bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, synthesis, biological evaluation, and molecular dynamics of novel cholinesterase inhibitors as anti‐Alzheimer's agents
Authors: Shamsimeymandi Reza , Pourshojaei Yaghoub , Eskandari Khalil , Mohammadi‐Khanaposhtani Maryam , Abiri Ardavan , Khodadadi Arash , Langarizadeh Amin , Sharififar Fariba , Amirheidari Bagher , Akbarzadeh Tahmineh , Lotfian Hania , Foroumadi Alireza , Asadipour Ali 
Published: May 2019

AbstractA series of novel chroman‐4‐one derivatives were designed and synthesized successfully with good to excellent yield (3a–l). In addition, the obtained products were evaluated for their cholinesterase (ChE) inhibitory activities. The results show that among the various synthesized compounds, analogs bearing the piperidinyl ethoxy side chain with 4‐hydroxybenzylidene on the 3‐positions of chroman‐4‐one (3l) showed the most potent activity with respect to acetylcholinesterase (anti‐AChE activity; IC50 = 1.18 μM). In addition, the structure–activity relationship was studied and the results revealed that the electron‐donating groups on the aryl ring of the 3‐benzylidene fragment (3k,3l) resulted in the designed compounds to be more potent ChE inhibitors in comparison with those having electron‐withdrawing groups (3h). In this category, the strongest ChE inhibition was found for the compound containing piperidine as cyclic amine, and a hydroxyl group (for AChE, compound3l) and fluoro group (for butyrylcholinesterase (BuChE, compound3i) on thepara‐position of the aryl ring of the benzylidene group. The molecular docking and dynamics studies of the most potent compounds (3iand3lagainst BuChE and AChE, respectively) demonstrated remarkable interactions with the binding pockets of the ChE enzymes and confirmed the results obtained through in vitro experiments.
The relationship between symptoms of autism spectrum disorder and visual impairment among adults with intellectual disability
Authors: Kiani Reza , Bhaumik Sabyasachy , Tyrer Freya , Bankart John , Miller Helen , Cooper Sally Ann , Brugha Traolach Sean 
Published: May 2019

The higher prevalence of autism reported in blind children has been commonly attributed to the confounding effects of an underlying intellectual disability. The aim of this study was to explore the relationship between symptoms of autism and blindness in adults with intellectual disability. We hypothesized that blindness can increase the probability of the autism phenotype, independent of known risk factors, that is, severity of intellectual disability and gender. A general population case register (population size of 0.7 million) was used to conduct two studies. The first study was on 3,138 adults with intellectual disability, using a validated autism risk indicator to study adults with visual impairment. This identified 386 adults with partial and complete visual impairment, both of which were associated with presence of high number of autistic traits (P < 0.001). The second study was only on those with congenital blindness using a standardized assessment tool, the Pervasive Developmental Disorder—Mental Retardation Scale. Those with hearing impairment or unilateral, partial, and acquired visual impairment were excluded. Control groups were randomly selected from those with normal hearing and vision. Prevalence of the autism phenotype was higher among those with congenital blindness (n = 46/60; 76.7%) than their controls (n = 36/67; 53.7%) and this association was statistically significant (adjusted odds ratio = 3.03; 95% confidence interval: 1.34–6.89; P = 0.008). Our results support the hypothesis that a congenital blindness independently affects psychosocial development and increases the probability of the autism phenotype. Early identification of autism could facilitate appropriate psychosocial interventions and educational opportunities to improve quality of life of people with blindness. Autism Res 2019, 12: 1411–1422. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryAlthough autism has been commonly reported in those with blindness, it is generally attributed to an accompanying intellectual disability. Current study, however, revealed that congenital blindness is independently associated with symptoms of autism. In spite of its high prevalence, autism can be overlooked in those with intellectual disability and blindness. Improving diagnosis in this population should, therefore, be advocated through raising awareness of this association to facilitate early access to services.
Economic evaluation and comparison of succinic acid and electricity co‐production from sugarcane bagasse and trash lignocelluloses in a biorefinery, using different pretreatment methods: dilute acid (H2SO4), alkaline (NaOH), organosolv, ammonia fibre expansion (AFEX™), steam explosion (STEX), and wet oxidation
Authors: Nieder‐Heitmann Mieke , Haigh Kathleen , Louw Janus , Görgens Johann F. 
Published: May 2019

