bluuebunny/crossref_metadata_2025 huggingface dataset:
Smart Tandem Catalyst Developed with Sundew's Predation Strategy, Capable of Catching, Decomposing and Assimilating Preys
Authors: Xiao Panpan , Wu Shuping , Shen Xiaojuan , Zhu Maiyong , Li Songjun
Published: September 2018

This study is aimed at the present challenge in tandem catalysts, addressing how to endow the catalysts with self‐controlled tandem catalytic‐ability. By borrowing the predation strategy from sundew, the objective was originally met by reporting a smart tandem catalyst which can self‐control the tandem catalytic behavior by catching, decomposing and assimilating the engaging molecules (such as 4‐nitrophenyl acetate). This catalyst was made of a unique leaf containing two functional layers where each may be responsible for one coupled process. The first layer in this catalyst was fabricated with a zipper‐like reactive polymer capable of opening and closing, which allowed the catalyst to catch and decompose 4‐nitrophenyl acetate. The second layer in this catalyst allowed, however, further access to assimilate the decomposed substrate (i. e., 4‐nitrophenol), made of an antibody‐like polymer and encapsulated metal nanoparticles. In this way, the use of this catalyst led to the occurrence of the self‐controlled tandem catalytic‐ability. This novel design suggests a new protocol for developing smart tandem catalysts, which opens new opportunities for controlled tandem catalytic processes.
Dual‐Mode, Anisotropy‐Encoded, Ratiometric Fluorescent Nanosensors: Towards Multiplexed Detection
Authors: Rampazzo Enrico , Bonacchi Sara , Juris Riccardo , Genovese Damiano , Prodi Luca , Zaccheroni Nelsi , Montalti Marco
Published: September 2018

A nanosensor with dual‐mode fluorescence response to pH and an encoded identification signal, was developed by exploiting excitation energy transfer and tailored control of molecular organization in core–shell nanoparticles. Multiple signals were acquired in a simple single‐excitation dual‐emission channels set‐up.
A Lasso‐Inspired Bicyclic Peptide: Synthesis, Structure and Properties
Authors: Martin‐Gómez Helena , Albericio Fernando , Tulla‐Puche Judit
Published: September 2018

The chemical synthesis of a bicycle inspired by the natural lasso peptide sungsanpin using a combination of solid‐phase and in‐solution chemistries is described. The bicyclic‐derived topoisomer was designed by introducing a covalent linkage between the ring and the loop, which allowed the tying of these two parts of the peptide, rendering the bicyclic structure. Several structural techniques, such as MS fragmentation, ion‐mobility and NMR spectroscopic analysis were used to characterize the bicycle. Ion‐mobility spectroscopy studies revealed that it showed lasso‐like behavior. Its 3D structure was predicted on the basis of the NMR restraints. In addition, the high proteolytic and thermal stability of the bicycle potentially make it a suitable scaffold for epitope grafting.
Influence of the Lewis Acid/Base Pairs on the Reactivity of Geminal E‐CH2‐E′ Frustrated Lewis Pairs
Authors: Cabrera‐Trujillo Jorge Juan , Fernández Israel
Published: September 2018

The influence of the nature of the acid/base pairs on the reactivity of geminal frustrated Lewis pairs (FLPs) (Me2E‐CH2‐E′Ph2) has been computationally explored within the density functional theory framework. To this end, the dihydrogen‐activation reaction, one of the most representative processes in the chemistry of FLPs, has been selected. It is found that the activation barrier of this transformation as well as the geometry of the corresponding transition states strongly depend on the nature of the E/E′ atoms (E=Group 15 element, E′=Group 13 element) in the sense that lower barriers are associated with earlier transition states. Our calculations identify the geminal N/Al FLP as the most active system for the activation of dihydrogen. Moreover, the barrier height can be further reduced by replacing the phenyl group attached to the acidic atom by C6F5 or 3,5‐(CF3)2C6H3 (Fxyl) groups. The physical factors controlling the computed reactivity trends are quantitatively described in detail by means of the activation strain model of reactivity combined with the energy decomposition analysis method.
Surface‐Active Fluorinated Quantum Dots for Enhanced Cellular Uptake
Authors: Argudo Pablo G. , Carril Mónica , Martín‐Romero María T. , Giner‐Casares Juan J. , Carrillo‐Carrión Carolina
Published: September 2018

Fluorescent nanoparticles, such as quantum dots, hold great potential for biomedical applications, mainly sensing and bioimaging. However, the inefficient cell uptake of some nanoparticles hampers their application in clinical practice. Here, the effect of the modification of the quantum dot surface with fluorinated ligands to increase their surface activity and, thus, enhance their cellular uptake was explored.
Regional vesicular acetylcholine transporter distribution in human brain: A [18F]fluoroethoxybenzovesamicol positron emission tomography study
Authors: Albin Roger L. , Bohnen Nicolaas I. , Muller Martijn L. T. M. , Dauer William T. , Sarter Martin , Frey Kirk A. , Koeppe Robert A.
Published: September 2018

