bluuebunny/crossref_metadata_2025 huggingface dataset:
Remnant cholesterol and risk of ischemic stroke in 112,512 individuals from the general population
Authors: Varbo Anette , Nordestgaard Børge G.
Published: February 2019

Objective

High remnant cholesterol concentrations are associated with high risk of ischemic heart disease, but whether this is also the case for ischemic stroke is unknown. We tested the hypothesis that high remnant cholesterol concentrations are associated with increased risk of ischemic stroke in the general population.

Methods

A total of 102,964 individuals from the Copenhagen General Population Study with information on remnant cholesterol at baseline in 2003–2015 were included in a prospective, observational association study. Individuals were followed for up to 14 years, during which time 2,488 were diagnosed with an ischemic stroke. Hazard ratios were estimated using Cox proportional hazard regression models. Results were independently confirmed in 9,548 individuals enrolled in the Copenhagen City Heart Study in 1991–1994; 983 ischemic strokes developed during up to 26 years of follow‐up.

Results

Step‐wise higher remnant cholesterol concentrations were associated with step‐wise higher ischemic stroke risk in the Copenhagen General Population Study, with multivariable adjusted hazard ratios up to 1.99 (95%confidence interval: 1.49–2.67) for individuals with remnant cholesterol concentrations ≥1.5 mmol/l (58 mg/dl), compared to individuals with remnant cholesterol <0.5 mmol/l (19 mg/dl). Results were similar in the Copenhagen City Heart Study. Cumulative incidence of ischemic stroke at age 80 in the Copenhagen General Population Study ranged from 7.3% for individuals with remnant cholesterol <0.5 mmol/l (19 mg/dl) to 11.5% for individuals with remnant cholesterol ≥1.5 mmol/l (58 mg/dl).

Interpretation

Individuals with high remnant cholesterol concentrations had higher risk of ischemic stroke. These results indicate that randomized clinical trials with remnant cholesterol lowering in individuals with high concentrations, with the aim of preventing ischemic strokes, are needed. Ann Neurol 2019;85:550–559
The success of dual‐functional templating for synthesizing hierarchical analcime zeolite
Authors: Wang Shiyao , Tian Ren , He Bo , Dai Rong , Li Xing , Wu Xu , An Xia , Xie Xianmei
Published: February 2019

Novel and innovative hierarchical analcime zeolites were prepared by adding a gemini surfactant which acted as a dual‐functional template. Through a one‐step hydrothermal process, a hierarchical analcime zeolite with abundant intracrystalline mesopores was synthesized. Powder X‐ray diffraction and N2 adsorption–desorption data show that the mesoporous composites possess both a quite a number of mesopores and analcime structure. The results suggest that the dual‐functional template can be effective in the synthesis of hierarchical analcime zeolites.
Applications of inorganic‐organic hybrid architectures based on polyoxometalates in catalyzed and photocatalyzed chemical transformations
Authors: Lotfian Nahid , Heravi Majid M. , Mirzaei Masoud , Heidari Bahareh
Published: February 2019

The scope of this article is to reveal the fruitful combination of POM species with metal coordination complexes, leading to the construction of several efficient multifunctional catalysts. In this review, we try to underscore various catalytic and photocatalytic reactions catalyzed by POM‐based inorganic‐organic hybrid. Notably, it has been well established that depending on the type of the reaction, the activity and selectivity of these hybrid catalyst can be drastically improved by the rational and correct choice of the organic metal complex and POM anion providing a marriage of convenience.
Selective functionalization of ferrocenyl compounds using a novel solvent free synthetic method for the preparation of bioactive unsymmetrical ferrocenyl derivatives
Authors: Ghosh Avishek , Barik Tulasi , Dewangan Smriti , Majhi Paresh Kumar , Sasamori Takahiro , Mobin Shaikh M. , Giri Santanab , Chatterjee Saurav
Published: February 2019

A novel solvent free synthetic method has been designed by using rice husk ash (RHA) as solid support for the selective functionalization of ferrocenyl derivatives and described the synthesis of a 1,1′‐unsymmetrically bi‐functionalized ferrocenyl compounds for their biological evaluation. Single crystal X‐ray structural evaluation showed some interesting intra‐molecular hydrogen bonding interactions across the chains of the ferrocenyl molecule, while DFT calculation revealed the significance of the orientation between the two cyclopentadienyl rings for the hydrogen bonding interaction. Redox and antibacterial properties have been studied to understand the electronic and biological effect of different hydrazone system and their potential for future application.
Efficient Fe‐Co‐N‐C Electrocatalyst Towards Oxygen Reduction Derived from a Cationic CoII‐based Metal–Organic Framework Modified by Anion‐Exchange with Potassium Ferricyanide
Authors: Chen Xiang‐Lan , Huang Jia‐Wei , Huang Yi‐Chen , Du Jie , Jiang Yu‐Fei , Zhao Yue , Zhu Hai‐Bin
Published: February 2019

