bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of selected commercial pharmacotherapeutic drugs as potential pancreatic lipase inhibitors and antiproliferative compounds
Authors: Mamdooh Noor , Kasabri Violet , Al‐Hiari Yusuf , Almasri Ihab , Al‐Alawi Sundus , Bustanji Yasser 
Published: December 2018

AbstractIn this study, 15 commercial acidic drugs have been evaluated for pancreatic lipase (PL) inhibitory activity using an in vitro spectrophotometric method. The acidity was the basis of selection, since most PL inhibitors exhibit acidic groups and high lipophilicity. Orlistat was the robust reference agent for potency and efficacy determinations. In comparison to the cisplatin, the evaluation of the antineoplastic activities of selected drugs in a panel of colorectal cancer cell lines (HT‐29, HCT‐116, SW620, CACO‐2, and SW480) and normal periodontal ligament fibroblasts for safety examination was performed by using a sulforhodamine procuring ascorbic acid as a reference in diphenyl‐2‐picryl‐hydrazyl assay of radical scavenging properties was performed. This research revealed three highly acidic pharmacological classes with reasonable PL inhibitory activity in comparison to orlistat out of 15 selected drugs, namely sulfonylureas, fluoroquinolones, and proton pump inhibitors. Docking studies supported the hypothesis of a selection based on acidity, since it showed that the sulfonamide acid group (glyburide) is a remarkably potent interacting group with the enzyme. Failing to fulfill other structure‐activity relationship requirements (lipophilicity) led to weak activity. Since the drugs are of different chemical classes with unknown mechanisms, they showed diverse antiproliferative activity. Some drugs such as atorvastatin and gemifloxacin showed higher antiproliferative activity than cisplatin with high‐safety profiles against SW620 and SW480 cell lines, respectively, whereas lansoprazole and clopidogrel revealed comparable activity to cisplatin against HCT‐116 and SW480, respectively. Unfortunately, selected tested drugs exhibited negligible radical scavenging activity versus ascorbic acid.

Hit, Lead & Candidate Discovery
Mechanism of penehyclidine hydrochloride on a dysmenorrhea rat model
Authors: Xiao Hongtao , Shi Tingting , Han Lizhu , Tong Rongsheng , Liao Zhi 
Published: December 2018

AbstractPrimary dysmenorrhea affects the quality of life in young women, particularly school and work performance. This study investigated the mechanisms of penehyclidine hydrochloride (PHC) efficacy on a rat model of primary dysmenorrhea. The model was induced by injecting both estradiol benzoate and oxytocin. Different doses of PHC were administrated intraperitoneally following estradiol benzoate administration. Writhing scores were assessed, and pathological changes of the uterus were observed via hematoxylin and eosin staining. Western blot and real‐time PCR were used to evaluate the expression level of the M3 receptor, both TLR3 and TLR4 in uterine tissue, and the level of Ca2+ was measured in uterine tissues. Writhing scores significantly decreased in the PHC treatment group compared to model, and PHC alleviated the occurrence of edema or necrosis in the uteri compared to model group. PHC can decrease the M3 receptor, TLR3, TLR4 expression, and the Ca2+ level compared to the model group. PHC is a potential candidate for the future treatment of primary dysmenorrhea due to its ability to attenuate muscarinic receptors and TLRs.

Preclinical Research & Development
Motivational interviewing to improve adherence behaviours for the prevention of diabetic foot ulceration
Authors: Binning Jodi , Woodburn Jim , Bus Sicco A. , Barn Ruth 
Published: December 2018

