bluuebunny/crossref_metadata_2025 huggingface dataset:
The Multiple Sclerosis Self-Management Scale–Revised (MSSM-R)
Authors: Saadat Sajjad , Kajbaf Mohammad Bagher , Kalantari Mehrdad , Hosseininezhad Mozaffar
Published: April 2019

Background:

Self-management is the most important component in the treatment of chronic diseases, including multiple sclerosis (MS). The Bishop and Frain Multiple Sclerosis Self-Management Scale–Revised (MSSM-R) is one of the valid tools available for self-management assessment. The purpose of this study was to evaluate the psychometric properties of the MSSM-R in Iranian people with MS.

Methods:

This cross-sectional study was conducted in 2018 in the 1600 people with MS in Guilan Province, Iran. In this study, 250 people were selected by convenience sampling. The reliability of the Persian version of this scale was examined by internal consistency and test-retest methods, and validity evidence was evaluated using confirmatory factor analysis.

Results:

The MSSM-R had acceptable face and content validity. Confirmatory factor analysis results showed that 24 items on this scale have factor loadings in five subscales. Other results showed the internal consistency, as measured by Cronbach α and test-retest reliability, for the MSSM-R overall (α = 0.85, r = 0.77) and for the following subscales: Healthcare Provider Relationship and Communication (α = 0.83, r = 0.70), Treatment Adherence/Barriers (α = 0.70, r = 0.71), Social/Family Support (α = 0.79, r = 0.85), MS Knowledge and Information (α = 0.89, r = 0.72), and Health Maintenance Behavior (α = 0.77, r = 0.75).

Conclusions:

This study provides evidence of the validity and reliability of the MSSM-R. To further ensure its psychometric properties, additional studies with this scale are suggested.
A Data-driven Approach for Estimating the Fundamental Diagram
Authors: Bhouri Neila , Aron Maurice , Hajsalem Habib
Published: April 2019

The fundamental diagram links average speed to density or traffic flow. An analytic form of this diagram, with its comprehensive and predictive power, is required in a number of problems. This paper argues, however, that, in some assessment studies, such a form is an unnecessary constraint resulting in a loss of accuracy. A non-analytical fundamental diagram which best fits the empirical data and respects the relationships between traffic variables is developed in this paper. In order to obtain an unbiased fundamental diagram, separating congested and non-congested observations is necessary. When defining congestion in parallel with a safety constraint, the density separating congestion and non-congestion appears as a decreasing function of the flow and not as a single critical density value. This function is here identified and used. Two calibration techniques – a shortest path algorithm and a quadratic optimization with linear constraints – are presented, tested, compared and validated.
Impact of Road Transport Means on Climate Change and Human Health in Poland
Authors: Burchart-Korol Dorota , Folęga Piotr
Published: April 2019

Operation of means of transport is one of major sources of environmental impact. The goal of this article was to analyse the greenhouse gas emissions and to assess the impact of operation of means of road transport in Poland on human health using the life cycle assessment technique based on an analysis of emission of dust and gas pollutants. Road transport was assessed by taking the following means of transport into account: passenger cars, other cars with weight of up to 3,500 kg, lorries, buses, motorcycles, mopeds and tractors. The analysis covered various dust and gas pollutants, including the emission of CO2, CO, N2O, CH4, NOx, NMVOC, PM and SO2. Using the IMPACT 2002+ life cycle impact assessment method, transport was assessed in a breakdown into the following impact categories: greenhouse gas emission and damage to human health, including damage caused by organic and inorganic compounds. It has been evidenced that the highest emissions of dust and gas pollutants are caused by passenger cars, which is mainly due to the number of vehicles of this type traversing Polish roads. The main cause of climate changes due to road transport is CO2 emission, while NOx emission is the main factor determining individual categories of damage to human health. The negative environmental impact is primarily related to the operation of combustion engine vehicles. Diesel oil and petrol are currently the main fuels used in Polish transport. In order to reduce their impact on the environment one should intensify the efforts aimed at increasing the share of alternative fuels in transport.
Regulation of subcellular dendritic synapse specificity by axon guidance cues
Authors: Sales Emily C , Heckman Emily L , Warren Timothy L , Doe Chris Q
Published: April 2019

Neural circuit assembly occurs with subcellular precision, yet the mechanisms underlying this precision remain largely unknown. Subcellular synaptic specificity could be achieved by molecularly distinct subcellular domains that locally regulate synapse formation, or by axon guidance cues restricting access to one of several acceptable targets. We address these models using two Drosophila neurons: the dbd sensory neuron and the A08a interneuron. In wild-type larvae, dbd synapses with the A08a medial dendrite but not the A08a lateral dendrite. dbd-specific overexpression of the guidance receptors Unc-5 or Robo-2 results in lateralization of the dbd axon, which forms anatomical and functional monosynaptic connections with the A08a lateral dendrite. We conclude that axon guidance cues, not molecularly distinct dendritic arbors, are a major determinant of dbd-A08a subcellular synapse specificity.
RETRACTED: Endocytic recycling and vesicular transport systems mediate transcytosis of Leptospira interrogans across cell monolayer
Authors: Li Yang , Li Kai-Xuan , Hu Wei-Lin , Ojcius David M , Fang Jia-Qi , Li Shi-Jun , Lin Xu'ai , Yan Jie
Published: April 2019