Prior efforts to image cholinergic projections in human brain in vivo had significant technical limitations. We used the vesicular acetylcholine transporter (VAChT) ligand [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) and positron emission tomography to determine the regional distribution of VAChT binding sites in normal human brain. We studied 29 subjects (mean age 47 [range 20–81] years; 18 men; 11 women). [18F]FEOBV binding was highest in striatum, intermediate in the amygdala, hippocampal formation, thalamus, rostral brainstem, some cerebellar regions, and lower in other regions. Neocortical [18F]FEOBV binding was inhomogeneous with relatively high binding in insula, BA24, BA25, BA27, BA28, BA34, BA35, pericentral cortex, and lowest in BA17–19. Thalamic [18F]FEOBV binding was inhomogeneous with greatest binding in the lateral geniculate nuclei and relatively high binding in medial and posterior thalamus. Cerebellar cortical [18F]FEOBV binding was high in vermis and flocculus, and lower in the lateral cortices. Brainstem [18F]FEOBV binding was most prominent at the mesopontine junction, likely associated with the pedunculopontine–laterodorsal tegmental complex. Significant [18F]FEOBV binding was present throughout the brainstem. Some regions, including the striatum, primary sensorimotor cortex, and anterior cingulate cortex exhibited age‐related decreases in [18F]FEOBV binding. These results are consistent with prior studies of cholinergic projections in other species and prior postmortem human studies. There is a distinctive pattern of human neocortical VChAT expression. The patterns of thalamic and cerebellar cortical cholinergic terminal distribution are likely unique to humans. Normal aging is associated with regionally specific reductions in [18F]FEOBV binding in some cortical regions and the striatum.
Available active power of the N‐port AC Thévenin source: A simple behavioral derivation
Authors: Sommariva Antonino M.
Published: September 2018

The available active power of a circuit component under AC operation is defined from the behavioral point of view. Then, the complete investigation of the N‐port AC Thévenin source is carried out using the simplest tools of linear algebra. Finally, the diagrams (normalized active power delivered and efficiency vs normalized current) pertaining to the one‐port AC Thévenin source with finite available active power are presented, in case of both real and complex parameters values.
Design, synthesis, and antifungal activity of novel cinnamon–pyrazole carboxamide derivatives
Authors: Ren Zi‐Li , Liu Hao , Jiao Di , Hu Hao‐Tian , Wang Wei , Gong Jie‐Xiu , Wang Ai‐Li , Cao Hai‐Qun , Lv Xian‐Hai
Published: September 2018

Hit, Lead & Candidate Discovery

To discover succinate dehydrogenase inhibitors with a novel structure, we introduced cinnamic acid structure to optimize the lead structure1and synthesized four series of cinnamon–pyrazole carboxamide derivatives. The bioassay data showed that compounds (E)‐N‐(1‐[4‐chlorophenyl]‐4‐cyano‐1H‐pyrazol‐5‐yl)‐3‐(2‐fluorophenyl) acrylamide (5III‐d)and (E)‐3‐(2‐chlorophenyl)‐N‐(1‐[4‐chlorophenyl]‐4‐cyano‐1H‐pyrazol‐5‐yl) acrylamide (5III‐f)showed the significant antifungal activity against three fungi. In addition,5III‐dand5III‐fexhibited the excellent inhibitory effect against succinate dehydrogenase (SDH) enzymes with IC50values ranging from 19.4 to 28.7 μM. The study demonstrates that the chlorine substituent group is present on both the phenyl and pyrazole rings that have a very good effect on the antifungal effect, and the compounds5III‐dand5III‐fcan act as potential SDH inhibitors (SDHI) and throw a sprat for a new generation of SDHI.
DAR (diversity–area relationship): Extending classic SAR (species–area relationship) for biodiversity and biogeography analyses
Authors: Ma Zhanshan (Sam)
Published: September 2018

I extend the classic SAR, which has achieved status of ecological law and plays a critical role in global biodiversity and biogeography analyses, to general DAR (diversity–area relationship). The extension was aimed to remedy a serious application limitation of the traditional SAR that only addressed one aspect of biodiversity scaling—species richness scaling over space, but ignoring species abundance information. The extension was further inspired by a recent consensus that Hill numbers offer the most appropriate measures for alpha‐diversity and multiplicative beta‐diversity. In particular, Hill numbers are essentially a series of Renyi's entropy values weighted differently along the rare‐common‐dominant spectrum of species abundance distribution and are in the units of effective number of species (or species equivalents such as OTUs). I therefore postulate that Hill numbers should follow the same or similar law of the traditional SAR. I test the postulation with the American gut microbiome project (AGP) dataset of 1,473 healthy North American individuals. I further propose three new concepts and develop their statistical estimation formulae based on the new DAR extension, including: (i) DAR profile—z–q relationship (DAR scaling parameter z at different diversity order q), (ii) PDO (pair‐wise diversity overlap) profile—g–q relationship (PDO parameter g at order q, and (iii) MAD (maximal accrual diversity: Dmax) profile—Dmax‐q. While the classic SAR is a special case of our new DAR profile, the PDO and MAD profiles offer novel tools for analyzing biodiversity (including alpha‐diversity and beta‐diversity) and biogeography over space.
Development of a PCR‐RFLP assay to identify Drosophila melanogaster among field‐collected larvae
Authors: Raquin Vincent , Henri Hélène , Vallat Marine , Leulier François , Gibert Patricia , Kremer Natacha
Published: September 2018

The fruit fly Drosophila melanogaster is a model organism to study several aspects of metazoan biology. Most of the work has been conducted in adult fruit flies, including laboratory and field‐derived specimens, but Drosophila melanogaster larvae recently became a valuable model to better understand animal physiology, development, or host–microbe interactions. While adult flies can be easily assigned to a given Drosophila species based on morphological characteristics, such visual identification is more intricate at the larval stage. This could explain the limited number of studies focusing on larvae, especially field‐derived samples. Here, we developed a polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay that discriminates D. melanogaster from other ecologically relevant Drosophila species at the larval stage. The method, which targets the cytochrome oxidase I (COI) gene, was validated using laboratory‐derived larvae from seven D. melanogaster populations originating from different geographic areas as well as six Drosophila species. We further validated this PCR‐RFLP assay in a natural context, by identifying wild larvae collected in two locations in France. Notably, among all PCR‐RFLP profiles that matched the D. melanogaster species, 100% were correctly identified, as confirmed by COI sequencing. In summary, our work provides a rapid, simple, and accurate molecular tool to identify D. melanogaster from field‐collected larvae.
The roles of extrinsic and intrinsic factors in the freshwater life‐history dynamics of a migratory salmonid
Authors: Bailey Colin J. , Braun Douglas C. , McCubbing Donald , Reynolds John D. , Ward Bruce , Davies Trevor D. , Moore Jonathan W.
Published: September 2018

