bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet Function: Meloxicam Intravenous in Whole Blood Samples From Healthy Volunteers
Authors: Jahr Jonathan S. , Searle Shawn , McCallum Stewart , Mack Randall , Minger Kim , Freyer Alex , Du Wei , Hobson Sue
Published: January 2020

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of cyclooxygenase (COX)‐1 impairing thromboxane production. An intravenous nanocrystal formulation of meloxicam, a COX‐2 preferential nonsteroidal anti‐inflammatory drug, is under development for the treatment of moderate to severe pain. This single‐center ex vivo study evaluated the effect of meloxicam intravenous and ketorolac on platelet function in whole blood samples from healthy volunteers. Each whole blood sample was aliquoted to allow analysis using a platelet function analyzer under negative control (untreated), positive control (2 therapeutic ketorolac concentrations), and meloxicam intravenous (1 therapeutic, 3 supratherapeutic concentrations) using both collagen with epinephrine and collagen with adenosine diphosphate reagent cartridges. The platelet function analyzer determines closure time by simulating platelet adhesion and aggregation following vascular injury. The final analysis set included data from 8 subjects. The collagen with adenosine diphosphate analysis (sensitive to thrombocytopathies) showed no significant differences in closure time for meloxicam‐ or ketorolac‐treated samples and untreated control. The collagen with epinephrine analysis (sensitive to aspirin‐induced platelet abnormalities) produced no significant difference in closure time between any meloxicam concentration and untreated control. Ketorolac was associated with significantly longer closure times vs untreated control at both the 2.5‐ and 5‐µg/mL concentrations (P = .003 and .0257, respectively) and vs meloxicam at several concentrations. Similar results were observed when all analyzed samples were included. Meloxicam intravenous had no significant effect on closure times at therapeutic or supratherapeutic concentrations in this ex vivo study.
A Phase 1, Randomized, Placebo‐Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Subcutaneous Tezepelumab in Healthy Japanese Men
Authors: Sakamoto Kei , Matsuki Shunji , Irie Shin , Uchida Naoki , Hayashi Nobuya , Horiuchi Masato , Ren Song
Published: January 2020

Tezepelumab, a human immunoglobulin G2 monoclonal antibody against thymic stromal lymphopoietin, is currently under clinical development for the treatment of severe, uncontrolled asthma. This phase 1, randomized, placebo‐controlled, single‐ascending‐dose study assessed the safety, tolerability, pharmacokinetics, and immunogenicity of subcutaneous tezepelumab in healthy Japanese men. Participants were assigned to 1 of 3 tezepelumab dose cohorts (35, 105, or 280 mg; n = 8 per cohort) and randomized (6:2) to receive a single subcutaneous dose of tezepelumab or placebo, with a follow‐up period of 84 to 112 days. The overall incidences and severities of treatment‐emergent adverse events were similar across tezepelumab doses and between the tezepelumab and placebo groups. Tezepelumab was absorbed slowly, reaching a maximum serum concentration (mean, 5.2‐39.7 µg/mL) after 7 to 10 days. Area under the concentration‐time curve (mean, 207.2‐1612.0 µg · day /mL) increased in an approximate dose‐proportional manner. Tezepelumab had a long terminal serum half‐life (mean, 23.9‐26.3 days) and a small apparent distribution volume, suggesting limited distribution into peripheral tissues. No participants developed anti‐tezepelumab antibodies. Single‐dose, subcutaneous administration of tezepelumab 35 to 280 mg resulted in an acceptable safety profile with linear pharmacokinetics in healthy Japanese men. No clear differences in tezepelumab safety and pharmacokinetics between Japanese and non‐Japanese populations were identified.
The relation between corporate social responsibility certification and financial performance: An empirical study in Spain
Authors: Brotons José M. , Sansalvador Manuel E.
Published: January 2020

The relation between corporate social responsibility (CSR) and financial performance (FP) has been widely dealt with in specialized literature. This study has two points of interest: first, we develop a new tool which financially quantifies the value contributed to companies that are committed to CSR; then, we make a practical application of this tool through an empirical study focused on Spanish companies. This study is especially innovative because of the fuzzy methodology used and the way it defines CSR through the IQNet SR10 certification of social responsibility systems. In addition, the measurement of CSR through IQNet SR10 certification is a completely new approach to the subject. An interesting conclusion can be drawn from the empirical study: IQNet SR10 CSR certification increases the value of businesses. However, neither size nor the economic sector they belong to influence this relationship significantly.
An exploration of the role of ethnic identity in students’ construction of ‘British stories’
Authors: Huber Julia , Kitson Alison
Published: January 2020