Many bacterial pathogens can cause septicemia and spread from the bloodstream into internal organs. During leptospirosis, individuals are infected by contact with Leptospira-containing animal urine-contaminated water. The spirochetes invade internal organs after septicemia to cause disease aggravation, but the mechanism of leptospiral excretion and spreading remains unknown. Here, we demonstrated that Leptospira interrogans entered human/mouse endothelial and epithelial cells and fibroblasts by caveolae/integrin-β1-PI3K/FAK-mediated microfilament-dependent endocytosis to form Leptospira (Lep)-vesicles that did not fuse with lysosomes. Lep-vesicles recruited Rab5/Rab11 and Sec/Exo-SNARE proteins in endocytic recycling and vesicular transport systems for intracellular transport and release by SNARE-complex/FAK-mediated microfilament/microtubule-dependent exocytosis. Both intracellular leptospires and infected cells maintained their viability. Leptospiral propagation was only observed in mouse fibroblasts. Our study revealed that L. interrogans utilizes endocytic recycling and vesicular transport systems for transcytosis across endothelial or epithelial barrier in blood vessels or renal tubules, which contributes to spreading in vivo and transmission of leptospirosis.
Translation affects mRNA stability in a codon-dependent manner in human cells
Authors: Wu Qiushuang , Medina Santiago Gerardo , Kushawah Gopal , DeVore Michelle Lynn , Castellano Luciana A , Hand Jacqelyn M , Wright Matthew , Bazzini Ariel Alejandro
Published: April 2019

mRNA translation decodes nucleotide into amino acid sequences. However, translation has also been shown to affect mRNA stability depending on codon composition in model organisms, although universality of this mechanism remains unclear. Here, using three independent approaches to measure exogenous and endogenous mRNA decay, we define which codons are associated with stable or unstable mRNAs in human cells. We demonstrate that the regulatory information affecting mRNA stability is encoded in codons and not in nucleotides. Stabilizing codons tend to be associated with higher tRNA levels and higher charged/total tRNA ratios. While mRNAs enriched in destabilizing codons tend to possess shorter poly(A)-tails, the poly(A)-tail is not required for the codon-mediated mRNA stability. This mechanism depends on translation; however, the number of ribosome loads into a mRNA modulates the codon-mediated effects on gene expression. This work provides definitive evidence that translation strongly affects mRNA stability in a codon-dependent manner in human cells.
A thalamocortical circuit for updating action-outcome associations
Authors: Fresno Virginie , Parkes Shauna L , Faugère Angélique , Coutureau Etienne , Wolff Mathieu
Published: April 2019

The ability to flexibly use knowledge is one cardinal feature of goal-directed behaviors. We recently showed that thalamocortical and corticothalamic pathways connecting the medial prefrontal cortex and the mediodorsal thalamus (MD) contribute to adaptive decision-making (Alcaraz et al., 2018). In this study, we examined the impact of disconnecting the MD from its other main cortical target, the orbitofrontal cortex (OFC) in a task assessing outcome devaluation after initial instrumental training and after reversal of action-outcome contingencies. Crossed MD and OFC lesions did not impair instrumental performance. Using the same approach, we found however that disconnecting the OFC from its other main thalamic afferent, the submedius nucleus, produced a specific impairment in adaptive responding following action-outcome reversal. Altogether, this suggests that multiple thalamocortical circuits may act synergistically to achieve behaviorally relevant functions.
CYP2C11 played a significant role in down-regulating rat blood pressure under the challenge of a high-salt diet
Authors: Liu Wei , Sui Danjuan , Ye Huanying , Ouyang Zhen , Wei Yuan
Published: April 2019

Background

Arachidonic acid (AA) is oxidized by cytochrome P450s (CYPs) to form epoxyeicosatrienoic acids (EETs), compounds that modulate ion transport, gene expression, and vasorelaxation. Both CYP2Cs and CYP2Js are involved in kidney EET epoxidation.

Methods

In this study, we used aCYP2C11-null rat model to explore the in vivo effects of CYP2C11 on vasorelaxation. For 2 months,CYP2C11-null and wild-type (WT) Sprague-Dawley rats were either fed normal lab (0.3% (w/w) sodium chloride) or high-salt (8% (w/w) sodium chloride) diets. Subsequently, an invasive method was used to determine blood pressure. Next, western blots, quantitative PCR, and immunohistochemistry were used to determine renal expression of CYPs involved in AA metabolism.

Results

AmongCYP2C11-null rats, a high-salt diet (females: 156.79 ± 15.89 mm Hg, males: 130.25 ± 16.76 mm Hg,n= 10) resulted in significantly higher blood pressure than a normal diet (females: 118.05 ± 8.43 mm Hg,P< 0.01; males: 115.15 ± 11.45 mm Hg,P< 0.05,n= 10). Compared with WT rats under the high-salt diet, western blots showed thatCYP2C11-null rats had higher renal expression of CYP2J2 and CYP4A. This was consistent with the results of immunohistochemistry and the qPCR, respectively. The two rat strains did not differ in the renal expression of CYP2C23 or CYP2C24.

Conclusion

Our findings suggested that CYP2C11 plays an important role in lowering blood pressure under the challenge of a high-salt diet.
Identification of a putative competitive endogenous RNA network for lung adenocarcinoma using TCGA datasets
Authors: Wang Yuanyong , Lu Tong , Wo Yang , Sun Xiao , Li Shicheng , Miao Shuncheng , Dong Yanting , Leng Xiaoliang , Jiao Wenjie
Published: April 2019

The mechanisms underlying the oncogenesis and progression of lung adenocarcinoma (LUAD) are currently unclear. The discovery of competitive endogenous RNA (ceRNA) regulatory networks has provided a new direction for the treatment and prognosis of patients with LUAD. However, the mechanism of action of ceRNA in LUAD remains elusive. In the present study, differentially expressed mRNAs, microRNAs (miRs) and long non-coding RNAs from the cancer genome atlas database were screened. CeRNAs for LUAD were then identified using online prediction software. Among the ceRNAs identified, family with sequence similarity 83 member A (FAM83A), miR-34c-5p, KCNQ1OT1 and FLJ26245 were observed to be significantly associated with the overall survival of patients with LUAD. Of note, FAM83A has potential significance in drug resistance, and may present a candidate biomarker for the prognosis and treatment of patients with LUAD.
Prevalence of Intestinal Parasitosis among Mentally Ill Persons in Neuropsychiatric Hospital, Calabar, Nigeria
Authors: Otu-Bassey Iquo Bassey , Udoh Dora Imefon , Ogba Ofonime Mark , Useh Monday Francis
Published: April 2019

Aim: The prevalence of intestinal parasitosis in relation to mental illness among inpatients of Federal Neuropsychiatric Hospital, Calabar was investigated with a view to improving the quality of their medical care.

