bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative homeostasis in oocyte competence for in vitro embryo development
Authors: Barros Fabiana Dakkach de Almeida , Adona Paulo Roberto , Guemra Samuel , Damião Bruno Cesar Michelette 
Published: August 2019

AbstractThe objective of this study was to evaluate the levels of reactive oxygen species (ROS) and glutathione (GSH) in oocytes from follicles of different diameters and their relevance in the in vitro production of embryos (IVPE). Bovine ovaries were aspirated according to the diameter of the follicle [2–8 (general), 4–8 (large), and 2 < 4 mm (small)]. The oocytes were evaluated for levels of ROS, GSH, in vitro maturation, and IVPE. Higher levels of ROS and GSH were observed (p < 0.05) in oocytes of the large group (85.6 ± 7.2 and 140.0 ± 9.6) followed by those in the general (81.1 ± 10.5 and 134.3 ± 7.8) and small (73.5 ± 10.1 and 125.0 ± 10.6) groups. However, the proportion of ROS/GSH did not differ (p > 0.05) between the general, large, and small groups. The maturation was higher (p < 0.05) in the large group (87.8 ± 3.0%) than in the small group (72.2 ± 5.8%), but both were similar (p > 0.05) to that in the general group (82.2 ± 2.5%), whereas the IVPE of the large group (57.3 ± 3.0%) was higher (p < 0.05) than those in the general (44.7 ± 4.4%) and small (34.0 ± 4.0%) groups. We report that oocytes from large follicles are more competent for IVPE, whereas higher levels of ROS and GSH appear to be correlated with oocyte competence, as long as oxidative homeostasis is retained.
CYP2E1 and miRNA‐378a‐3p contribute to acetaminophen‐ or tripterygium glycosides‐induced hepatotoxicity
Authors: Chen Keguang , Guo Nan , Zhang Rui , Wei Chunmin , Guo Ruichen 
Published: August 2019

AbstractIncreased expression of CYP2E1 may represent the main factor contributing to oxidative stress‐mediated liver damage in drug‐induced liver injury (DILI). However, the regulation mechanism of CYP2E1 expression is poorly described. The present study was aimed to investigate the role of CYP2E1 in acetaminophen (APAP)‐ or tripterygium glycosides (TG)‐induced hepatotoxicity as well as the regulation of CYP2E1 and miR‐378a‐3p expression by APAP or TG. Rats were randomly divided and treated with APAP, TG, chlormethiazole (CMZ), APAP + CMZ and TG + CMZ, respectively, for 4 weeks. Then, blood and liver samples were collected. Serum and hepatic biochemical parameters were measured using commercial kits. Liver histopathology was tested by H&E staining. Expression levels of CYP2E1 mRNA and miR‐378a‐3p were detected by qRT‐PCR. CYP2E1 protein expression was determined by Western blot. Our results showed that CMZ effectively restored the hepatic histopathological changes, oxidative stress biomarkers and TNF‐α levels induced by APAP or TG. CYP2E1 mRNA and/or protein expression levels were dramatically increased after chronic APAP or TG treatment, while this induction was significantly reversed by CMZ co‐treatment. Of note, miR‐378a‐3p expression levels were significantly suppressed after APAP, TG and/or CMZ treatment. These results suggested that CYP2E1 were highly induced after chronic APAP or TG treatment, which in turn play an important role in APAP‐ or TG‐induced hepatotoxicity. These inductions of CYP2E1 expression were probably carried out by inhibition of miR‐378a‐3p. Our findings might provide a new molecular basis for DILI.
A journey through infectious risk associated with ruxolitinib
Authors: Sant’Antonio Emanuela , Bonifacio Massimiliano , Breccia Massimo , Rumi Elisa 
Published: August 2019