Much of the research into history teaching and ethnicity concludes that the historical narratives that children from minority ethnic groups construct differ significantly from ‘mainstream’ or official national narratives and are often accompanied by a sense of disengagement or even alienation from the dominant history narratives taught in schools. Our research suggests that in England (or more specifically in London) the picture is more complicated than this. First, we did not find compelling evidence that students from black and minority ethnic backgrounds feel alienated or disengaged from the British history they are taught. Second, we found a surprising similarity across the narratives that different ethnic groups chose to tell us about British history, suggesting amongst other things some curriculum inertia in schools. Where differences did exist, we suggest that these can be explained as much by gender and broad cultural influences as by ethnicity. Third, whilst what students chose to include in their narratives was broadly similar across different ethnic groups, the reasons for including them did differ. Finally, and perhaps most positively, we conclude that students of all ethnic groups are keen to engage more critically with British narratives and would relish more opportunities to do so than current school curricula appear to encourage.
Vertebrate scavenger guild composition and utilization of carrion in an East Asian temperate forest
Authors: Inagaki Akino , Allen Maximilian L. , Maruyama Tetsuya , Yamazaki Koji , Tochigi Kahoko , Naganuma Tomoko , Koike Shinsuke
Published: January 2020

Scavenging is a common feeding behavior by many species that plays an important role in ecosystem stability and function while also providing ecosystem services. Despite its importance, facultative scavenging on large animal carcasses has generally been overlooked in Asian temperate forest ecosystems. The aim of this study was to determine the composition and feeding behavior of the facultative scavenger guild as it relates to sika deer (Cervus nippon) carcasses in Japanese forests. There are no obligate scavengers or large predators that kill adult ungulates, but humans fill the role of large predators by culling deer for population management. We documented nine vertebrate species scavenging on deer carcasses and found that mammals were more frequent scavengers than birds and also fed for longer durations. This result suggests that there is a facultative scavenger guild composed mainly of mammals in our forest ecosystem and that carcass utilization by birds was restricted to only forest species. Raccoon dogs (Nyctereutes procyonoides) and Asian black bears (Ursus thibetanus) were the most frequent scavenger species and also fed for longer durations than other scavengers. There were significant seasonal differences in scavenging by Asian black bear, Japanese marten (Martes melampus), and mountain hawk‐eagle (Nisaetus nipalensis), suggesting the availability of other food resources may alter facultative scavenging by each species. Our results support that scavenging is widespread in this system and likely has important functions including building links in the food web.
A meta‐analysis reveals temperature, dose, life stage, and taxonomy influence host susceptibility to a fungal parasite
Authors: Sauer Erin L. , Cohen Jeremy M. , Lajeunesse Marc J. , McMahon Taegan A. , Civitello David J. , Knutie Sarah A. , Nguyen Karena , Roznik Elizabeth A. , Sears Brittany F. , Bessler Scott , Delius Bryan K. , Halstead Neal , Ortega Nicole , Venesky Matthew D. , Young Suzanne , Rohr Jason R.
Published: January 2020

Complex ecological relationships, such as host–parasite interactions, are often modeled with laboratory experiments. However, some experimental laboratory conditions, such as temperature or infection dose, are regularly chosen based on convenience or convention, and it is unclear how these decisions systematically affect experimental outcomes. Here, we conducted a meta‐analysis of 58 laboratory studies that exposed amphibians to the pathogenic fungus Batrachochytrium dendrobatidis (Bd) to understand better how laboratory temperature, host life stage, infection dose, and host species affect host mortality. We found that host mortality was driven by thermal mismatches: hosts native to cooler environments experienced greater Bd‐induced mortality at relatively warm experimental temperatures and vice versa. We also found that Bd dose positively predicted Bd‐induced host mortality and that the superfamilies Bufonoidea and Hyloidea were especially susceptible to Bd. Finally, the effect of Bd on host mortality varied across host life stages, with larval amphibians experiencing lower risk of Bd‐induced mortality than adults or metamorphs. Metamorphs were especially susceptible and experienced mortality when inoculated with much smaller Bd doses than the average dose used by researchers. Our results suggest that when designing experiments on species interactions, researchers should carefully consider the experimental temperature, inoculum dose, and life stage, and taxonomy of the host species.
Harmony on the prairie? Grassland plant and animal community responses to variation in climate across land‐use gradients
Authors: Bruckerhoff Lindsey A. , Connell R. Kent , Guinnip James P. , Adhikari Elina , Godar Alixandra , Gido Keith B. , Boyle Alice W. , Hope Andrew G. , Joern Anthony , Welti Ellen
Published: January 2020

Human induced climate and land‐use change are severely impacting global biodiversity, but how community composition and richness of multiple taxonomic groups change in response to local drivers and whether these responses are synchronous remains unclear. We used long‐term community‐level data from an experimentally manipulated grassland to assess the relative influence of climate and land use as drivers of community structure of four taxonomic groups: birds, mammals, grasshoppers, and plants. We also quantified the synchrony of responses among taxonomic groups across land‐use gradients and compared climatic drivers of community structure across groups. All four taxonomic groups responded strongly to land use (fire frequency and grazing), while responses to climate variability were more pronounced in grasshoppers and small mammals. Animal groups exhibited asynchronous responses across all land‐use treatments, but plant and animal groups, especially birds, exhibited synchronous responses in composition. Asynchrony was attributed to taxonomic groups responding to different components of climate variability, including both current climate conditions and lagged effects from the previous year. Data‐driven land management strategies are crucial for sustaining native biodiversity in grassland systems, but asynchronous responses of taxonomic groups to climate variability across land‐use gradients highlight a need to incorporate response heterogeneity into management planning.
Trimethylamine N‐oxide and cardiovascular outcomes in patients with chronic heart failure after myocardial infarction
Authors: Zhou Xiang , Jin Mengchao , Liu Lei , Yu Zongliang , Lu Xiang , Zhang Hao
Published: January 2020

Aim

Accumulating evidence has demonstrated that intestinal microbiota‐dependent trimethylamine N‐oxide (TMAO) is involved in the pathogenesis of various cardiovascular diseases. The present study was designed to investigate the prognostic value of TMAO in patients with chronic heart failure (CHF) after myocardial infarction (MI).