Fe‐Co‐N‐C electrocatalysts have proven superior to their counterparts (e.g. Fe‐N‐C or Co‐N‐C) for the oxygen reduction reaction (ORR). Herein, we report on a unique strategy to prepare Fe‐Co‐N‐C−x (x refers to the pyrolysis temperature) electrocatalysts which involves anion‐exchange of [Fe(CN)6]3− into a cationic CoII‐based metal‐organic framework precursor prior to heat treatment. Fe‐Co‐N‐C‐900 exhibits an optimal ORR catalytic performance in an alkaline electrolyte with an onset potential (Eonset: 0.97 V) and half‐wave potential (E1/2: 0.86 V) comparable to that of commercial Pt/C (Eonset=1.02 V; E1/2=0.88 V), which outperforms the corresponding Co‐N‐C‐900 sample (Eonset=0.92 V; E1/2=0.84 V) derived from the same MOF precursor without anion‐exchange modification. This is the first example of Fe‐Co‐N‐C electrocatalysts fabricated from a cationic CoII‐based MOF precursor that dopes the Fe element via anion‐exchange, and our current work provides a new entrance towards MOF‐derived transition‐metal (e.g. Fe or Co) and nitrogen‐codoped carbon electrocatalysts with excellent ORR activity.
A comparative study for detecting CYP3A induction by CYP3A probe drugs and endogenous markers in cynomolgus monkeys
Authors: Tahara Harunobu , Watanabe Miwa , Hasegawa Maki
Published: February 2019

CYP3A probe drugs such as midazolam and endogenous markers, and plasma 4β‐hydroxycholesterol (4β‐OHC) and urinary 6β‐hydroxycortisol‐to‐cortisol ratios (6β‐OHC/C) have been used as markers of CYP3A induction in cynomolgus monkeys, as with humans. However, there is limited information on their sensitivity and ability to detect CYP3A induction, as most studies were evaluated only at a high dose of the inducer, rifampicin (RIF; 20 mg/kg). In the present study, the CYP3A induction by RIF over a range doses of 0.2, 2 and 20 mg/kg (n = 4) was examined using CYP3A probe drugs (midazolam, triazolam and alprazolam) and the plasma and urinary endogenous CYP3A markers (4β‐OHC and 6β‐OHC/C). The sensitivity and relationship for detecting CYP3A induction was compared among the markers. Four days repeated oral administration of rifampicin to cynomolgus monkeys reduced the area under the plasma concentration–time curve of all CYP3A probe drugs in a rifampicin dose‐dependent manner. Although the endogenous CYP3A markers (4β‐OHC and 6β‐OHC/C) were also changed for the middle (2 mg/kg) and high (20 mg/kg) doses of rifampicin, the fold‐changes were relatively small, and CYP3A induction could not be detected at the lowest dose of rifampicin (0.2 mg/kg). In conclusion, CYP3A probe drugs are more sensitive for detecting CYP3A induction than endogenous CYP3A markers in cynomolgus monkeys, even for a short experimental period.
A high sensitivity system for luminescence measurement of materials
Authors: Finch Adrian A. , Wang Yafang , Townsend Peter D. , Ingle Martin
Published: February 2019

A unique combined and multi‐disciplinary wavelength multiplexed spectrometer is described. It is furnished with high‐sensitivity imaging plate detectors, the power to which can be gated to provide time‐resolved data. The system is capable of collecting spectrally resolved luminescence data following X‐ray excitation [radioluminescence (RL) or X‐ray excited optical luminescence (XEOL)], electron irradiation [cathodoluminescence (CL)] and visible light from light emitting diodes (LEDs) [photoluminescence (PL)]. Time‐resolved PL and CL data can be collected to provide lifetime estimates with half‐lives from microsecond timeframes. There are temperature stages for the high and low temperature experiments providing temperature control from 20 to 673 K. Combining irradiation, time resolved (TR) and TR‐PL allows spectrally‐resolved thermoluminescence (TL) and optically stimulated luminescence (OSL). The design of two detectors with matched gratings gives optimum sensitivity for the system. Examples which show the advantages and multi‐use of the spectrometer are listed. Potential future experiments involving lifetime analysis as a function of irradiation, dose and temperature plus pump‐probe experiments are discussed.
Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer
Authors: Machens A , Lorenz K , Dralle H
Published: February 2019

Background

It remains unclear when postoperative serum calcitonin levels should be measured in patients with medullary thyroid cancer (MTC) and, specifically, whether this decision should be based on the preoperative calcitonin level or nodal status.

Methods

A cohort of patients with previously untreated MTC was studied. Kaplan–Meier analyses, stratified by preoperative calcitonin level, nodal status and number of nodal metastases, were performed to determine time to calcitonin normalization after initial surgery, with statistical analysis by means of the log rank test.

Results

Some 213 patients with node-negative and 182 with node-positive MTC were included in the study. Postoperative calcitonin levels normalized in a mean of 3·5 versus 3·7 days respectively among patients with preoperative calcitonin levels of 10–100 pg/ml (P = 0·815); 4·8 versus 5·3 days in those with preoperative calcitonin levels of 100·1–500 pg/ml (P = 0·026); 5·3 versus 9·9 days in patients with preoperative calcitonin levels of 500·1–1000 pg/ml (P = 0·004); and 6·6 versus 57·7 days among those with preoperative calcitonin levels exceeding 1000 pg/ml (P < 0·001). Calcitonin levels normalized in a mean of 4·7 days when nodal metastasis was not present, 5·2 days in those with one to five nodal metastases, 7·0 days in patients with six to ten nodal metastases, and 57·1 days among patients with more than ten nodal metastases. Postoperative calcitonin normalization curves paralleled each other in patients with node-negative MTC, but diverged in those with node-positive disease and with more nodal metastases.

