bluuebunny/crossref_metadata_2025 huggingface dataset:
First Demonstration of Magnetoelectric Coupling in a Polynuclear Molecular Nanomagnet: Single‐Crystal EPR Studies of [Fe3O(O2CPh)6(py)3]ClO4⋅py under Static Electric Fields
Authors: Boudalis Athanassios K. , Robert Jérôme , Turek Philippe
Published: August 2018

Single‐crystal EPR experiments show that the highly symmetric antiferromagnetic half‐integer spin triangle [Fe3O(O2CPh)6(py)3]ClO4⋅py (1, py=pyridine) possesses a ST=1/2 ground state exhibiting high g‐anisotropy due to antisymmetric exchange (Dzyaloshinskii–Moriya) interactions. EPR experiments under static electric fields parallel to the triangle's plane (i.e., perpendicular to the magnetic z‐axis) reveal that this ground state couples to externally applied electric fields. This magnetoelectric coupling causes an increase in the intensity of the intradoublet EPR transition and does not affect its resonance position when B0∥z. The results are discussed on the basis of theoretical models correlating the spin chirality of the ground state with the magnetoelectric effect.
Room‐Temperature Ionic‐Liquid‐Assisted Microwave Preparation of Tunable Photoluminescent Copper‐Indium‐Zinc‐Sulfide Quantum Dots
Authors: Chen Ting , Xu Yanqiao , Wang Lianjun , Jiang Weihui , Jiang Wan , Xie Zhixiang
Published: August 2018

A facile approach towards photoluminescent (PL) Cu‐In‐Zn‐S quantum dots (CIZS QDs) has been developed, comprising microwave treatment with the assist of room‐temperature ionic liquid (RTIL). Because of its high polarizability, RTIL served as a microwave absorbent, which resulted in the increase of the instantaneous nucleation rate and the rapid synthesis of CIZS QDs at low temperature. Moreover, the surface decoration of QDs with RTIL can passivate the surface defects greatly. The PL intensity of the CIZS QDs depends on the anion species, alkyl chain length of the RTIL, and the metal element ratios of the QDs. On the basis of the variable PL peak position and extended luminescence lifetime of the CIZS QDs, the superior emission behavior of the QDs was confirmed by surface etching with fluoride produced by the hydrolysis of RTIL 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([Bmim]BF4). Moreover, the intermediate alkyl chain length of the RTIL can avoid aggregation, which results in the construction of CIZS QDs with homogenous size distribution. The shape‐controlled CIZS QDs show a broadened tunable emission peak from 677 to 579 nm compared with that of QDs prepared by a conventional one‐pot method by mixing the raw materials. CIZS QDs also exhibit a high quantum yield (QY) of 24.1 % after coating with a ZnS shell. This method is expected to be a useful technique for the rapid synthesis of multiple QDs with a wider range of emission wavelengths and higher QY for a variety of applications.
Rhodium Complexes of a New‐Generation Sapphyrin: Unique Structures, Axial Chirality, and Catalysis
Authors: Chen Qiu‐Cheng , Saltsman Irena , Kaushansky Alexander , Xiao Zi‐Ye , Fridman Natalia , Zhan Xuan , Gross Zeev
Published: August 2018

Rhodium insertion into the new 5,10,15,20‐tetrakis(trifluoromethyl)sapphyrin was found to be much more facile than for other analogues, owing to NH⋅⋅⋅F hydrogen‐bonding interactions that stabilise the pyrrole‐inverted structure characteristic of the metallated product. The thus‐obtained rhodium(I) complexes have axial chirality, and the enantiomers were resolved. The latter were found to interconvert quite rapidly in a process that involves a tautomerisation‐like movement of the metal fragment between the five N atoms. The rhodium sapphyrins were investigated as catalysts for organic synthesis, by studying their carbene‐transfer activity in the cyclopropanation of styrene with ethyl diazoacetate and comparing it to that of rhodium corroles.
Expedient Access to 2‐Benzazepines by Palladium‐Catalyzed C−H Activation: Identification of a Unique Hsp90 Inhibitor Scaffold
Authors: Virelli Matteo , Moroni Elisabetta , Colombo Giorgio , Fiengo Lorenzo , Porta Alessio , Ackermann Lutz , Zanoni Giuseppe
Published: August 2018

Bioactive 2‐benzazepines were accessed in an atom‐ and step‐economical manner through a versatile palladium‐catalyzed C−H activation strategy. The C−H arylation required low catalyst loading and a mild base, which was reflected by a broad scope and high functional‐group tolerance. The benzotriazolodiazepinones were identified as new heat shock protein 90 (Hsp90) inhibiting lead compounds, with considerable potential for anti‐cancer applications.
The importance of considering skin diseases from a temporal perspective: Special emphasis on the effects of corticosteroids and virally induced diseases
Authors: Shiohara Tetsuo , Mizukawa Yoshiko
Published: August 2018