Methods and results

We included 1208 CHF patients after MI in a prospective cohort study and determined the association between plasma TMAO and cardiovascular outcomes using Cox regression analysis. Patients with elevated TMAO levels were more likely to be older and have histories of atrial fibrillation and diabetes. Cox regression analysis indicated that TMAO was a significant predictor of major adverse cardiac events (MACE) (hazard ratio = 2.31, 95% confidence interval 1.42–3.59, P < 0.01) following adjustment for conventional risk factors. Integrated discrimination and net reclassification improvements for MACE were markedly improved by addition of TMAO to the model of traditional risk factors. The Kaplan–Meier survival analysis showed that MACE risk increased with the elevation in TMAO levels and this positive correlation became more significant when TMAO levels were higher than the median. TMAO was also found to be an independent predictor of all‐cause mortality (hazard ratio = 2.15, 95% confidence interval 1.37–3.24, P < 0.01) after adjusting for traditional risk factors.

Conclusions

Our study suggests that TMAO is a valuable prognostic indicator of MACE in patients with CHF after MI.
Alcohol Oxidations by Schiff Base Manganese(III) Complexes
Authors: Neshat Abdollah , Kakavand Meysam , Osanlou Farzane , Mastrorilli Piero , Schingaro Emanuela , Mesto Ernesto , Todisco Stefano
Published: January 2020

Asymmetric Schiff base manganese(III) complexes involving salen ligands, N,N'‐bis(salicylidene)2,3‐diaminopyridine, N,N'‐bis(3‐methoxysalicylidene)2,3‐diaminopyridine, N,N'‐bis(3,5‐di‐tert‐butylsalicylidene)2,3‐diaminopyridine and N,N'‐bis(3,5‐di‐chloro‐salicylidene)2,3‐diaminopyridine were prepared and their catalytic activity was investigated in the oxidation of some primary and secondary alcohols. During optimization of oxidation reactions, Mn‐4, bearing electron withdrawing N,N'‐Bis(3,5‐di‐chloro‐salicylidene)2,3‐diaminopyridine ligand, showed higher activity than other catalysts tested. The catalytic reactions were carried out in the presence of various oxidants such as oxygen, hydrogen peroxide or tert‐butyl hydroperoxide (TBHP) and additives such as acetic acid and imidazole. The oxidant/additive combination of TBHP and imidazole was shown to be effective for the oxidation process and the degree of their impact on oxidation reaction was found highly dependent on a balanced ratio between them. Mn‐4 was selected as the most effective catalyst under optimized reaction conditions and revealed efficient for the oxidation of secondary alcohols.
Sesame Oil Oxidation Control by Active and Smart Packaging System Using Wheat Gluten/Chlorophyll Film to Increase Shelf Life and Detecting Expiration Date
Authors: Chavoshizadeh Sona , Pirsa Sajad , Mohtarami Forough
Published: January 2020

In this study, a smart biodegradable film based on wheat gluten modified with chlorophyll (WG/Ch) is presented. The effect of chlorophyll on the antioxidant activity and mechanical properties of WG/Ch film is studied. Scanning electron microscopy and Fourier‐transform infrared spectroscopy (FT‐IR) analyses are used to study the structure and chemical composition of gluten‐based films. The WG/Ch film is used in the packaging of sesame oil. The effect of WG/Ch film on increasing the shelf life and detecting expiration time of oil is studied. FT‐IR results show that weak interactions are created between gluten and chlorophyll. The antioxidant activity of the WG film is 60% and it increases to 85% by the addition of chlorophyll. The results show that with the increasing storage time of oil samples, oxidative indices are increased, but the WG/Ch film decreases the sesame oil oxidation significantly (almost in the all oxidative indices 50% decrease is observed).

Practical Applications: The WG/Ch film is used in the packaging of sesame oil. The effect of WG/Ch film on the increasing of shelf life and detecting expiration time of oil is studied. By increasing storage time and oxidant, acidity, acid number, PA, and oil color change are increased, but the WG/Ch active film decreases the sesame oil oxidation significantly. Also, by examining the color properties of the active film, it is observed that with increasing storage time and oxidant percent, the color of the film is changed (from green to yellow), which can be used to estimate the oil expiration time. It should be mentioned that the film's color changes are visible to the naked eye.
Damping estimation of high‐rise buildings considering structural modal directions
Authors: Li Qiu‐Sheng , Zhou Kang , Li Xiao
Published: January 2020

