bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and neuroimaging risk factors for cognitive decline in community‐dwelling older adults living in rural Ecuador. A population‐based prospective cohort study
Authors: Del Brutto Oscar H. , Mera Robertino M. , Del Brutto Victor J. , Zambrano Mauricio , Wright Clinton B. , Rundek Tatjana 
Published: November 2018

ObjectiveThere is limited information on factors influencing cognitive decline in rural settings from low‐ and middle‐income countries. Using the Atahualpa Project cohort, we aimed to assess the burden of cognitive decline in older adults living in a rural Ecuadorian village.MethodsThe study included Atahualpa residents aged greater than or equal to 60 years who had a follow‐up Montreal Cognitive Assessment (MoCA) repeated at least 1 year after baseline. MoCA decline was assessed by multivariable longitudinal linear models, adjusted for demographics, days between MoCA tests, cardiovascular risk factors, and neuroimaging signatures of structural brain damage.ResultsWe included 252 individuals who contributed 923.7 person‐years of follow‐up (mean: 3.7 ± 0.7 years). The mean baseline MoCA was 19.5 ± 4.5 points, and the follow‐up MoCA was 18.1 ± 4.9 points (P = 0.001). Overall, 154 individuals (61%) had lower MoCA scores at follow‐up. The best fitted longitudinal linear model showed a decline of follow‐up MoCA from baseline (β: 0.14; 95% CI, 0.0‐0.21; P < 0.001). High glucose levels, global cortical atrophy, and white matter hyperintensities were independently and significantly associated with greater MoCA decline.ConclusionThis study provides evidence of cognitive decline in older adults living in a rural setting. Main targets for prevention should include glucose control and the control of factors that are deleterious for the development of cortical atrophy and white matter hyperintensities.
Reactions of aminopyrimidine derivatives with chloroacetyl and isophthaloyl chlorides
Authors: Çimen Zeynep , Akkoç Senem , Kökbudak Zülbiye 
Published: November 2018

Abstract1‐Aminopyrimidine‐2‐one derivatives (1a‐c) were prepared in two steps from furan‐2,3‐diones and semicarbazones in toluene/benzene. Pyrimidin‐[1(2H)‐yl] acetamide derivatives and isophthalimide derivatives were synthesized from the nucleophilic acyl substitution reactions of compounds 1a‐c with chloroacetyl chloride. The structures of compounds 2a‐f were verified by IR, 1H NMR, 13C NMR and elemental analyses. The obtained final organic compounds were tested as catalysts in the Mizoroki‐Heck coupling reaction. They mostly exhibited very high catalytic activity results for the coupling reaction of styrene with different aryl bromide derivatives.
Diagnostic accuracy of chest ultrasound in patients with pneumonia in the intensive care unit: A single‐hospital study
Authors: Bitar Zouheir Ibrahim , Maadarani Ossama Sajeh , El‐Shably AlAsmar Mohammed , Al‐Ajmi Mubarak Juwaied 
Published: November 2018

AbstractBackground and aimsChest radiography (CXR) and computerized tomography (CT) scan are the preferred methods for lung imaging in diagnosing pneumonia in the intensive care unit, in spite of their limitations. The aim of this study was to assess the performance of bedside lung ultrasound examination by a critical care physician, compared with CXR and chest CT, in the diagnosis of acute pneumonia in the ICU.Materials and MethodsThis was an observational, prospective, single‐center study conducted in the intensive care unit of Ahmadi General Hospital. Lung ultrasound examinations (LUSs) were performed by trained critical care physicians, and a chest radiograph was interpreted by another critical care physician blinded to the LUS results. CT scans were obtained when clinically indicated by the senior physician.ResultsOut of 92 patients with suspected pneumonia, 73 (79.3%) were confirmed to have a diagnosis of pneumonia based on radiological reports, clinical progress, inflammatory markers, and microbiology studies. Of the 73 patients, 31 (42.5%) were male, with a mean age of 68.3 years, and a range of 27 to 94 years. Eleven (15%) patients had community‐acquired pneumonia, and 62 (85%) had hospital‐acquired pneumonia. In the group of patients with confirmed pneumonia, 72 (98.6%) had LUSs positive for consolidation (sensitivity 98.6%, 95% CI 92.60%‐99.97%), and in the group without pneumonia, 16 (85%) had LUS negative for consolidation (specificity 84.2%, 95% CI 60.42%‐96.62%), compared with 40 (55%) with CXRs positive for consolidation (sensitivity 54.8%, 95% CI 42.70%‐66.48%) and 33 (45%) with CXRs negative for consolidation (specificity 63.16%, 95% CI 38.36%‐83.71%).A chest CT was performed in 38 of the 92 enrolled patients and was diagnostic for pneumonia in 32 cases. LUSs were positive in 31 of 32 patients with CT‐confirmed pneumonia (sensitivity 96%), and CXR was positive in 5 of 32 patients with CT‐confirmed pneumonia (sensitivity 15.6%).ConclusionBedside lung ultrasound is a reliable and accurate tool that appears to be superior to CXR for diagnosing pneumonia in the ICU setting. LUS allows for a faster, non‐invasive, and radiation‐free method to diagnose pneumonia in the ICU.
Isotopic composition of precipitation during strong El Niño–Southern Oscillation events in the Southeast Region of Brazil
Authors: dos Santos Vinícius , Dias de Oliveira Marcelo , Boll Jan , Sánchez‐Murillo Ricardo , Menegário Amauri Antonio , Gozzo Luiz Felippe , Gastmans Didier 
Published: November 2018