SummaryRuxolitinib has proved to be effective for the treatment of patients with myelofibrosis (either primary or secondary) and polycythaemia vera, and its approval led to a significant change in the current treatment algorithm. Despite its efficacy and beyond its well described haematological toxicity, a peculiar immunosuppressive effect emerged as our clinical experience grew, both within and outside of a clinical trial setting. Definite and negative interactions with multiple pathways of the immune system of patients have been reported so far, involving both adaptive and innate immune responses. These pathophysiological mechanisms may contribute to the increased risk of reactivation of silent infections (e.g., tuberculosis, hepatitis B virus and varicella zoster virus) that have been associated with the drug. Even though such infectious events may be fatal or may lead to significant impairment of organ function, compromising the eligibility of patients for an allotransplant procedure, there are no dedicated guidelines that may help us in assessing and managing the risk of developing serious infections. On this basis, our aim for the present work was to review the current knowledge on the pathophysiological mechanisms through which ruxolitinib may exert its immunosuppressive effect, and to illustrate our personal approach to the management of three peculiar clinical scenarios, for which a risk‐based algorithm is suggested.
Screening protocol for the identification of modulators by immunofluorescent cell‐based assay
Authors: Klett Javier , Gómez‐Casero Elena , Méndez‐Pertuz Marinela , Urbano‐Cuadrado Manuel , Megias Diego , Blasco María A. , Martínez Sonia , Pastor Joaquín , Blanco‐Aparicio Carmen 
Published: August 2019

AbstractHigh‐throughput assays are a common strategy for the identification of compounds able to modulate a certain cellular activity. Here, we show an automatized analysis platform for the quantification of nuclear foci as inhibitory effect of compounds on a target protein labeled by fluorescent antibodies. Our experience led us to a fast analysis platform that combines cell‐based assays, high‐content screening, and confocal microscopy, with an automatic and user‐friendly statistical analysis of plate‐based assays including positive and negative controls, able to identify inhibitory effect of compounds tested together with the Z‐prime and Window of individual plate‐based assays to assess the reliability of the results. The platform integrates a web‐based tool implemented in Pipeline Pilot and R, and allows computing the inhibition values of different parameters obtained from the high‐content screening and confocal microscopy analysis. This facilitates the exploration of the results using the different parameters, providing information at different levels as the number of foci observed, the sum of intensity of foci, area of foci, etc, the detection and filtering of outliers over the assay plate, and finally providing a set of statistics of the parameters studied together with a set of plots that we believe significantly helps to the interpretation of the assay results.
Adopting a utilitarian approach to culling wild animals for conservation in National Parks
Authors: Gordon Iain J. 
Published: August 2019

AbstractAs human populations increase and become wealthier, the demand for red meat will increase. Much of this increased demand will be supplied through the traditional livestock supply chains; however, there are alternative commodities that can be used to meet some of the demand. Game meat harvested from wildlife is a growing commodity in the developed world, valued for its nutritional qualities and taste. However, there are some perverse management actions whereby wildlife, culled for conservation purposes (usually because they are deemed to be overabundant within National Parks and Protected Areas), are often not utilized as either human or pet food. In this Perspective, I highlight how the products from these culled animals in NPs are used, or not, and discuss some innovative ways in which the products are, or could be, brought into the economic and livelihood system (i.e., utilitarian conservation). These include bringing products from culled animals into the human and pet food supply chains.
Complex and subtle structural changes in prefrontal cortex induced by inhibitory control training from childhood to adolescence
Authors: Delalande Lisa , Moyon Marine , Tissier Cloélia , Dorriere Valérie , Guillois Bernard , Mevell Katel , Charron Sylvain , Salvia Emilie , Poirel Nicolas , Vidal Julie , Lion Stéphanie , Oppenheim Catherine , Houdé Olivier , Cachia Arnaud , Borst Grégoire 
Published: August 2019