Conclusion

Calcitonin levels typically normalize within 1 week; and within a fortnight in those with node-positive MTC and preoperative calcitonin levels of 500·1–1000 pg/ml. With node-positive MTC and preoperative calcitonin levels exceeding 1000 pg/ml, and with more than ten nodal metastases, calcitonin normalization takes longer.
Clinical and experimental studies of intraperitoneal lipolysis and the development of clinically relevant pancreatic fistula after pancreatic surgery
Authors: Uchida Y , Masui T , Nakano K , Yogo A , Sato A , Nagai K , Anazawa T , Takaori K , Tabata Y , Uemoto S
Published: February 2019

Background

Visceral obesity is one of the risk factors for clinically relevant pancreatic fistula after pancreatic resection. The objective of this study was to evaluate the impact of intraperitoneal lipolysis on postoperative pancreatic fistula.

Methods

The degree of intraperitoneal lipolysis was investigated by measuring the free fatty acid concentration in drain discharge in patients after pancreatic resection. An experimental pancreatic fistula model was prepared by pancreatic transection, and the impact of intraperitoneal lipolysis was evaluated by intraperitoneal administration of triolein (triglyceride) with, or without orlistat (lipase inhibitor).

Results

Thirty-three patients were included in the analysis. The free fatty acid concentration in drain discharge on postoperative day 1 was significantly associated with the development of a clinically relevant pancreatic fistula (P = 0·004). A higher free fatty acid concentration in drain discharge was associated with more visceral adipose tissue (P = 0·009). In the experimental model that included 98 rats, intraperitoneal lipolysis caused an increased amount of pancreatic juice leakage and multiple organ dysfunction. Intraperitoneal administration of a lipase inhibitor reduced lipolysis and prevented deterioration of the fistula.

Conclusion

Intraperitoneal lipolysis significantly exacerbates pancreatic fistula after pancreatic resection. Inhibition of lipolysis by intraperitoneal administration of a lipase inhibitor could be a promising therapy to reduce clinically relevant postoperative pancreatic fistula.
Monolayer Behaviors of Carborane Poly(Ethylene Glycol) Complexes
Authors: Kim Sunhye , Yang Jingying , Jang Eunsuk , Paeng Keewook , Sohn Daewon
Published: February 2019

Carborane (CB), a cluster composed of boron, carbon and hydrogen atoms, has been recognized for its unique properties and potential as a boron neutron capture therapy (BNCT) material. Solubility problems of CB can be solved by connecting each CB with polyethylene glycol (PEG). PEG's having three different molecular weights (Mwt. 3800, 5010, and 6000) were connected to CB, and their Langmuir films were studied by surface pressure (Π)‐surface area (Å) isotherm, hysteresis, and atomic force microscopy (AFM). CB‐PEG complexes have different limiting areas according to the molecular weight of PEG and form a close‐packed arrangement for higher molecular weights of PEG. CB‐PEG complexes create dot domains at low pressure, and the domains aggregate to larger domains as the surface pressure is increased. With a smaller molecular weight of PEG, a more rigid and well‐ordered monolayer is obtained by interaction of the hydrophilic PEG and hydrophobic CB. Intermolecular interactions are lowered by adding salt to the subphase, which generates more reversible monolayers.
A New Computational Method for Protein–Ligand Binding Thermodynamics
Authors: Chong Song‐Ho , Ham Sihyun
Published: February 2019

We develop a new computational method for protein–ligand binding thermodynamics that combines alchemical transformations and the liquid theory. This method requires only the solute configurations during alchemical transformations, and solvent effects are incorporated through the solvation free energy. It is demonstrated that the new method yields the relative binding free energy that agrees well with the one from the conventional explicit solvent‐free energy simulations. The development reported here opens up new possibilities for faster binding free energy computations and easier access to the enthalpy and entropy components.
Decreasing serum 25‐hydroxyvitamin D levels and risk of early neurological deterioration in patients with ischemic stroke
Authors: Hu Wei , Liu Dezhi , Li Qin , Wang Li , Tang Qiqiang , Wang Guoping
Published: February 2019

Background and Aims

Vitamin D deficiency has been linked to a higher risk of ischemic stroke. We therefore explored the relationship between serum 25‐hydroxyvitamin D [25(OH)D] levels and early neurological deterioration (END) after acute ischemic stroke in a hospital‐based prospective study.

Methods

From June 2016 to June 2018, patients with ischemic stroke within 48 hr from symptom onset were consecutively recruited. Serum 25(OH)D levels were measured at admission. END was defined as an increase of ≥1 point in motor power or ≥2 points in the total National Institute of Health Stroke Scale score within 7 days after admission. Multiple logistic regression models were performed to calculate the odds ratio (OR) and confidence intervals (CI) of 25(OH)D levels in predicting END.

Results

A total of 478 subjects were enrolled, of which 136 (28.5%) patients developed END. The mean 25(OH)D levels were 49.5 ± 15.8 nmol/L. Univariate logistic regression analysis showed that advanced age, white matter lesions, high level of body mass index, diastolic blood pressure, fasting blood glucose and homocysteine, and low 25(OH)D levels were associated with END. Furthermore, multivariate regression analysis demonstrated that the first quartile of 25(OH)D concentrations [OR, 2.628; 95% CI,1.223–5.644; p = 0.013] was independently risk factor for END.