Study Design: This was cross sectional study. Ethical approval and patients’ informed consent were sought and obtained before collection and processing of samples.

Place and Duration of Study: Federal Neuropsychiatric Hospital, Calabar, between February and August, 2016.

 Methodology: We included 246 (126 patients, 120 apparently healthy) subjects. Intestinal parasites were detected by direct stool microscopy and formol ether concentration technique and the cellophane anal swab method for Enterobius vermicularis. Chi square analysis was used to compare percentages.

Results: The prevalence of intestinal parasitosis among the 126 studied patients was 49.2% compared to 11.7% recorded among the 120 apparently healthy (control) subjects examined (P < 0.0001).  There was no significant association between intestinal parasites prevalence and gender in test as well as control subjects 60.0% v. 45.1%, respectively, p = 0.2022) and 14.3% v. 8.8%, respectively, P = 0.3113). Subjects with chronic mental cases insignificantly harbored more intestinal parasites than those with acute cases (53.8% v. 47.1%, respectively; P = 0.5699). Parasites detected in the study were Hookworm 34.6%, Entamoeba histolytica/dispar 25%, Ascaris lumbricoides 17.3%, Trichuris trichiura 9.6%, Enterobius vermicularis 5.8%, Giardia intestinalis 3.8%, Taenia species and Schistosoma mansoni 1.9% each.  Hookworm ranked highest 34.6% among the parasites encountered in the test subjects while Ascaris lumbricoides 33.3% took the lead in the control group. People diagnosed with Variance Psychosis disorder recorded highest infection rate (68.4%) while those with substance abuse had the least (28.0%).

Conclusion: Intestinal parasitosis may possibly play aetiologic or enhancement role in mental ill health. For effective management of the mental challenge, periodic parasitic investigations and appropriate therapy before and after admittance should be effected in all psychiatric institutions.
Statistical Analysis of the Mixture of Inverted Exponential Distribution Under Bayesian Approach
Authors: Sultana Tabasam , Aslam Muhammad , Shabbir Javid
Published: April 2019

This paper is about studying a 3-component mixture of the Inverted Exponential distributions under Bayesian view point. The type-I right censored sampling scheme is considered because of its extensive use in reliability theory and survival analysis. The expressions for the Bayes estimators and their posterior risks are derived under dierent loss scenarios. In case, no or little prior information is available, elicitation of hyper parameters is given. In order to study numerically, the execution of the Bayes estimators under dierent loss functions, their statistical properties have been simulated for dierent sample sizes and test termination times. A real life data example is given to illustrate the study. Graphical representation of the simulation analysis results is also given to study the properties of the Bayes estimators.
Reduction of the Forage Seeds Physiological Quality by the Contact with Fertilizer in the Crop-Livestock Integration
Authors: Avelino Anne Caroline Dallabrida , De Faria Dayana Aparecida , Avelino Cabral Carlos Eduardo , De Abreu Joadil Gonçalves , Camili Elisangela Clarete , Dos Santos Alyce Raiana Monteiro
Published: April 2019

The aim of this study was to evaluate the effects of Brachiaria seed contact time with 05-25-15 fertilizer (N-P2O5-K2O) on the seed’s physiological quality. The experimental design was a completely randomized design with four replicates. Treatments were arranged in a 5x4 factorial, being: five seeds contact times with fertilizer (0, 24, 48, 72 and 96 hours); four forages: Marandu palisadegrass, Piatã palisadegrass, Xaraés palisadegrass and Ruziziensis grass. The performed tests were: water content, germination (first count and germination percentage), tetrazolium (viability), electrical conductivity, accelerated aging, sand emergency and emergence speed index. Contact time of 05-25-15 fertilizer with Brachiaria seeds reduces linearly: Germination, emergence and emergence speed index of Brachiaria seeds; Piatã and Xaraés palisadegrass seeds viability; vigor (electrical conductivity), except in Ruziziensis grass seeds; and seeds germination of Piatã palisadegrass submitted to accelerated aging test (vigor). Piatã palisadegrass is the least recommended, among the analyzed grasses, for intercropping in simultaneous sowing.
Oblique Propagation of Nonlinear Solitary Waves in Magnetized Plasma with Nonextensive Electrons
Authors: Bala Parveen , Kaur Harpreet
Published: April 2019

In this paper, authors have studied the properties of obliquely propagating nonlinear solitary waves in a plasma system consisting of warm ions and nonextensively distributed electrons. The nonlinear Korteweg-de-Vries (KdV) equation and its solution have been derived using the standard reductive perturbation method. The effect of ion temperature on the propagation of solitary waves has been investigated numerically. The critical value of nonextensivity at which solitary structures transit from negative to positive potential is found to shift to the lower value under the effect of finite temperature. The numerical results are interpreted graphically. The results may be useful for understanding the wave propagation in laboratory and space plasmas where magnetic field is present.
Effect of SPD Processing on the Strength and Conductivity of AA6061 Alloy
Authors: Qi Yuanshen , Kosinova Anna , Lakin Eugene , Popov Vladimir V. , Rabkin Eugen , Lapovok Rimma
Published: April 2019