SummaryDiabetic foot ulceration is a major complication associated with high morbidity. Little evidence exists on which interventions are effective at preventing ulceration. Participants who are adherent to self‐care behaviours have significantly better outcomes. Motivational interviewing is an intervention that has been used successfully for conditions where adherence is important, such as reduction of obesity and HbA1c levels. A systematic review was conducted to determine whether motivational interviewing is effective at improving adherence for the prevention of Diabetic Foot Ulceration. Electronic searches were run without date or language restrictions in MEDLINE (viaEBSCOhost), CINAHL (viaEBSCOhost), ProQuest (Health and Medical Collection, Nursing and Allied Health Database, PsycINFO, Psychology, PsychArticles), AMED, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, and Web of Science Core Collections. Papers were included if participants had or were at risk of diabetic foot ulceration. Studies required motivational interviewing or a motivational approach as the sole intervention or as a component. Randomised controlled trials and quasi‐experimental studies were included if ulceration and/or at least one behavioural outcome was measured before and after the intervention. Five studies met the inclusion criteria. Heterogeneity prevented the pooling of data. One study used motivational interviewing as the sole intervention. This study found a short‐term positive effect on footwear adherence. The remaining four studies had a motivational component within their interventions. Two of these studies showed the intervention to be effective but both were at a high risk of bias. This review demonstrates an evidence gap. More research is needed.
Can drones count gulls? Minimal disturbance and semiautomated image processing with an unmanned aerial vehicle for colony‐nesting seabirds
Authors: Rush Graham P. , Clarke Lucy E. , Stone Meg , Wood Matt J. 
Published: December 2018

AbstractAccurate counts of wild populations are essential to monitor change through time, but some techniques demand specialist surveyors and may result in unacceptable disturbance or inaccurate counts. Recent technological developments in unmanned aerial vehicles (UAVs) offer great potential for a range of survey and monitoring approaches. They literally offer a bird's‐eye view, but this increased power of observation presents the challenge of translating large amounts of imagery into accurate survey data. Seabirds, in particular, present the particular challenges of nesting in large, often inaccessible colonies that are difficult to view for ground observers, which are commonly susceptible to disturbance. We develop a protocol for carrying out UAV surveys of a breeding seabird colony (Lesser Black‐backed Gulls, Larus fuscus) and subsequent image processing to provide a semiautomated classification for counting the number of birds. Behavioral analysis of the gull colonies demonstrated that minimal disturbance occurred during UAV survey flights at an altitude of 15 m above ground level, which provided high‐resolution imagery for analysis. A protocol of best practice was developed using the expertise from both a UAV perspective and that of a dedicated observer. A GIS‐based semiautomated classification process successfully counted the gulls, with a mean agreement of 98% and a correlation of 99% with manual counts of imagery. We also propose a method to differentiate between the different gull species captured by our survey. Our UAV survey and analysis approach provide accurate counts (when comparing manual vs. semi‐automated counts taken from the UAV imagery) of a wild seabird population with minimal disturbance, with the potential to expand this to include species differentiation. The continued development of analytical and survey tools whilst minimizing the disturbance to wild populations is both key to unlocking the future of the rapid advances in UAV technology for ecological survey.
Numerical investigation of the current transition regimes in nanochannels
Authors: Villegas Arturo , Berardi David , Javier Diez Francisco 
Published: December 2018

AbstractThe concentration polarization phenomena and its effects represent one of the main challenges for the optimal operation of many nanofluidic systems. A numerical investigation of the different electric current transition regimes observed during the concentration polarization phenomena in nanochannels is performed. This included a 2D‐axisymmetric simulation of the nanofluidic system (reservoir‐nanochannel‐reservoir). From these simulations, a novel mechanism is discovered that explains that different current transition regimes. This driving mechanism involves the applied electric field penetration while the convective flow mechanism is found to be negligible. This differs with the classical statement that the mixing process with less depleted areas initiated by an electrokinetic vortex instability starts the overlimiting regime. Additionally, the numerical approach allows us to identify new characteristics of the linear‐limiting transition such as source‐like and saddle‐like points of the electric field streamlines. The three voltage–current regimes (linear, limiting and overlimiting) are explained by observing and quantifying changes in electric field, potential, ion concentration and ion concentration gradients within the system.
Electric field assisted multicomponent reaction in a microfluidic reactor for superior conversion and yield
Authors: Maity Surjendu , Chaudhuri Joydip , Mitra Shirsendu , Rarotra Saptak , Bandyopadhyay Dipankar 
Published: December 2018