AbstractA number of training interventions have been designed to improve executive functions and inhibitory control (IC) across the lifespan. Surprisingly, no study has investigated the structural neuroplasticity induced by IC training from childhood to late adolescence, a developmental period characterized by IC efficiency improvement and protracted maturation of prefrontal cortex (PFC) subregions involved in IC. The aim of the present study was to investigate the behavioral and structural changes induced by a 5‐week computerized and adaptive IC training in school‐aged children (10‐year‐olds) and in adolescents (16‐year‐olds). Sixty‐four children and 59 adolescents were randomly assigned to an IC (i.e. Color‐Word Stroop and Stop‐Signal tasks) or an active control (AC) (knowledge‐ and vocabulary‐based tasks) training group. In the pre‐ and posttraining sessions, participants performed the Color‐Word Stroop and Stop‐signal tasks, and an anatomical resonance imaging (MRI) was acquired for each of them. Children's IC efficiency improved from the pre‐ to the posttraining session in boys but not in girls. In adolescents, IC efficiency did not improve after IC training. Similar to the neuroplastic mechanisms observed during brain maturation, we observed IC training‐related changes in cortical thickness and cortical surface area in several PFC subregions (e.g. the pars opercularis, triangularis, and orbitalis of the inferior frontal gyri) that were age‐ and gender‐specific. Because no correction for multiple comparisons was applied, the results of our study provide only preliminary evidence of the complex structural neuroplastic mechanisms at the root of behavioral changes in IC efficiency from pre‐ to posttraining in school‐aged children and adolescents.
Physical activity and sedentary behaviour in children with spina bifida
Authors: Claridge Everett A , Bloemen Manon A T , Rook Rosanne A , Obeid Joyce , Timmons Brian W , Takken Tim , Van Den Berg‐Emons Rita J G , De Groot Janke F , Gorter Jan Willem 
Published: August 2019

AimTo describe active and sedentary time in children with spina bifida and to compare their physical activity on weekdays versus weekends.MethodIn this exploratory cross‐sectional study, data from 13 Canadian and 22 Dutch children with spina bifida (14 females, 21 males; mean age 10y 11mo, standard deviation [SD] 3y 6mo, range 5y 6mo–18y; Hoffer classification distribution: community [n=28], household [n=3], non‐functional [n=3], and non‐ambulator [n=1]) were analysed. Objective measures of physical activity and sedentary behaviour were obtained by using ActiGraph or Actiheart activity monitors. Data for the participants wearing the ActiGraph were compared with age‐ and sex‐matched controls that were developing typically using independent‐samples t‐tests. Activity data collected on weekdays was compared to those on weekends.ResultsActiGraph data demonstrated children with spina bifida spent more time sedentary (mean [SD] 49.5min/h [5.78]) and less time in moderate to vigorous physical activity (mean [SD] 2.33min/h [1.61]) compared with the typically developing group (mean [SD] 41.0min/h [5.76] and 5.46min/h [2.13], p=0.001 and p<0.001 respectively). For both ActiGraph‐ and Actiheart‐derived data, physical activity and sedentary time were not significantly different between weekdays and weekends.InterpretationChildren with spina bifida have reduced levels of physical activity and increased sedentary behaviour, with no statistical differences seen between weekdays and weekends. Several methodological issues related to activity monitoring warrant consideration when choosing the appropriate method to quantify physical activity and sedentary behaviour.What this paper adds

Reduced levels of physical activity and sedentary time were quantified in children with spina bifida.

Objective quantification of physical behaviour in ambulatory and non‐ambulatory school‐aged children with spina bifida is possible.
Systematic literature review and network meta‐analysis of sodium‐glucose co‐transporter inhibitors vs metformin as add‐on to insulin in type 1 diabetes
Authors: Langford Bryony E. , Evans Marc , Haskins‐Coulter Tao , O'Connor Molly , Cant Harriet E. O. , Eddowes Lucy A. , Edmonds Christopher , Tank Amarjeet 
Published: August 2019

AbstractAimsTo identify and synthesize phase 3 and phase 4 randomized controlled trials (RCTs) of sodium‐glucose co‐transporter (SGLT) inhibitors and metformin as adjuncts to insulin in type 1 diabetes (T1DM) using network meta‐analysis (NMA).Materials and methodsA systematic literature review (SLR) identified relevant RCTs of ≥12 Weeks duration. MEDLINE, Embase, the Cochrane Library and grey literature were searched through October 2018. NMAs indirectly compared SGLT inhibitors and metformin for change from baseline in HbA1c, weight, total daily insulin dose and systolic blood pressure at Week 24 to 26 and Week 52. Safety outcomes were also explored.ResultsNine trials (N = 6780) were included in the SLR. NMAs indicated that all therapies performed better than placebo for the efficacy outcomes at both time points. Compared with metformin at Week 24 to 26, the SGLT inhibitors dapagliflozin (5 mg), sotagliflozin (200 mg) and empagliflozin (10 mg) had larger reductions in HbA1c (mean difference [MD] = −0.24, 95% credible interval [CrI], −0.41 to −0.07, MD = −0.23, 95% CrI, −0.39 to −0.08 and MD = −0.35, 95% CrI, −0.51 to −0.19, respectively) and in weight, which were sustained in sensitivity analyses. There were few differences observed in the results of safety outcomes, such as risk of diabetic ketoacidosis (DKA), which should be interpreted cautiously because of wide CrIs.ConclusionsAdjunctive use of SGLT inhibitors in T1DM can improve glycaemic control compared with metformin while enabling weight loss, with consistent efficacy across the class. However, these results are based on indirect evidence so confirmation in a head‐to‐head study would be valuable.
Identifying routine clinical predictors of non‐adherence to second‐line therapies in type 2 diabetes: A retrospective cohort analysis in a large primary care database
Authors: Shields Beverley M. , Hattersley Andrew T. , Farmer Andrew J. 
Published: August 2019