AbstractThe sugar yield achieved during pretreatment of lignocelluloses has an impact on the economic outcome of biorefineries. Chemical and physiochemical pretreatment methods were evaluated and compared to determine the most favorable pretreatment method for the commercial co‐production of succinic acid and electricity in a sugarcane lignocellulosic biorefinery. Nine methods were identified and simulated in Aspen Plus®. All the pretreatment methods were profitable except organosolv and wet oxidation. Steam explosion (STEX), sulfur dioxide (SO2), catalyzed STEX, and ammonia fibre expansion (AFEX™) resulted in the highest succinic acid yields, with 45.7, 43.5 and 33.4 kg succinic acid per 100 tonnes of dry feedstock, respectively, and they are recommended for commercial application. However, due to the high cost of enzymatic hydrolysis (46.23 million US$), the AFEX™ pretreatment method was the most expensive scenario at 385.7 million US$ total capital cost with an internal rate of return (IRR) of 22.81%. This may be compared with 384.2 million US$ for STEX pretreatment, which resulted in the most profitable biorefinery scenario with an IRR of 28.04%. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer
Authors: Liebs Sandra , Keilholz Ulrich , Kehler Inge , Schweiger Caroline , Haybäck Johannes , Nonnenmacher Anika 
Published: May 2019

AbstractEnthusiasm has emerged for the potential of liquid biopsies to provide easily accessible genetic biomarkers for early diagnosis and mutational cancer characterization. We here systematically investigated the suitability of circulating cell‐free DNA (cfDNA) analysis for mutation detection in colorectal cancer (CRC) patients with respect to clinicopathological disease stage. Droplet Digital PCR (ddPCR) was performed to detect common point mutations in the KRAS and BRAF oncogenes in cfDNA from 65 patients and compared to mutations in tumor tissue. Stage of disease was classified according to UICC (Union for International Cancer Control) criteria. In tumor tissue, KRAS or BRAF mutations were present in 35 of 65 cases (44% UICC stage I, 50% stage II, 47% stage III, and 62% stage IV). Although cfDNA was detected in 100% of patients, ddPCR displayed the tumor tissue mutation in only 1 of 6 (17%) stage II patients, whereas 10 of 18 (56%) reported variants were verified in cfDNA samples of the stage IV cohort. No BRAF or KRAS mutation was detected in cfDNA from patients with wild‐type tumor tissue. In one case of mutant stage II colon cancer (KRAS‐G12C), the G12D variant was detected in cfDNA instead. Further workup revealed that circulating tumor‐derived DNA and liver metastases originated from a synchronous KRAS‐mutated cancer of the pancreas. Our results demonstrate that ddPCR‐based analysis is highly specific and useful for mutation monitoring, but the sensitivity limits its usefulness for early cancer detection.
Chemical Strategies for Visualizing and Analyzing Endogenous Nonribosomal Peptide Synthetase (NRPS) Megasynthetases
Authors: Ishikawa Fumihiro , Tanabe Genzoh 
Published: May 2019