One widespread problem in damping estimation of high‐rise buildings is the neglect of structural modal directions, which may induce beating in measured dynamic responses along building geometric axes and thereby induce errors in damping estimations to some extent. Based on a proposed two degrees of freedom (2‐DOF) simulation model, the effects of neglecting the modal directions on damping estimate are systematically investigated. The results show that the angular differences between the modal directions and the building geometric axes, as well as the frequency difference between the involved modes, both have significant effects on the damping estimate of high‐rise buildings. This paper proposes a spectral method to determine the modal directions of high‐rise buildings and further validate this method by an analysis of full‐scale measurements from four skyscrapers. The damping ratios estimated based on the responses along the identified modal directions are more accurate than those based on those measured along the building geometric axes. Furthermore, an empirical prediction model for damping ratio of high‐rise buildings with heights over 200 m is proposed based on the field measured damping results of several buildings with consideration of the modal directions. The objective of this study is to improve the accuracy of damping estimation of high‐rise buildings and therefore provide useful information for the structural design of future skyscrapers.
Performance of the LandSoil expert‐based model to map erosion and sedimentation: application to a cultivated catchment in central Belgium
Authors: Cantreul Vincent , Pineux Nathalie , Swerts Gilles , Bielders Charles , Degré Aurore
Published: January 2020

Intensive agricultural practices on sensitive soils induce high erosion rates in central Belgium. Expert‐rules models quantify runoff and erosion at catchment scale, avoiding over‐parameterization, and can include some direct or indirect connectivity features. The aim of this article is to test the ability of an expert‐based model, LandSoil, to quantify runoff and to locate erosion and sedimentation areas in a small cultivated loamy catchment in Belgium during the years 2014, 2015 and 2016. Spatialized data are important for assessing model outputs and the erosive response. Measurements of runoff and observation of spatial erosion/deposition patterns, especially around major connectivity points, permitted an assessment of the reliability of the model results. Runoff modelling gave contrasting results (good linear adjustment at the outlet of the 83 ha sub‐catchment (point 1): r2 of 0.96, Nash–Sutcliffe criterion of 0.95; less good at the outlet of the 3.9 ha sub‐catchment (point 2): r2 of 0.28, Nash–Sutcliffe criterion of –0.47). For point 2 the poor results are explained by the very few runoff events observed, a scaling effect and the small area with a single land use. Graduated rulers demonstrate that the model is able to provide a coherent pattern of erosion/deposition. The study highlights great sensitivity to the effect of land use, land allocation, landscape design and slope gradients. Grass strips induce deposition of eroded particles when slopes are gentle (< 2%). Woodland strips decrease connectivity by being in the stream but deposit thinner sediment layers. Field boundaries have a role in the transport, but not really the quantity, of sediments. This model validation in the Belgian loess context allows us to use LandSoil in other similar environments in order to estimate the effects of landscape management scenarios. © 2020 John Wiley & Sons, Ltd.
Forecasting models in the manufacturing processes and operations management: Systematic literature review
Authors: Agostino Icaro Romolo Sousa , da Silva Wesley Vieira , Pereira da Veiga Claudimar , Souza Adriano Mendonça
Published: January 2020

The purpose of this paper is to present the result of a systematic literature review regarding the application and development of forecasting models in the industrial context, especially the context of manufacturing processes and operations management. The study was conducted considering the preparation of an established research protocol to know, discuss, and analyze the main approaches adopted by researchers in the field. To achieve this objective, we analyzed 354 recent papers published in periodicals between 2008 and 2018. This paper makes three main contributions to the field: (i) it presents an updated portfolio of prediction models in the industrial context, providing a reference point for researchers and industrial managers; (ii) it presents a characterization of the field of study through the identification of publication vehicles, frequency, and the principal authors and countries related to the development of research on the theme; (iii) it proposes a unified framework, listing the characteristics of the prediction models with their respective application contexts, identifying the current research directions to provide theoretical aids for the development of new approaches to forecasting in industry. The results of this study provide an empirical base for further discussions on studies that focus on forecasting in the industrial context.
Design of an intelligent controller for a grain dryer: A support vector machines for regression inverse model proportional–integral–derivative controller
Authors: Dai Aini , Zhou Xiaoguang , Wu Zidan
Published: January 2020

Grain drying control is a challenging task owing to the complex heat and mass exchange process. To precisely control the outlet grain moisture content (MC) of a continuous mixed‐flow grain dryer, in this paper, we proposed a genetically optimized inverse model proportional–integral–derivative (PID) controller based on support vector machines for regression algorithm which is named the GO‐SVR‐IMCPID controller. The structure of the GO‐SVR‐IMCPID controller consists of a genetic optimization algorithm, an indirect inverse model predictive controller, and a PID controller. In addition, to verify the control performances of the proposed controller in the simulation study, we have established a nonlinear mathematical model for the mixed‐flow grain dryer to represent the nonlinear grain drying process. Finally, the control performance and the robustness of the GO‐SVR‐IMCPID controller were simulated and compared with the other controllers. By the simulation results, it is shown that this proposed algorithm can track the target value precisely and has fewer steady errors and strong ability of anti‐interference. Furthermore, it has further confirmed the superiority of the proposed grain drying controller by comparing it with the other controllers.
Nondestructive measurement of kiwifruit firmness, soluble solid content (SSC), titratable acidity (TA), and sensory quality by vibration spectrum
Authors: Zhang Wen , Wang Aichen , Lv Zhenzhen , Gao Zongmei
Published: January 2020

