bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Control Variate Method Driven by Diffusion Approximation
Authors: Garnier Josselin , Mertz Laurent 
Published: January 2021

AbstractIn this paper we introduce a control variate estimator for a quantity of interest that can be expressed as the expectation of a function of a random process, that is itself the solution of a differential equation driven by fast mean‐reverting ergodic random forces. The control variate is built with the same function and with the limit diffusion process that approximates the original random process when the mean reversion time of the driving forces goes to 0. We propose a coupling of the original process and the limit diffusion process that gives a control variate estimator with small variance. We show that the correlation between the two processes indeed goes to 1 when the mean reversion time goes to 0 and we quantify the convergence rate, which allows us to characterize the variance reduction of the proposed control variate estimator. The efficiency of the method is illustrated on a few examples. © 2021 Wiley Periodicals LLC.
Safety, Pharmacokinetics, and Pharmacodynamics of a Dipeptidyl Peptidase‐4 Inhibitor: A Randomized, Double‐Blinded, Placebo‐Controlled Daily Administration of Fotagliptin Benzoate for 14 Days for Type 2 Diabetes Mellitus
Authors: Wu Min , Li Qian‐Qian , Zhang Hong , Zhu Xiao‐Xue , Li Xiao‐Jiao , Li Ying , Sun Hai‐Gang , Ding Yan‐Hua 
Published: January 2021

AbstractThis study investigated the pharmacokinetics, pharmacodynamics, and safety of fotagliptin benzoate (fotagliptin), a dipeptidyl peptidase‐4 (DPP‐4) inhibitor, in Chinese patients with type 2 diabetes mellitus (T2DM). In a randomized, double‐blinded, placebo‐controlled study, 10 and 4 patients with T2DM were randomized and received, respectively, once‐daily oral fotagliptin (24 mg) or placebo, for 14 days. The pharmacokinetics and pharmacodynamics were assessed throughout the study, including monitoring DPP‐4, glucagon‐like peptide‐1 (GLP‐1), glycosylated hemoglobin, and fasting blood glucose. Fotagliptin was rapidly absorbed, and the median time to maximum concentration value was ∼1.5 hours. Plasma fotagliptin levels were stable after 14 days of once‐daily dosage. The accumulation ratios for the area under the plasma concentration–time curve of fotagliptin, M1, and M2‐1, were 1.19 ± 0.10, 1.59 ± 0.27, and 1.39 ± 0.26, respectively. The durations for DPP‐4 inhibition >80% in the fotagliptin group on days 1 and 14 were 23.5 and 24.0 hours, respectively. The concentrations of GLP‐1 were higher on days 1 and 14 than at the baseline. No serious complications occurred. Fotagliptin showed favorable pharmacokinetics and pharmacodynamics and was well tolerated. Treatment with fotagliptin can achieve high DPP‐4 inhibition and increase plasma GLP‐1. A once‐per‐day dosing regimen may be recommended as clinically efficacious.
Exploiting If This Then That and Usage Control obligations for Smart Home security and management
Authors: Giorgi Giacomo , La Marra Antonio , Martinelli Fabio , Mori Paolo , Rizos Athanasios , Saracino Andrea 
Published: January 2021

SummaryIn this article we present an application of the Usage Control paradigm to a Smart Home infrastructure, based on a model extension and structured use of obligations. In the proposed extended model obligations are exploited to enforce two different access revocation time, namely revoke and suspend. This increases the policy expressiveness and enable to optimize the resource usage. Furthermore, obligations are exploited to send commands via IFTTT to different interconnected Smart Home devices, to impose safety‐relevant behaviors, or to act on policy attributes to implement a self‐healing paradigm for revoked sessions. The article is motivated by a parental control use case where deep learning is used in combination with Usage Control to regulate dynamically viewing rights of a smart‐TV and interactions with interconnected devices. Accuracy and performance experiments show the effectiveness and feasibility of the proposed work.
Therapeutic interventions in in‐person and remote psychotherapy: Survey with psychotherapists and patients experiencing in‐person and remote psychotherapy during COVID‐19
Authors: Probst Thomas , Haid Barbara , Schimböck Wolfgang , Reisinger Andrea , Gasser Marion , Eichberger‐Heckmann Heidrun , Stippl Peter , Jesser Andrea , Humer Elke , Korecka Nicole , Pieh Christoph 
Published: January 2021