AbstractNonribosomal peptide (NRP) natural products are among the most promising resources for drug discovery and development, owing to their wide range of biological activities and therapeutic applications. These peptide metabolites are biosynthesized by large multienzyme machinery known as NRP synthetases (NRPSs). The structural complexity of a number of NRPs poses an enormous challenge in their synthesis. A major issue in this field is reprogramming NRPS machineries to allow the biosynthetic production of artificial peptides. NRPS adenylation (A) domains are responsible for the incorporation of a wide variety of amino acids and can be considered as reprogramming sites; therefore, advanced methods to accelerate the functional prediction and assessment of A‐domains are required. This Concept article demonstrates that activity‐based protein profiling of NRPSs offers a simple, rapid, and robust analytical platform for A‐domains and provides insights into enzyme–substrate candidates and active‐site microenvironments. It also describes the background associated with the development and application of a method to analyze endogenous NRPS machinery in its natural environment.
Hyperglycemia induces NF‐κB activation and MCP‐1 expression via downregulating GLP‐1R expression in rat mesangial cells: inhibition by metformin
Authors: Kang Zhanfang , Zeng Jianwen , Zhang Tian , Lin Shuyun , Gao Jun , Jiang Chonghe , Fan Rongrong , Yin Dazhong 
Published: May 2019

AbstractHyperglycemia impairs glucagon‐like peptide‐1 receptor (GLP‐1R) signaling in multiple cell types and thereby potentially attenuates the therapeutic effects of GLP‐1R agonists. We hypothesized that the downregulation of GLP‐1R by hyperglycemia might reduce the renal‐protective effects of GLP‐1R agonists in diabetic nephropathy (DN). In this study, we examined the effects of high glucose on the expression of GLP‐1R and its signaling pathways in the HBZY‐1 rat mesangial cell line. We found that high glucose reduced GLP‐1R messenger RNA (mRNA) levels in HBZY‐1 cells and in the renal cortex in db/db mice comparing with control groups. In consistence, GLP‐1R agonist exendin‐4 induced CREB phosphorylation was attenuated by high glucose but not low glucose treatment, which is paralleled with abrogated anti‐inflammatory functions in HBZY‐1 cells linked with nuclear factor‐κB (NF‐κB) activation. In consistence, GLP‐1R inhibition aggravated the high glucose‐induced activation of NF‐κB and MCP‐1 protein levels in cultured HBZY‐1 cells while overexpression of GLP‐1R opposite effects. We further proved that metformin restored high glucose‐inhibited GLP‐1R mRNA expression and decreased high glucose evoked inflammation in HBZY‐1 cells. On the basis of these findings, we conclude that high glucose lowers GLP‐1R expression and leads to inflammatory responses in mesangial cells, which can be reversed by metformin. These data support the rationale of combinative therapy of metformin with GLP‐1R agonists in DN.
A case of neck xanthogranulomatous inflammation‐suspected malignant tumor
Authors: Nomura Tsutomu , Momose Syuji , Takashima Masatoshi , Kikuchi Shigeru 
Published: May 2019

AbstractXanthogranulomatous inflammation (XGI) is an uncommon chronic inflammatory disease. A 59‐year‐old male presented with a neck mass which had been diagnosed as an undifferentiated carcinoma. From CD68 staining, XGI was confirmed. It is important to consider the possibility of XGI for a neck mass mimicking a malignant tumor.
Hydrochlorination of Acetylene Over the Activated‐Carbon‐Supported Au Catalysts Modified by N−P−O‐Containing Ligand
Authors: Zhang Chuanming , Zhang Haiyang , Li Yanqin , Xu Liang , Li Jian , Li Linfeng , Cai Ming , Zhang Jinli 
Published: May 2019

AbstractEtidronic acid (HEDP) and Nitrilotri(methylphosphonic acid) (ATMP) were selected as heteroatoms‐containing ligands to modify Au catalysts for acetylene hydrochlorination. Results from several analytical methods reveal an optimal mole ratio of Au/ligand (L) of 1 : 1, with obvious increments over the Au1‐L1/AC catalyst. The coordination between the Au and the heteroatoms, especially the collocative presence of N, P, and O promoted electron transfer from the heteroatoms to the Aun+ and increased the density of the electron cloud around active centers. This stabilized the Aun+ and increased the difficulty in the reduction of Au species, and re‐oxidized the Au0 to active Aun+ species. Moreover, the coordination inhibited the migration of active components. The increased density of the electron cloud around active centers also weakens the adsorption capacity for C2H2 and strengthens the adsorption ability for HCl of the catalysts, which is conductive for constructing the micro‐environment favorable to the reaction. DFT calculations proved the stabilization effect of the heteroatoms‐containing ligands, and the energy sequence of the transition states supported the experimental results.
Chiroptical study of cryptophanes subjected to self‐encapsulation
Authors: Baydoun Orsola , Buffeteau Thierry , Daugey Nicolas , Jean Marion , Vanthuyne Nicolas , Chapellet Laure‐Lise , De Rycke Nicolas , Brotin Thierry 
Published: May 2019

