcysteine has been delivered at a fixed dose and duration of 300 mg/kg over 20 to 21 hours to nearly every patient deemed to be at any risk for hepatotoxicity following acetaminophen overdose. We investigated a 12‐hour treatment regimen for selected low‐risk patients. This was a multicenter, open‐label, cluster‐controlled trial at six metropolitan emergency departments. We enrolled subjects following single or staggered acetaminophen overdose with normal serum alanine transaminase (ALT) and creatinine on presentation and at 12 hours, and less than 20 mg/L acetaminophen at 12 hours. Patients were allocated to intervention (250 mg/kg over 12‐hour) or control (300 mg/kg over 20‐hour) regimens by site. The primary outcome was incidence of “hepatic injury” 20 hours following initiation of acetylcysteine treatment, defined as ALT doubling and peak ALT greater than 100 IU/L, indicating the need for further antidotal treatment. Secondary outcomes included incidence of hepatotoxicity (ALT > 1,000 IU/L), peak international normalized ratio (INR), and adverse drug reactions. Of the 449 acetaminophen overdoses receiving acetylcysteine, 100 were recruited to the study. Time to acetylcysteine (median 7 hours [interquartile ratio 6,12] versus 7 hours [6,10]) and initial acetaminophen (124 mg/L [58,171] versus 146 mg/L [66,204]) were similar between intervention and control groups. There was no difference in ALT (18 IU/L [13,22] versus 16 IU/L [13,21]) or INR (1.2 versus 1.2) 20 hours after starting acetylcysteine between groups. No patients developed hepatic injury or hepatotoxicity in either group (odds ratio 1.0 [95% confidence interval 0.02, 50]). No patients represented with liver injury, none died, and 96 of 96 were well at 14‐day telephone follow‐up. Conclusion: Discontinuing acetylcysteine based on laboratory testing after 12 hours of treatment is feasible and likely safe in selected patients at very low risk of liver injury from acetaminophen overdose.
Interference with the androgen receptor protein stability in therapy‐resistant prostate cancer
Authors: Lakshmana Gopinath , Baniahmad Aria
Published: August 2018

The androgen receptor (AR) plays a central role in the pathogenesis of prostate cancer (PCa). Most PCa cases develop eventually from an androgen‐dependent stage to castration‐resistant prostate cancer (CRPC) with AR‐signaling still being active. Thus, inhibition of AR remains a well‐established promising drug target in CRPC. However, despite the improvements of current treatment for CRPC by targeting the AR, the evolution of adaptive AR‐signaling leads to therapy‐resistant CRPC. Treatment failure is based mostly on the inability to keep AR under long‐term restraint due to adaptive responses of AR‐signaling. One underlying mechanism appears to be the increased AR protein stability. Therefore, the regulation of AR protein stability and its degradation is another interesting path that could enhance our knowledge of carcinogenesis and tumor evolution possibly leading to novel therapeutic targets. In this review, we discuss various molecular mechanisms and factors that stabilize AR protein levels directly or indirectly. We summarize novel approaches to interfere with AR stability including targeting the glucocorticoid receptor (GR), heat shock proteins, and co‐chaperones as well as E3‐ligases using small chimeric molecules. These novel approaches in combination with antiandrogen treatment inhibit PCa growth through the regulation of AR protein levels.
Retracted: MicroRNA‐150‐5p affects cell proliferation, apoptosis, and EMT by regulation of the BRAFV600E mutation in papillary thyroid cancer cells
Authors: Yan Ruihong , Yang Tianzheng , Zhai Hongyan , Zhou Zhenhu , Gao Lei , Li Yuhong
Published: August 2018