Maturity is a key attribute to evaluate the quality and acceptability of fruit products. In this study, the impact method was used for nondestructive measurement of kiwifruit maturity. The fruit was vertically dropped onto an impact plate, and an accelerometer was used to measure the response signal. Then, fruit firmness, soluble solid content (SSC), titratable acidity (TA), and sensory scores were measured to determine the kiwifruit maturity. In addition, different modeling methods were proposed for data analysis. The results showed that the optimized prediction results were obtained by the principal component analysis–back‐propagation neural network (PCA‐BPNN) method for both quantitative and qualitative analysis. The optimized correlation coefficient between prediction and actual values (rp) and root mean square error of prediction (RESEP) for firmness, SSC, TA, and sensory score were 0.881 (2.359N), 0.641 (1.511 Brix), 0.568 (0.023%), and 0.935 (0.693), respectively. The optimized discriminant accuracy for immature, mature, and overmature kiwifruits was 94.2% and 92.1% for calibration and validation, respectively. Such results indicated the feasibility of the proposed impact method for kiwifruit maturity evaluation.
Equal long‐term care for equal needs with universal and comprehensive coverage? An assessment using Dutch administrative data
Authors: Tenand Marianne , Bakx Pieter , van Doorslaer Eddy
Published: January 2020

The Netherlands is one of the few countries that offer generous universal public coverage of long‐term care (LTC). Does this ensure that the Dutch elderly with similar care needs receive similar LTC, irrespective of their income? In contrast with previous studies of inequity in care use that relied on a statistically derived variable of needs, our paper exploits a readily available, administrative measure of LTC needs stemming from the eligibility assessment organized by the Dutch LTC assessment agency. Using exhaustive administrative register data on 616,934 individuals aged 60 and older eligible for public LTC, we find a substantial pro‐poor concentration of LTC use that is only partially explained by poorer individuals' greater needs. Among those eligible for institutional care, higher‐income individuals are more likely to use—less costly—home care. This pattern may be explained by differences in preferences, but also by their higher copayments for nursing homes and by greater feasibility of home‐based LTC arrangements for richer elderly. At face value, our findings suggest that the Dutch LTC insurance “overshoots” its target to ensure that LTC is accessible to poorer elderly. Yet, the implications depend on the origins of the difference and one's normative stance.
Anterior and posterior hippocampus macro‐ and microstructure across the lifespan in relation to memory—A longitudinal study
Authors: Langnes Espen , Sneve Markus H. , Sederevicius Donatas , Amlien Inge K. , Walhovd Kristine B. , Fjell Anders M.
Published: January 2020

There is evidence for a hippocampal long axis anterior–posterior (AP) differentiation in memory processing, which may have implications for the changes in episodic memory performance seen across development and aging. The hippocampus shows substantial structural changes with age, but the lifespan trajectories of hippocampal sub‐regions along the AP axis are not established. The aim of the present study was to test whether the micro‐ and macro‐structural age‐trajectories of the anterior (aHC) and posterior (pHC) hippocampus are different. In a single‐center longitudinal study, 1,790 cognitively healthy participants, 4.1–93.4 years of age, underwent a total of 3,367 MRI examinations and 3,033 memory tests sessions over 1–6 time points, spanning an interval up to 11.1 years. T1‐weighted scans were used to estimate the volume of aHC and pHC (macrostructure), and diffusion tensor imaging to measure mean diffusion (MD, microstructure) within each region. We found that the macro‐ and microstructural lifespan‐trajectories of aHC and pHC were clearly distinguishable, with partly common and partly unique variance shared with age. aHC showed a protracted period of microstructural development, while pHC microstructural development as indexed by MD was more or less completed in early childhood. In contrast, pHC showed larger unique aging‐related changes. An aHC–pHC difference was also observed for volume, with pHC changing relatively more with higher age. All regions showed age‐dependent relationships with episodic memory. aHC micro‐ and macrostructure was significantly related to verbal memory independently of age, but the relationships were still strongest among the older participants. We suggest that memory processes supported by each sub‐region improve or decline in concert with volumetric and microstructural changes in the same age‐period. Future research should disentangle the lifespan relationship between changes in these structural properties and different memory processes, encoding versus retrieval in particular, as well as other cognitive functions depending on the hippocampal long‐axis specialization.
Asymptotic Behavior of the Exchange‐Correlation Energy Density and the Kohn‐Sham Potential in Density Functional Theory: Exact Results and Strategy for Approximations
Authors: Kraisler Eli
Published: January 2020