The efficacy and safety of medical therapies assessed on the basis of short‐term outcomes are often considered to inform the long‐term outcomes. Even in corticosteroid therapy, either systemic or topical, which is most frequently used as a first‐line therapy to control inflammation, few studies have reported the risk/benefit ratio for long‐term outcomes. Thus, a temporal perspective should be added to our conventional understanding of the effectiveness of medical therapies. In this review, we initially describe the importance of considering the efficacy of corticosteroid therapy based not only on short‐term outcomes, but also on long‐term outcomes of a certain type of severe drug eruption, drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS). Our view is exemplified by our recent analysis of previously reported cases of DiHS/DRESS, revealing that aggressive treatment such as pulsed corticosteroids and intravenous immunoglobulin, although beneficial in the short term, paradoxically has deleterious effects such as autoimmune sequelae in the long term. Thus, measuring the therapeutic efficacy from only a short‐term perspective is insufficient and follow‐up examination of these patients for at least three years is required even after complete resolution is observed. Various cutaneous diseases refractory to conventional therapies that occur after resolution of herpes zoster also require a temporal perspective to understand how cutaneous diseases develop at a certain site. We describe the clinical usefulness of considering the dual actions of corticosteroids, antiinflammatory, and immunostimulatory, depending on the situations in which they are used.
On the Role of Ferromagnetic Interactions in Highly Active Mo‐Based Catalysts for Ammonia Synthesis
Authors: Munarriz Julen , Polo Victor , Gracia Jose
Published: August 2018

Reactions involving nitrogen fixation and transfer are of great industrial interest. In this regard, unveiling all the physical principles that determine their activity would be enormously beneficial for the rational design of novel catalysts with improved performance. Within this context, this work explores the activity of bulk molybdenum‐based transition metal nitrides in ammonia synthesis. Our results highlight that the most active compositions show increasing ferromagnetism in the metal–nitrogen bonds, which constitute the active sites. We observe that the total spin accumulated in the bonds at the active sites is a physically meaningful descriptor to discriminate optimum catalysts. Higher activities are associated with ferromagnetic phases, and the underlying reason is an enhanced overlapping of the electronic wavefunctions; which also make the reaction steps spin‐sensitive. These finding provides strong evidence of the general influence of electrons magnetic moment in catalysis, being part of the specific field of spintro‐catalysis.
State‐of‐the‐Art Review of HIV‐TB Coinfection in Special Populations
Authors: Weld Ethel D. , Dooley Kelly E.
Published: August 2018

Children and pregnant and postpartum women experience an undue burden of HIV‐associated tuberculosis (TB), but data are lacking on key aspects of their complex management. Often excluded from clinical trials, they are left with limited options for HIV‐TB cotreatment. This review will focus on pharmacologic aspects of the treatment of HIV‐TB coinfection in the special populations of children and pregnant and postpartum women. Pharmacogenomic considerations, rational dosing, drug–drug interactions, safety, immune reconstitution inflammatory syndrome, and ethical and policy aspects of the inclusion of special populations in research will be surveyed. Considerations related to the treatment of both HIV‐associated TB disease and HIV‐associated latent TB infection will be summarized. Relevant knowledge gaps and research priorities in special populations will be outlined.
Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective
Authors: Kenna J. Gerry , Taskar Kunal S. , Battista Christina , Bourdet David L. , Brouwer Kim L.R. , Brouwer Kenneth R. , Dai David , Funk Christoph , Hafey Michael J. , Lai Yurong , Maher Jonathan , Pak Y. Anne , Pedersen Jenny M. , Polli Joseph W. , Rodrigues A. David , Watkins Paul B. , Yang Kyunghee , Yucha Robert W. ,   On behalf of the International Transporter Consortium
Published: August 2018

Bile salt export pump (BSEP) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug‐induced liver injury (DILI). Proactive evaluation and understanding of BSEP inhibition is recommended in drug discovery and development to aid internal decision making on DILI risk. BSEP inhibition can be quantified using in vitro assays. When interpreting assay data, it is important to consider in vivo drug exposure. Currently, this can be undertaken most effectively by consideration of total plasma steady state drug concentrations (Css,plasma). However, because total drug concentrations are not predictive of pharmacological effect, the relationship between total exposure and BSEP inhibition is not causal. Various follow‐up studies can aid interpretation of in vitro BSEP inhibition data and may be undertaken on a case‐by‐case basis. BSEP inhibition is one of several mechanisms by which drugs may cause DILI, therefore, it should be considered alongside other mechanisms when evaluating possible DILI risk.
Tuning Cobalt and Nitrogen Co‐Doped Carbon to Maximize Catalytic Sites on a Superabsorbent Resin for Efficient Oxygen Reduction
Authors: Liu Mengran , Lin Hai , Mei Zongwei , Yang Jinlong , Lin Jie , Liu Yidong , Pan Feng
Published: August 2018

The electrocatalytic performance and cost of oxygen reduction reaction (ORR) catalysts are crucial to many renewable energy conversion and storage systems/devices. Recently, transition‐metal/nitrogen‐doping carbon catalysts (M–N–C) have attracted tremendous attention due to their low cost and excellent catalytic activities; however, they are restricted in large‐scale commercial applications by complex preparation processing. Here, a facile strategy to prepare Co–N–C catalysts has been developed. A kind of superabsorbent resin normally found in diapers, poly(acrylic acid‐acrylamide), is used to adsorb a transition‐metal cobalt salt and a pyrolysis strategy at 800 °C under an argon atmosphere is followed. The resin simultaneously plays a multiple role, which includes structural support, dispersing cobalt ions by coordinate bonds, and providing a carbon and nitrogen source. Attributed to the conductive carbon frameworks and abundant catalytic sites, the Co–N–C catalyst exhibits an excellent electrocatalytic performance. High onset potential (0.96 V vs. reversible hydrogen electrode, RHE), half‐wave potential (0.80 V vs. RHE), and a large diffusion‐limited current density (4.65 mA cm−2) are achieved for the ORR, which are comparable or superior to the commercial 20 % Pt/C and reported M–N–C ORR electrocatalysts. This work provides a universal dispersion technology for Co–N–C catalyst, which makes it a very promising candidate toward the ORR.
Development of a Novel FIJI‐Based Method to Investigate Neuronal Circuitry in Neonatal Mice
Authors: Mei‐ling Liu Jillian , Fair Summer Rose , Kaya Behiye , Zuniga Jessica Nabile , Mostafa Hasnaa Rashad , Alves Michele Joana , Stephens Julie A. , Jones Mikayla , Aslan M. Tahir , Czeisler Catherine , Otero José Javier
Published: August 2018