AbstractIn 1,1,2,2‐tetrachloroethane‐d2, the 129Xe NMR spectrum of the Xe@cryptophane‐223 complex bearing seven acetate groups (Xe@1 complex) shows an unusually broad signal compared with that of its congeners (Chapellet, LL. et al. J. Org. Chem. 2015;80:6143–6151). To interpret this unexpected behaviour, a 1H NMR analysis and a thorough study of the chiroptical properties of 1 as a function of the nature of the solvent have been performed. The 1H NMR spectra of 1 reveal that a self‐encapsulation phenomenon takes place in DMSO‐d6 and 1,1,2,2‐tetrachloroethane‐d2 solvents. Thanks to the separation of the two enantiomers of 1 by HPLC on chiral stationary phase, the two enantiomers of 1 have been studied in detail by polarimetry, electronic (ECD), and vibrational (VCD) circular dichroism spectroscopies. Except for ECD spectroscopy, these chiroptical techniques reveal spectroscopic changes as a function of the nature of the solvent. For instance, in DMSO and 1,1,2,2‐tetrachloroethane, in which the self‐encapsulation phenomenon takes place, the sign of the specific optical rotation of [CD(−)254]‐1 and [CD(+)254]‐1 is changed. These results have then been compared with those obtained with cryptophane‐223 bearing only one acetate group on the propylenedioxy linker (compound 2) and with cryptophane‐223 bearing six acetate groups (compound 3). A self‐encapsulation phenomenon is also observed with compound 2. Finally, compounds 2 and 3 show different chiroptical properties compared with those obtained with the two enantiomers of compound 1.
Entsalzung von Umkehrosmosekonzentraten mittels elektrisch getriebenen Membranverfahren zur Maximierung der Permeatausbeute einer Prozesswasseraufbereitungsanlage
Authors: Londoño David , Cumbana Rivelino , Gilbert Eva Marianne 
Published: May 2019

AbstractWeltweit größer werdende Wasserstress‐Probleme führen zu einer Verwendung von alternativen Wasserquellen wie Brack‐ oder Abwasser. Das Anschließen solcher Wasserquellen setzt die Verwendung von neuen Entsalzungstechnologien, wie die elektrisch getriebenen Membranverfahren, voraus. Hiermit wurden die Konzentrate einer Umkehrosmose so weit entsalzt, dass das Diluat erneut mittels Umkehrosmose behandelt werden konnte. Die zu entsorgende Konzentratmenge halbierte sich bei gleichzeitiger Erhöhung der Permeatausbeute. Im Fokus der Untersuchungen lag zudem der für die Behandlung notwendige Energiebedarf.
L'utilisation des forces au travail et les comportements proactifs et de citoyenneté organisationnelle: examen du rôle médiateur du bien‐être
Authors: Belleville Karel , Dubreuil Philippe , Courcy François 
Published: May 2019