AbstractObjectiveFirst, to investigate how psychotherapists and patients experience the change from in‐person to remote psychotherapy or vice versa during COVID‐19 regarding the therapeutic interventions used. Second, to explore the influence of therapeutic orientations on therapeutic interventions in in‐person versus remote psychotherapy.MethodPsychotherapists (N = 217) from Austria were recruited, who in turn recruited their patients (N = 133). The therapeutic orientation of the therapists was psychodynamic (22.6%), humanistic (46.1%), systemic (20.7%) or behavioural (10.6%). All the data were collected remotely via online surveys. Therapists and patients completed two versions of the ‘Multitheoretical List of Therapeutic Interventions’ (MULTI‐30) (version 1: in‐person; version 2: remote) to investigate differences between in‐person and remote psychotherapy in the following therapeutic interventions: psychodynamic, common factors, person‐centred, process‐experiential, interpersonal, cognitive, behavioural and dialectical‐behavioural.ResultsTherapists rated all examined therapeutic interventions as more typical for in‐person than for remote psychotherapy. For patients, three therapeutic interventions (psychodynamic, process‐experiential, cognitive interventions) were more typical for in‐person than for remote psychotherapy after correcting for multiple testing. For two therapeutic interventions (behavioural, dialectical‐behavioural), differences between the four therapeutic orientations were more consistent for in‐person than for remote psychotherapy.ConclusionsTherapeutic interventions differed between in‐person and remote psychotherapy and differences between therapeutic orientations in behavioural‐oriented interventions become indistinct in remote psychotherapy.
Inbred and hybrid sweet corn genotype performance in diverse organic environments
Authors: Zystro Jared , Peters Tessa E. , Miller Kathleen M. , Tracy William F. 
Published: January 2021

AbstractThe value of selection in conventional breeding trials of cultivars destined for organic systems depends on the correlation between systems and relative heritability of key traits. Genotype × environment interaction is a common phenomenon in plant breeding trials. Thus, multiple‐environment testing to identify stable genotypes is a high priority for organic systems. In addition, because organic systems have limited inputs to buffer the environment, they may have greater spatial heterogeneity, which may be better accounted for by additional spatial blocking terms beyond traditional randomized complete‐block design. Over 2 yr, we evaluated 100 hybrid and 40 inbred sweet corn (Zea mays L.) genotypes in 11 trials in organic systems across six locations and evaluated the addition of augmented incomplete block and row–column design to estimate the performance of sweet corn genotypes. Hybrids differed in their performance for all tested traits. Inbred parents differed in per se performance and general combining ability for all traits. For the hybrid entries, modeling spatial factors beyond the replicated complete blocks improved the model fit for days to anthesis, plant height, ear height, husk protection, ear width, and ear length. For inbred entries, modeling spatial factors beyond the replicated complete blocks improved ∖ model fit for plant height, ear height, tenderness, and ear width. Wricke's ecovalence (W2i) was a useful measure of stability, correlating reasonably well with two of the three stability statistics considered in this analysis. Based on Wricke's ecovalence, some inbred parents were more stable than others across tested environments in their combining ability for all traits.
Arrested development: suppression of NK cell function in the tumor microenvironment
Authors: Riggan Luke , Shah Siya , O’Sullivan Timothy E 
Published: January 2021

AbstractNatural killer (NK) cells are cytotoxic innate lymphocytes that protect against viral infection and tumor metastasis. Despite their inherent ability to kill a broad range of virally infected, stressed and transformed cells, low numbers of dysfunctional NK cells are often observed in many advanced solid human cancers. Here, we review the potential mechanisms that influence suboptimal mature NK cell recruitment and function in the tumor microenvironment (TME) of solid tumors. We further highlight current immunotherapy approaches aimed to circumvent NK cell dysfunction and discuss next‐generation strategies to enhance adoptive NK cell therapy through targeting intrinsic and extrinsic checkpoints the regulate NK cell functionality in the TME. Understanding the mechanisms that drive NK cell dysfunction in the TME will lead to novel immunotherapeutic approaches in the fight against cancer.
Prognostic value of early leukocyte fluctuations for recovery from traumatic spinal cord injury
Authors: Jogia Trisha , Lübstorf Tom , Jacobson Esther , Scriven Elissa , Atresh Sridhar , Nguyen Quan H. , Liebscher Thomas , Schwab Jan M. , Kopp Marcel A. , Walsham James , Campbell Kate E. , Ruitenberg Marc J. 
Published: January 2021