The emergence of systems neuroscience tools requires parallel generation of objective analytical workflows for experimental neuropathology. We developed an objective analytical workflow that we used to determine how specific autonomic neural lineages change during postnatal development. While a wealth of knowledge exists regarding postnatal alterations in respiratory neural function, how these neural circuits change and develop in the weeks following birth remains less clear. In this study, we developed our workflow by combining genetic mouse modeling and quantitative immunofluorescent confocal microscopy and used this to examine the postnatal development of neural circuits derived from the transcription factors NKX2.2 and OLIG3 into three medullary respiratory nuclei. Our automated FIJI‐based image analysis workflow rapidly and objectively quantified synaptic puncta in user‐defined anatomic regions. Using our objective workflow, we found that the density and estimated total number of Nkx2.2‐derived afferents into the pre‐Bötzinger Complex significantly decreased with postnatal age during the first three weeks of postnatal life. These data indicate that Nkx2.2‐derived structures differentially influence pre‐Bötzinger Complex respiratory oscillations at different stages of postnatal development.
Efficient Synthesis of Multifunctional Chelating Agents Based on Tetraazacycloalkanes
Authors: Sok Nicolas , Bernhard Claire , Désogère Pauline , Goze Christine , Rousselin Yoann , Boschetti Frédéric , Baglin Isabelle , Denat Franck
Published: August 2018

An efficient route has been developed for the synthesis of multifunctional tetraazacycloalkanes (in particular 1,4,7,10‐tetraazacyclotridecane) incorporating an aminomethyl pendant arm on the carbon skeleton. Starting from the appropriate C‐functionalized bisaminal‐protected intermediate, the target macrocycles were easily obtained by means of a step‐by‐step introduction of the desired functional groups onto the free primary amine group, followed by deprotection of the bisaminal intermediates. This straightforward and versatile synthetic approach paves the way for the design of a new family of multifunctional chelators.
Mechanistic Insights into FLP‐Catalyzed Iodoperfluoroalkylations
Authors: Spittler Michael , Helmecke Lucas , Czekelius Constantin
Published: August 2018

The frustrated Lewis pair‐catalyzed iodoperfluoroalkylation of olefins, its substrate activation mode, and catalyst degradation pathways are mechanistically investigated by kinetic measurements. The transformation most likely proceeds via coordination of the phosphane to the perfluoroalkyl iodide and involves radical intermediates.
Enhanced Penta(organo)[60]fullerenes by Electroactive Donor Units for Supramolecular Polymers
Authors: Busseau Antoine , Villegas Carmen , Dabos‐Seignon Sylvie , Hudhomme Piétrick , Legoupy Stéphanie
Published: August 2018

New penta(organo)fullerene donor–acceptor systems bearing five recognition units have been prepared in order to promote their self‐assembly in solution and in the solid state. The host cavity formed due to the perfect organization of electro‐ and/or photoactive substituents around the fullerene, together with π–π and electronic interactions, leads to a supramolecular arrangement similar to shuttlecocks nested inside each other.
Co/Co‐N@Nanoporous Carbon Derived from ZIF‐67: A Highly Sensitive and Selective Electrochemical Dopamine Sensor
Authors: Srinivas Chandrasekaran , Sudharsan Murugesan , Reddy G. Rajendra Kumar , Kumar P. Suresh , Amali Arlin Jose , Suresh D.
Published: August 2018

Co/Co‐N nanoparticles incorporated nitrogen‐doped nanoporous carbon (Co/Co‐N@NPC) nanostructures were fabricated via pyrolysis of metal organic framework, ZIF‐67, under argon atmosphere. The ZIF‐67 derived Co/Co‐N@NPC modified carbon paste electrode exhibited excellent performance during electroanalysis of dopamine, displaying two linear ranges; 10 nM to 50 μM, and 50 μM–500 μM with sensitivity of 12.4±0.3 μA/μM/cm2 and11.69±0.06 μA/μM/cm2, respectively. The modified electrodes were observed to be highly selective towards dopamine even in presence of other interfering biomolecules such as ascorbic acid, glucose and uric acid. To the best of our knowledge, the sensing ability of Co/Co‐N@NPC with a lower limit of detection as 6 nM is the best compared to the previously reported cobalt mediated sensors for dopamine. Practical feasibility of the sensor was demonstrated in real sample analysis of dopamine measurement in human urine samples and dopamine hydrochloride injection samples.
Simultaneous Determination of Antioxidants in Edible Oils Using Graphene Oxide/β‐Cyclodextrin‐modified Electrochemical Sensor
Authors: Shi Zhaoxia , Tan Jie , Hu Yufei , Li Gongke , Xiao Xiaohua
Published: August 2018

In this work, graphene oxide/β‐cyclodextrin (GO/β‐CD) composite was synthesised and applied to construct a highly sensitive electrochemical sensor for the determination of propyl gallate (PG) and butyl hydroxy anisole (BHA) in edible oil, simultaneously. Various methods were used to characterize the properties of GO/β‐cyclodextrin composite. Furthermore, the oxidation peak currents of PG and BHA were increased obviously at the modified glassy carbon electrode, which improved the sensitivity of proposed method. Under optimal conditions, the peak currents of PG and BHA increased linearly with its concentration in the range of 0.1–30.0 μmol/L and 0.05–30 μmol/L, respectively. The limit of detections were as low as 0.01 μmol/L and 0.03 μmol/L, respectively. Finally, the sensor was successfully applied to edible oil sample analysis. The recoveries varied from 95.3 % to 108.6 % with the RSDs 2.9 %–4.9 %, indicated that the proposed sensor can be used for the simultaneous determination of PG and BHA in edible oil.
The effect of different emotional states on olfactory perception: A preliminary study
Authors: Hamakawa Masayuki , Okamoto Tsuyoshi
Published: August 2018