Key life‐cycle transitions, such as metamorphosis or migration, can be altered by a variety of external factors, such as climate variation, strong species interactions, and management intervention, or modulated by density dependence. Given that these life‐history transitions can influence population dynamics, understanding the simultaneous effects of intrinsic and extrinsic controls on life‐history expression is particularly relevant for species of management or conservation importance. Here, we examined how life histories of steelhead (Oncorhynchus mykiss) are affected by weather, pink salmon abundance (Oncorhynchus gorbuscha), experimental nutrient addition, and density‐dependent processes. We tested for impacts on the size of steelhead smolts (juveniles migrating to the sea), as well as their age and abundance across four decades in the Keogh River, British Columbia, Canada. Larger steelhead smolts were associated with warmer years and artificial nutrient addition. In addition, higher pink salmon abundance and artificial nutrient addition correlated with juvenile steelhead migrating at younger ages. While density dependence appeared to be the primary factor regulating the abundance of steelhead smolts, nutrient addition and temperature were positively and negatively associated with smolt production, respectively, prior to 1991, and pink salmon spawning abundance was positively associated with smolt production after 1990. Thus, this study provides evidence that the temporal dynamics of one species of salmon is linked to the juvenile life history of co‐occurring steelhead. A complex interplay of species interactions, nutrient subsidies, density dependence, and climatic variation can control the life‐history expression of species with complex life cycles.
Impact of exercise‐based cardiac rehabilitation in patients with heart failure (ExTraMATCH II) on mortality and hospitalisation: an individual patient data meta‐analysis of randomised trials
Authors: Taylor Rod S. , Walker Sarah , Smart Neil A. , Piepoli Massimo F. , Warren Fiona C. , Ciani Oriana , O'Connor Christopher , Whellan David , Keteyian Steven J. , Coats Andrew , Davos Constantinos H. , Dalal Hasnain M. , Dracup Kathleen , Evangelista Lorraine , Jolly Kate , Myers Jonathan , McKelvie Robert S. , Nilsson Birgitta B. , Passino Claudio , Witham Miles D. , Yeh Gloria Y. , Zwisler Ann‐Dorthe O. ,   on behalf of the ExTraMATCH II Collaboration
Published: September 2018

Aims

To undertake an individual patient data (IPD) meta‐analysis to assess the impact of exercise‐based cardiac rehabilitation (ExCR) in patients with heart failure (HF) on mortality and hospitalisation, and differential effects of ExCR according to patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischaemic aetiology, ejection fraction, and exercise capacity.

Methods and results

Randomised trials of exercise training for at least 3 weeks compared with no exercise control with 6‐month follow‐up or longer, providing IPD time to event on mortality or hospitalisation (all‐cause or HF‐specific). IPD were combined into a single dataset. We used Cox proportional hazards models to investigate the effect of ExCR and the interactions between ExCR and participant characteristics. We used both two‐stage random effects and one‐stage fixed effect models. IPD were obtained from 18 trials including 3912 patients with HF with reduced ejection fraction. Compared to control, there was no statistically significant difference in pooled time to event estimates in favour of ExCR although confidence intervals (CIs) were wide [all‐cause mortality: hazard ratio (HR) 0.83, 95% CI 0.67–1.04; HF‐specific mortality: HR 0.84, 95% CI 0.49–1.46; all‐cause hospitalisation: HR 0.90, 95% CI 0.76–1.06; and HF‐specific hospitalisation: HR 0.98, 95% CI 0.72–1.35]. No strong evidence was found of differential intervention effects across patient characteristics.

Conclusion

Exercise‐based cardiac rehabilitation did not have a significant effect on the risk of mortality and hospitalisation in HF with reduced ejection fraction. However, uncertainty around effect estimates precludes drawing definitive conclusions.
2,2′‐Azobispyridine in Phosphorus Coordination Chemistry: A New Approach to 1,2,4,3‐Triazaphosphole Derivatives
Authors: Panova Yulia S. , Sheyanova Alexandra V. , Zolotareva Nataliya V. , Sushev Vyacheslav V. , Arapova Alla V. , Novikov Alexander S. , Baranov Evgenii V. , Fukin Georgy K. , Kornev Alexander N.
Published: September 2018