AbstractBackgroundAcute traumatic spinal cord injury (SCI) induces a systemic immune response involving circulating white blood cells (WBCs). How this response is influenced by overall trauma severity, the neurological level of injury and/or correlates with patient outcomes is poorly understood. The objective of this study was to identify relationships between early changes in circulating WBCs, injury characteristics and long‐term patient outcomes in individuals with traumatic SCI.MethodsWe retrospectively analysed data from 161 SCI patients admitted to Brisbane's Princess Alexandra Hospital (exploration cohort). Logistic regression models in conjunction with receiver operating characteristic (ROC) analyses were used to assess the strength of specific links between the WBC response, respiratory infection incidence and neurological outcomes (American Spinal Injury Association Impairment Scale (AIS) grade conversion). An independent validation cohort from the Trauma Hospital Berlin, Germany (n = 49) was then probed to assess the robustness of effects and disentangle centre effects.ResultsWe find that the extent of acute neutrophilia in human SCI patients is positively correlated with New Injury Severity Scores but inversely with the neurological outcome (AIS grade). Multivariate analysis demonstrated that acute SCI‐induced neutrophilia is an independent predictor of AIS grade conversion failure, with an odds ratio (OR) of 4.16 and ROC area under curve (AUC) of 0.82 (P < 0.0001). SCI‐induced lymphopenia was separately identified as an independent predictor of better recovery (OR = 24.15; ROC AUC = 0.85, P < 0.0001). Acute neutrophilia and increased neutrophil‐lymphocyte ratios were otherwise significantly associated with respiratory infection presentation in both patient cohorts.ConclusionsOur findings demonstrate the prognostic value of modelling early circulating neutrophil and lymphocyte counts with patient characteristics for predicting the longer term recovery after SCI.
Role of miR‐466 in mesenchymal stromal cell derived extracellular vesicles treating inoculation pneumonia caused by multidrug‐resistant Pseudomonas aeruginosa
Authors: Shi Meng‐meng , Zhu Ying‐gang , Yan Jia‐yang , Rouby Jean‐Jacques , Summah Hanssa , Monsel Antoine , Qu Jie‐ming 
Published: January 2021

AbstractRationaleThe effects of mesenchymal stromal cells (MSCs) and MSC‐derived extracellular vesicles (MSC EVs) on multidrug‐resistant pseudomonas aeruginosa (MDR‐PA)‐induced pneumonia remain unclear.Materials and methodsMicroRNA array and RT‐PCR were used to select the major microRNA in MSC EVs. Human peripheral blood monocytes were obtained and isolated from qualified patients. The crosstalk between MSCs/MSC EVs and macrophages in vitro was studied. MDR‐PA pneumonia models were further established in C57BL/6 mice and MSC EVs or miR‐466 overexpressing MSC EVs were intratracheally instilled.ResultsMiR‐466 was highly expressed in MSC EVs. MSCs and miR‐466 promoted macrophage polarization toward Type 2 phenotype through TIRAP‐MyD88‐NFκB axis. Moreover, cocultured macrophages with miR‐466 overexpressing MSCs significantly increased the phagocytosis of macrophages. MSC EVs significantly reduced mortality and decreased influx of BALF neutrophils, proinflammatory factor levels, protein, and bacterial load in murine MDR‐PA pneumonia. Administration of miR‐466 overexpressing MSC EVs further alleviated the inflammatory severity.ConclusionsMSC‐derived EVs containing high levels of miR‐466 may partly participate in host immune responses to MDR‐PA. Both MSCs and MSC EVs have therapeutic effects in treating MDR‐PA‐induced pneumonia.
Diversity aided millimeter‐wave/free space optical cooperative relaying systems
Authors: Goel Amit , Upadhya Abhijeet , Dwivedi Vivek K. 
Published: January 2021