AbstractWe explore the improvements in yield and conversion of a chemical reaction inside a two‐phase microfluidic reactor when subjected to an externally applied alternating current (AC) electric field. A computational fluid dynamic (CFD) framework has been developed to incorporate the descriptions of the two‐phase flow, multicomponent transport and reaction, and the Maxwell's stresses generated at oil‐water interface owing to the presence of the externally applied electric field. The CFD model ensures that the reactants are flown into a microchannel together with the oil and water phases before the reaction takes place at the interface and products diffuse back to the bulk phases. The study unveils that the variation in the intensity of the AC field helps in converting a two‐phase stratified flow into an oil‐in‐water microemulsion composed of oil slugs, plugs, or droplets. Importantly, the results also suggest that harnessing the vortices inside or outside these flow patterns helps in the improvement in mass transfer across the interface, which can be employed to improve the yield and conversion of a reaction. We have shown an example case of a pseudo‐first order reaction for which the variation in frequency and intensity of AC field is found to form higher surface‐to‐volume‐ratio flow patterns having a higher throughput. The convective recirculation in and around these miniaturized flow morphologies increase the rate of mass transfer, mixing of reactant and products, conversion of reactant, and yield of products. The results reported can be of significance in the design and development of future advanced‐flow rector technologies.
Short‐term forecasts of economic activity: Are fortnightly factors useful?
Authors: Monteforte Libero , Raponi Valentina 
Published: December 2018

AbstractA short‐term mixed‐frequency model is proposed to estimate and forecast Italian economic activity fortnightly. We introduce a dynamic one‐factor model with three frequencies (quarterly, monthly, and fortnightly) by selecting indicators that show significant coincident and leading properties and are representative of both demand and supply. We conduct an out‐of‐sample forecasting exercise and compare the prediction errors of our model with those of alternative models that do not include fortnightly indicators. We find that high‐frequency indicators significantly improve the real‐time forecasts of Italian gross domestic product (GDP); this result suggests that models exploiting the information available at different lags and frequencies provide forecasting gains beyond those based on monthly variables alone. Moreover, the model provides a new fortnightly indicator of GDP, consistent with the official quarterly series.
Predictive likelihood for coherent forecasting of count time series
Authors: Mukhopadhyay Siuli , Sathish Vurukonda 
Published: December 2018

AbstractA new forecasting method based on the concept of the profile predictive likelihood function is proposed for discrete‐valued processes. In particular, generalized autoregressive moving average (GARMA) models for Poisson distributed data are explored in detail. Highest density regions are used to construct forecasting regions. The proposed forecast estimates and regions are coherent. Large‐sample results are derived for the forecasting distribution. Numerical studies using simulations and two real data sets are used to establish the performance of the proposed forecasting method. Robustness of the proposed method to possible misspecifications in the model is also studied.
Quantitation of 2‐acetyl‐1‐pyrroline in aseptic‐packaged cooked fragrant rice by HS‐SPME/GC‐MS
Authors: Lee Young‐Sang , Oh Yejin , Kim Tae‐Hyung , Cho Yoo‐Hyun 
Published: December 2018

AbstractAseptic‐packaged cooked rice (APCR) is a rice‐based food product with a rapidly increasing market size, and APCR made of fragrant rice (FR) has recently appeared on the market. The fragrance of FR is produced by a combination of odoriferous compounds, among which 2‐acetyl‐1‐pyrroline (2AP) has been identified as the most important contributor to overall aroma. This study describes the development of a method to quantify 2AP in FR‐based APCR using headspace solid‐phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC‐MS). The recovery of 2AP spiked into APCR was lower than 10%, which suggests significant matrix effects and inappropriateness of external standard‐based calibration. For standard addition calibration method, up to 1,000 ng of 2AP were spiked into APCR containing 0% to 100% FR. Subsequent regression analyses of recovered peak area (Y) as a function of the amount of 2AP spiked (X) yielded highly linear calibration curves (R2 > 0.9917) with consistent slopes (RSD = 2.7%), regardless of FR composition. Y‐intercepts, however, which represent the amount of 2AP in APCR without spiking, increased linearly (R2 = 0.9898) in proportion to the composition of FR in the APCR. The amount of 2AP in APCR, determined by extrapolating the standard addition calibration curves, also increased linearly (R2 = 0.9963) as a function of FR composition. Practicality of developed method was tested by monitoring 2AP contents in APCR under realistic storage conditions, which successfully demonstrated 38% and 60% 2AP reductions in APCR of 20% FR after 1 and 2 months of storage at 25°C, respectively. The present study demonstrates that a standard addition method, whereby up to 1,000 ng of 2AP standard is spiked into 4 g of APCR containing 5%–100% FR in a 20‐mL headspace vial followed by SPME/GC‐MS, may serve as an effective means of quantitating 2AP in fragrant rice‐based APCR.
Cuprizone‐induced graded oligodendrocyte vulnerability is regulated by the transcription factor DNA damage‐inducible transcript 3
Authors: Fischbach Felix , Nedelcu Julia , Leopold Patrizia , Zhan Jiangshan , Clarner Tim , Nellessen Lara , Beißel Christian , van Heuvel Yasemin , Goswami Anand , Weis Joachim , Denecke Bernd , Schmitz Christoph , Hochstrasser Tanja , Nyamoya Stella , Victor Marion , Beyer Cordian , Kipp Markus 
Published: December 2018