The extruded and artificially aged at 177 °C high strength commercial alloy AA6061‐T651 is subjected to severe plastic deformation (SPD) by cyclic extrusion up to 1000% of the true strain at 400 °C. Unexpectedly, the electrical conductivity of the deformed alloy increased by 10% International Annealed Copper Standard (IACS), while the hardness dropped by only 40 HV. Further, it is shown that low temperature aging at 130 °C after SPD results in the following phenomena: the hardness of the alloy is restored almost to the initial level, with a slight decrease in conductivity, which still remained higher than in the original state. All microstructural parameters of the alloy including aluminum matrix composition, grain size, grain boundaries fraction, and morphology of the precipitates are characterized and correlated with the observed effect of SPD on the strength and electrical conductivity of alloy AA6061.
Molecular Imaging in the Second Near‐Infrared Window
Authors: Wan Hao , Du Haotian , Wang Feifei , Dai Hongjie
Published: April 2019

In the past decade, noticeable progress has been achieved regarding fluorescence imaging in the second near‐infrared (NIR‐II) window. Fluorescence imaging in the NIR‐II window demonstrates superiorities of deep tissue penetration and high spatial and temporal resolution, which are beneficial for profiling physiological processes. Meanwhile, molecular imaging has emerged as an efficient tool to decipher biological activities on the molecular and cellular level. Extending molecular imaging into the NIR‐II window would enhance the imaging performance, providing more detailed and accurate information of the biological system. In this progress report, selected achievements made in NIR‐II molecular imaging are summarized. The organization of this report is based on strategies underlying rational designs of NIR‐II imaging probes, and their applications in molecular imaging are highlighted. This progress report may provide guidance and reference for further development of functional NIR‐II probes designed for high‐performance molecular imaging.
Inorganic and Layered Perovskites for Optoelectronic Devices
Authors: Fakharuddin Azhar , Shabbir Umair , Qiu Weiming , Iqbal Tahir , Sultan Muhammad , Heremans Paul , Schmidt‐Mende Lukas
Published: April 2019

Organic–inorganic halide perovskites are making breakthroughs in a range of optoelectronic devices. Reports of >23% certified power conversion efficiency in photovoltaic devices, external quantum efficiency >21% in light‐emitting diodes (LEDs), continuous‐wave lasing and ultralow lasing thresholds in optically pumped lasers, and detectivity in photodetectors on a par with commercial GaAs rivals are being witnessed, making them the fastest ever emerging material technology. Still, questions on their toxicity and long‐term stability raise concerns toward their market entry. The intrinsic instability in these materials arises due to the organic cation, typically the volatile methylamine (MA), which contributes to hysteresis in the current–voltage characteristics and ion migration. Alternative inorganic substitutes to MA, such as cesium, and large organic cations that lead to a layered structure, enhance structural as well as device operational stability. These perovskites also provide a high exciton binding energy that is a prerequisite to enhance radiative emission yield in LEDs. The incorporation of inorganic and layered perovskites, in the form of polycrystalline films or as single‐crystalline nanostructure morphologies, is now leading to the demonstration of stable devices with excellent performance parameters. Herein, key developments made in various optoelectronic devices using these perovskites are summarized and an outlook toward stable yet efficient devices is presented.
Liquid Crystal Elastomer Waveguide Actuators
Authors: Kuenstler Alexa S. , Kim Hyunki , Hayward Ryan C.
Published: April 2019

While most photomechanical materials developed to date have relied on free‐space illumination to drive actuation, this strategy fails when direct line‐of‐site access is precluded. In this study, waveguided light is harnessed by liquid crystal elastomer (LCE) nanocomposites to drive actuation. Using photo‐chemical reduction of gold salts to plasmonic nanoparticles, prescription of photoresponsive regions within fibers of mono‐domain LCEs is demonstrated with control over both the location along the fiber axis, as well as in the azimuthal direction. Due to localized photothermal heating provided by plasmonic absorption of waveguided light and resulting inhomogeneous thermally induced deformation of the LCE, reversible bending along multiple axes is demonstrated.
High‐Efficiency Perovskite Light‐Emitting Diodes with Synergetic Outcoupling Enhancement
Authors: Shen Yang , Cheng Li‐Peng , Li Yan‐Qing , Li Wei , Chen Jing‐De , Lee Shuit‐Tong , Tang Jian‐Xin
Published: April 2019

Perovskite light‐emitting diodes (PeLEDs) show great application potential in high‐quality flat‐panel displays and solid‐state lighting due to their steadily improved efficiency, tunable colors, narrow emission peak, and easy solution‐processing capability. However, because of high optical confinement and nonradiative charge recombination during electron–photon conversion, the highest reported efficiency of PeLEDs remains far behind that of their conventional counterparts, such as inorganic LEDs, organic LEDs, and quantum‐dot LEDs. Here a facile route is demonstrated by adopting bioinspired moth‐eye nanostructures at the front electrode/perovskite interface to enhance the outcoupling efficiency of waveguided light in PeLEDs. As a result, the maximum external quantum efficiency and current efficiency of the modified cesium lead bromide (CsPbBr3) green‐emitting PeLEDs are improved to 20.3% and 61.9 cd A−1, while retaining spectral and angular independence. Further reducing light loss in the substrate mode using a half‐ball lens, efficiencies of 28.2% and 88.7 cd A−1 are achieved, which represent the highest values reported to date for PeLEDs. These results represent a substantial step toward achieving practical applications of PeLEDs.
Superhydrophobic Melamine–Formaldehyde Sponge Functionalized by Coupling Agent–Isocyanate Siloxane as Efficient Absorbents for Oil and Organic Solvents
Authors: Zhu Jundong , Hu Jiang , Peng Tangping , Jiang Chongwen , Liu Siyuan , Li Ying , Guo Tianyu , Xie Le
Published: April 2019