Conclusions

This study illustrated that lower 25(OH)D levels might be associated with an increasing risk of END in acute ischemic stroke patients.
Case report: Gastric cancer‐associated membranous nephropathy that recurred after complete remission and formation of peritoneal dissemination
Authors: Kajiwara Nobuyuki , Wada Noriko , Kusumoto Takuya , Akamaru Yusuke , Ohashi Hiroshi , Hayashi Kazuyuki
Published: February 2019

Key Clinical Message

Membranous nephropathy associated with malignant neoplasm may remit completely with treatment of the underlying disease. In such cases, recurrence is very rare. However, after a recurrence, attention should be paid to the possible recurrence of the underlying disease.
Catalytic Evaluation of CuO/[Si]MCM‐41 in Fenton‐like Reactions
Authors: Bonfim Daniela P. F. , Santana Cássia S. , Batista Marcelo S. , Fabiano Demian P.
Published: February 2019

CuO/[Si]MCM‐41 catalysts with various Si/Cu molar ratios were prepared and characterized by X‐ray diffraction, nitrogen physisorption, temperature‐programmed reduction by H2, and UV‐vis and Raman spectroscopy. The effects of copper loading and pH on their activity in the decolorization of methyl orange were studied in a heterogeneous Fenton‐like process. With decreasing Si/Cu ratio, dye decolorization increased from 18 to 75 % at pH 3. CuO/[Si]MCM‐41 catalysts showed 75, 50, and 40 % conversion of methyl orange at pH 3, 5, and 7, respectively. This is a significant improvement to Fenton‐like reactions involving copper, and thus CuO/[Si]MCM‐41 catalysts are quite promising for pollutant degradation.
Activated Carbon from Renewable Material as an Efficient Support for Palladium Oxidation Catalysts
Authors: Topka Pavel , Hejtmánek Vladimír , Cruz Gerardo J. F. , Šolcová Olga , Soukup Karel
Published: February 2019

Activated carbon prepared from cocoa pod husk, which is an abundant agricultural waste, was employed as a green support for palladium oxidation catalysts. Systematic characterization of the support and palladium catalysts by atomic emission spectroscopy, N2 and CO2 physisorption measurements, X‐ray powder diffraction, infrared spectroscopy, electron microscopy, temperature‐programmed reduction by hydrogen, and temperature‐programmed desorption of NH3 and CO2 allowed detailed monitoring of their characteristics. Subsequently, the catalytic performance and selectivity in the oxidation of ethanol as a model volatile organic compound (VOC) was studied and linked to physicochemical properties of the catalysts.
Using inclusion complexes for achieving second‐order advantage: A novel technique for cinnamic acid derivatives analysis with second‐order calibration methods
Authors: Nikpour Hamidreza , Mousavi Mehdi , Asadollahzadeh Hamideh
Published: February 2019

As a novel performance, to attempt cinnamic acid derivatives (CAs), including caffeic acid, ferulic acid, and p‐coumaric acid quantification by fluorescence spectroscopy in complex chemical systems with unknown interferences in water, creating second‐order data was demanded. In the present study, α,β‐cyclodextrin (α,β‐CD) inclusion complexes application for second‐order data generation joined with bilinear least squares/residual bilinearization (BLLS/RBL) and parallel factor analysis (PARAFAC) as second‐order calibration methods. In the first step, inclusion complexes formation between CA analytes with α,β‐CDs at the optimized condition was evaluated. The resolution of model compounds was possible in the base to the differences in the fluorescence spectral changes of the inclusion complexes signals of the investigated analytes as a function of CD concentrations opening a new approach for second‐order data generation. In light of these facts, due to severe profiles overlapping between CAs, we propose creating third‐order data for each sample using α and β‐CD media to produce inclusion complexes as a new additional selectivity mode while the obtained data in two media were augmented next. Three‐way arrays were constructed by stacking augmented data in a third way and then analyzed by two powerful second‐order calibration methods (BLLS/RBL and PARAFAC) to get spectral and concentration profiles of CAs as a function of α,β‐CD concentrations. The concentrations were between 0 to 6.0, 0 to 10.0, and 0 to 8.0 mg L−1 for caffeic acid, ferulic acid, and p‐coumaric acid, respectively. The results of both methods are in good agreement, and reasonable recoveries are achieved.
The Electrophilic Fluorination of Enol Esters Using SelectFluor: A Polar Two‐Electron Process
Authors: Wood Susanna H. , Etridge Stephen , Kennedy Alan R. , Percy Jonathan M. , Nelson David J.
Published: February 2019

The reaction of enol esters with SelectFluor is facile and leads to the corresponding α‐fluoroketones under mild conditions and, as a result, this route is commonly employed for the synthesis of medicinally important compounds such as fluorinated steroids. However, despite the use of this methodology in synthesis, the mechanism of this reaction and the influence of structure on reactivity are unclear. A rigorous mechanistic study of the fluorination of these substrates is presented, informed primarily by detailed and robust kinetic experiments. The results of this study implicate a polar two‐electron process via an oxygen‐stabilised carbenium species, rather than a single‐electron process involving radical intermediates. The structure–reactivity relationships revealed here will assist synthetic chemists in deploying this type of methodology in the syntheses of α‐fluoroketones.
Distributed Fog‐to‐Cloud computing system: A minority game approach
Authors: AbdElhalim Eman , Obayya Marwa , Kishk Sherif
Published: February 2019

With the ever‐increasing popularity of resource‐intensive mobile applications, today, Fog‐to‐Cloud (F2C) computing system becomes a prominent technology for the next generation wireless networks. Despite the benefits of fog computing regarding localized storage and processing, it suffers from restricted power allowance and computational capability of the edge nodes. User nodes also may suffer from extensive delay, especially in offloading periods. Therefore, it is essential to develop a distributed mechanism for users' computation in offloading periods. According to this mechanism, not only the computational servers are exploited at their best capacity but also the users' latency constraints fulfilled. Consequently, this paper develops automated distributed fog computing for computational offloading using the theory of minority game. The proposed scheme achieves user satisfaction latency deadline as well as Quality‐of‐Experience. Moreover, it guarantees an adaptive equilibrium level of F2C computing system, which is suitable for heterogeneous wireless networks.
TAP: Timeliness‐aware predication‐based replica selection algorithm for key‐value stores
Authors: Zhou Xianqian , Fang Liyuan , Xie Haiming , Jiang Wanchun
Published: February 2019