Oxidative addition of 2,2′‐azobispyridine (abpy) to PCl3in CH2Cl2or THF gave the 1:1 addition product, containing phosphorus in high oxidation state (+5) and a reduced form of the ligand. 2,2′‐Hydrazobispyridine (hbpy) was prepared by reduction ofabpywith hydrazine‐hydrate in 63 % yield. Interaction ofhbpywith PCl3in the presence of triethylamine gave (abpy)2–PCl (2) in 25 % preparative yield. A similar reaction ofhbbywith (Et2N)2PCl afforded (abpy)2–PNEt2(4) in 89 % yield. Compound4after work‐up with PCl3or PBr3gave2and (abpy)2–PBr (6) respectively in high yields. Diethylamino‐derivative4formed (κ2‐N,N) adduct with SiCl47(coordination by Py and azo‐functions), while the chloro‐derivative2did not. Reaction of2with PCl5is accompanied with liberation of PCl3and formation of spirocyclicatecomplex [(abpy)2–2P]+PCl6–. All structurally characterized compounds demonstrated short distances between pyridyl nitrogen and the phosphorus atom. However, the QTAIM analysis did not reveal the presence of appropriate bond critical points (3, –1) for the intramolecular noncovalent interactions N···P in2,4, and6. We theoretically estimated values of the rotation barriers for the pyridyl and Et2N moieties in4using the relaxed potential energy surface scan at the B3LYP/6‐31G(d) level of theory. The values of rotation barriers are very close to each other, viz. 13.2 (pyridyl) and 13.0 (Et2N) kcal/mol.
Copper‐Catalyzed Four‐Component Reaction for the Synthesis of N‐Difluoroethyl Imides
Authors: Gao Yu , Peng Shan‐Qing , Liu De‐Yong , Rui Pei‐Xin , Hu Xiang‐Guo
Published: September 2018

A general and efficient method for the synthesis N‐difluoroethyl imides has been developed. This copper‐catalyzed four‐component reaction proceeds via in‐situ generated difluorodiazomethane, which does not require prior formation and transferring. The reaction is scalable, tolerant toward a range of functional groups, and also suitable for the late‐stage functionalization of drugs and drug‐like molecules.
On hybrid electroosmotic kinetics for field‐effect‐reconfigurable nanoparticle trapping in a four‐terminal spiral microelectrode array
Authors: Ren Yukun , Song Chunlei , Liu Weiyu , Jiang Tianyi , Song Jingni , Wu Qisheng , Jiang Hongyuan
Published: September 2018

Induced‐charge electroosmosis (ICEO) has attracted tremendous popularity for driving fluid motion from the microfluidic community since the last decade, while less attention has been paid to ICEO‐based nanoparticle manipulation. We propose herein a unique concept of hybrid electroosmotic kinetics (HEK) in terms of bi‐phase ICEO (BICEO) actuated in a four‐terminal spiral electrode array, for effective electrokinetic enrichment of fluorescent polystyrene nanoparticles on ideally polarizable metal strips. First, by alternating the applied AC voltage waves between consecutive discrete terminals, the flow stagnation lines where the sample nanoparticles aggregate can be switched in time between two different distribution modes. Second, we innovatively introduce the idea of AC field‐effect flow control on BICEO; by altering the combination of gating voltage sequence, not only the number of circulative particle trapping lines is doubled, but the collecting locations can be flexibly reconfigured as well. Third, hydrodynamic streaming of DC‐biased BICEO is tested in our device design, wherein the global linear electroosmosis dominates BICEO contributed from both AC and DC components, resulting in a reduction of particle enrichment area, while with a sharp increase in sample transport speed inside the bulk phase. The flow field associated with HEK is predicted using a linear asymptotic analysis under Debye–Huckel limit, with the simulation results in qualitative agreement with in‐lab observations of nanoparticle trapping by exploiting a series of improved ICEO techniques. This work provides an affordable and field‐deployable platform for real‐time nanoparticle trapping in the context of dilute electrolyte.
Adaptive predictive principal components for modeling multivariate air pollution
Authors: Bose Maitreyee , Larson Timothy , Szpiro Adam A.
Published: September 2018

Air pollution monitoring locations are distributed across the United States; however, prediction of measured pollutant concentrations at new locations is often of interest for various purposes, for example, for pollution–health association studies. For a pollution measure like PM2.5 (fine particulate matter) comprised of multiple chemical components, the predictive principal component analysis (PCA) algorithm derives a low‐dimensional representation of component profiles. Geographic covariates and spatial splines help determine the principal component (PC) loadings of the pollution data to give improved prediction accuracy of the PC scores. While predictive PCA can accommodate pollution data of arbitrary dimension, it is currently limited to a small number of preselected geographic covariates. We propose an adaptive predictive PCA algorithm, which automatically identifies a combination of covariates that is most informative in choosing the PC directions in the pollutant space. We show, by means of simulation and empirical studies, that adaptive predictive PCA improves the accuracy of multicomponent pollutant concentration predictions at unmonitored locations.
Avoidance response by shrimps to a copper gradient: Does high population density prevent avoidance of contamination?
Authors: Araújo Cristiano V.M. , Pereira Karyna C. , Blasco Julián
Published: September 2018

Bioassays using the nonforced exposure approach have been shown to be a relevant tool that might complement the traditional ecotoxicological risk assessment. Because the nonforced exposure approach is based on spatial displacement of organisms and the consequent habitat selection processes, the population density might play an important role in the decision to avoid or prefer an ecosystem. Therefore, the aim of the present study was to assess if the avoidance response to contamination, measured in a nonforced exposure system, is density-dependent and how determinant contamination could be for the habitat-selection process in comparison with the population density. The freshwater shrimp Atyaephyra desmarestii was exposed to a copper gradient in a nonforced exposure system formed by 7 interconnected compartments (total volume 600 mL), which contained different copper concentrations. The density treatments used were 3, 5, and 10 organisms per compartment, corresponding to 0.5, 0.8, and 1.7 organisms per 100 mL, respectively. Clearly, the avoidance response to copper was more intense in the population with the lower density: the highest population density showed the lowest avoidance. The concentrations that triggered an avoidance of 50% of the population were 47, 134, and 163 μg L−1. In summary, it was observed that shrimps were able to detect and avoid potentially toxic copper concentrations but that the avoidance response was affected by population density. Environ Toxicol Chem 2018;37:3095–3101. © 2018 SETAC
Target site model: Application of the polyparameter target lipid model to predict aquatic organism acute toxicity for various modes of action
Authors: Boone Kathleen S. , Di Toro Dominic M.
Published: September 2018