AbstractEquatorial Pacific sea surface temperature variations interact with processes of atmospheric circulation, creating conditions for the occurrence of El Niño–Southern Oscillation (ENSO). ENSO events represent the most important interannual phenomena affecting climate patterns worldwide and causing significant socio‐economic impacts. In the Brazilian territory, ENSO leads to an increase in drought episodes in the north‐eastern region and an increase in precipitation in the southern region, whereas the effects over the south‐east region are yet not well understood. The main goal of this study is to compare variations of isotopic composition in precipitation across the south‐east portion of the Brazilian territory during two very strong ENSO events: 1997–1998 (ENSO 1) and 2014–2016 (ENSO 2). Daily isotopic records, available from the Global Network of Isotopes in Precipitation database for ENSO 1, and samples collected during ENSO 2 were used to compare the influence of both events on the isotopic composition of precipitation. Seasonal variations indicated more depleted precipitation during the wet seasons (δ18O = −5.4 ± 4.0‰) and enriched precipitation during the dry seasons (δ18O = −2.8 ± 2.3‰). Observed rainfall variations were associated with atmospheric large‐scale processes and moisture transport from the Amazon region, whereas extreme values (enriched or depleted) appear to be associated with particular convective and stratiform precipitation events. Overall, more depleted isotopic composition of precipitation (δ18O = −4.60‰) and higher d‐excess (up to +15‰) were observed during the dry season of ENSO 1 when compared with ENSO 2 dry season (δ18O‰ = −2.80‰, d‐excess lower than +14‰). The latter is explained by greater atmospheric moisture content, particularly associated with recycling of transpiration fluxes from the Amazon region, during dry season of ENSO 1. No significant differences for δ18O and δ2H were observed during the wet season; however, d‐excess from ENSO 2 was greater than ENSO 1, due to the slightly greater atmospheric moisture content and very strong upward motion observed. Our findings highlight the opportunity that environmental isotopes offer towards understanding hydrometeorological processes, particularly, the evolution of extreme climatic events of global resonance such as ENSO.
Synthesis, Structure and Sensing Property of Novel Zinc(II) Framework with Mixed 3,3′,5,5′‐Tetra(1H‐imidazol‐1‐yl)biphenyl and 2,6‐Naphthalenedicarboxylate Ligands
Authors: Xu Yong‐Liang , Liu Yi , Liu Xiao‐Hui , Zhao Yue , Wang Zheng‐Liang , Sun Wei‐Yin 
Published: November 2018

AbstractWith increasing use of antibiotics, it becomes more and more important for selectively and sensitively detecting antibiotics. In this work, a new Zn(II) framework [Zn2(L)(NDC)(HCOO)2] ⋅ 2H2O (1) was achieved by using organic ligands 3,3′,5,5′‐tetra(1H‐imidazol‐1‐yl)biphenyl (L) and 2,6‐naphthalenedicarboxylic acid (H2NDC). 1 has three‐dimensional (3D) framework structure and exhibits strong luminescence in the solid state as well as in the suspended acetonitrile solution. Furthermore, it was found that the emission of 1 can be quenched efficiently by trace amounts of nitrofuran antibiotics (NFs) including nitrofurazone (NZF), furazolidone (FZD) and nitrofurantoin (NFT) with detection limits of 184, 243 and 263 ppb for NZF, FZD and NFT, respectively, even in the presence of other antibiotics such as penicillin (PCL).
Gelatin nonwovens‐based epithelial morphogenesis involves a signaling axis comprising EGF‐receptor, MAP kinases ERK 1/2, and β1 integrin
Authors: Jedrusik Nicole , Steinberg Thorsten , Husari Ayman , Volk Lukas , Wang Xiaoling , Finkenzeller Günter , Strassburg Sandra , Tomakidi Pascal 
Published: November 2018