In current large‐scale distributed key‐value stores, a single end‐user request may lead to key‐value access across tens or hundreds of servers. The tail latency of these key‐value accesses is crucial to user experience and greatly impacts the revenue. To cut the tail latency, it is crucial for clients to choose the best replica server as much as possible for the service of each key‐value access operation. Aware of the challenges on the time‐varying performance across servers and the herd behaviors, an adaptive replica selection scheme C3 has been proposed recently. In C3, feedback from individual servers is brought into replica ranking to reflect the time‐varying performance of servers, and the distributed rate control and backpressure mechanisms are invented. Despite C3's good performance, we reveal the timeliness issue of C3, which has large impacts on both the replica ranking and the rate control. To address this issue, we propose the TAP (timeliness‐aware predication‐based) replica selection algorithm, which predicts the queue size of replica servers under the poor timeliness condition, instead of utilizing the exponentially weighted moving average of the piggybacked queue sizes in history as in C3. Consequently, compared with C3, TAP can obtain more accurate queue‐size estimation to guide the replica selection at clients. Simulation results also confirm the advantage of TAP over C3 in terms of cutting the tail latency.
Human Cardiac Ventricular‐Like Organoid Chambers and Tissue Strips From Pluripotent Stem Cells as a Two‐Tiered Assay for Inotropic Responses
Authors: Keung Wendy , Chan Patrick K.W. , Backeris Peter C. , Lee Eugene K. , Wong Nicodemus , Wong Andy O.T. , Wong Gabriel K.Y. , Chan Camie W.Y. , Fermini Bernard , Costa Kevin D. , Li Ronald A.
Published: February 2019

Traditional drug discovery is an inefficient process. Human pluripotent stem cell‐derived cardiomyocytes can potentially fill the gap between animal and clinical studies, but conventional two‐dimensional cultures inadequately recapitulate the human cardiac phenotype. Here, we systematically examined the pharmacological responses of engineered human ventricular‐like cardiac tissue strips (hvCTS) and organoid chambers (hvCOC) to 25 cardioactive compounds covering various drug classes. While hvCTS effectively detected negative and null inotropic effects, the sensitivity to positive inotropes was modest. We further quantified the predictive capacity of hvCTS in a blinded screening, with accuracies for negative, positive, and null inotropic effects at 100%, 86%, and 80%, respectively. Interestingly, hvCOC, with a pro‐maturation milieu that yields physiologically complex parameters, displayed enhanced positive inotropy. Based on these results, we propose a two‐tiered screening system for avoiding false positives and negatives. Such an approach would facilitate drug discovery by leading to better overall success.
Climate change, woodpeckers, and forests: Current trends and future modeling needs
Authors: Walsh Eric S. , Vierling Kerri T. , Strand Eva , Bartowitz Kristina , Hudiburg Tara W.
Published: February 2019

The structure and composition of forest ecosystems are expected to shift with climate‐induced changes in precipitation, temperature, fire, carbon mitigation strategies, and biological disturbance. These factors are likely to have biodiversity implications. However, climate‐driven forest ecosystem models used to predict changes to forest structure and composition are not coupled to models used to predict changes to biodiversity. We proposed integrating woodpecker response (biodiversity indicator) with forest ecosystem models. Woodpeckers are a good indicator species of forest ecosystem dynamics, because they are ecologically constrained by landscape‐scale forest components, such as composition, structure, disturbance regimes, and management activities. In addition, they are correlated with forest avifauna community diversity. In this study, we explore integrating woodpecker and forest ecosystem climate models. We review climate–woodpecker models and compare the predicted responses to observed climate‐induced changes. We identify inconsistencies between observed and predicted responses, explore the modeling causes, and identify the models pertinent to integration that address the inconsistencies. We found that predictions in the short term are not in agreement with observed trends for 7 of 15 evaluated species. Because niche constraints associated with woodpeckers are a result of complex interactions between climate, vegetation, and disturbance, we hypothesize that the lack of adequate representation of these processes in the current broad‐scale climate–woodpecker models results in model–data mismatch. As a first step toward improvement, we suggest a conceptual model of climate–woodpecker–forest modeling for integration. The integration model provides climate‐driven forest ecosystem modeling with a measure of biodiversity while retaining the feedback between climate and vegetation in woodpecker climate change modeling.
Mitochondrial divergence suggests unexpected high species diversity in the opsariichthine fishes (Teleostei: Cyprinidae) and the revalidation of Opsariichthys macrolepis
Authors: Wang Xue , Liu Fei , Yu Dan , Liu Huanzhang
Published: February 2019