AbstractPositive psychology suggests relying on workers' strengths to maintain balance between personal fulfillment and organizational goals. This article assesses whether the use of strengths in the workplace are associated with proactive behaviours and organizational citizenship behaviours (OCB) through the mediating role of well‐being. Data were collected from 142 French‐speaking Canadian professionals working in various non‐profit organizations. Results show that the use of strengths can predict some OCBs (notably mutual aid and civic virtue) as well as proactivity. Only the affective dimension of well‐being shows a mediation effect for mutual aid and proactivity. Theoretical contributions, implications for practitioners, limitations, and future research directions are also discussed.
Microenvironment and tumor inflammatory features improve prognostic prediction in gastro‐entero‐pancreatic neuroendocrine neoplasms
Authors: Milione Massimo , Miceli Rosalba , Barretta Francesco , Pellegrinelli Alessio , Spaggiari Paola , Tagliabue Giovanna , Centonze Giovanni , Paolino Cinzia , Mangogna Alessandro , Kankava Ketevani , Pusceddu Sara , Giacomelli Luca , Corti Ambra , Cotsoglou Christian , Mazzaferro Vincenzo , Sozzi Gabriella , de Braud Filippo , Pruneri Giancarlo , Anichini Andrea 
Published: May 2019

AbstractMicroenvironment‐related immune and inflammatory markers, when combined with established Ki‐67 and morphology parameters, can improve prognostic prediction in gastro‐entero‐pancreatic neuroendocrine neoplasms (GEP‐NENs). Therefore, we evaluated the prognostic value of microenvironment and tumor inflammatory features (MoTIFs) in GEP‐NENs. For this purpose, formalin‐fixed paraffin‐embedded tissue sections from 350 patients were profiled by immunohistochemistry for immune, inflammatory, angiogenesis, proliferation, NEN‐, and fibroblast‐related markers. A total of 314 patients were used to generate overall survival (OS) and disease‐free survival (DFS) MoTIFs prognostic indices (PIs). PIs and additional variables were assessed using Cox models to generate nomograms for predicting 5‐year OS and DFS. A total of 36 patients were used for external validation of PIs and nomograms' prognostic segregations. From our analysis, G1/G2 versus G3 GEP‐NENs showed phenotypic divergence with immune‐inflammatory markers. HLA, CD3, CD8, and PD‐1/PD‐L1 IHC expression separated G3 into two sub‐categories with high versus low adaptive immunity‐related features. MoTIFs PI for OS based on COX‐2Tumor(T) > 4, PD‐1Stromal(S) > 0, CD8S < 1, and HLA‐IS < 1 was associated with worst survival (hazard ratio [HR] 2.50; 95% confidence interval [CI], 2.12–2.96; p < 0.0001). MoTIFs PI for DFS was based on COX‐2T > 4, PD‐1S > 4, HLA‐IS < 1, HLA‐IT < 2, HLA‐DRS < 6 (HR 1.77; 95% CI, 1.58–1.99; p < 0.0001). Two nomograms were developed including morphology (HR 4.83; 95% CI, 2.30–10.15; p < 0.001) and Ki‐67 (HR 11.32; 95% CI, 5.28–24.24; p < 0.001) for OS, and morphology (PI = 0: HR 10.23; 95% CI, 5.67–18.47; PI = 5: HR 2.87; 95% CI, 1.21–6.81; p < 0.001) and MoTIFs PI for DFS in well‐differentiated GEP‐NENs (HR 6.21; 95% CI, 2.52–13.31; p < 0.001). We conclude that G1/G2 to G3 transition is associated with immune‐inflammatory profile changes; in fact, MoTIFs combined with morphology and Ki‐67 improve 5‐year DFS prediction in GEP‐NENs. The immune context of a subset of G3 poorly differentiated tumors is consistent with activation of adaptive immunity, suggesting a potential for responsiveness to immunotherapy targeting immune checkpoints.
Oxygen‐Doped Ta3N5 Nanoparticles for Enhanced Z‐Scheme Carbon Dioxide Reduction with a Binuclear Ruthenium(II) Complex under Visible Light
Authors: Muraoka Kanemichi , Vequizo Junie Jhon M. , Kuriki Ryo , Yamakata Akira , Uchiyama Tomoki , Lu Daling , Uchimoto Yoshiharu , Ishitani Osamu , Maeda Kazuhiko 
Published: May 2019