AbstractAimsTo investigate whether combinations of routinely available clinical features can predict which patients are likely to be non‐adherent to diabetes medication.Materials and MethodsA total of 67 882 patients with prescription records for their first and second oral glucose‐lowering therapies were identified from electronic healthcare records (Clinical Practice Research Datalink). Non‐adherence was defined as a medical possession ratio (MPR) ≤80%. Potential predictors were examined, including age at diagnosis, sex, body mass index, duration of diabetes, glycated haemoglobin, Charlson index and other recent prescriptions.ResultsRoutine clinical features were poor at predicting non‐adherence to the first diabetes therapy (c‐statistic = 0.601 for all in combined model). Non‐adherence to the second drug was better predicted for all combined factors (c‐statistic =0.715) but this improvement was predominantly a result of including adherence to the first drug (c‐statistic =0.695 for this alone). Patients with an MPR ≤80% for their first drug were 3.6 times (95% confidence interval 3.3,3.8) more likely to be non‐adherent to their second drug (32% vs. 9%).ConclusionsAlthough certain clinical features were associated with poor adherence, their performance for predicting who is likely to be non‐adherent, even when combined, was weak. The strongest predictor of adherence to second‐line therapy was adherence to the first therapy. Examining previous prescription records could offer a practical way for clinicians to identify potentially non‐adherent patients and is an area warranting further research.
Comparison of lixisenatide in combination with basal insulin vs other insulin regimens for the treatment of patients with type 2 diabetes inadequately controlled by basal insulin: Systematic review, network meta‐analysis and cost‐effectiveness analysis
Authors: Men Peng , Qu Shuli , Luo Wenting , Li Chaoyun , Zhai Suodi 
Published: August 2019

AbstractAimsTo evaluate the comparative efficacy and safety of lixisenatide combined with basal insulin (BI) vs intensive premix insulin (premix), BI plus prandial insulin with the main meal (basal‐plus) or progressively covering all meals (basal‐bolus) in patients with type 2 diabetes mellitus (T2DM) inadequately controlled by BI, and the long‐term cost‐effectiveness of lixisenatide from a Chinese healthcare system perspective.Materials and methodsRandomized controlled trials (RCTs) published between 1998 and 2018 were systematically searched. The clinical efficacy and safety of each treatment were compared by network meta‐analysis (NMA). The IQVIA CORE Diabetes Model was used to estimate the lifetime quality‐adjusted life‐years (QALYs) and direct medical costs of patients treated with different strategies.ResultsEight RCTs were finally included. Lixisenatide plus BI showed a similar reduction in HbA1c from baseline compared with premix, basal‐plus and basal‐bolus. There were significant differences in the change of body weight in favour of lixisenatide plus BI compared with the three insulin regimens. The risk of symptomatic hypoglycaemia of lixisenatide plus BI was significantly lower compared with premix and basal‐bolus. Lixisenatide plus BI was cost‐effective compared with premix, basal‐plus and basal‐bolus with incremental cost‐effectiveness ratios of Chinese yuan (CNY) 87 219, 48 173 and 48 670 per QALY gained, respectively, under the threshold of three times the gross domestic product (GDP) per capita in China.ConclusionsLixisenatide plus BI shows a similar HbA1c reduction compared with insulin regimens, accompanied by lower risk of hypoglycaemia and greater body weight reduction. It is a cost‐effective treatment alternative for patients with T2DM inadequately controlled by BI in China.
The attitudinal view and the integration of the particular object of emotions
Authors: Hernández Juan Pablo 
Published: August 2019