Sponge‐like sorbent materials with superhydrophobic/oleophilic properties have drawn significant attention for effective clean‐up of oil spills and complex water treatment. However, their cost‐effective and high‐selectivity adsorption remain a great challenge. Herein, a novel superhydrophobic melamine–formaldehyde (MF) sponge is treated with coupling agent–isocyanate siloxane 3‐isocyanatopropyltriethoxysilane (ICPTES) via a urea cross‐linking process, and then condensing with hydrophobic silane (dodecyltrimethoxysilane, DTMS) in alcohol solution. The as‐prepared Si–MF–DTMS sponge (water contact angle as high as 155.4°) demonstrates favorable chemical and thermal stability in harsh environment, high absorption capacity (74.9–161.4 g g−1) for organic liquids, and outstanding separation capability for emulsions. Meanwhile, excellent elasticity and durability allow the organics and oil to squeeze out of the sponge during recycling process easily. Moreover, modified sponge can continuously separate oil and organic pollutants from water by collection device. Thus, a facile, appropriate, and effective strategy used in this work to fabricate superhydrophobic advanced sorbent materials for oil–water separation application is based on surface modification strategy by a coupling agent, which shows enormous potential in oil‐spill remediation and industrial chemistry pollution control.
Preoperative lymphocyte‐to‐monocyte ratio is useful for stratifying the prognosis of hepatocellular carcinoma patients with a low Cancer of the Liver Italian Program score undergoing curative resection
Authors: Shimizu Takayuki , Ishizuka Mitsuru , Park Kyung Hwa , Shiraki Takayuki , Sakuraoka Yuhki , Mori Shozo , Iso Yukihiro , Kato Masato , Aoki Taku , Kubota Keiichi
Published: April 2019

Background and Aim

Although the Cancer of the Liver Italian Program (CLIP) score is useful for prognostication of patients with hepatocellular carcinoma (HCC), a previous study has reported that the CLIP score was unable to stratify the postoperative outcomes of HCC patients in whom the score was low (0‐1). Recent studies have reported that the preoperative lymphocyte‐to‐monocyte ratio (LMR) is useful for prognostication of patients with various cancer.

Methods

We reviewed 329 HCC patients with a low CLIP score (0‐1) undergoing curative resection. This study had the approval of the Institutional Review Board (28068). Multivariate analyses were carried out to detect clinical factors correlating with overall survival (OS). Kaplan‐Meier analysis and the log‐rank test were used for comparison of OS.

Results

Multivariate analysis showed that LMR (<4.35/≥4.35) was significantly associated with OS (hazard ratio [HR], 2.022; 95% CI, 1.141‐3.583; P = 0.016) as well as portal vein invasion (HR, 2.410; 95%CI, 1.258‐4.618; P = 0.008). Kaplan‐Meier analysis and the log‐rank test showed a significant difference in OS and relapse‐free survival between patients with high LMR and those with low LMR.

Conclusion

Preoperative LMR is useful for stratifying the prognosis of HCC patients with a low CLIP score (0‐1) undergoing curative resection.
C3‐Functionalized Chromones Synthesis by Tandem C−H Elaboration and Chromone Annulation of Enaminones
Authors: Fu Leiqing , Wan Jie‐Ping
Published: April 2019

Chromone is a heterocyclic entity presents in a number of natural products, clinical pharmaceuticals, as well as molecules with enriched biological functions. As cutting‐edge area, the synthesis of chromones has seen spectacular progress over the past decade. Among the available synthetic modes toward chromone scaffolds, the annulation of ortho‐hydroxyphenyl functionalized N,N‐disubstituted enaminones has turned out to be one of the most reliable and practical ones. By combining this annulation with the featured transformation of the vinyl α‐C−H bond in the enaminone structure, a large number of tandem reactions providing structurally diverse chromones with C3‐functionalization have been recently realized. As a practical strategy in the synthesis of valuable heterocyclic molecules and an important branch in the enaminone‐based organic synthesis, such synthetic reactions are highly instructive for organic chemistry and many other disciplines related to this heterocyclic moiety. Herein, we present for the first time the research advances on the synthesis of C3‐functionalized chromones via tandem vinyl C−H bond elaboration and chromone annulation of ortho‐hydroxyphenyl functionalized tertiary enaminones.
In Situ Generated Gold Nanoparticles on Active Carbon as Reusable Highly Efficient Catalysts for a C−C Stille Coupling
Authors: Holz Julia , Pfeffer Camilla , Zuo Hualiang , Beierlein Dennis , Richter Gunther , Klemm Elias , Peters René
Published: April 2019

Gold nanoparticle catalysts are important in many industrial production processes. Nevertheless, for traditional C−Ccross‐coupling reactions they have been rarely used and Pd catalysts usually give a superior performance. Herein we report that in situ formed gold metal nanoparticles are highly active catalysts for the cross coupling of allylstannanes and activated alkylbromides to form C−Cbonds. Turnover numbers up to 29 000 could be achieved in the presence of active carbon as solid support, which allowed for convenient catalyst recovery and reuse. The present study is a rare case where a gold metal catalyst is superior to Pd catalysts in a cross‐coupling reaction of an organic halide and an organometallic reagent.
Synthesis and biological evaluation of novel benzo[c]acridine‐diones as potential anticancer agents and tubulin polymerization inhibitors
Authors: Behbahani Fatemeh Shaebani , Tabeshpour Jamshid , Mirzaei Salimeh , Golmakaniyoon Sima , Tayarani‐Najaran Zahra , Ghasemi Ali , Ghodsi Razieh
Published: April 2019