Opsariichthine (sensu Oceanologi Et Limnologia Sinica, 1982, 13, 293–298) is a cyprinid group consisting of five genera and endemic to East Asia. Previous studies suggested that there may be many possible cryptic species in this group, but this has not been confirmed. In this study, using mitochondrial cyt b sequences on 1,388 samples and 739 haplotypes, we showed very high species diversity within this group. The results showed that phylogenetic relationships of the opsariichthine group were as ([Nipponocypris‐Parazacco‐Candidia] + [Zacco + Opsariichthys]), and there were multiple deep lineages within several species, flagging putative cryptic species. When a 3% genetic distance was used as a threshold for species delimitation, 35 haplogroups were found, nine haplogroups in Candidia‐Parazacco‐Nipponocypris group, six haplogroups in the Zacco group, and 20 haplogroups in the Opsariichthys group. We consider all of them to be putative until determination of distinct species based on the tree topology, geographic distributions, or a combination of both. In addition, two kinds of species delimitation tools, ABGD and PTP, were applied to construct molecular operational taxonomic units (MOTUs). The ABGD method revealed nine MOTUs in Candidia‐Parazacco‐Nipponocypris group, two MOTUs in the Zacco group, and 17 MOTUs in the Opsariichthys group. And the PTP method revealed 10 MOTUs in Candidia‐Parazacco‐Nipponocypris group, 10 MOTUs in the Zacco group, and 29 MOTUs in the Opsariichthys group. Therefore, there should be more species in the opsariichthine group than presently described. Based on the molecular data and morphological characteristics, we proposed Opsariichthys macrolepis as a valid species and described its morphological diagnostic characters.
A distributed experiment demonstrates widespread sodium limitation in grassland food webs
Authors: Welti Ellen A. R. , Sanders Nathan J. , de Beurs Kirsten M. , Kaspari Michael
Published: February 2019

Sodium (Na) has a unique role in food webs as a nutrient primarily limiting for plant consumers, but not other trophic levels. Environmental Na levels vary with proximity to coasts, local geomorphology, climate, and with anthropogenic inputs (e.g., road salt). We tested two key predictions across 54 grasslands in North America: Na shortfall commonly limits herbivore abundance, and the magnitude of this limitation varies inversely with environmental Na supplies. We tested them with a distributed pulse experiment and evaluated the relative importance of Na limitation to other classic drivers of climate, macronutrient levels, and plant productivity. Herbivore abundance increased by 45% with Na addition. Moreover, the magnitude of increase on Na addition plots decreased with increasing levels of plant Na, indicating Na satiation at sites with high Na concentrations in plant tissue. Our results demonstrate that invertebrate primary consumers are often Na limited and track local Na availability, with implications for the geography of invertebrate abundance and herbivory.
Ceric(IV) Ammonium Nitrate Mediated Phosphorylation of Alkenes: Easy Access to (E)‐Vinylphosphonates
Authors: Shen Jian , Yu Rui‐Xiao , Luo Yan , Zhu Li‐Xuan , Zhang Yue , Wang Xue , Xiao Bo , Cheng Jian‐Bo , Yang Bin , Li Gui‐Zhi
Published: February 2019

An inexpensive Ceric(IV) ammonium nitrate mediated phosphorylation of alkenes has been developed. Without adding expensive metals and other additives, various (E)‐alkenylphosphane oxides are obtained through an easy route in a one‐pot manner. Preliminary mechanistic studies reveal that a spontaneous elimination process is involved in this process.
Graphene Quantum Dots Modified Screen‐printed Electrodes as Electroanalytical Sensing Platform for Diethylstilbestrol
Authors: Gevaerd Ava , Banks Craig E. , Bergamini Márcio F. , Marcolino‐Junior Luiz Humberto
Published: February 2019

In present work a simple methodology for electroanalytical sensing of diethylstilbestrol (DES) using graphene quantum dots (GQD) surface modified screen‐printed electrodes (SPE) is reported. GQD was synthesized by simple bottom‐up method based on citric acid pyrolysis at 200 °C and electrodeposited directly at electrode surface under cyclic voltammetric conditions. The obtained GQD presented an average diameter of 7 nm and was characterized by techniques such as transmission and scanning electron microscopy, and electrochemical impedance spectroscopy. The proposed sensor exhibits a linear response from 0.05 to 7.5 μmol L−1, with limit of detection and quantification of 8.8 nmol L−1 and 29.0 nmol L−1, respectively. The repeatability study presented RSD=3.6 % for 6 consecutive measurements using the same electrode surface and the reproducibility study showed RSD=6.6 % for measurements with 6 different electrode surfaces. The proposed sensor was successfully applied for DES determination in synthetic urine and tap water spiked samples and good recoveries were obtained without any sample pre‐treatment, showing its promising analytical performance.
A Zirconium Oxide Nanoparticle Modified Screen‐printed Electrode for Anodic Stripping Determination of Daclatasvir Dihydrochloride
Authors: Hendawy Hassan A. M. , Eldin Ghada M. G. , Fekry Amany M.
Published: February 2019

A novel, sensitive and rapid voltammetric method applied for daclatasvir dihydrochloride (DSV.2HCl) detection in raw material, human plasma and urine using square wave voltammetry at a nano‐screen printed electrode (SPE) based on synthesized zirconium oxide nanoparticles (ZrO2 NPs). The attention to zirconium oxide nanoparticle syntheses arises from its likely use in making an electrode material in the electroanalytical process. Anodic stripping square wave voltammetric peaks have been recorded at the optimum conditions of drug solution as pH, scan rate, accumulation time and accumulation potential. Morphology of the used nanoparticles has been performed by scanning electron microscope (SEM) and transmission microscope (TEM). ZrO2 NPs were applied to screen printed electrode (ZrO2‐MSPE) giving a new sensor to detect the DSV.2HCl drug. ZrO2 NPs were tested for their electroactivity in improving electrodes sensitivity. The modified electrode has been used for the analysis of DSV.2HCl in spiked serum, spiked urine and pharmaceutical formulation.
Acute Effects of Binary Mixtures of Imidacloprid and Tebuconazole on 4 Freshwater Invertebrates
Authors: Raby Melanie , Maloney Erin , Poirier David G. , Sibley Paul K.
Published: February 2019