AbstractOligodendrocytes are integral to efficient neuronal signaling. Loss of myelinating oligodendrocytes is a central feature of many neurological diseases, including multiple sclerosis (MS). The results of neuropathological studies suggest that oligodendrocytes react with differing sensitivity to toxic insults, with some cells dying early during lesion development and some cells being resistant for weeks. This proposed graded vulnerability has never been demonstrated but provides an attractive window for therapeutic interventions. Furthermore, the biochemical pathways associated with graded oligodendrocyte vulnerability have not been well explored. We used immunohistochemistry and serial block‐face scanning electron microscopy (3D‐SEM) to show that cuprizone‐induced metabolic stress results in an “out of phase” degeneration of oligodendrocytes. Although expression induction of stress response transcription factors in oligodendrocytes occurs within days, subsequent oligodendrocyte apoptosis continues for weeks. In line with the idea of an out of phase degeneration of oligodendrocytes, detailed ultrastructural reconstructions of the axon–myelin unit demonstrate demyelination of single internodes. In parallel, genome wide array analyses revealed an active unfolded protein response early after initiation of the cuprizone intoxication. In addition to the cytoprotective pathways, the pro‐apoptotic transcription factor DNA damage‐inducible transcript 3 (DDIT3) was induced early in oligodendrocytes. In advanced lesions, DDIT3 was as well expressed by activated astrocytes. Toxin‐induced oligodendrocyte apoptosis, demyelination, microgliosis, astrocytosis, and acute axonal damage were less intense in the Ddit3‐null mutants. This study identifies DDIT3 as an important regulator of graded oligodendrocyte vulnerability in a MS animal model. Interference with this stress cascade might offer a promising therapeutic approach for demyelinating disorders.
Dehydrogenative Sn–E (E = S, Se) bond formation catalyzed by an iron complex
Authors: Itazaki Masumi , Ogawa Yudai , Nakamura Wataru , Nakazawa Hiroshi 
Published: December 2018

AbstractIron complex‐catalyzed dehydrogenative Sn–E (E = S, Se) bond formation of hydrostannane with thiol and selenol was achieved. All new compounds were fully characterized using 1H, 13C{1H}, 77Se{1H}, and 119Sn{1H} NMR measurements and elemental analyses. The structure of 1,1′‐(1,3‐dithia‐2,2‐dibutylstanyl)‐[3]ferrocenophane was confirmed by single‐crystal X‐ray diffraction.
Photochemical Reactions in Supramolecular Assemblies of Gels: Dimerizations and Polymerizations via Pericyclic Reactions
Authors: Dey Avishek , Biradha Kumar 
Published: December 2018

AbstractGel state reactions offer new direction for the reactivity of the organic molecules or metal‐organic materials upon photoirradiation with shorter reaction times and high yields compared to solid and solution states. The restricted molecular movement among the molecules in the soft solids control the stereoselectivity of the photoproducts in the gel state reactions. To date, most of the strategies based on self‐assembly have been demonstrated in the solid state, in particular for [2+2] reactions of olefins and polymerization reactions of diacetylenes via 1,4 addition. The soft materials are of emerging materials in recent days given their many applicative day‐to‐day aspects. This review gives a glimpse of recent reports on pericyclic reactions in the gel state that are designed based on the self‐assembly concept. Also it highlights how such reactions accompany the physical changes in the structure of the gels and stereo controlled products with high yields.
DNA damage in BV‐2 cells: An important supplement to the neurotoxicity of CdTe quantum dots
Authors: He Keyu , Liang Xue , Wei Tingting , Liu Na , Wang Yan , Zou Linyue , Lu Jie , Yao Ying , Kong Lu , Zhang Ting , Xue Yuying , Wu Tianshu , Tang Meng 
Published: December 2018