SummaryIn this paper, we investigate the performance of mixed millimeter‐wave (mmWave)/multiple input multiple output (MIMO)‐free space optics (FSO) cooperative relaying system. The mmWave link is assumed to undergo multipath fading and shadowing which has been modeled as generalized‐K distributed fading, whereas the diversity aided FSO link is considered to experience Gamma–Gamma turbulence. We consider amplify‐and‐forward (AF) relaying strategy and multiple signals arriving at the receiver are combined using equal gain combining (EGC) scheme. Analytical closed form expressions for performance metrics such as outage probability, bit error rate (BER), and the ergodic channel capacity are derived in terms of bivariate Fox's H‐function for the considered mixed mmWave/MIMO‐FSO relaying system. In order to further simplify the obtained results, we analyze the system performance for the case of high signal‐to‐noise ratio (SNR) to present the asymptotic expressions for the outage probability and BER in terms of elementary functions. To this end, we have formulated an optimum power allocation scheme which minimizes the probability of outage experienced by the end user by allocating the optimum power on the FSO link. We also analyze the proposed system for the impact of pointing errors in a separate section by deriving closed‐form expressions for the outage probability and BER. Finally, numerical results have been demonstrated the findings of the research work which have supplemented by Monte Carlo simulations.
Protection of clozapine‐induced oxidative stress and mitochondrial dysfunction by kaempferol in rat cardiomyocytes
Authors: Bakhshii Saba , Khezri Saleh , Ahangari Roya , Jahedsani Asal , Salimi Ahmad 
Published: January 2021

AbstractClozapine (CLZ) is unusually efficient in psychotic diseases. Nonetheless, its use is confined due to potentially life‐threatening adverse events, including cardiotoxicity. Since the cardiotoxicity of CLZ is mediated through the generation of active metabolites, free radical, and inflammation. Here, we tested this hypothesis that kaempferol (KP) as antioxidant and anti‐inflammatory agent could attenuate CLZ‐induced mitochondrial/lysosomal and oxidative damages in rat ventricular cardiomyocytes. Rat ventricular cardiomyocytes were isolated by collagenase perfusion. Then isolated cardiomyocytes were simultaneously treated with different concentrations of KP (10, 20, and 50 μM) and CLZ (50 μM) for 4 h at 37°C. After 4 h of incubation, using by flow cytometry and biochemical evaluations, the parameters of cellular toxicity including: cell viability, reactive oxygen species (ROS) formation, mitochondria membrane potential (ΔΨm) collapse, lysosomal membrane integrity, malondialdehyde, and oxidized/reduced glutathione were analyzed. The results showed that CLZ (50 μM) induced a significant increase in cytotoxicity, ROS formation, mitochondrial membrane potential collapse, lipid peroxidation, and oxidative stress while KP reverted the above toxic effect of CLZ on isolated cardiomyocytes. Our data suggest that KP prevents and reverses CLZ‐induced oxidative and mitochondrial/lysosomal damages in isolated cardiomyocytes, providing an experimental basis for clinical treatment on CLZ‐induced cardiotoxicity.
Early life adversity, pubertal timing, and epigenetic age acceleration in adulthood
Authors: Hamlat Elissa J. , Prather Aric A. , Horvath Steve , Belsky Jay , Epel Elissa S. 
Published: January 2021

AbstractBackgroundGiven associations linking early life adversity, pubertal timing, and biological aging, we examined the direct and indirect effects of early life trauma on adult biological aging (via age of menarche).MethodsParticipants were premenopausal women (N = 183). Path models evaluated whether early life trauma predicted early pubertal timing and thereby, adult epigenetic age acceleration (indexed via four epigenetic clocks: Horvath DNAm Age, Hannum DNAm Age, DNAm PhenoAge, and DNAm GrimAge). Secondary analyses explored the effects of type of trauma (abuse and neglect) and adult chronic stress status (caregiver of child with autism and non‐caregiver).ResultsEarly life trauma and earlier age at menarche independently predicted accelerated aging based on one of the four epigenetic clocks, DNAm GrimAge, though early life trauma was not associated with age of menarche. Childhood abuse, but not neglect, predicted faster epigenetic aging; results did not differ by chronic stress status.ConclusionsEarly trauma and early menarche appear to exert independent effects on DNAm GrimAge, which has been shown to be the strongest epigenetic predictor of mortality risk. This study identifies a potential correlate or determinant of accelerated epigenetic aging—menarcheal age. Future research should address the limitations of this study by using racially diverse samples.
Recent bark beetle outbreaks influence wildfire severity in mixed‐conifer forests of the Sierra Nevada, California, USA
Authors: Wayman Rebecca B. , Safford Hugh D. 
Published: January 2021