AbstractIn biomaterials research, biomechanics which support tissue regeneration steadily gains of importance. Hence, we have previously shown that gelatin‐based electrospun nonwoven mats (NWMs) with a distinct modulus of elasticity (3.2 kPa) promotes epithelial morphogenesis. Since molecular mechanisms of this morphogenesis are still unknown, the present study aims at identifying molecules, involved herein. Epithelia established on the NMWs showed persistence of the activated state of the epidermal growth factor receptor (EGF‐R), phosphorylated at the src‐specific tyrosine 845 (EGF‐RT845) throughout the observation period of 10 days. To elucidate whether the observed morphogenesis mechanistically involves EGF‐R signaling, we inhibited EGF‐R, by employing the EGF‐RT845 specific inhibitor Gefitinib (IRESSA®). Gefitinib administration yielded a reduced expression of the β1 integrin subunit, a well‐known cell–matrix interaction receptor, concomitant with downregulation of p42/44 ERK1/2 MAP‐kinase activity. To elucidate whether the observed downregulation of β1 is EGF‐RT845‐dependent or emerging from ERK1/2 signaling, we exposed epithelia, grown on the NWMs, with the ERK1/2‐directed inhibitor U0126. In the absence of Gefitinib, inhibition of p42/44 MAP‐kinase activity resulted in decreased β1 integrin protein levels, thus indicating that β1 expression is dependent on ERK1/2 and not EGF‐RT845. Our results showed the first time that an EGF‐R‐β1 integrin‐signaling axis, including ERK1/2, promotes NWM‐elasticity‐based epithelial morphogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 663–677, 2019.
Balancing biofunctional and biomechanical properties using porous titanium reinforced by carbon nanotubes
Authors: Pavón Juan Jose , López Diana , Mondragón Fanor , Gallego Jaime , Arias Sandra L. , Luitjohan Kara , Holybee Brandon , Torres Yadir , Rodríguez José A. , Echeverry‐Rendón Mónica , Civantos Ana , Allain Jean Paul 
Published: November 2018

AbstractDespite the well‐known advantages of the titanium‐based implant systems, they still lack an optimal balance between biofunctionality and mechanical strength, especially regarding the modulation of cellular response and a desired implant osseointegration. In this work, we fabricated a nanocomposite based on porous commercially pure grade 4 titanium (c.p. Ti) reinforced with carbon nanotubes (CNT) at 5% and 10% w/w, with the aim of obtaining a nanocomposite with lower stiffness compared to traditional titanium‐based implants and with the mechanical strength and bioactivity owed by the CNT. Results obtained by scanning electron microscopy, X‐ray photoelectron spectroscopy, and atomic force microscopy characterization showed that the CNT dispersed and incorporated into the porous c.p. Ti matrix. Interestingly, CNT were associated with a higher twining within neighbor Ti grains, which was indeed consistent with an increased in nano‐hardness. Biological evaluation by MTT and Comet assay revealed that the nanocomposites did not induce genotoxicity and cytotoxicity on two different cells lines despite the presence of nickel at the surface. Accordingly, a purification step would be required before these CNT can be used for biomedical applications. Our results indicate that incorporation of CNT into porous c.p. Ti is a promising avenue to achieve an adequate balance between biofunctionality and mechanical strength in Ti‐based scaffolds for tissue replacement. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 719–731, 2019.
Retracted: MicroRNA‐34a inhibit hepatocellular carcinoma progression by repressing hexokinase‐1
Authors: Zhou Yitong , Liu Kai , Liu Yahui , Tan Ludong 
Published: November 2018