A new series of novel benzo[c]acridine‐diones possessing pharmacophoric elements of antitubulins with central dihydropyridine bridge were designed and synthesized as potential anticancer agents and tubulin polymerization inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against eight cancer cell lines including MCF‐7, A2780, HeLa, HepG2, DU145, A549, PC3, and LNCAP cancer cells and normal cells human umbilical vein endothelial cell (HUVEC) through 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide (MTT) assay, wherein β‐lapachone and combretastatin A‐4 were used as positive controls. Some of our compounds (4c and 4g) showed significant cytotoxic activity on cancer cells with IC50 values in the range of 5.23–24.32 μM. None of the synthesized compounds showed significant cytotoxicity on normal HUVEC cells. Among all investigated derivatives, compound 4g showed promising greater antiproliferative activity against all tested cancer cells with the highest sensitivity observed for the PC3 cell line. Results from the flow cytometry analysis of PC3 and MCF‐7 cancer cells treated with 4g showed an induced cell‐cycle arrest at G2/M, and therefore induced apoptosis which occurred at low concentration of test compound, whereas annexin V‐FITC/propidium iodide staining assay in the aforementioned cancer cell lines treated with 4g showed that 4g can cause necrosis in PC3 and MCF‐7 cancer cells at higher concentration. Compound 4g proved to be an inhibitor of tubulin polymerization in a mode similar to that of colchicine and in a dose‐dependent manner. Molecular docking studies of 4g into the colchicine‐binding site of tubulin exhibited a possible mode of interaction between this compound and tubulin.
Two‐Dimensional Metal‐Organic Layers for Electrochemical Acceptorless Dehydrogenation of N‐Heterocycles
Authors: Yang Ling , Ma Fa‐Xue , Xu Fan , Li Dong , Su Liangmei , Xu Hai‐Chao , Wang Cheng
Published: April 2019

The catalytic acceptorless dehydrogenation (CAD) is an attractive synthetic route to unsaturated compounds because of its high atomic efficiency. Here we report electrochemical acceptorless dehydrogenation of N‐heterocycles to obtain quinoline or indole derivatives using metal‐organic layer (MOL) catalyst. MOL is the two‐dimensional version of metal‐organic frameworks (MOF), and it can be constructed on conductive multi‐walled carbon nanotubes via facile solvothermal synthesis to overcome the conductivity constraint for MOFs in electrocatalysis. TEMPO‐OPO32− was incorporated into the system through a ligand exchange with capping formate on the MOL surface to serve as the active catalytic centers. The hybrid catalyst is efficient in the organic conversion and can be readily recycled and reused.
Processes of intraseasonal snow cover variations over the eastern China during boreal winter
Authors: Song Lei , Wu Renguang , Zhu Jialei
Published: April 2019

This study reveals that the dominant time scale of intraseasonal snow cover variation over the eastern China is within 30 days by using the latest satellite snow cover data from the moderate resolution imaging spectroradiometer (MODIS)/Terra product. The leading empirical orthogonal function (EOF) mode of 10–30‐day snow cover variation during boreal winter from 2004 to 2018 over the eastern China has two centers: northwest part of the eastern China and north of the Yangtze River. Composite analysis based on 25 snow events identified from normalized leading principal time series (PC1) indicates that the southeastward intrusion of surface anticyclonic anomalies and accompanying low temperature anomalies provide the temperature condition for snow events. Negative Arctic Oscillation induces mid‐latitude wave train and leads to the development of surface anticyclonic anomalies and upper‐level cyclonic anomalies over East Asia. The cyclonic anomalies induce ascending motion and anomalous convergence of water vapor fluxes over the eastern China, which supplies moisture for snowfall.
Active contractile properties of fascia
Authors: Schleip Robert , Klingler Werner
Published: April 2019

The ubiquitous network of fascial tissues in the human body is usually regarded as a passive contributor to musculoskeletal dynamics. This review aims to highlight the current understanding of fascial stiffness regulation. Notably the ability for active cellular contraction which may augment the stiffness of fascial tissues and thereby contribute to musculoskeletal dynamics. A related narrative literature search via PubMed and Google Scholar reveals a multitude of studies indicating that the intrafascial presence of myofibroblasts may enable these tissues to alter their stiffness. This contractile tissue behavior occurs not only in several pathological fibrotic contractures but has also been documented in normal fasciae. When viewed at time frames of seconds and minutes the force of such tissue contractions is not sufficient for exerting a significant effect on mechanical joint stability. However, when viewed in a time‐window of several minutes and longer, such cellular contractions can impact motoneuronal coordination. In addition, over a time frame of days to months, this cellular activity can induce long‐term and severe tissue contractures. These findings tend to question the common clear distinction between active tissues and passive tissues in musculoskeletal dynamics. Clin. Anat. 32:891–895, 2019. © 2019 Wiley Periodicals, Inc.
Synthesis of the N‐methyl Derivatives of 2‐Aminothiazol‐4(5H)‐one and Their Interactions with 11βHSD1‐Molecular Modeling and in Vitro Studies
Authors: Studzińska Renata , Kołodziejska Renata , Płaziński Wojciech , Kupczyk Daria , Kosmalski Tomasz , Jasieniecka Katarzyna , Modzelewska‐Banachiewicz Bożena
Published: April 2019