AbstractIn temperate forests, elevated frequency of drought related disturbances will likely increase the incidence of interactions between disturbances such as bark beetle epidemics and wildfires. Our understanding of the influence of recent drought and insect‐induced tree mortality on wildfire severity has largely lacked information from forests adapted to frequent fire. A recent unprecedented tree mortality event in California’s Sierra Nevada provides an opportunity to examine this disturbance interaction in historically frequent‐fire forests. Using field data collected within areas of recent tree mortality that subsequently burned in wildfire, we examined whether and under what conditions wildfire severity relates to severity of prefire tree mortality in Sierra Nevada mixed‐conifer forests. We collected data on 180 plots within the 2015 Rough Fire and 2016 Cedar Fire footprints (California, USA). Our analyses identified prefire tree mortality as influential on all measures of wildfire severity (basal area killed by fire, RdNBR, and canopy torch) on the Cedar Fire, although it was less influential than fire weather (relative humidity). Prefire tree mortality was influential on two of three fire‐severity measures on the Rough Fire, and was the most important predictor of basal area killed by fire; topographic position was influential on two metrics. On the Cedar Fire, the influence of prefire mortality on basal area killed by fire was greater under milder weather conditions. All measures of fire severity increased as prefire mortality increased up to prefire mortality levels of approximately 30–40%; further increases did not result in greater fire severity. The interacting disturbances shifted a pine‐dominated system (Rough Fire) to a cedar–pine–fir system, while the pre‐disturbance fir–cedar system (Cedar Fire) saw its dominant species unchanged. Managers of historically frequent‐fire forests will benefit from utilizing this information when prioritizing fuels reduction treatments in areas of recent tree mortality, as it is the first empirical study to document a relationship between prefire mortality and subsequent wildfire severity in these systems. This study contributes to a growing body of evidence that the influence of prefire tree mortality on wildfire severity in temperate coniferous forests may depend on other conditions capable of driving extreme wildfire behavior, such as weather.
Fractal dimension of tree crowns explains species functional‐trait responses to urban environments at different scales
Authors: Arseniou Georgios , MacFarlane David W. 
Published: January 2021

AbstractThe evolution of form and function of trees of diverse species has taken place over hundreds of millions of years, while urban environments are relatively new on an evolutionary time scale, representing a novel set of environmental constraints for trees to respond to. It is important to understand how trees of different species, planted in these anthropogenically‐structured urban ecosystems, are responding to them. Many theories have been advanced to understand tree form and function, including several that suggest the fractal‐like geometry of trees is a direct reflection of inherent and plastic morphological and physiological traits that govern tree growth and survival. In this research, we analyzed the “fractal dimension” of thousands of tree crowns of many different tree species, growing in different urban environments across the United States, to learn more about the nature of trees and their responses to urban environments at different scales. Our results provide new insights regarding how tree crown fractal dimension relates to balances between hydraulic‐ and light‐capture‐related functions (e.g., drought and shade tolerance). Our findings indicate that trees exhibit reduced crown fractal dimension primarily to reduce water loss in hotter cities. More specifically, the intrinsic drought tolerance of the studied species arises from lower surface to volume ratios at both whole‐crown and leaf scales, preadapting them to drought stress in urban ecosystems. Needle‐leaved species showed a clear trade‐off between optimizing the fractal dimension of their crowns for drought vs. shade tolerance. Broad‐leaved species showed a fractal crown architecture that responded principally to inherent drought tolerance. Adjusting for the temperature of cities and intrinsic species effects, the fractal dimension of tree crowns was lower in more heavily urbanized areas (with greater paved area or buildings) and due to crowns conflicting with utility wires. With expectations for more urbanization and generally hotter future climates, worldwide, our results add new insights into the physiological ecology of trees in urban environments, which may help humans to provide more hospitable habitats for trees in urbanized areas and to make better decisions about tree selection in urban forest management.