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Studies have confirmed an association between microRNA (miRNA) and the BRAFV600E mutation in various cellular biological processes of PTC. This study aimed to clarify the potential relationship between miR‐150‐5p and the BRAFV600E mutation in PTC. Human PTC cell lines B‐CPAP and TPC‐1 were transfected with the miR‐150‐5p mimic, an inhibitor, and the corresponding controls. Then, cell proliferation, viability, and apoptosis were detected by bromodeoxyuridine, trypan blue exclusion, and flow cytometry assays. The expressions of the main factors of cell cycle, epithelial mesenchymal transition (EMT), and DNA mismatch repair were examined by Western blot analysis and a real‐time quantitative polymerase chain reaction. Additionally, pc‐BRAFV600E was transfected into B‐CPAP and TPC‐1 cells to determine the relationship between miR‐150‐5p and BRAFV600E. In addition, the methyl ethyl ketone (MEK)/extracellular signal‐regulated kinase (ERK) signal pathway was examined using Western blot analysis. Overexpression of miR‐150‐5p promoted cell proliferation and viability, inhibited apoptosis, and upregulated cell cycle factor expressions at 50 passages of B‐CPAP and TPC‐1 cells after transfection. Overexpression of miR‐150‐5p led to an obvious decrease in E‐cadherin expression, but enhanced N‐cadherin, Slug and Vimentin, ZEB1, and Snail expression. Moreover, overexpression of miR‐150‐5p markedly suppressed POLD3, MSH2, and MSH3 expression. Furthermore, BRAFV600E overexpression increased the expression level of miR‐150‐5p in TPC cells, and overexpression of telomerase reverse transcriptase further enhanced the promoting effect of BRAFV600E on miR‐150‐5p expression in B‐CPAP and TPC‐1 cells. Finally, BRAFV600E overexpression activated the MEK/ERK signal pathway in B‐CPAP and TPC‐1 cells. These data indicated that miR‐150‐5p promoted cell proliferation, suppressed apoptosis, and accelerated the EMT process by regulation of the BRAFV600E mutation. Our findings will help elucidate the pathogenesis of PTC and identify biomarkers.
microRNA‐146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical periodontitis
Authors: Lina Shao , Lihong Qiu , Di Yang , Bo Yu , Xiaolin Li , Jing Mi
Published: August 2018

Chronic apical periodontitis (CAP) is defined as chronic inflammation of the dental pulp and root canal system. Porphyromonas endodontalis lipopolysaccharide (
P. endodontalis LPS) plays an important role in inducing an inflammatory response in CAP. microRNA‐146a (miR‐146a) is a key regulator of inflammation and is induced by LPS. Hairy and enhancer‐of‐split related with YRPW motif 2 (Hey2) has been confirmed to be induced by the Notch signaling pathway, which is involved in tooth development, pulp regeneration, and repair after injury. Our study aimed to investigate the functional role of miR‐146a via the targeting of Hey2 in CAP as well as the underlying mechanism. Compared with 13 healthy controls, miR‐146a and Hey2 expressions were significantly higher in 20 patients with CAP. In addition, miR‐146a, Hey2, interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α expressions were significantly increased in MC3T3‐E1 cells stimulated with different concentrations (0‐20 μg/mL) of P. endodontalis LPS for different amounts of time (0‐48 hours). Moreover, miR‐146a, which acts as an anti‐inflammatory mediator, negatively regulated the expression of IL‐6, IL‐1β, and TNF‐α, and Hey2 was confirmed as a target gene of miR‐146a by a luciferase reporter assay. Hey2 also negatively regulated miR‐146a, IL‐6, IL‐1β, and TNF‐α expressions, and P. endodontalis LPS strongly induced Hey2 recruitment to the IL‐6 promoter (−400 ~ −200 bp). These findings suggest that miR‐146a and Hey2 form a mutual negative feedback regulatory loop, demonstrating a novel mechanism that regulates inflammatory responses in CAP.
Improving ruminal digestibility of various wheat straw types by white‐rot fungi
Authors: Nayan Nazri , van Erven Gijs , Kabel Mirjam A , Sonnenberg Anton SM , Hendriks Wouter H , Cone John W
Published: August 2018

BACKGROUND

This study investigated the ruminal degradability of various wheat straw types by the white‐rot fungi Ceriporiopsis subvermispora (CS) and Lentinula edodes (LE). Different cultivars (CV) of wheat straw at different maturity stages (MS) were treated with the fungi for 7 weeks and assessed for chemical composition and in vitro gas production (IVGP).

RESULTS

Both fungi showed a more pronounced degradation of lignin on a more mature straw (MS3; 89.0%) in comparison with the straw harvested at an earlier stage (MS1; 70.7%). Quantitative pyrolysis coupled to gas chromatography and mass spectrometry, using 13C lignin as an internal standard 13C‐IS Py‐GC/MS revealed that lignin in more mature straw was degraded and modified to a greater extent. In contrast, cellulose was less degraded in MS3, as compared to MS1 (8.3% versus 14.6%). There was no effect of different MS on the IVGP of the fungus‐treated straws. Among the different straw cultivars, the extent of lignin degradation varied greatly (47% to 93.5%). This may explain the significant (P < 0.001) effect of cultivar on the IVGP of the fungal‐treated straws. Regardless of the factors tested, both fungi were very capable of improving the IVGP of all straw types by 15.3% to 47.6%, (as compared to untreated straw), with CS performing better than LE – on different MS (33.6% versus 20.4%) and CVs (43.2% versus 29.1%).