A database of 2049 chemicals with 47 associated modes of action (MoA) was compiled from the literature. The database includes alkanes, polycyclic aromatic hydrocarbons, pesticides, inorganic, and polar compounds. Brief descriptions of some critical MoA classification groups are provided. The MoA from the 14 sources were assigned using a variety of reliable experimental and modeling techniques. Toxicity information, chemical parameters, and solubility limits were combined with the MoA label information to create the data set used for model development. The model database was used to generate linear free energy relationships for each specific MoA using multilinear regression analysis. The model uses chemical-specific Abraham solute parameters estimated from AbSolv to determine MoA-specific solvent parameters. With this procedure, critical target site concentrations are determined for each genus. Statistical analysis showed a wide range in values of the solvent parameters for the significant MoA. Environ Toxicol Chem 2019;38:222–239. © 2018 SETAC
Clonal evolution through genetic bottlenecks and telomere attrition: Potential threats to in vitro data reproducibility
Authors: Gisselsson David , Lichtenzstejn Daniel , Kachko Polina , Karlsson Jenny , Manor Esther , Mai Sabine
Published: September 2018

Tissue cultures of immortalized human cells, also known as established cell lines, are broadly accessible and cost‐efficient tools for biomedical research. We here review potential genetic sources of systematic error in cell line experiments due to clonal evolution in vitro. In particular, the authors highlight alterations in telomere function over prolonged culture and population bottlenecks, respectively, as two commonly overlooked phenomena that can result in significant alterations in cell line genotypes over just one or a few passages in vitro. These alterations may include changes in mutation status of oncogenes and large scale chromosomal imbalances. We introduce a simple list of factors to be avoided in order to reduce the risk of data misinterpretation due to clonal evolution, including unacknowledged in vitro selection pressures, prolonged culture per se, harsh population size reductions, experiments at early phases after establishment, and the employment of cell lines not sufficiently analyzed by high resolution genetic techniques.
#Smartphone Communities
Authors: Unterstell Rembert
Published: September 2018

WhatsApp, Snapchat and Pokémon GO: Konstanz‐based media researcher and Heinz Maier‐Leibnitz Prize recipient Isabell Otto is studying modern digital media from a cultural studies perspective / Media and participation between demand and entitlement
Neuropsychiatric symptoms among older adults living in two countries in Central Africa (EPIDEMCA study)
Authors: Yoro‐Zohoun Inès , Nubukpo Philippe , Houinato Dismand , Mbelesso Pascal , Ndamba‐Bandzouzi Bébène , Clément Jean‐Pierre , Dartigues Jean‐Francois , Preux Pierre‐Marie , Guerchet Maëlenn ,   for the EPIDEMCA Group
Published: September 2018

Objectives

Our study aimed at estimating the prevalence of neuropsychiatric symptoms and investigating associated factors among older adults living in two countries in Central Africa (Central African Republic [CAR] and Republic of Congo [ROC]).

Methods

The EPIDEMCA multicentre population‐based study was carried out in rural and urban areas of CAR and ROC between 2011 and 2012 among people aged 65 and over. After cognitive screening using the Community Screening Interview for Dementia, participants with low performances underwent neurological examination including the brief version of the Neuropsychiatric Inventory Questionnaire (NPI‐Q). Multivariate logistic regression analyses were performed to identify factors independently associated with neuropsychiatric symptoms in this population.

Results

NPI‐Q data were available for 532 participants. Overall, 333 elderly people (63.7%) reported at least one neuropsychiatric symptom. The prevalence of neuropsychiatric symptoms was 89.9% (95% CI, 84.6‐95.1) in participants with dementia, 73.4% (95% CI, 65.1‐81.7) in participants with mild cognitive impairment (MCI), and 48.7% (95% CI, 42.9‐54.6) in participants with no MCI nor dementia after neurological examination (P < 0.0001). The most common symptoms were depression, anxiety, and irritability. Participants living in Gamboma, with normal hearing and with friends in the community, were less likely to present neuropsychiatric symptoms. Physical disability, difficulties in eating, female sex, and dementia were significantly associated with neuropsychiatric symptoms.

Conclusion

Neuropsychiatric symptoms are common among older people with neurocognitive disorders in CAR and ROC. Our results confirm those from previous studies in Nigeria and Tanzania. Nevertheless, knowledge of these symptoms remains limited in sub‐Saharan Africa, hampering their appropriate management.
Randomized, Double‐Blind, Placebo‐Controlled, Single Ascending Dose Trial of Synthetic Preimplantation Factor in Autoimmune Hepatitis
Authors: O’Brien Christopher B. , Barnea Eytan R. , Martin Paul , Levy Cynthia , Sharabi Eden , Bhamidimarri Kalyan R. , Martin Eric , Arosemena Leopold , Schiff Eugene R.
Published: September 2018