AbstractHepatocellular carcinoma (HCC) is known as a frequent type of primary cancer in the liver, and it is the third‐most common cause of cancer‐related death all over the world. However, the molecular mechanism in the progression of HCC is still unclear. The current study was designed to investigate the expression and function of microRNA‐34a (miR‐34a) in HCC. In HCC tissues and cells, the expression levels of miR‐34a were analyzed by quantitative real‐time polymerase chain reaction. The association between the level of miR‐34a and hexokinase (HK)‐1 was also investigated via luciferase reporter assay. Cell viability and proliferation were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and flow cytometry. To assess whether miR‐34a can limit tumor growth in vivo, animal models and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used for examining the role of miR‐34a on the development of HCC and cell apoptosis. The expression level of miR‐34a was reduced in HCC samples and cells. The expression of miR‐34a was associated with the viability and proliferation capacity of HCC cells, and miR‐34a could inhibit HCC cells proliferation by inhibiting HK1. In the mouse model of HCC, volumes and weight of the tumors were significantly decreased by transfection with miR‐34a mimic compared with the control group. Furthermore, miR‐34a mimics could induce apoptosis in a greater proportion of cells compared with the control group. Taken together, the data may provide some novel insights into the molecular mechanism of miR‐34a and HK1 in the progression of HCC. Thus, miR‐34a/HK1 axis might be a novel promising therapeutic target for treating HCC.
Analysis of long noncoding RNA expression profiles in the whole blood of neonates with hypoxic‐ischemic encephalopathy
Authors: Dong Xiaohua , Zhao Yingmin , Huang Yun , Yu Lingling , Yang Xiaojing , Gao Feng 
Published: November 2018

AbstractLong noncoding RNAs (lncRNAs) have been shown to participate in many biological processes. To investigate the expression profiles of lncRNAs and their potential functions in neonatal hypoxic‐ischemic encephalopathy (HIE), we detected the lncRNA and messenger RNA (mRNA) expression in the peripheral blood samples from HIE patients and controls using a microarray. A total of 376 lncRNAs and 126 mRNAs were differentially expressed between the HIE and the non‐HIE samples (fold change > 2). Quantitative real‐time polymerase chain reaction was used to validate the microarray data. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to determine the gene function. Furthermore, the lncRNA‐mRNA coexpression network was generated to predict the potential targets of lncRNAs. In conclusion, our study first demonstrated the differential expression profiles of lncRNAs in the whole blood of infants with HIE and may provide a new view of the distinct lncRNA functions in HIE.
Virtual screening of National Cancer Institute database for claudin‐4 inhibitors: Synthesis, biological evaluation, and molecular dynamics studies
Authors: Rambabu Majji , Jayanthi Sivaraman 
Published: November 2018

AbstractClaudin‐4 (CLDN4) is a vital member of tight‐junction proteins that is often overexpressed in cancer and other malignancies. The three‐dimensional structure of human CLDN4 was constructed based on homology modeling approach. A total of 265 242 molecules from the National Cancer Institute (NCI) database has been utilized as a dataset for this study. In the present work, structure‐based virtual screening is performed with the NCI database using Glide. By molecular docking, 10 candidate molecules with high scoring functions, which binds to the active site of CLDN4 were identified. Subsequently, molecular dynamics simulations of membrane protein were used for optimization of the top‐three lead compounds (NCI110039, NCI344682, and NCI661251) with CLDN4 in a dynamic system. The lead molecule from NCI database NCI11039 (purpurogallin carboxylic acid) was synthesized and cytotoxic properties were evaluated with A549, MCF7 cell lines. Our docking and dynamics simulations predicted that ARG31, ASN142, ASP146, and ARG158 as critically important residues involved in the CLDN4 activity. Finally, three lead candidates from the NCI database were identified as potent CLDN4 inhibitors. Cytotoxicity assays had proved that purpurogallin carboxylic acid had an inhibitory effect towards breast (MCF7) and lung (A549) cancer cell lines. Computational insights and in vitro (cytotoxicity) studies reported in this study are expected to be helpful for the development of novel anticancer agents.
Abuse Potential of Samidorphan: A Phase I, Oxycodone‐, Pentazocine‐, Naltrexone‐, and Placebo‐Controlled Study
Authors: Pathak Sanjeev , Vince Bradley , Kelsh Debra , Setnik Beatrice , Nangia Narinder , DiPetrillo Lauren , Puhl Matthew D. , Sun Lei , Stanford Arielle D. , Ehrich Elliot 
Published: November 2018