Emotion evoked by odours can be determined or modulated by several factors, including odorant–receptor interactions and olfactory experiences. As a result of these factors, some odours can induce an emotional discrepancy, such as a conflict between innately determined and experience‐based emotions. This study examined whether the difference between two subjective ratings, pleasantness and liking, for an odour can influence olfactory perception, and explored whether the emotional discrepancy had any effect on olfaction. We conducted a psychophysical experiment wherein 12 participants (six women and six men, mean age = 22.0 years) evaluated 36 odours. Participants were instructed to evaluate each odorant in terms of four qualities: (i) pleasantness, (ii) liking, (iii) olfactory perceptual descriptors, and (iv) odour intensity. Participants were also asked to note the difference between pleasantness and liking, whereby the former referred to instinctive and innate feelings and the latter to experience‐based and acquired feelings. Ten odorants exhibited a discrepancy between pleasantness and liking ratings. Another 10 odorants exhibited a significant relationship between the choice of perceptual descriptors and intensity; this was not true of the 10 discrepant odorants. This preliminary study showed that differences in pleasantness and liking ratings can affect the selection of olfactory descriptors, according to odour intensity. The findings suggest that olfactory lexical semantic representations could be confused by discrepant odour‐evoked emotions.
Mortality effects of economic fluctuations in selected eurozone countries
Authors: Seklecka Malgorzata , Md. Lazam Norazliani , Pantelous Athanasios A. , O'Hare Colin
Published: August 2018

Socioeconomic status is commonly conceptualized as the social standing or well‐being of an individual or society. Higher socioeconomic status has long been identified as a contributing factor for mortality improvement. This paper studies the impact of macroeconomic fluctuations (having gross domestic product (GDP) as a proxy) on mortality for the nine most populous eurozone countries. Based on the statistical analysis between the time‐dependent indicator of the Lee and Carter (Journal of the American Statistical Association, 1992, 87(419), 659–671) model and GDP, and adaptation of the good features of the O'Hare and Li (Insurance: Mathematics and Economics, 2012, 50, 12–25) model, a new mortality model including this additional economic‐related factor is proposed. Results for male and female from ages between 0 and 89, and similar for unisex data, are provided. This new model shows a better fitting and more plausible forecast among a significant number of eurozone countries. An in‐depth analysis of our findings is provided to give a better understanding of the relationship between mortality and GDP fluctuations.
Learning dynamics in the formation of European inflation expectations
Authors: Bräuning Christina , van der Cruijsen Carin
Published: August 2018

We investigate learning dynamics in the formation of household inflation expectations in the six largest euro area countries. Our findings reveal heterogeneity in the learning rules that European households use to forecast inflation. We also find pronounced heterogeneity in the way consumers process new data. These differences vary not only across countries but also over time, suggesting that the learning behavior of households is state dependent.
Objective PET study of glucose metabolism asymmetries in children with epilepsy: Implications for normal brain development
Authors: Pilli Vinod K. , Jeong Jeong‐Won , Konka Praneetha , Kumar Ajay , Chugani Harry T. , Juhász Csaba
Published: August 2018

Clinical interpretation of cerebral positron emission tomography with 2‐deoxy‐2[F‐18]fluoro‐d‐glucose (FDG‐PET) images often relies on evaluation of regional asymmetries. This study was designed to establish age‐related variations in regional cortical glucose metabolism asymmetries in the developing human brain. FDG‐PET scans of 58 children (age: 1–18 years) were selected from a large single‐center pediatric PET database. All children had a history of epilepsy, normal MRI, and normal pattern of glucose metabolism on visual evaluation. PET images were analyzed objectively by statistical parametric mapping with the use of age‐specific FDG‐PET templates. Regional FDG uptake was measured in 35 cortical regions in both hemispheres using an automated anatomical labeling atlas, and left/right ratios were correlated with age, gender, and epilepsy variables. Cortical glucose metabolism was mostly symmetric in young children and became increasingly asymmetric in older subjects. Specifically, several frontal cortical regions showed an age‐related increase of left > right asymmetries (mean: up to 10%), while right > left asymmetries emerged in posterior cortex (including portions of the occipital, parietal, and temporal lobe) in older children (up to 9%). Similar trends were seen in a subgroup of 39 children with known right‐handedness. Age‐related correlations of regional metabolic asymmetries showed no robust gender differences and were not affected by epilepsy variables. These data demonstrate a region‐specific emergence of cortical metabolic asymmetries between age 1–18 years, with left > right asymmetry in frontal and right > left asymmetry in posterior regions. The findings can facilitate correct interpretation of cortical regional asymmetries on pediatric FDG‐PET images across a wide age range.
Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma
Authors: Hlady Ryan A. , Sathyanarayan Aishwarya , Thompson Joyce J. , Zhou Dan , Wu Qunfeng , Pham Kien , Lee Jeong‐Heon , Liu Chen , Robertson Keith D.
Published: August 2018