Preimplantation factor (PIF) is an evolutionary conserved peptide secreted by viable embryos which promotes maternal tolerance without immune suppression. Synthetic PIF (sPIF) replicates native peptide activity. The aim of this study was to conduct the first‐in‐human trial of the safety, tolerability, and pharmacokinetics of sPIF in patients with autoimmune hepatitis (AIH). We performed a randomized, double‐blind, placebo‐controlled, prospective phase I clinical trial. Patients were adults with documented AIH with compensated chronic liver disease. Diagnosis of AIH was confirmed by either a pretreatment International Criteria for the Diagnosis of AIH score of 15 or more, or a posttreatment score of 17 or more. Patients were divided into three dosing cohorts (0.1, 0.5, or 1.0 mg/kg) of 6 patients in each group. Three patients in each group had normal liver tests and 3 patients had abnormal liver tests. They were randomized to receive a single, subcutaneous dose of either sPIF or a matching placebo. Eighteen patients were enrolled, and all successfully completed the trial. There were no clinically significant adverse events and all doses were well tolerated. Ascending doses of sPIF produced a linear increase in the respective serum levels with a half‐life of 90 minutes. There were no grade 2, 3 or 4 laboratory abnormalities. No patient developed detectable anti‐sPIF antibodies. Conclusion: This first‐in‐human trial of the safety and pharmacokinetics of sPIF (a novel biologic immune modulatory agent) demonstrated both excellent safety and tolerability. The data support further studies of multiple ascending doses of sPIF in autoimmune hepatitis and potentially other autoimmune disorders.
Inhibition of Plasminogen Activator Inhibitor 1 Attenuates Hepatic Steatosis but Does Not Prevent Progressive Nonalcoholic Steatohepatitis in Mice
Authors: Henkel Anne S. , Khan Sadiya S. , Olivares Shantel , Miyata Toshio , Vaughan Douglas E.
Published: September 2018

Plasminogen activator inhibitor 1 (PAI‐1), an essential regulator of fibrinolysis, is increasingly implicated in the pathogenesis of metabolic disorders, such as obesity and nonalcoholic fatty liver disease (NAFLD). Pharmacologic inhibition of PAI‐1 is emerging as a highly promising therapeutic strategy for obesity and its sequelae. Given the well‐established profibrotic function of PAI‐1, we considered whether PAI‐1 may serve as a target for antifibrotic therapy in nonalcoholic steatohepatitis (NASH). We therefore determined the effect of genetic Pai‐1 deletion and pharmacologic PAI‐1 inhibition on the development of NASH‐related fibrosis in mice. Pai‐1 knockout (Pai‐1
–/–) and wild‐type control (Pai‐1
+/+) mice were fed a high‐fat/high‐cholesterol high‐sugar (HFHS) diet or a methionine‐ and choline‐deficient (MCD) diet to induce steatohepatitis with fibrosis. PAI‐1 was pharmacologically inhibited using the small molecule inhibitor TM5441 in wild‐type C57BL/6 mice fed an HFHS or MCD diet. Either genetic deletion of Pai‐1 or pharmacologic inhibition of PAI‐1 attenuated MCD diet‐induced hepatic steatosis but did not prevent hepatic inflammation or fibrosis. Targeted inhibition of PAI‐1 conferred transient protection from HFHS diet‐induced obesity and hepatic steatosis, an effect that was lost with prolonged exposure to the obesigenic diet. Neither genetic deletion of Pai‐1 nor pharmacologic inhibition of PAI‐1 prevented HFHS diet‐induced hepatic inflammation or fibrosis. Conclusion:
Pai‐1 regulates hepatic lipid accumulation but does not promote NASH progression. The PAI‐1 inhibitor TM5441 effectively attenuates diet‐induced obesity and hepatic steatosis but does not prevent NASH‐related fibrosis in mice.
Are π–π Interactions in Ionic Liquids Related to Conductivities?
Authors: Fei Zhaofu , Huang Zhangjun , Tirani Farzaneh Fadaei , Scopelliti Rosario , Dyson Paul J.
Published: September 2018

A series of functionalised imidazolium halide salts with substituents able to form π‐bonds have been prepared and characterised. Subsequent reaction of these imidazolium halides with Ag[C(CN)3] affords imidazolium‐based ionic liquids (ILs), some of which are characterised by extensive π–π interactions between the cation and [C(CN)3] anion. The conductivities of the room temperature ILs with the [C(CN)3] anion were determined and the IL with an alkene functionality exhibits the highest conductivity, exceeding that of 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide, a commonly used IL electrolyte. No clear correlations between the extent of π–π interactions and the conductivities were observed.
Soil water content and temporal stability in an arid area with natural and planted grasslands
Authors: Huang Ze , Miao Hai‐Tao , Liu Yu , Tian Fu‐Ping , He Honghua , Shen Weibo , López‐Vicente Manuel , Wu Gao‐Lin
Published: September 2018

Soil water content (SWC) is a key factor for successful vegetation restoration in arid and semiarid regions, and vegetation has significant influences on the spatial patterns and temporal dynamics of SWC. The aim of this study was to investigate the temporal stability of SWC under different restored grasslands in an arid hilly area of Central China. SWC was measured in the 0‐ to 300‐cm soil profile in the natural grassland (Stipa capillata) and three typical planted grasslands (Medicago sativa, Agropyron cristatum, and Caragana korshinskii) over two growing seasons (from June to October 2015 and 2016) under natural rainfall conditions. The results showed that the mean SWC in the natural grassland was approximately 30% higher than those in the planted grasslands. The SWC consumption of the planted legume grasslands in the deepest soil layers (below 200 cm) was higher than that of the natural grassland, owing to the deep root system of the legumes. Both natural and planted grasslands had low SWC temporal stability in the top soil layers (0–50 cm), whereas more stable conditions were gradually observed with increasing the soil depth. The mean value of the mean relative differences of SWC in natural grassland (ca. 15%) was lower than that in the planted grasslands (A. cristatum grasslands) and much lower than that in the scrubland, highlighting the stronger temporal stability of SWC in the natural grassland. In conclusion, natural grassland could maintain higher and stable SWC and is recommended to be used for achieving sustainable vegetation restoration in arid and semiarid regions.
Clinical outcomes of EGFR kinase domain duplication to targeted therapies in NSCLC
Authors: Wang Jinguang , Li Xingya , Xue Xingyang , Ou Qiuxiang , Wu Xue , Liang Ying , Wang Xiaonan , You Ming , Shao Yang W. , Zhang Zhihong , Zhang Shucai
Published: September 2018