AbstractMicroglial cells are resident immune cells in the central nervous system. Activation of microglia as induced by CdTe quantum dots (QDs) can trigger damage to neurons. To quantify the intracellular QDs, we monitored the intracellular Cd concentration in the QD‐exposed mouse microglial cells (BV‐2 cell line). The extent of cell injury at different times correlated with the Cd concentration in cells at that time. In addition to Cd ion detection, we also monitored the intracellular fluorescence of the QDs. More QDs accumulated in the nucleus than in the cytoplasm. Comet assays confirmed that QDs induce DNA damage. However, DNA cannot interact with QDs, so the DNA damage was not caused by CdTe QDs adducts to DNA but by the increase of the Cd ion concentration and the secondary oxidative damage. In addition to DNA damage, biofilm injury and endogenous reduced glutathione depletion were also apparent in QD‐exposed BV‐2 cells. These changes can be prevented or even reversed by exogenous reduced glutathione administration.
Overexpression of KCNJ4 correlates with cancer progression and unfavorable prognosis in lung adenocarcinoma
Authors: Wu Xiao‐Yan , Yu Xue‐Yan 
Published: December 2018

AbstractKCNJ4 (potassium voltage‐gated channel subfamily J member 4) belongs to the inward rectifier potassium channel family, which is inhibited by novel anticancer agents. However, the biologic significance of KCNJ4 in lung adenocarcinoma (LADC) is largely unknown. Therefore, in this study, we evaluated the expression, clinical correlation, and prognostic value of KCNJ4 in LADC and normal lung tissues according to data from The Cancer Genome Atlas datasets. A small interfering RNA (siRNA)‐mediated technology was used to inhibit the expression level of KCNJ4. Cell counting kit‐8 and plate colony formation assays were used to measure cell proliferation. Wound‐healing and transwell assays were applied to detect cell mobility and metastasis. Quantitative real‐time polymerase chain reaction and western blot analysis were used to examine messenger RNA and protein expressions, respectively. It was found that KCNJ4 was significantly upregulated in LADC tissues and cells. The high level of KCNJ4 predicted shorter overall survival and was identified as an independent prognostic factor in patients with LADC. siRNA‐mediated KCNJ4 silencing impeded LADC cell proliferation, migration, and invasion. Knockdown of KCNJ4 suppressed the expression of phosphorylated mitogen‐activated protein kinase/extracellular signal regulated kinase (p‐MEK) and phosphorylated extracellular signal‐regulated kinase (p‐ERK). Collectively, these results shed some light on the contribution of KCNJ4 functioning as a significant player in LADC, implying that KCNJ4 might be a valuable prognostic biomarker and a potential therapeutic target for LADC treatment.
IL‐6/YAP1/β‐catenin signaling is involved in intervertebral disc degeneration
Authors: Chen Jian , Mei Zhengfeng , Huang Bao , Zhang Xuyang , Liu Junhui , Shan Zhi , Wang Jiasheng , Wang Xianjun , Zhao Fengdong 
Published: December 2018

AbstractYes‐associated protein 1 (YAP1) is a transcriptional coactivator and negative regulator of the Hippo pathway. It regulates diverse cellular processes, such as cell proliferation, contact inhibition, and tissue size. However, the role of YAP1 in intervertebral disc degeneration (IDD) remains elusive. Here, we demonstrated that YAP1 was activated by Interleukin 6 (IL‐6) through tyrosine phosphorylation in nucleus pulposus cells (NP cells). Overexpression of YAP1 decreased Sox‐9, Col‐II, aggrecan expression, whereas increased matrix metalloproteinases 13 level. In contrast, knockdown of YAP1 by small interfering RNA (siRNA) showed opposite effects and rescued IL‐6 induced NP cells degeneration. In addition, western blot showed that IL‐6 treatment increased YAP1 and β‐catenin protein level; co‐immunoprecipitation (Co‐IP) and immunofluorescence analysis showed that IL‐6 enhanced YAP1 and β‐catenin interaction and nuclear accumulation. Knockdown of β‐catenin by siRNA blocked IL‐6 treatment or YAP1 overexpression induced degeneration. Moreover, we found that verteporfin, a specific inhibitor of YAP1, effectively alleviated IDD development in rat disks. Taken together, our findings indicated that YAP1 plays an important role in IDD, and β‐catenin is essential for IL‐6/YAP1 signaling.