Disruption of epigenetic mechanisms has been intimately linked to the etiology of human cancer. Understanding how these epigenetic mechanisms (including DNA methylation [5mC], hydroxymethylation [5hmC], and histone post‐translational modifications) work in concert to drive cancer initiation and progression remains unknown. Hepatocellular carcinoma (HCC) is increasing in frequency in Western countries but lacks efficacious treatments. The epigenome of HCC remains understudied. To better understand the epigenetic underpinnings of HCC, we performed a genome‐wide assessment of 5mC, 5hmC, four histone modifications linked to promoter/enhancer function (H3K4me1, H3K27ac, H3K4me3, and H3K27me3), and transcription across normal, cirrhotic, and HCC liver tissue. Implementation of bioinformatic strategies integrated these epigenetic marks with each other and with transcription to provide a comprehensive epigenetic profile of how and when the liver epigenome is perturbed during progression to HCC. Our data demonstrate significant deregulation of epigenetic regulators combined with disruptions in the epigenome hallmarked by profound loss of 5hmC, locus‐specific gains in 5mC and 5hmC, and markedly altered histone modification profiles, particularly remodeling of enhancers. Data integration demonstrates that these marks collaborate to influence transcription (e.g., hyper‐5hmC in HCC‐gained active enhancers is linked to elevated expression) of genes regulating HCC proliferation. Two such putative epigenetic driver loci identified through our integrative approach, COMT and FMO3, increase apoptosis and decrease cell viability in liver‐derived cancer cell lines when ectopically re‐expressed. Conclusion: Altogether, integration of multiple epigenetic parameters is a powerful tool for identifying epigenetically regulated drivers of HCC and elucidating how epigenome deregulation contributes to liver disease and HCC.
The approximate solution of finite‐horizon discrete‐choice dynamic programming models
Authors: Eisenhauer Philipp
Published: August 2018

The estimation of finite‐horizon discrete‐choice dynamic programming (DCDP) models is computationally expensive. This limits their realism and impedes verification and validation efforts. Keane and Wolpin (Review of Economics and Statistics, 1994, 76(4), 648–672) propose an interpolation method that ameliorates the computational burden but introduces approximation error. I describe their approach in detail, successfully recompute their original quality diagnostics, and provide some additional insights that underscore the trade‐off between computation time and the accuracy of estimation results.
MiR‐145 affected the circular RNA expression in prostate cancer LNCaP cells
Authors: He Jin‐Hua , Han Ze‐Ping , Zhou Jia‐Bin , Chen Wei‐Ming , Lv Yu‐Bing , He Men Ling , Li Yu‐Guang
Published: August 2018

Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine‐tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). Their interaction with disease‐associated miRNAs indicates that circRNAs are important for the development of disease, and miR‐145 has been previously shown to have antitumor effect in prostate cancer. In the current study, we successfully established the miR‐145‐overexpressed prostate cancer LNCaP cells (LNCaP‐miR‐145) using lentiviral vectors. LNCaP cells expressing the empty vector (LNCaP‐NC) were used as the negative control. The circRNA expression in LNCaP‐miR‐145 cells was detected by microarray analysis, and the miRNA targets of circRNAs were predicted using the bioinformatics software TargetScan and miRanda. Quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of circRNAs in the prostate cancer tissue, nonmalignant tissue, LNCaP‐miR‐145 cells, and LNCaP‐NC cells. The interaction of miRNA and circRNA was further confirmed by the dual‐luciferase reporter assay. A total of 267 and 149 circRNAs were significantly up‐ and downregulated in LNCaP‐miR‐145 cells, respectively. hsa_circRNA_101981, hsa_circRNA_101996 and hsa_circRNA_09142 were the 3 circRNAs that interacted with hsa‐miR‐145‐5p; hsa_circRNA_008068 and hsa_circRNA_406557 were the 2 circRNAs that interacted with hsa‐miR‐145‐3p. Most of the circRNAs corresponded to the protein‐coding exons. The expression levels of hsa_circRNA_101981, hsa_circRNA_00806, and hsa_circRNA_406557 were upregulated in the LNCaP‐miR‐145 cells, but downregulated in the prostate cancer tissue. In contrast, the expression levels of hsa_circRNA_101996 and hsa_circRNA_091420 were downregulated in the LNCaP‐miR‐145 cells, but upregulated in the prostate cancer tissue. Moreover, miR‐145‐5P might regulate the expression of hsa_circRNA_101981, hsa_circRNA_101996, and hsa_circRNA_09142, while miR‐145‐3P might regulate the expression of hsa_circRNA_008068 and hsa_circRNA_406557. Overexpression of miR‐145 promoted the expression of hsa_circRNA_101981, hsa_circRNA_008068, and hsa_circRNA_406557 but suppressed the expressions of hsa_circRNA_101996 and hsa_circRNA_091420 in LNCaP cells. The results from the current study should give us a clue to clarify the tumor suppressive effect of miR‐145.
MicroRNA‐16 functions as a tumor‐suppressor gene in oral squamous cell carcinoma by targeting AKT3 and BCL2L2
Authors: Wang Xi , Li Guang‐hui
Published: August 2018