11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is an enzyme that affects the body's cortisol levels. The inhibition of its activity can be used in the treatment of Cushing's syndrome, metabolic syndrome and type 2 diabetes. In this study, we synthesized new derivatives of 2‐(methylamino)thiazol‐4(5H)‐one and tested their activity towards inhibition of 11β‐HSD1 and its isoform – 11β‐HSD2. The results were compared with the previously tested allyl derivatives. We found out that methyl derivatives are weaker inhibitors of 11β‐HSD1 in comparison to their allyl analogs. Due to significant differences in the activity of the compounds, molecular modeling was performed, which was aimed at comparing the interactions between 11β‐HSD1 and ligands differing by substituent at the amine group (allyl vs. methyl). Modeling showed that the absence of the allyl group can lead to the rotation of whole ligand molecule which affects its interaction with the enzyme.
Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update
Authors: Meninno Sara , Volpe Chiara , Lattanzi Alessandra
Published: April 2019

Discovered more than one decade ago, α,α‐diaryl prolinols, most of them commercially available compounds, demonstrated to be distinctive organocatalysts in asymmetric synthesis. Their application successfully spanned across different carbon‐carbon or carbon‐heteroatom bond forming reactions and cascade processes, exploiting covalent and noncovalent activation of the reagents. In this minireview, the advances from 2013 up to the end of 2018 in α,α‐diaryl prolinols promoted stereoselective catalysis and synthesis of biologically active compounds, are illustrated.
Four‐dimensional quantitative structure‐activity analysis of 1,4‐naphthoquinone derivatives tested against HL‐60 human promyelocytic leukemia cells
Authors: Costa Maria Cristina A. , Carvalho Pedro O. Mariz , Ferreira Márcia M. C.
Published: April 2019

Four‐dimensional quantitative structure‐activity relationship (4D‐QSAR) models were developed to predict biological activity of 1,4‐naphthoquinones derivatives tested against human HL‐60 leukemic cells, in order to better investigate the action mode of these compounds. Quinones can generate reactive oxygen species (ROS) through the activation by the cytochrome P450 and P450 reductase enzymes acting as anticancer agents. Molecular dynamics (MD) simulations were performed in the 3D optimized geometries, and the field descriptors were calculated. Partial least squares (PLS) regression method was applied to build the QSAR model, which presented the following statistics, with two factors and explaining 51.11% of total variance: R2 = 0.83; SEC = 0.28; Q2 = 0.77; SEV = 0.31. For external validation, the results were R2pred = 0.76 and SEP = 0.30. Among the nine Coulomb (C) and Lennard‐Jones (LJ) descriptors selected by the model, one of them, C13838, is located close to quinone oxygens involved in the production of radical anions (O2−·) and to hydroxyl in position 5 that may stabilize catalytically important water molecules. The negative LJ descriptors around R1 and R2 substituents might indicate that apolar substituents in these regions are unfavorable to the activity. Coulomb descriptors located at the vicinities of the substituent R2 gave information about the bioactive conformation.
Substitution of an Internal Disulfide Bridge with a Diselenide Enhances both Foldability and Stability of Human Insulin
Authors: Weil‐Ktorza Orit , Rege Nischay , Lansky Shifra , Shalev Deborah E. , Shoham Gil , Weiss Michael A. , Metanis Norman
Published: April 2019

Insulin analogues, mainstays in the modern treatment of diabetes mellitus, exemplify the utility of protein engineering in molecular pharmacology. Whereas chemical syntheses of the individual A and B chains were accomplished in the early 1960s, their combination to form native insulin remains inefficient because of competing disulfide pairing and aggregation. To overcome these limitations, we envisioned an alternative approach: pairwise substitution of cysteine residues with selenocysteine (Sec, U). To this end, CysA6 and CysA11 (which form the internal intrachain A6–A11 disulfide bridge) were each replaced with Sec. The A chain[C6U, C11U] variant was prepared by solid‐phase peptide synthesis; while sulfitolysis of biosynthetic human insulin provided wild‐type B chain‐di‐S‐sulfonate. The presence of selenium atoms at these sites markedly enhanced the rate and fidelity of chain combination, thus solving a long‐standing challenge in chemical insulin synthesis. The affinity of the Se‐insulin analogue for the lectin‐purified insulin receptor was indistinguishable from that of WT‐insulin. Remarkably, the thermodynamic stability of the analogue at 25 °C, as inferred from guanidine denaturation studies, was augmented (ΔΔGu ≈0.8 kcal mol−1). In accordance with such enhanced stability, reductive unfolding of the Se‐insulin analogue and resistance to enzymatic cleavage by Glu‐C protease occurred four times more slowly than that of WT‐insulin. 2D‐NMR and X‐ray crystallographic studies demonstrated a native‐like three‐dimensional structure in which the diselenide bridge was accommodated in the hydrophobic core without steric clash.
Efficient Syntheses of Traumatic Lactone and Rhizobialide
Authors: Zhou Jing , Song Shihua , Jiang Feng , Fu Chunling , Ma Shengming
Published: April 2019

Herein, we report the total synthesis of traumatic lactone and rhizobialide by utilizing allenoic acid to construct the lactone ring. The key starting materials, allenoic acids, could be prepared by the ATA (allenation of terminal alkynes) of a terminal alkyne with an aldehyde that contained a protected hydroxyl group followed by hydrolysis. Importantly, the asymmetric synthesis could be realized just by replacing racemic diphenylprinol with (R)‐ or (S)‐diphenylprinol to deliver the optically active allenoate.
Activating p53 family member TAp63: A novel therapeutic strategy for targeting p53‐altered tumors
Authors: Gunaratne Preethi H. , Pan Yinghong , Rao Abhi K. , Lin Chunru , Hernandez‐Herrera Anadulce , Liang Ke , Rait Antonina S. , Venkatanarayan Avinashnarayan , Benham Ashley L. , Rubab Farwah , Kim Sang Soo , Rajapakshe Kimal , Chan Clara K. , Mangala Lingegowda S. , Lopez‐Berestein Gabriel , Sood Anil K. , Rowat Amy C. , Coarfa Cristian , Pirollo Kathleen F. , Flores Elsa R. , Chang Esther H.
Published: April 2019

Background

Over 96% of high‐grade ovarian carcinomas and 50% of all cancers are characterized by alterations in the p53 gene. Therapeutic strategies to restore and/or reactivate the p53 pathway have been challenging. By contrast, p63, which shares many of the downstream targets and functions of p53, is rarely mutated in cancer.