CONCLUSION

The extent of lignin degradation caused by fungal treatment was more pronounced on the more mature and lignified straw, while variable results were obtained with different cultivars. Both fungi were capable of improving the IVGP of various straw types. © 2018 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Fluorescence‐guided surgery for high‐grade gliomas
Authors: Lakomkin Nikita , Hadjipanayis Constantinos G.
Published: August 2018

5‐aminolevulinic acid (5‐ALA) is a prodrug that results in the fluorescence of high‐grade gliomas relative to the surrounding brain parenchyma. 5‐ALA has been increasingly utilized in fluorescence‐guided surgery for these tumors, and its intraoperative use has been associated with a significantly improved extent of resection and progression‐free survival. This review outlines the growing body of evidence that has culminated in the recent Food and Drug Administration approval of 5‐ALA, as well as emerging applications for this agent.
Dispersive liquid–liquid microextraction combined with dispersive solid‐phase extraction for gas chromatography with mass spectrometry determination of polycyclic aromatic hydrocarbons in aqueous matrices
Authors: Mohd Hassan Farah Wahidah , Muggundha Raoov  , Kamaruzaman Sazlinda , Sanagi Mohd Marsin , Yoshida Nao , Hirota Yuichiro , Nishiyama Norikazu , Yahaya Noorfatimah
Published: August 2018

This study describes a dispersive liquid–liquid microextraction combined with dispersive solid‐phase extraction method based on phenyl‐functionalized magnetic sorbent for the preconcentration of polycyclic aromatic hydrocarbons from environmental water, sugarcane juice, and tea samples prior to gas chromatography with mass spectrometry analysis. Several important parameters affecting the extraction efficiency were investigated thoroughly, including the mass of sorbent, type and volume of extraction solvent, extraction time, type of desorption solvent, desorption time, type and amount of salt‐induced demulsifier, and sample volume. Under the optimized extraction and gas chromatography‐mass spectrometric conditions, the method revealed good linearity (10–100000 ng/L) with coefficient of determination (R2) of ≥0.9951, low limits of detection (3–16 ng/L), high enrichment factors (61–239), and satisfactory analyte recoveries (86.3–109.1%) with the relative standard deviations < 10% (n = 5). The entire sample preparation procedure was simple, rapid and can be accomplished within 10 min. This method was applied (after pretreatment) to 30 selected samples, and the presence of studied analytes was quantified in 17 samples.
Reversible Electrochemical Intercalation and Deintercalation of Fluoride Ions into Host Lattices with Schafarzikite‐Type Structure
Authors: Nowroozi Mohammad Ali , de Laune Benjamin , Clemens Oliver
Published: August 2018

Herein, we report the successful electrochemical fluorination and defluorination of schafarzikite‐type compounds with the composition Fe0.5M0.5Sb2O4 (M=Mg or Co). We show that electrochemical methods can present a more controllable and less environmentally damaging route for fluorinating compounds in contrast to traditional methods that involve heating samples in F2‐rich atmospheres. The reactivity of the host lattices with fluoride during electrochemical fluorination makes this material an interesting candidate for fluoride‐ion battery applications. However, deleterious side reactions with the conductive carbon matrix during fluorination suggests to the contrary. Regardless of the side reactions, the schafarzikite structure was found to be an alternative reversible host lattice for fluoride incorporation and removal in addition to the previously reported Ruddlesden–Popper‐type compounds.
Specific Residue Interactions Regulate the Binding of Dengue Antigens to Broadly Neutralizing EDE Antibodies
Authors: Lapelosa Mauro , Burrone Oscar , Rocchia Walter
Published: August 2018

Antibodies binding to antigens present on the dengue virus (DENV) represent the main defense mechanism of the host organism against the pathogen. Among the antibodies elicited by DENV and that bind to DII of protein E, EDE1‐C8 can bind all DENV serotypes. Our analysis reveals the key residues in this interaction as well as structurally conserved hydrogen bonds located at the binding interface. They stabilize the dengue antigen–antibody complex among the EDE1 group of antibodies (Abs). Combining structural alignments with molecular dynamics simulations in the EDE1 Abs, we identified the critical elements that provide a major energetic contribution to the association of antigens from protein E with Abs. We discuss possible molecular insights into the binding mechanism by using a surrogate molecular entity resembling the protein E that forms native salt bridges and hydrogen bonds, including inferences on the light of high‐resolution crystal structures of dengue Fab complexes. Finally, the molecular determinants, the free energy profile, and the binding mechanism provide inspiration for potential strategies in protein engineering to design novel immunogens of protein E against DENV.
Modeling and experimental investigation of a Wurster type fluidized bed reactor coupled with an air atmospheric pressure plasma jet for the surface treatment of polypropylene particles
Authors: Tabibian Seyedshayan , Arefi‐Khonsari Farzaneh , Anagri Abdessadk , Leturia Mikel , Moussalem Antoine , Moscosa Santillan Mario , Saleh Khashayar , Touari Yasmine , Pulpytel Jerome
Published: August 2018