Aberrant expressions of microRNAs have been reported to be strongly associated with the progression and prognosis of various tumors, including oral squamous cell carcinoma (OSCC). Recent studies on miRNA expression profiling have suggested that microRNA‐16 (miR‐16) may be dysregulated in OSCC. However, the tumorigenic roles and mechanisms of miR‐16 in OSCC are still largely unknown. In this study, we demonstrated that miR‐16 was specifically downregulated in both OSCC patients and cancer cell lines. In addition, functional roles of miR‐16 in vitro suggested that the miR‐16 mimic inhibited cell proliferation and induced apoptosis, whereas miR‐16 inhibitor displayed the opposite effects. Luciferase reporter assay and correlation analysis showed that AKT3 and BCL2L2 were directly targeted by miR‐16 and were inversely expressed with miR‐16 in OSCC. Moreover, restoration of AKT3 and BCL2L2 expression could partially reverse the cell proliferation inhibition and apoptosis induction caused by miR‐16. In xenograft nude mice, miR‐16 mimics decreased the expression of AKT3 and BCL2L2 and reduced the tumors volumes and weights, whereas the miR‐16 inhibitor exhibited adverse effects in the derived xenografts. In conclusion, the findings suggested that miR‐16 functions as a tumor suppressor miRNA to inhibit cell proliferation and induce apoptosis in OSCC through decreasing the oncogenes AKT3 and BCL2L2 and that miR‐16 could be a potential therapeutic target for OSCC.
What drives the decadal variation of global land monsoon precipitation over the past 50 years?
Authors: Zhang Yanfang , Guo Yan , Dong Wenjie , Li Chunxiang
Published: August 2018

Global land monsoon precipitation (GLMP) has shown quasi‐20‐year oscillations overlying a significant downwards trend over the past 50 years (1951–2004). However, what drives this decadal variation remains an open question. Based on Coupled Model Intercomparison Project Phase 5 (CMIP5) models, in this study we explored the possible drivers for the decadal variation of GLMP and quantified their contributions. A downwards trend of −0.30 mm/day (100 years) is observed in GLMP over 1951–2004 that explains 30% of total decadal variance, and it is primarily attributed to anthropogenic aerosols (AAs) external forcing. Further analyses showed that the downwards trend in GLMP mainly results from the widespread drying over Northern Hemisphere (NH) monsoon domain. Faster growth of AAs amount in NH than Southern Hemisphere (SH) over the past 50 years results in a reduced hemispheric thermal contrast (cooler NH–warmer SH) due to more AA‐forced cooling in NH. Reduced hemispheric thermal contrast facilitates a weakened NH summer monsoon circulation and finally suppresses monsoon precipitation. Besides the downwards trend, the remaining variation of GLMP exhibited quasi‐20‐year oscillations that explain 70% of total decadal variance. The decadal oscillations are primarily attributed to internal variability, in which the central tropical Pacific sea surface temperature anomaly and Arctic Oscillation together can explain 55% of its variation.
Silver Nanoparticles Engineered Polystyrene‐Poly(N‐isopropylmethacrylamide‐acrylic acid) Core Shell Hybrid Polymer Microgels for Catalytic Reduction of Congo Red
Authors: Naseem Khalida , Farooqi Zahoor H. , Begum Robina , Wu Weitai , Irfan Ahmad , Al‐Sehemi Abdullah G.
Published: August 2018

Polystyrene‐poly(N‐isopropylmethacrylamide‐acrylic acid) [pSty‐p(NIpmam‐AC)] core shell microgels loaded with silver nanoparticles (NPs) as a recyclable catalyst for rapid reduction of Congo Red (CR) dye in aqueous medium is reported for the first time. Catalytic activity of Ag‐pSty‐p(NIpmam‐AC) core shell composite microgels is measured by adopting the reduction of CR as a benchmark reaction. Restriction of Ag NPs in single layered p(NIpmam‐AC) shell of Ag‐pSty‐p(NIpmam‐AC) core shell composite microgels enhances the diffusion of reactants to access the Ag NPs, surface during reaction with respect to previously reported core shell and homogenous composite microgels, and thus enhances the rate of CR reduction. The solid nonresponsive pSty core induces easy recyclability in core shell composite microgel catalysts. The effect of different reaction parameters such as amount of catalyst, concentration of NaBH4 and CR on the reaction completion time for CR reduction, as well as on the value of apparent rate constant (kapp), is also studied by keeping all other parameters constant, separately. Reduction efficiency of Ag‐pSty‐p(NIpmam‐AC) catalyst is also measured under different reaction conditions for the reduction of CR. A slight decrease in the percentage activity of Ag‐pSty‐p(NIpmam‐AC) catalyst is observed for up to four cycles for CR reduction. The reported Ag‐pSty‐p(NIpmam‐AC) composite microgel catalysts can be used to degrade other pollutants.
Dihydroartemisinin induces apoptosis and autophagy‐dependent cell death in cholangiocarcinoma through a DAPK1‐BECLIN1 pathway
Authors: Thongchot Suyanee , Vidoni Chiara , Ferraresi Alessandra , Loilome Watcharin , Yongvanit Puangrat , Namwat Nisana , Isidoro Ciro
Published: August 2018

Cholangiocarcinoma (CCA) is a very aggressive cancer arising from the malignant transformation of cholangiocytes. Intrahepatic CCA is associated with reactive inflammation and intense fibrosis of the hepatobiliary tract. Dihydroartemisinin (DHA), the active compound found in Artemisia annua, has been shown to possess anti‐tumor activity in a variety of human cancers, including hepatoma. Here, we tested the ability of DHA to specifically kill CCA cells and have investigated the underlying mechanisms. DHA induced both apoptosis and autophagy‐dependent caspase‐independent cell death in many CCA cell lines, while being slightly toxic to immortalized cholangiocytes. DHA induced the expression of many apoptosis‐ and autophagy‐related genes in CCA cells. In particular, it greatly induced the expression of DAPK1, and reduced the interaction of BECLIN1 with BCL‐2 while promoting its interaction with PI3KC3. Genetic silencing of DAPK1 prevented DHA‐induced autophagy. Pharmacologic and genetic inhibition of BECLIN1 function prevented autophagy and cell death induced by DHA in CCA cells. These data unravel a novel pathway of DHA cancer toxicity and open the possibility to introduce DHA in the therapeutic regimen for the treatment of CCA.
Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules
Authors: Liu Chun‐Ping , Hu You , Lin Ju‐Chun , Fu Hua‐Lin , Lim Lee Yong , Yuan Zhi‐Xiang
Published: August 2018