Receiving waters from agricultural areas can contain multiple pesticides such as the neonicotinoid imidacloprid and the fungicide tebuconazole, leading to the potential for aquatic life to be exposed to such mixtures. In the present study, the effects of tebuconazole were tested alone and in binary mixtures with imidacloprid on 4 aquatic invertebrates: Chironomus dilutus, Hyalella azteca, Lumbriculus variegatus, and Neocloeon triangulifer. Acute (96‐h) median lethal concentrations (LC50s) were derived for individual compounds and used to design a binary mixture study to determine cumulative effects. The LC50s showed that imidacloprid was more potent than tebuconazole by 1 to 3 orders of magnitude for the 4 species. Lethality data from mixture experiments were analyzed using MIXTOX to determine deviations from independent action, followed by the model deviation ratio (MDR) technique to determine the biological significance and reproducibility of observed mixture effects. MIXTOX showed that the cumulative toxicities of imidacloprid–tebuconazole differed between the species: for C. dilutus there was no deviation from independent action; however, for H. azteca the mixture was antagonistic (specifically dose ratio–dependent), and for N. triangulifer it was synergistic. The MDR method showed that only observations with H. azteca significantly deviated from independent action. Because of the lack of evidence of a clear deviation from independent action and the much greater potency of imidacloprid, the weight of evidence indicates that the presence of tebuconazole is unlikely to appreciably increase the hazard from imidacloprid exposure to aquatic invertebrates. Environ Toxicol Chem 2019;00:1–17. © 2019 SETAC
Protective effect of walnut on d‐galactose‐induced aging mouse model
Authors: Liu Ji , Chen Dan , Wang Zukun , Chen Chaoyin , Ning Delu , Zhao Shenglan
Published: February 2019

Objective (s)

Accumulating evidence has suggested that oxidative stress and apoptosis are involved in the aging process. d‐galactose (gal) has been reported to cause symptoms of aging in mice, accompanied by liver and brain injuries. Our present work was to study the potential antioxidative and anti‐apoptotic effects of walnut and to explore how these effects act on mice in a d‐gal‐induced aging model.

Materials and Methods

Aging mice were induced by subcutaneous injection of d‐gal (200 mg kg−1 d−1 for 8 weeks). Walnut samples were simultaneously administered to the d‐gal‐induced aging mice once daily by intragastric gavage. Finally, body weight, organ index, cognitive function, levels of antioxidative enzymes, and liver function were monitored.

Results

The kernel pellicles of walnut could not only improve the learning and memory ability, and the organ index, but also significantly decrease body weight and normalize the levels of activity of antioxidative enzymes in aging mice. Further, the walnut seed coat would protect damages of hippocampus and liver in aging mice.

Highlights

In the current study, we investigated the effects of walnut kernels and walnut seed coats (WSCs) on d‐galactose‐induced aging mice. WSC was firstly found to have beneficial effects on d‐gal‐treated mouse's brain with learning and memory impairment, which probably through the underlying mechanism reduces oxidative damage and limits neuroinflammation. In addition, WSC had a protective effect on liver damage in d‐galactose sensing mice.
Refined cottonseed oil as a replacement for soybean oil in broiler diet
Authors: Yang Ao , Qi Ming , Wang Xu , Wang Shuai , Sun Lvhui , Qi Desheng , Zhu Luoyi , Duan Yongzhi , Gao Xin , Ali Rajput Shahid , Zhang Niya
Published: February 2019

With the shortage of common vegetable fat sources, such as soybean oil (SBO), it is urgent to find alternative oil sources for broiler producers. The objective of this study was to evaluate the potential of refined cottonseed oil (CSO) as a replacement for SBO in broiler diets. A total of 180 chickens at 1 d of age were randomly assigned to five treatments of six replicates. One treatment was the basal diet (control), and the other four experimental diets were formulated from the basal diet by replacing (w/w) 25%, 50%, 75%, and 100% of the SBO with refined CSO (only containing 0.2% cyclopropenoid fatty acids, and no free gossypol was detected). At the end of week 6, blood samples were obtained from the jugular vein and the breast muscle was aseptically isolated from two birds per replicate. The results showed that substitution of CSO for low‐level SBO had no significant effect (p > 0.05) on broiler performance during the starter period (week 1–3), while 50% level of CSO inclusion significantly increased (p < 0.05) ADG and improved FCR compared with the control group during the finisher period (week 4–6). Broilers fed 100% CSO diets had lower (p < 0.05) levels of serum total protein (TP), albumin (ALB), cholesterol (CHO) concentrations, and serum alkaline phosphatase (AKP) activity than that of the control broilers. Furthermore, the serum antioxidant status appeared to be enhanced by CSO. Additionally, high levels of CSO (75 and 100%) significantly increased the proportions of C14:0 and C18:0 but decreased the proportions of C18:1n9t, C18:2n6c, and ∑ n‐6 polyunsaturated fatty acids in breast muscles of broilers. Overall, the SBO could be replaced with refined CSO up to 50% in diets for broilers without adversely affecting the performance, liver functions, and breast muscle fatty acid composition of these broilers.
Pain assessment and pain treatment for community‐dwelling people with dementia: A systematic review and narrative synthesis
Authors: Bullock Laurna , Bedson John , Jordan Joanne L. , Bartlam Bernadette , Chew‐Graham Carolyn A. , Campbell Paul
Published: February 2019

Objectives

To describe the current literature on pain assessment and pain treatment for community‐dwelling people with dementia.