Density functional theory (DFT) is nowadays the leading theoretical framework for quantum description of materials from first principles. Being an exact theory on one hand and computationally efficient on the other hand, DFT allows to address large and complex many‐electron systems and accurately predict their properties. The predictive power of DFT critically depends though on an accurate approximation to the generally unknown exchange‐correlation (xc) energy functional. Approximations can be constructed from first principles by satisfying known properties of the exact functional. In this work I review two such exact properties: the asymptotic behavior of the xc energy density per particle and the asymptotic behavior of the Kohn‐Sham potential, in finite many‐electron systems. The derivation of the asymptotic forms for both quantities is reviewed, employing the concepts of the adiabatic connection and of the xc hole with relation to the first quantity and the exact electron factorization approach for the second one. Furthermore, it is shown that the correct asymptotic behavior of one of the aforementioned quantities does not guarantee a correct behavior of the other. These quantities are related via the xc hole response function, which is defined, examined and its exact exchange part is analytically derived. The extent to which existing xc approximations satisfy the named exact properties is reviewed and the relationship between correct asymptotics and freedom from one‐electron self‐interaction in DFT is discussed. Finally, a strategy for development of advanced approximations for exchange and correlation with a correct asymptotic behavior is suggested.
Biomarkers of exposure, effect, and susceptibility in occupational exposure to traffic‐related air pollution: A review
Authors: Brucker Natália , do Nascimento Sabrina Nunes , Bernardini Letícia , Charão Mariele Feiffer , Garcia Solange Cristina
Published: January 2020

There is a well‐recognized association between environmental air pollution exposure and several human diseases. However, the relationship between diseases related to occupational air pollution exposure on roads and high levels of traffic‐related air pollutants (TRAPs) is less substantiated. Biomarkers are essential tools in environmental and occupational toxicology, and studies on new biomarkers are increasingly relevant due to the need to determine early biomarkers to be assessed in exposure conditions. This review aimed to investigate the main advances in the biomonitoring of subjects occupationally exposed to air pollution, as well as to summarize the biomarkers of exposure, effect, and susceptibility. Furthermore, we discuss how biomarkers could be used to complement the current application of methods used to assess occupational exposures to xenobiotics present in air pollution. The databases used in the preparation of this review were PubMed, Scopus, and Science Direct. Considering the significant deleterious effects on health associated with chronic occupational exposure to xenobiotics, this topic deserves attention. As it is difficult to avoid occupational exposure to TRAPs, biomonitoring should be applied as a strategy to reduce the toxic effects of workplace exposure.
Circular RNA RSF1 promotes inflammatory and fibrotic phenotypes of irradiated hepatic stellate cell by modulating miR‐146a‐5p
Authors: Chen Yuhan , Yuan Baoying , Chen Genwen , Zhang Li , Zhuang Yuan , Niu Hao , Zeng Zhaochong
Published: January 2020

The role of circular RNA (circRNA) in radiation‐induced liver disease (RILD) remains largely unknown. In this study, Ras‐related C3 botulinum toxin substrate 1 (RAC1) was elevated in irradiated human hepatic stellate cell (HSC) line LX2, the important effector cell mediating RILD. Overexpression of RAC1 promotes cell proliferation, proinflammatory cytokines production, and α‐smooth muscle actin expression, which were blocked by microRNA (miR)‐146a‐5p mimics. CircRNA RSF1 (circRSF1) was upregulated in irradiated LX2 cells and predicted to harbor binding site for miR‐146a‐5p. Biotinylated‐RNA pull down and dual‐luciferase reporter detection confirmed the direct interaction of circRSF1 and miR‐146a‐5p. Enforced expression of circRSF1 increased RAC1 expression by acting as miR‐146a‐5p sponge to inhibit miR‐146a‐5p activity, and thus enhanced the cell viability, and promoted inflammatory and fibrotic phenotype of irradiated LX2 cells. These findings indicate a functional regulatory axis composing of circRSF1, miR‐146a‐5p, and RAC1 in irradiated HSC, which may provide attractive therapeutic targets for RILD.
Mesenchymal stem cell‐conditioned media: A novel alternative of stem cell therapy for quality wound healing
Authors: Joseph Anand , Baiju Indu , Bhat Irfan A. , Pandey Sriti , Bharti Mukesh , Verma Megha , Pratap Singh Anuj , Ansari Matin M. , Chandra Vikash , Saikumar Gutulla , Amarpal  , Taru Sharma Gutulla
Published: January 2020

Mesenchymal stem cells‐conditioned media (MSCs‐CM) contains several growth factors and cytokines, thus may be used as a better alternative to stem cell therapy, which needs to be elucidated. The present study was conducted to evaluate the therapeutic potential of caprine, canine, and guinea pig bone marrow‐derived MSCs‐CM in excision wound healing in a guinea pig model. MSCs were obtained from bone marrow, expanded ex vivo and characterized as per ISCT criteria. CM was collected assayed by western blot to ascertain the presence of important secretory biomolecules. Quantitative estimation by enzyme‐linked immunosorbent assay was done for a vascular epidermal growth factor (VEGF) and interleukin‐6 (IL‐6) in caprine MSCs‐CM and optimum time for collection of CM was decided as 72 hr. CM from all the species was lyophilized by freeze‐drying method. Full‐thickness (2 × 2 cm2) excision skin wounds were created in guinea pigs (six animals in each group) and respective lyophilized CM mixed with laminin gel was applied topically at weekly interval. On Day 28, histopathological examinations of healed skin were done by hemotoxylin and eosin staining. MSCs were found to secrete important growth factors and cytokines (i.e., VEGF, transforming growth factor‐β1, fibroblast growth factor‐2, insulin‐like growth factor‐1, stem cell factor, and IL‐6) as demonstrated by immunohistochemistry and western blot assay. It was found that allogenic and xenogenic application of CM significantly improved quality wound healing with minimal scar formation. Thus, MSCs‐CM can be used allogenically as well as xenogenically for quality wound healing.
Resistance training‐induced muscle hypertrophy is mediated by TGF‐β1‐Smad signaling pathway in male Wistar rats
Authors: Nikooie Rohollah , Jafari‐Sardoie Sohil , Sheibani Vahid , Nejadvaziri Chatroudi Amir
Published: January 2020