Kidney diseases have become a global public health problem. The application of kidney‐targeted drug‐delivery systems in the management of kidney diseases has profound transformative potential. Kidney‐targeted drug delivery can reduce the undesired side effects of often potent drugs and enhance drug efficacy in alleviating the kidney disease. Here, we review the literature on the potential strategies for targeting drugs to the kidneys. Specifically, we provide a broad overview of the targeting vectors and targeting pathways for renal tubules and glomeruli, as well as how the unique structural features of the glomerulus and the receptor‐mediated internalization pathways of the tubules allows for drug targeting. Finally, we summarized the literature examples of drug delivery to the kidneys and elaborated strategies suitable for renal targeting to provide new therapeutic approaches for kidney diseases.
Almost global existence for 2D magnetohydrodynamics boundary layer system
Authors: Lin Xueyun , Zhang Ting
Published: August 2018

In this paper, we study the almost global existence and uniqueness of the small solution for the two‐dimensional (2D) magnetohydrodynamics (MHD) boundary layer system with small initial data, which are analytic in the x variable. If the initial data lie within ϵ of a stable shear flow, then we can extend the life span at least up to time
. The analytical estimates and the nonlinear terms of this system with the special structure play essential roles in proving this result.
Fully automatic multi‐organ segmentation for head and neck cancer radiotherapy using shape representation model constrained fully convolutional neural networks
Authors: Tong Nuo , Gou Shuiping , Yang Shuyuan , Ruan Dan , Sheng Ke
Published: August 2018

Purpose

Intensity modulated radiation therapy (IMRT) is commonly employed for treating head and neck (H&N) cancer with uniform tumor dose and conformal critical organ sparing. Accurate delineation of organs‐at‐risk (OARs) on H&N CT images is thus essential to treatment quality. Manual contouring used in current clinical practice is tedious, time‐consuming, and can produce inconsistent results. Existing automated segmentation methods are challenged by the substantial inter‐patient anatomical variation and low CT soft tissue contrast. To overcome the challenges, we developed a novel automated H&N OARs segmentation method that combines a fully convolutional neural network (FCNN) with a shape representation model (SRM).

Methods

Based on manually segmented H&N CT, the SRM and FCNN were trained in two steps: (a) SRM learned the latent shape representation of H&N OARs from the training dataset; (b) the pre‐trained SRM with fixed parameters were used to constrain the FCNN training. The combined segmentation network was then used to delineate nine OARs including the brainstem, optic chiasm, mandible, optical nerves, parotids, and submandibular glands on unseen H&N CT images. Twenty‐two and 10 H&N CT scans provided by the Public Domain Database for Computational Anatomy (PDDCA) were utilized for training and validation, respectively. Dice similarity coefficient (DSC), positive predictive value (PPV), sensitivity (SEN), average surface distance (ASD), and 95% maximum surface distance (95%SD) were calculated to quantitatively evaluate the segmentation accuracy of the proposed method. The proposed method was compared with an active appearance model that won the 2015 MICCAI H&N Segmentation Grand Challenge based on the same dataset, an atlas method and a deep learning method based on different patient datasets.

Results

An average DSC = 0.870 (brainstem), DSC = 0.583 (optic chiasm), DSC = 0.937 (mandible), DSC = 0.653 (left optic nerve), DSC = 0.689 (right optic nerve), DSC = 0.835 (left parotid), DSC = 0.832 (right parotid), DSC = 0.755 (left submandibular), and DSC = 0.813 (right submandibular) were achieved. The segmentation results are consistently superior to the results of atlas and statistical shape based methods as well as a patch‐wise convolutional neural network method. Once the networks are trained off‐line, the average time to segment all 9 OARs for an unseen CT scan is 9.5 s.

Conclusion

Experiments on clinical datasets of H&N patients demonstrated the effectiveness of the proposed deep neural network segmentation method for multi‐organ segmentation on volumetric CT scans. The accuracy and robustness of the segmentation were further increased by incorporating shape priors using SMR. The proposed method showed competitive performance and took shorter time to segment multiple organs in comparison to state of the art methods.
Does videourodynamic classification depend on patient positioning in patients with stress urinary incontinence?
Authors: Ecclestone Hazel , Cashman Sophia , Solomon Eskinder , Pakzad Mahreen , Hamid Rizwan , Greenwell Tamsin , Ockrim Jeremy
Published: August 2018

Introduction and Aims: Videocystometrogram (VCMG) is used to assess patients with SUI. A common classification system of SUI is the Blaivas and Olsson classification. The position this grading is performed in has never been established.

Materials and Methods: One hundred twenty‐one women complaining of SUI refractory to conservative measures had video‐urodynamic assessment prior to operative intervention. Grading of stored video SUI image traces was assessed as per Blaivas and Olsson criteria by two independent investigators whilst women were both lying and standing with bladder at maximum cystometric capacity.

Results: Seventy‐two (56.7%) patients’ grading remained the same in both lying and standing positions. 49(40.5%) patients’ grading altered on standing. twenty had non‐demonstrable incontinence converted to demonstrable incontinence and 29 had demonstrable incontinence on lying that changed grading on standing; 22 of these by one grade and seven by two grades (from I to IIb). A Fisher's exact test demonstrated a statistically significant difference in the distribution of SUI grading between supine and standing positions (P < 0.01).