Methods

A novel strategy is presented for circumventing alterations in p53 by inducing the tumor‐suppressor isoform TAp63 (transactivation domain of tumor protein p63) through its direct downstream target, microRNA‐130b (miR‐130b), which is epigenetically silenced and/or downregulated in chemoresistant ovarian cancer.

Results

Treatment with miR‐130b resulted in: 1) decreased migration/invasion in HEYA8 cells (p53 wild‐type) and disruption of multicellular spheroids in OVCAR8 cells (p53‐mutant) in vitro, 2) sensitization of HEYA8 and OVCAR8 cells to cisplatin (CDDP) in vitro and in vivo, and 3) transcriptional activation of TAp63 and the B‐cell lymphoma (Bcl)‐inhibitor B‐cell lymphoma 2‐like protein 11 (BIM). Overexpression of TAp63 was sufficient to decrease cell viability, suggesting that it is a critical downstream effector of miR‐130b. In vivo, combined miR‐130b plus CDDP exhibited greater therapeutic efficacy than miR‐130b or CDDP alone. Mice that carried OVCAR8 xenograft tumors and were injected with miR‐130b in 1,2‐dioleoyl‐sn‐glycero‐3‐phosphatidylcholine (DOPC) liposomes had a significant decrease in tumor burden at rates similar to those observed in CDDP‐treated mice, and 20% of DOPC–miR‐130b plus CDDP‐treated mice were living tumor free. Systemic injections of scL–miR‐130b plus CDDP in a clinically tested, tumor‐targeted nanocomplex (scL) improved survival in 60% and complete remissions in 40% of mice that carried HEYA8 xenografts.

Conclusions

The miR‐130b/TAp63 axis is proposed as a new druggable pathway that has the potential to uncover broad‐spectrum therapeutic options for the majority of p53‐altered cancers.
Rare cancers in childhood and adolescence in Brazil: First report of data from 19 population‐based cancer registries
Authors: Balmant Nathalie V. , de Souza Reis Rejane , de Oliveira Santos Marceli , de Camargo Beatriz , Gatta Gemma
Published: April 2019

Background

Rare childhood cancer is challenging to define. The Italian Pediatric Rare Tumor (TREP) Study considers rare tumors to include solid malignancies characterized by an annual incidence rate of <2 cases per 1 million and not enrolled in clinical trials. The objective of the current study was to analyze the population incidence rate of rare tumors among children and adolescents (those aged birth‐19 years) in Brazil.

Methods

Incidence data were obtained from 19 population‐based cancer registries covering the 5 geographic regions in Brazil. Newly diagnosed cases were selected according to the TREP definition, using the International Classification of Diseases for Oncology. To calculate the crude incidence rate, the numbers of incident children and adolescents with a specific rare cancer were divided by the corresponding person‐years lived for the population aged <20 years during the same period.

Results

Two tumors had an incidence rate that was >2 cases per 1 million (thyroid and skin cancers) in adolescents only. Several tumors demonstrated variations in incidence across the Brazilian regions. Adrenocortical carcinoma had a high incidence rate (4 cases per 1 million) in the south region among children aged <10 years. Thyroid and skin carcinoma had higher incidence rates in the midwest, southeast, and south regions.

Conclusions

Due to the extraordinary rarity of these events, networking is important for improving basic research, clinical studies, and trials. Centralization of diagnosis is the only way to improve the diagnosis and treatment of children affected by these rare diseases. The registration and surveillance of rare pediatric cancers are crucial from a public health point of view, and therefore the quality of registration has to be improved.
One‐Pot Hydrothermal Synthesis of Co3O4/MWCNTs/Graphene Composites with Enhanced Microwave Absorption in Low Frequency Band
Authors: Tao Yu , Yin Pengfei , Zhang Limin , Feng Xing , Wang Jian , Zhang Yi , Wu Wenjuan , Liu Yuntao , Li Shiping , Qiu Zehao
Published: April 2019

In this paper, the Co3O4/MWCNTs/Graphene ternary composite was synthesized by a facile one‐pot hydrothermal method. The crystal structure, microstructure and elementary composition, electromagnetic parameters and microwave absorption property were systemically investigated by the XRD, SEM, TEM and VNA respectively. The results showed that the as‐prepared ternary composite exhibits enhanced absorption property in the frequency range of 0.1–3.0 GHz, which is mainly attributed to the synergistic effects of the dielectric loss and magnetic loss. The enhanced dielectric loss mainly generates from the strong dipole and interfacial polarization of the adherent MWCNTs and embedded graphene fragments, and the enhanced magnetic loss derives from eddy current loss and nature resonance together. The maximum reflection loss of this composite can reach −42.56 dB at 0.39 GHz with a thickness of 5 mm, while the maximum effective absorption bandwidth covers from 0.77 GHz to 1.99 GHz with a relatively thinner thickness of 2 mm. This study provides a facile method to synthesize Co3O4/MWCNTs/Graphene composite with excellent properties that is a potential candidate for microwave absorption in low frequency band.