The TGF‐β1‐Smad pathway is a well‐known negative regulator of muscle growth; however, its potential role in resistance training‐induced muscle hypertrophy is not clear. The present study proposed to determine whether and how this pathway may be involved in resistance training‐induced muscle hypertrophy. Skeletal muscle samples were collected from the control, trained (RT), control + SB431542 (CITGF), and trained + SB431542 (RTITGF) animals following 3, 5, and 8 weeks of resistance training. Inhibition of the TGF‐β1‐Smad pathway by SB431542 augmented muscle satellite cells activation, upregulated Akt/mTOR/S6K1 pathway, and attenuated FOXO1 and FOXO3a expression in the CITGF group (all p < .01), thereby causing significant muscle hypertrophy in animals from the CITGF. Resistance training significantly decreased muscle TGF‐β1 expression and Smad3 (P‐Smad3S423/425) phosphorylation at COOH‐terminal residues, augmented Smad2 (P‐Smad2‐LS245/250/255) and Smad3 (P‐Smad3‐LSer208) phosphorylation levels at linker sites (all p < .01), and led to a muscle hypertrophy which was unaffected by SB431542, suggesting that the TGF‐β1‐Smad signaling pathway is involved in resistance training‐induced muscle hypertrophy. The effects of inhibiting the TGF‐β1‐Smad signaling pathway were not additive to the resistance training effects on FOXO1 and FOXO3a expression, muscle satellite cells activation, and the Akt/mTOR/S6K1 pathway. Resistance training effect of satellite cell differentiation was independent of the TGF‐β1‐Smad signaling pathway. These results suggested that the effect of the TGF‐β1‐Smad signaling pathway on resistance training‐induced muscle hypertrophy can be attributed mainly to its diminished inhibitory effects on satellite cell activation and protein synthesis. Suppressed P‐Smad3S423/425 and enhanced P‐Smad2‐LS245/250/255 and P‐Smad3‐LSer208 are the molecular mechanisms that link the TGF‐β1‐Smad signaling pathway to resistance training‐induced muscle hypertrophy.
CircTIMELESS regulates the proliferation and invasion of lung squamous cell carcinoma cells via the miR‐136‐5p/ROCK1 axis
Authors: Zhang Wenjing , Shi Jingjing , Cheng Chuanhao , Wang Huaqi
Published: January 2020

Numerous studies demonstrate that circular RNAs (circRNAs) are critical regulators of the occurrence and progression of tumors. However, research on the involvement of circRNAs in lung squamous cell carcinoma (LUSC) is limited. In our study, circTIMELESS (also named hsa_circ_0000408 in the Human circRNA Database) was upregulated in both LUSC tissues and LUSC cells, and circTIMELESS expression was positively associated with the TNM stage. Moreover, circTIMELESS silencing markedly suppressed invasion in vitro and disrupted proliferation in vitro as well as in vivo. Additional investigations have shown that circTIMELESS functions as a miR‐136‐5p “sponge” and regulates miR‐136‐5p expression. Furthermore, the impact of miR‐136‐5p upregulation was consistent with the results of circTIMELESS silencing, both of which inhibited the proliferation and invasion of LUSC cells. Additional results showed that Rho‐associated coiled‐coil containing protein kinase 1 (ROCK1) is targeted by miR‐136‐5p. The results of recovery experiments showed that ROCK1 overexpression partly rescued the impact of circTIMELESS silencing and miR‐136‐5p upregulation on proliferation and invasion. Consequently, our findings confirmed that circTIMELESS exists in LUSC and acts as a tumor promoter through the miR‐136‐5p/ROCK1 axis. Based on these findings, circTIMELESS may be potentially utilized as a therapeutic target for LUSC.
Novel insights into Dhh signaling in antler chondrocyte proliferation and differentiation: Involvement of Foxa
Authors: Ma Li , Duan Cui‐Cui , Yang Zhan‐Qing , Ding Jun‐Li , Liu Shu , Yue Zhan‐Peng , Guo Bin
Published: January 2020

The desert hedgehog (Dhh) is crucial for spermatogenesis and Leydig cell differentiation, but little is known regarding its physiological function in cartilage. In this study, Dhh mRNA was abundant in antler chondrocytes, where it advanced cell proliferation concomitant with accelerated transition from the G1 to the S phase and induced elevation of the hypertrophic chondrocyte markers, Col X and Runx2. Silencing of Ptch1 resulted in appreciable Smo accumulation and enhanced rDhh stimulation of Smo, whose impediment by cyclopamine obscured the proliferative function of Dhh and alleviated its guidance of chondrocyte differentiation. Further analysis evidenced the noteworthy positive action of Smo in the bridging between Dhh and Gli transcription factors. Obstruction of Gli1 by GANT58 caused the failed stimulation of Col X and Runx2 by rDhh. Analogously, siRNA against Gli1‐3 hindered chondrocyte differentiation in the context of rDhh. Simultaneously, Gli transcription factors mediated the regulation of Dhh on Foxa1, Foxa2, and Foxa3, whose knockdown impaired chondrocyte differentiation. Attenuation of Foxa antagonized the augmentation of Col X and Runx2 generated by rDhh. Collectively, Dhh signaling through its target Foxa appears to induce antler chondrocyte proliferation and differentiation.
Species and termination method effects on phosphorus loss from plant tissue
Authors: Carver R. Elliott , Nelson Nathan O. , Roozeboom Kraig L. , Kirkham M. B.
Published: January 2020