Kinase domain duplications of the epidermal growth factor receptor (EGFR‐KDD) have been identified and implicated to be oncogenic in nonsmall cell lung cancers (NSCLCs). However, its prevalence and clinical contributions in lung cancer are largely unknown. Here, we conducted a multicenter record review of 10,759 NSCLC patients who underwent genetic testing using next‐generation sequencing (NGS) targeting EGFR exons and the introns involved in EGFR‐KDD rearrangements. EGFR‐KDDs were identified in a total of 13 patients, which is approximately 0.12% of the total population reviewed, and also consisted of 0.24% (13/5394) of EGFR mutation‐positive patients. A total of 85% of patients (11/13) were identified with the canonical EGFR‐KDD duplication of exons 18–25, while the remaining two cases harbored duplications of EGFR exons 14–26 and exons 17–25, which have not been previously described. Importantly, none of the 13 patients had other coexisting driver mutations, highlighting the potential oncogenic role of this type of alteration. Three out of five patients who had exon 18–25 duplications showed partial antitumor responses to targeted therapies, while the other two patients demonstrated no clinical improvement. Furthermore, our data suggested that the EGFR T790 M mutation and EGFR amplification may represent the major resistance mechanisms against targeted therapies in tumors bearing EGFR‐KDD. In summary, our findings provide valuable insight into the prevalence of EGFR‐KDDs in NSCLCs and their clinical outcomes to targeted therapies.
Bootstrap inference for impulse response functions in factor‐augmented vector autoregressions
Authors: Yamamoto Yohei
Published: September 2018

In this study, we consider residual‐based bootstrap methods to construct the confidence interval for structural impulse response functions in factor‐augmented vector autoregressions. In particular, we compare the bootstrap with factor estimation (Procedure A) with the bootstrap without factor estimation (Procedure B). Both procedures are asymptotically valid under the condition
, where N and T are the cross‐sectional dimension and the time dimension, respectively. However, Procedure A is also valid even when
with 0 ≤ c < ∞ because it accounts for the effect of the factor estimation errors on the impulse response function estimator. Our simulation results suggest that Procedure A achieves more accurate coverage rates than those of Procedure B, especially when N is much smaller than T. In the monetary policy analysis of Bernanke et al. (Quarterly Journal of Economics, 2005, 120(1), 387–422), the proposed methods can produce statistically different results.
Tyramine‐conjugated alginate hydrogels as a platform for bioactive scaffolds
Authors: Schulz André , Gepp Michael M. , Stracke Frank , von Briesen Hagen , Neubauer Julia C. , Zimmermann Heiko
Published: September 2018

Alginate‐based hydrogels represent promising microenvironments for cell culture and tissue engineering, as their mechanical and porous characteristics are adjustable toward in vivo conditions. However, alginate scaffolds are bioinert and thus inhibit cellular interactions. To overcome this disadvantage, bioactive alginate surfaces were produced by conjugating tyramine molecules to high‐molecular‐weight alginates using the carbodiimide chemistry. Structural elucidation using nuclear magnetic resonance spectroscopy and contact angle measurements revealed a surface chemistry and wettability of tyramine‐alginate hydrogels similar to standard cell culture treated polystyrene. In contrast to stiff cell culture plastic, tyramine‐alginate scaffolds were found to be soft (60–80 kPa), meeting the elastic moduli of human tissues such as liver and heart. We further demonstrated an enhanced protein adsorption with increasing tyramine conjugation, stable for several weeks. Cell culture studies with human mesenchymal stem cells and human pluripotent stem cell‐derived cardiomyocytes qualified tyramine‐alginate hydrogels as bioactive platforms enabling cell adhesion and contraction on (structured) 2‐D layer and spherical matrices. Due to the alginate functionalization with tyramines, stable cell–matrix interactions were observed beneficial for an implementation in biology, biotechnology, and medicine toward efficient cell culture and tissue substitutes. © 2018 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 114–121, 2019.
Electrosprayed genipin cross‐linked alginate–chitosan microcarriers for ex vivo expansion of mesenchymal stem cells
Authors: Chui Chih‐Yao , Odeleye Akinlolu , Nguyen Linh , Kasoju Naresh , Soliman Erfan , Ye Hua
Published: September 2018

Mesenchymal stem cells (MSCs) are potential therapeutic candidates, owing to their ability to differentiate into several cell types. However, the gap between availability and demand of MSCs requires alternative expansion methods from 2D culture flasks. Microcarriers are a promising approach for MSC expansion due to their high surface area‐to‐volume ratio. However, current commercial microcarriers do not provide the highest cell yield due to low cell attachment efficiencies and difficulty in cell detachment. This study developed a hydrogel‐based microcarrier from genipin cross‐linked alginate–chitosan beads. Alginate beads were produced by electrospraying before being coated with chitosan and cross‐linked in genipin. The degree of cross‐linking was determined through fluorescence reading of the genipin‐chitosan conjugates. MSCs cultured on these microcarriers had a 26% higher cell attachment and twice the proliferation rate compared to the commercial microcarrier Cytodex 1. Cells easily detached from the hydrogel beads and did not require extended incubation periods or intense agitation during cell harvest. There was no significant difference in gene expression between the two microcarriers for the positive MSC surface markers CD‐90, CD‐105, and CD‐73 as well as showing either low or no signal for negative MSC surface markers CD‐45 and CD‐34. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 122–133, 2019.
Design, synthesis, and characterization of novel pyrimidines bearing indole as antimicrobial agents
Authors: Sayed Mostafa , Kamal El‐Dean Adel M. , Ahmed Mostafa , Hassanien Reda
Published: September 2018