AbstractSamidorphan is a μ‐opioid receptor antagonist in development for the treatment of schizophrenia, in combination with olanzapine, and major depressive disorder, in combination with buprenorphine, at proposed therapeutic doses of samidorphan 10 mg and 2 mg, respectively. A double‐blind, double‐dummy, active‐ and placebo‐controlled, crossover study evaluated the abuse potential of samidorphan in healthy, nondependent, recreational opioid users. Following a qualification phase, participants were randomized to 1 of 6 treatment sequences of study drugs: placebo, samidorphan (10 or 30 mg), oxycodone (40 mg), pentazocine (30 mg), and naltrexone (100 mg) in a 6 × 6 Williams design. The primary end point was maximum effect (Emax) for “at‐the‐moment” Drug Liking visual analog scale scores. Secondary end points included Emax visual analog scale scores for Take Drug Again and Overall Drug Liking and safety assessments. Among 47 participants, at‐the‐moment Emax Drug Liking scores for positive study controls oxycodone and pentazocine were significantly higher than placebo (P < .001) and samidorphan (both doses; P < .001). Both samidorphan doses had Emax Drug Liking scores similar to placebo and naltrexone (median within‐subject differences of 0.0). Emax Take Drug Again scores for samidorphan (both doses) were higher than placebo, but similar to naltrexone, an unscheduled μ‐opioid receptor antagonist. Adverse events to evaluate abuse potential occurred less frequently with samidorphan, naltrexone, and placebo than with oxycodone and pentazocine. Findings from this study support a lack of abuse potential with samidorphan at doses up to 30 mg and a safety profile consistent with previous samidorphan clinical studies.
Catalytic performance of Ni supported on ZnO‐Al2O3 composites with different Zn content in methane dry reforming
Authors: Masoom Nataj Seyedeh Molood , Alavi Seyed Mehdi , Mazloom Golshan 
Published: November 2018

AbstractBACKGROUNDBecause of increasing environmental contaminations, hydrogen has attracted much attention as an effective and clean energy source. In addition, hydrogen and syngas are raw materials used in the production of valuable compounds. Methane dry reforming is one common method for syngas production. In this work, Ni catalysts supported on different ZnO–Al2O3 composite oxides were prepared. The effects of variation in Zn/Al ratio (Zn/Al = 0, 0.33, 0.5, 1, 2 and 3) on physico‐chemical properties and their activity and stability in methane dry reforming were investigated.RESULTSThe results indicated that Zn addition led to decreasing surface area, weakening the interaction between active phase and support, improving Ni reduction and therefore enhancing initial activity.CONCLUSIONWhen Zn content was low or just enough to produce ZnAl2O4 phase, only metallic Ni particles were detected after reaction which led to carbon filaments formation and deactivation of catalysts. Increasing Zn content formed NiZn alloy that played essential roles in activity and stability. High amounts of Zn (Zn/Al = 3) did not favor promoting effects due to the increasing active phase sizes and decreasing contact area. Ni/ZnO–Al2O3 with Zn/Al = 2 exhibited the highest activity and stability in methane dry reforming. © 2018 Society of Chemical Industry
Design, Synthesis, and Antifungal Activity of 3‐(Thiophen‐2‐yl)‐1,5‐dihydro‐2H‐pyrrol‐2‐one Derivatives Bearing a Carbonic Ester Group
Authors: Wang Xiaobin , Ren Zhengjiao , Mei Yudong , Liu Menghan , Chen Min , Si Weijie , Yang Chunlong , Song Yimin 
Published: November 2018

A series of 3‐(thiophen‐2‐yl)‐1,5‐dihydro‐2H‐pyrrol‐2‐one derivatives bearing a carbonic ester group were designed and synthesized by integrating a thiophene nucleus and a pyrroline‐2‐one scaffold in a single molecular architecture. Their structures were confirmed by IR, 1H‐NMR, EI‐MS, and elemental analyses, and their antifungal activities against Fusarium graminearum (Fg), Rhizoctorzia solani (Rs), and Botrytis cinerea (Bc) were evaluated. The antifungal bioassays indicated that some title compounds exhibited desirable antifungal effects against the tested fungi. Strikingly, the title compounds 4i, 4k, 4n, and 4o showed obvious antifungal activities against Rs, with corresponding EC50 values of 35.26, 33.56, 23.90, and 30.48 μg/mL, respectively, which are better than that of hymexazol (37.86 μg/mL). These results indicated that 3‐(thiophen‐2‐yl)‐1,5‐dihydro‐2H‐pyrrol‐2‐one derivatives bearing a carbonic ester group can serve as potential structural templates in the search for novel high‐efficient fungicides.
Immune rebalancing by oral immunotherapy: A novel method for getting the immune system back on track
Authors: Ilan Yaron 
Published: November 2018

Abstract
Immune modulating treatments are often associated with immune suppression or an opposing anti-inflammatory paradigm. As such, there is a risk of exposing patients to infections and malignancies. Contrarily, eliciting only mild immune modulation can be insufficient for alleviating immune-mediated damage. Oral immunotherapy is a novel approach that uses the inherent ability of the gut immune system to generate signals that specifically suppress inflammation at affected sites, without inducing generalized immune suppression. Oral immunotherapy is being developed as a method to rebalance systemic immunity and restore balance, getting it back on track, rather than pushing the immune response too much or too little in opposing directions. Here, I review recent preclinical and clinical data examining the technique and describe its primary advantages.