Cover crops are often recommended as a best management practice to reduce erosion, weed pressure, and nutrient loss. However, cover crops may be sources of phosphorus (P) to runoff water after termination. Two greenhouse trials were conducted to determine the effects of cover crop species, termination method, and time after termination on water‐extractable P (WEP) release from crop biomass. Treatments were structured in a 3 × 3 × 3 factorial and arranged in a randomized complete block design with six replicates. Treatments included three cover crop species (triticale [× Triticosecale; Triticum × Secale ‘Trical’], rapeseed [Brassica napus L. ‘Winfred’], and crimson clover [Trifolium incarnatum L.]); three termination methods (clipping, freezing, and herbicide); and three WEP extraction times (1, 7, and 14 d after termination). Rapeseed consistently resulted in the least WEP when exposed to the same method of termination and at the same extraction time as the other species. For both trials, terminating crop tissue via freezing increased concentrations of WEP compared with other termination methods. The WEP release from cover crop tissue increased as the time after extraction increased, but the effect was greater for herbicide‐ and freeze‐terminated cover crops and less for clipping‐terminated cover crops. Future studies on WEP release from cover crops should pay close attention to the effects of extraction timing. Producers may be able to reduce P loss from cover crop tissue by selecting cover crop species with low WEP and minimizing the amount of biomass exposed to freezing conditions.
Synthesis and solvent‐dependent photophysics of a novel fluorescent triazole‐coumarin‐based dye
Authors: Kaya Mehmet , Menteşe Emre
Published: January 2020

Synthesis of a new coumarin‐triazole‐based dye and its photophysical parameters such as absorption, fluorescence emission, and fluorescence quantum yield were investigated. Studies have shown that the present dye has symmetry with a mirror image, especially in the ethanol solvent, with respect to the absorption and fluorescence spectra. As a result of the UV‐vis and fluorescence spectroscopy techniques used, it was determined that absorption and emission spectra were shifted to the red with increasing solvent polarity. In addition, the spectral data of the synthesized compound exhibited that the stokes shifts are small, usually less than 50 nm, and the quantum yields are significantly high. In accordance with the results obtained, it can be stated that this novel dye synthesized here can offer an insight into application in sensor applications as analytical or biosensors, optoelectronic devices, and medicine industry.
Estimating the costs and cost‐effectiveness of HIV self‐testing among men who have sex with men, United States
Authors: Shrestha Ram K , Chavez Pollyanna R , Noble Meredith , Sansom Stephanie L , Sullivan Patrick S , Mermin Jonathan H , MacGowan Robin J
Published: January 2020

Introduction

HIV testing is an essential prerequisite for accessing treatment with antiretroviral therapy or prevention using pre‐exposure prophylaxis. Internet distribution of HIV self‐tests is a novel approach, and data on the programmatic cost of this approach are limited. We analyse the costs and cost‐effectiveness of a self‐testing programme.

Methods

Men who have sex with men (MSM) reporting unknown or negative HIV status were enrolled from March to August 2015 into a 12‐month trial of HIV self‐testing in the United States. Participants were randomly assigned either to the self‐testing arm or the control arm. All participants received information on HIV testing services and locations in their community. Self‐testing participants received up to four self‐tests each quarter, which they could use themselves or distribute to their social network associates. Quarterly follow‐up surveys collected testing outcomes, including number of tests used and new HIV diagnoses. Using trial expenditure data, we estimated the cost of implementing a self‐testing programme. Primary outcomes of this analysis included total programme implementation costs, cost per self‐test completed, cost per person tested, cost per new HIV diagnosis among those self‐tested and cost per quality adjusted life year (QALY) saved.

Results

A total of 2665 men were assigned either to the self‐testing arm (n = 1325) or the control arm (n = 1340). HIV testing was reported by 971 self‐testing participants who completed a total of 5368 tests. In the control arm, 619 participants completed 1463 HIV tests. The self‐testing participants additionally distributed 2864 self‐tests to 2152 social network associates. Testing during the trial identified 59 participants and social network associates with newly diagnosed HIV infection in the self‐testing arm; 11 control participants were newly diagnosed with HIV. The implementation cost of the HIV self‐testing programme was $449,510. The cost per self‐test completed, cost per person tested at least once, and incremental cost per new HIV diagnosis was $61, $145 and $9365 respectively. We estimated that self‐testing programme potentially averted 3.34 transmissions, saved 14.86 QALYs and nearly $1.6 million lifetime HIV treatment costs.

Conclusions

The HIV self‐testing programme identified persons with newly diagnosed HIV infection at low cost, and the programme is cost saving.