AbstractMetal‐complex/semiconductor hybrids are promising photocatalysts for visible‐light CO2 reduction with high selectivity for the formation of a desired product. Herein we applied nanoparticulate Ta3N5/SiO2 as the semiconductor component of a hybrid system with the aid of a binuclear ruthenium(II) complex. The Ta3N5/SiO2 material was prepared by the nitridation of nanoparticulate Ta2O5/SiO2 (which had been previously synthesized by a sol‐gel method) under a flow of NH3 gas at 973–1223 K. The synthesized hybrid reduced CO2 into formate with very high selectivity (>99 %) under irradiation with visible light (λ>480 nm). The activity increased with nitridation temperature up to 1023 K, beyond which it began to drop. The optimized photocatalyst, which consisted of oxygen‐doped Ta3N5 as revealed by UV‐visible diffuse reflectance spectroscopy and X‐ray photoelectron spectroscopy, exhibited 6 times higher activity than that for an analogous hybrid constructed with bulk Ta3N5. Physicochemical analyses indicated that reducing the defect density by high‐temperature nitridation contributed to the suppression of charge recombination, which resulted in higher activity of Ta3N5/SiO2, while a nitridation temperature that was too high was undesirable because of a decrease in the reactivity of photogenerated holes due to a loss of the doped oxygen content in Ta3N5.
Using Density Functional Theory Based Methods to Investigate the Photophysics of Polycyclic Aromatic Hydrocarbon Radical Cations: A Benchmark Study on Naphthalene, Pyrene and Perylene Cations
Authors: Boggio‐Pasqua Martial , Bearpark Michael J. 
Published: May 2019

AbstractUnrestricted DFT (UDFT), time‐dependent DFT (TDDFT) and spin‐flip TDDFT (SF‐TDDFT) were used to investigate the potential energy surfaces of the ground and first two electronic excited states of the naphthalene, pyrene and perylene radical cations. In particular, conical intersections (which play a central role in the photophysics of these cations) were located with these DFT‐based methods. The results are consistent with accurate multiconfigurational wavefunction‐based ab initio methods. These show that naphthalene and pyrene cations can quickly relax nonradiatively from their excited states back down to the original ground state species through easily accessible conical intersections, but the perylene cation cannot do so, due to the absence of any accessible funnels between the lowest excited state and the ground state, leaving radiative decay as the most probable photophysical pathway. This study paves the way for using computationally efficient density functional theory (DFT)‐based methods in future investigations of the photophysics of much larger polycyclic aromatic hydrocarbons, for which multiconfigurational wavefunction‐based methods become prohibitively expensive.
Developmental Changes in Task‐Induced Brain Deactivation in Humans Revealed by a Motor Task
Authors: Morita Tomoyo , Asada Minoru , Naito Eiichi 
Published: May 2019

AbstractPerforming tasks activates relevant brain regions in adults while deactivating task‐irrelevant regions. Here, using a well‐controlled motor task, we explored how deactivation is shaped during typical human development and whether deactivation is related to task performance. Healthy right‐handed children (8–11 years), adolescents (12–15 years), and young adults (20–24 years; 20 per group) underwent functional magnetic resonance imaging with their eyes closed while performing a repetitive button‐press task with their right index finger in synchronization with a 1‐Hz sound. Deactivation in the ipsilateral sensorimotor cortex (SM1), bilateral visual and auditory (cross‐modal) areas, and bilateral default mode network (DMN) progressed with development. Specifically, ipsilateral SM1 and lateral occipital deactivation progressed prominently between childhood and adolescence, while medial occipital (including primary visual) and DMN deactivation progressed from adolescence to adulthood. In adults, greater cross‐modal deactivation in the bilateral primary visual cortices was associated with higher button‐press timing accuracy relative to the sound. The region‐specific deactivation progression in a developmental period may underlie the gradual promotion of sensorimotor function segregation required in the task. Task‐induced deactivation might have physiological significance regarding suppressed activity in task‐irrelevant regions. Furthermore, cross‐modal deactivation develops to benefit some aspects of task performance in adults.