Pyrimidines and pyrimidine bearing indole derivatives are very important species in organic chemistry due to their wide use as bioactive compounds with a broad range of good biological activities. Due to the wide spread of different species of bacteria and fungi nowadays, in the present work, a novel series of indolyl‐pyrimidines (2–13) were synthesized starting from 3‐chloro‐1H‐indole‐2‐carbaldehyde (1). Elemental analysis, IR, 1H‐NMR, 13C‐NMR, and mass spectral data elucidated the structure of newly synthesized compounds. All compounds were screened for their in vitro antibacterial and antifungal activity, and they demonstrated promising results; all the new compounds synthesized from compound (1), which allowed reactions with thiourea and ethyl cyanoacetate, gave the target compound (2), which was used as a precursor for the synthesis of indolylthiazolopyrimidine derivatives (3–8) by reactions with halocarbonyl compounds such as chloroacetone, phancyl bromide, and chloroacetic acid through alkylation of the mercapto group followed by cyclization through a nucleophilic attack. When compound (2) subjected to react with hydrazine hydrate gave 4‐indolyl‐2‐hydrazinopyrimidine (5), the latter compound, when allowed to react with ethyl chloroacetate or diethyloxalate, gave indolylpyrimidotriazine derivatives (10,11); in contrast, when the compound reacted with acetic anhydride or formic acid, it gave triazolopyrimidine derivatives (12, 13).
Ewing‐like sarcoma: An emerging family of round cell sarcomas
Authors: Renzi Samuele , Anderson Nathaniel D. , Light Nicholas , Gupta Abha
Published: September 2018

Ewing‐like sarcomas are an emerging subgroup of small round blue cell sarcomas that share various degrees of morphological, immunohistochemical, molecular, and clinical similarity with Ewing sarcoma. Despite these similarities, Ewing‐like sarcomas lack the pathognomonic molecular hallmark of Ewing sarcoma: A translocation between a gene of the RNA‐binding TET family (EWSR1 or
FUS) with a gene of the ETS‐transcription family (
FLI1,
ERG,
ETV1,
ETV4, or
FEV). Recently, increased use of modern molecular methods based on next‐generation sequencing have enabled the identification of distinct subgroups within this previously uncharacterized group of Ewing‐like sarcomas based on the discovery of novel molecular driving events. The focus of this review is to provide an update on the main subcategories of Ewing‐like sarcomas discovered to date:
CIC‐rearranged sarcomas,
BCOR‐rearranged sarcomas, sarcomas with a rearrangement between
EWSR1 and a non‐ETS family gene, and the substantial fraction of tumors which remain uncharacterized by molecular methods. There is increasing evidence that these tumors represent stand‐alone entities with unique characteristics rather than simply a subgroup of Ewing sarcoma; thus, the question of the best therapeutic approach for these often aggressive sarcomas remains of primary importance. Ultimately, large collaborative efforts will be necessary to better determine the characteristics of this rare, heterogeneous family of tumors.
IL1R1 and IL1R2 polymorphisms were associated with tuberculosis risk: A pilot study
Authors: Ren Guoxia , Dong Qi , Huyan Baojuan , Jin Pu , Chen Mingwei
Published: September 2018

Background

Interleukin (IL)‐1 has been reported to be involved in the development of tuberculosis (TB). IL1R1 and IL1R2 encode a cytokine receptor that belongs to the IL‐1 receptor family. However, few studies have reported on the polymorphisms of IL1R1 and IL1R2 in TB patients.

Methods

We investigated nine single‐nucleotide polymorphisms (SNPs) in IL1R1 and IL1R2 in 300 TB patients and 300 controls, aiming to evaluate their association with TB risk. Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for age and gender.

Results

On comparing the allele frequencies of candidate SNPs, we found that the minor allele ‘A’ of rs4851527 in IL1R2 was associated with a decreased risk of TB, whereas the minor alleles of rs10490571, rs956730 and rs3917225 in IL1R1 were associated with an increased risk of TB (p < 0.05). In the genetic model analysis, we found that the allele ‘A’ of rs4851527 was correlated with a decreased risk of TB in a log‐additive model, whereas the minor alleles of rs719250, rs3218977, rs10490571, rs956730 and rs3917225 were correlated with an increased risk of TB in dominant and log‐additive models (p < 0.05). Additionally, we found three haplotypes that were associated with an increased risk of TB: TGCT and TGTT haplotypes constructed by rs11674595, rs4851527, rs719250 and rs3218896, as well as GA haplotype constructed by rs3218977 and rs2072472 (p < 0.05).

Conclusions

Our data shed new light on the association between genetic polymorphisms of IL1R1 and IL1R2 and TB susceptibility in the Chinese Han population.
Thiazolidine‐4‐ones from Thiocarbohydrazides
Authors: Hassan Alaa A. , Makhlouf Maysa M.
Published: September 2018

Several methods for the preparation of thiazolidin‐4‐ones from thiocarbohydrazides over the last 15 years are highlighted. Thiosemicarbazides, thiocarbohydrazides, thioamides, and hydrazinecarbothioamides as well as thioureas were used to obtain different substituted thiazolidinones under reaction conditions. Thiazolidinones can be synthesized either by a one‐pot three‐component condensation or a two‐step process. Also, the mechanism of formation, regioselectivity issues, and biological activities of different thiazolidinones were discussed.