Conclusion: 40.5% of women have a changed Blaivas and Olsson grade of SUI when assessed standing as opposed to lying. This has implications for surgical treatment options and patient counselling. While the Blaivas and Olsson grading system for SUI is simple and reproducible there is little standardisation as to which position this grading is to be performed. We recommend that an international consensus is agreed upon in order for results to be comparable and to help with future outcome studies.
Comparability between adult female anogenital distance and perineal measurements standardized by POP‐Q system (GH and PB)
Authors: Sánchez‐Ferrer María L. , Prieto‐Sánchez María T. , Moya‐Jiménez Luis C. , Adoamnei Evdochia , Mendiola Jaime , Torres‐Cantero Alberto M.
Published: August 2018

Aims

Anogenital distance (AGD) has been proposed as a marker of the prenatal hormonal milieu and potential environmental insults. The measures of the Pelvic Organ Prolapse‐Questionnaire (POP‐Q) system is being widely used in the evaluation of the perineum in women with POP pathologies. Genital hiatus (GH) and perineal body (PB) lengths have been related to both prolapse incidence and recurrence and for pessary treatment failure. The use of AGD in female human studies is now emerging and its comparability with other anthropometric measurements could be relevant. The aim of the study was to compare AGD and POP‐Q system in adult females.

Methods

The study included 155 pregnant women in the first stage of labor. Perineal measurements were performed on women in the lithotomy position: AGD from the anus to the clitoris (AGDAC); AGD from the anus to the fourchette (AGDAF); GH from the external urethral meatus to the posterior midline hymen, and length of the PB from the posterior midline hymen to the mid‐anal opening. Coefficients of variations (CV) were calculated. Intraclass correlation coefficients (ICC) and Bland‐Altman graphs were used to compare both set of measurements.

Results

CV were below 15% for AGDAC and GH + PB, though higher for AGDAF and PB (20% and 17%, respectively). ICCs for each pair of measurements were above 80%, (excellent agreement between methods). Concordance between measurements was confirmed by Bland‐Altman graphs.

Conclusions

Comparable measurements were obtained using AGDs and POP‐Q system. Further studies are needed to explore clinical and epidemiological implications of these findings.
Attempt to Replicate Evidence that Weight and Shape Concerns Amplify the Effects of Gradual Lifestyle Improvement Obesity Prevention Programs
Authors: Stice Eric , Rohde Paul
Published: August 2018

See accompanying article, pg. 1270.
Optimization of pH conditions and characterization of polyelectrolyte complexes between gellan gum and cationic guar gum
Authors: Kaur Jasleen , Kaur Gurpreet
Published: August 2018

The present study was aimed to investigate optimum pH conditions for polyelectrolyte complexation between gellan gum (GG) and cationic guar gum (CGG). The pKa of both the polymers was determined using potentiometric titrations. The complex formation was investigated at three pH values (based upon the pKa interval of two polymers) and at different mixing ratios (ranging from 10:90 to 90:10). Zeta potential and turbidity studies elucidated the optimum pH and mixing ratio at which maximum interaction takes place between the polymers. The studies revealed neutral zeta potential, highest turbidity, and low transmittance at mixing ratio 30:70 and 40:60 (GG:CGG; pH 5.5), indicating maximum complex formation at these ratios. The percentage yield and viscosity studies of supernatant also revealed maximum interaction at these mixing ratios of polymers. The polyelectrolyte complexes (PECs) were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and for their swelling behavior in pH progression medium. The FTIR spectra confirmed formation of bonds between COO¯ and –N+(CH3)3 of GG and CGG, respectively. DSC studies revealed the stability, affinity, and spontaneous nature of complexation between these polymers. The morphological changes detected through SEM studies in GG‐CGG PECs exposed to different pH buffers also found to exhibit pH‐dependent swelling. The FTIR spectra, DSC, SEM, and swelling studies of PECs treated with buffer pH 1.2 followed by buffer pH 7.4 suggested that PECs comprising 40:60 ratio of GG:CGG, prepared at pH 5.5, could be used to formulate a pH‐sensitive drug delivery system.
Treatment with montelukast and antidepressive medication—a symmetry analysis
Authors: Winkel Jane Sterndorff , Damkier Per , Hallas Jesper , Henriksen Daniel Pilsgaard
Published: August 2018

Purpose

Leukotriene receptor antagonists are used in asthma and rhinitis treatment. Pharmacovigilance data have suggested an association between montelukast and depression, but the association has not been established in controlled study designs. We described the association between initiation of montelukast and depression, using prescriptions of antidepressants as a surrogate marker, and assessed whether the association was related to the underlying asthma disease.

Methods

We performed a symmetry analysis, with a study period from January 1, 2000 to December 31, 2016, using 3 nationwide Danish registers. We included all adults, who filled their first prescription of montelukast and antidepressants within an interval of 1 year. In the absence of an association between montelukast and antidepressant use, a symmetrical distribution of prescriptions is expected before and after montelukast initiation (ie, a sequence ratio [rc] of 1.0). We subcategorized the subjects after the severity of underlying asthma disease.

Results

In total, 4450 subjects filled their first prescriptions of both montelukast and antidepressants within a 1‐year interval: 2434 redeemed their first prescription of montelukast before antidepressants, and 2016 redeemed the medications in the opposite order (rc 1.21 [95% CI 1.14‐1.28]). We found rc above unity in groups with long‐acting asthma treatment, but no increase in antidepressant prescription, when stratifying by the asthma severity.

Conclusion

We found a weak association between the use of montelukast and the risk of being prescribed an antidepressant, unlikely to be of clinical relevance. Stratified analyses suggest that this association may relate to asthma, rather than to montelukast.