Polypropylene (PP) particles are used for various purposes, however, the good mechanical properties of PP are counterbalanced by a poor wettability. The wettability of PP particles was therefore improved by an atmospheric pressure blown‐arc air plasma jet treatment in a new designed homemade Wurster fluidized bed reactor (Wurster‐FBR). This reactor, was used to treat 200 g of particles per batch. The surface free energy of PP particles determined by the Zisman method showed an increase from 30.7 to 38.6 mN m−1 after 120 s of treatment. XPS results showed a 5% increase of the atomic concentration of oxygen on the surface of the treated particles. In order to describe the process, a 2D axisymmetric non‐isothermal k‐ϵ turbulent model was used to determine the velocity field, pressure, and temperature profile of the gas phase inside the reactor. Furthermore an Eulerian‐Eulerian multiphasic CFD model was added to determine the dynamics of the particles inside the reactor, and the results were compared with fast imaging, thermocouple, and anemometry measurements. These investigations are very important to monitor the homogeneity of the particle treatments, to determine the average effective treatment time for each particle and to avoid overheating of thermally sensitive PP.
Pulmonary hemorrhage in infancy: A 10‐year single‐center experience
Authors: Welsh Sebastian K. , Casey Alicia M. , Fishman Martha P.
Published: August 2018

Aim

Pulmonary hemorrhage in infancy is rare, with challenges in determining its incidence, causes, and outcomes across diverse groups. Our aim was to better understand the incidence and identified causes. We further analyzed the subgroup of patients meeting criteria for acute idiopathic pulmonary hemorrhage of infancy (AIPHI) to determine recurrence, mortality, and treatment.

Methods

We performed a 10‐year retrospective cohort study of infants with pulmonary hemorrhage in a large tertiary care center. One‐hundred fifty‐seven patients overall were identified.

Results

The most common diagnoses in infants with pulmonary hemorrhage were congenital heart disease (36.6%), prematurity/premature lung disease (34.6%), congenital or acquired lung disorders (15.0%), and congenital or acquired coagulopathies (13.7%). Nonaccidental trauma (NAT; n = 3) was also an important cause of pulmonary hemorrhage. All patients diagnosed with NAT had normal retinal examinations and skeletal surveys. Only four patients were identified with AIPHI. There was no mortality in this group of infants. One of four patients with AIPHI had a recurrence. Steroids were the consistent treatment for AIPHI, with a large range of treatment duration.

Conclusion

Diagnostic studies should focus on identifying non‐pulmonary sources of bleeding, infection, underlying lung disease, congenital heart defects, coagulopathies, infection, and NAT, as these were the most frequently identified causes of bleeding. NAT is not adequately identified with ophthalmology exam and skeletal survey. Overall, we found AIPHI to be a rare diagnosis. All of the patients with idiopathic hemorrhage received systemic steroids with varying doses and lengths of treatment.
Highlights of the Clinical Pharmacy Congress 2018
Authors: David Felix
Published: August 2018

Optimising COPD management, tackling hypoglycaemia in diabetes and NHS England's Medicines Value Programme were among the topics discussed at Clinical Pharmacy Congress 2018 held in London in April. This article provides an overview of some of the presentations.
Can LDL cholesterol ever be lowered too much?
Authors: Laight David
Published: August 2018

Current guidelines recommend reducing LDL cholesterol by specified amounts; however, a new treatment ‘lower is better’ paradigm advocates more dramatic LDL cholesterol reduction beyond current targets to maximise global cardiovascular risk benefits. This article examines the benefits and drawbacks of this approach.
The microbiome: a gut feeling about drug metabolism
Authors: Greener Mark
Published: August 2018

The human gut microbiome has a crucial role in both health and disease, including drug metabolism. Recent research indicates that boosting the microbiome (for example, by using pro or prebiotics) is a promising therapeutic strategy that could enhance the efficacy and reduce the toxicity of many medicines.
Efficient Photoelectrocatalytic Activity of CuWO4 Nanoplates towards the Oxidation of NADH Driven in Visible Light
Authors: Mohanty Bishnupad , Naik Kusha Kumar , Sahoo Satyapriya , Jena Bijayalaxmi , Chakraborty Brahmananda , Rout Chandra Sekhar , Jena Bikash Kumar
Published: August 2018

Herein, we report the visible light driven photo‐electrocatalytic activity of CuWO4 towards the oxidation of NADH. The CuWO4 possesses high sensitivity towards NADH oxidation with the sensing response in a linear dynamic range of 10–50 μM. The sensitivity and low detection limit (LOD) was estimated to be 0.14 μA/μM and 100 nM (S/N ≥ 3) respectively. The photo‐generated hole expedites the oxidation processing by accepting the electrons from NADH that reduces the overpotential and increases the current response and validated by the Density Functional Theory (DFT) simulations study.