Method

A comprehensive systematic search of the literature with narrative synthesis was conducted. Eight major bibliographic databases were searched in October 2018. Titles, abstracts, and full‐text articles were sequentially screened. Standardised data extraction and quality appraisal exercises were conducted.

Results

Thirty‐two studies were included in the review, 11 reporting findings on pain assessment tools or methods and 27 reporting findings on treatments for pain.

In regard to pain assessment, a large proportion of people with moderate to severe dementia were unable to complete a self‐report pain instrument. Pain was more commonly reported by informal caregivers than the person with dementia themselves. Limited evidence was available for pain‐focused behavioural observation assessment.

In regard to pain treatment, paracetamol use was more common in community‐dwelling people with dementia compared with people without dementia. However, non‐steroidal anti‐inflammatory drugs (NSAIDs) were used less. For stronger analgesics, community‐dwelling people with dementia were more likely to receive strong opioids (eg, fentanyl) than people without dementia.

Conclusion

This review identifies a dearth of high‐quality studies exploring pain assessment and/or treatment for community‐dwelling people with dementia, not least into non‐pharmacological interventions. The consequences of this lack of evidence, given the current and projected prevalence of the disease, are very serious and require urgent redress. In the meantime, clinicians should adopt a patient‐ and caregiver‐centred, multi‐dimensional, longitudinal approach to pain assessment and pain treatment for this population.
Implementation of submandibular gland transfer: A multi‐institutional study of feasibility and time to treatment
Authors: Pang John , Ching Harry H. , Sobel Ryan H. , Orosco Ryan K. , Califano Joseph A. , Wang Robert C. , Sanghvi Parag , Coffey Charles S.
Published: February 2019

Background

Submandibular gland transfer (SMGT) mitigates radiation‐induced xerostomia but has yet to be widely adopted. We evaluate the feasibility of incorporating SMGT at multiple academic institutions and report the incidence of treatment delay.

Methods

Forty‐nine patients were identified who underwent SMGT. Time points pertaining to diagnosis and key treatment events including SMGT, surgery, chemotherapy, and radiation were extracted. Treatment delay was defined as either >60 days from diagnosis to definitive therapy or >6 weeks between surgery and adjuvant therapy.

Results

Median time from diagnosis to primary treatment was 42 days (IQR, 32‐54). Median time from surgery to adjuvant therapy was 33 days (IQR, 28‐47). Delay in starting treatment was observed in 7/49 patients (14%). Six patients incurred a delay in postoperative radiation therapy (6/19; 32%).

Conclusions

With appropriate care coordination, SMGT can be implemented into a clinical pathway with a goal of decreasing radiation‐induced xerostomia without increasing treatment delays.
Amelioration of Ductular Reaction by Stem Cell Derived Extracellular Vesicles in MDR2 Knockout Mice via Lethal‐7 microRNA
Authors: McDaniel Kelly , Wu Nan , Zhou Tianhao , Huang Li , Sato Keisaku , Venter Julie , Ceci Ludovica , Chen Demeng , Ramos‐Lorenzo Sugeily , Invernizzi Pietro , Bernuzzi Francesca , Wu Chaodong , Francis Heather , Glaser Shannon , Alpini Gianfranco , Meng Fanyin
Published: February 2019

Cholangiopathies are diseases that affect cholangiocytes, the cells lining the biliary tract. Liver stem cells (LSCs) are able to differentiate into all cells of the liver and possibly influence the surrounding liver tissue by secretion of signaling molecules. One way in which cells can interact is through secretion of extracellular vesicles (EVs), which are small membrane‐bound vesicles that contain proteins, microRNAs (miRNAs), and cytokines. We evaluated the contents of liver stem cell–derived EVs (LSCEVs), compared their miRNA contents to those of EVs isolated from hepatocytes, and evaluated the downstream targets of these miRNAs. We finally evaluated the crosstalk among LSCs, cholangiocytes, and human hepatic stellate cells (HSCs). We showed that LSCEVs were able to reduce ductular reaction and biliary fibrosis in multidrug resistance protein 2 (MDR2)‐/‐ mice. Additionally, we showed that cholangiocyte growth was reduced and HSCs were deactivated in LSCEV‐treated mice. Evaluation of LSCEV contents compared with EVs derived from hepatocytes showed a large increase in the miRNA, lethal‐7 (let‐7). Further evaluation of let‐7 in MDR2‐/‐ mice and human primary sclerosing cholangitis samples showed reduced levels of let‐7 compared with controls. In liver tissues and isolated cholangiocytes, downstream targets of let‐7 (identified by ingenuity pathway analysis), Lin28a (Lin28 homolog A), Lin28b (Lin28 homolog B), IL‐13 (interleukin 13), NR1H4 (nuclear receptor subfamily 1 group H member 4) and NF‐κB (nuclear factor kappa B), are elevated in MDR2‐/‐ mice, but treatment with LSCEVs reduced levels of these mediators of ductular reaction and biliary fibrosis through the inhibition of NF‐κB and IL‐13 signaling pathways. Evaluation of crosstalk using cholangiocyte supernatants from LSCEV‐treated cells on cultured HSCs showed that HSCs had reduced levels of fibrosis and increased senescence. Conclusion: Our studies indicate that LSCEVs could be a possible treatment for cholangiopathies or could be used for target validation for future therapies.