AbstractIn recent years, Julien Deonna and Fabrice Teroni have proposed to understand emotions as embodied evaluative attitudes we take towards objects that figure in nonevaluative representational states. Although their account nicely explains some of the key features that emotions are widely taken to have, it runs into a version of what I call the problem of integration. In the case of the attitudinal view, the integration problem takes the form of explaining how, from the point of view of the subject, the bodily responses that make up the attitude part of the emotion and the representational states that provide the particular object of the emotion come to form an intentionally structured unitary experience, that is, one in which the bodily responses are intentionally directed towards the object. I argue that what explains this integration is the way in which the experience of bodily responses and the experience of the representational states interact. This, I propose, produces what I call an experience of convergence. I also suggest that understanding emotional experience in this way not only solves the problem of the integration but also provides a more solid ground for the claim that emotionsquaembodied attitudes are evaluative.
Variable tree establishment in bauxite mine restoration in south‐west Australia linked to rainfall distribution, seasonal temperatures and seed rain
Authors: White‐Toney Tai , Korczynskyj Dylan , Grigg Andrew , Bulsara Max 
Published: August 2019

SummaryReasons for variable establishment of Jarrah (Eucalyptus marginata D. Don ex Sm.) and Marri (Corymbia calophylla (Lindl). K. D. Hill & L. A. S. Johnson) on restored forest sites after bauxite mining in south‐west Australia are not well understood. To refine restoration outcomes, we compiled tree seedling density establishment data from surveys of 654 previously mined sites restored between 1998 and 2017, and applied generalised linear models to discriminate the effects of 24 climatic and restoration practice variables. Final models explained 50% and 31% of the variation in Jarrah and Marri density, respectively. Broadcast seeding and fertiliser rates were positively related to seedling density. A more even rainfall distribution in the early wet season increased seedling density. However, persistent rain later in the wet season decreased density, possibly as a result of ripline soil saturation or ponding. Higher average daily maximum temperatures in the dry season decreased seedling density probably due to drought stress, but warmer daily temperature minima in both wet and dry seasons increased density. Seed rain from surrounding unmined forest was implicated as a significant, but highly variable, source of additional seed to restored sites. Restoration practices that influence soil moisture relations (tillage, depth and texture of returned soil), shallow burial of applied seed and timing of fertiliser application are likely to be important in refining restoration outcomes.
How to measure, report and verify soil carbon change to realize the potential of soil carbon sequestration for atmospheric greenhouse gas removal
Authors: Smith Pete , Soussana Jean‐Francois , Angers Denis , Schipper Louis , Chenu Claire , Rasse Daniel P. , Batjes Niels H. , van Egmond Fenny , McNeill Stephen , Kuhnert Matthias , Arias‐Navarro Cristina , Olesen Jorgen E. , Chirinda Ngonidzashe , Fornara Dario , Wollenberg Eva , Álvaro‐Fuentes Jorge , Sanz‐Cobena Alberto , Klumpp Katja 
Published: August 2019

AbstractThere is growing international interest in better managing soils to increase soil organic carbon (SOC) content to contribute to climate change mitigation, to enhance resilience to climate change and to underpin food security, through initiatives such as international ‘4p1000’ initiative and the FAO's Global assessment of SOC sequestration potential (GSOCseq) programme. Since SOC content of soils cannot be easily measured, a key barrier to implementing programmes to increase SOC at large scale, is the need for credible and reliable measurement/monitoring, reporting and verification (MRV) platforms, both for national reporting and for emissions trading. Without such platforms, investments could be considered risky. In this paper, we review methods and challenges of measuring SOC change directly in soils, before examining some recent novel developments that show promise for quantifying SOC. We describe how repeat soil surveys are used to estimate changes in SOC over time, and how long‐term experiments and space‐for‐time substitution sites can serve as sources of knowledge and can be used to test models, and as potential benchmark sites in global frameworks to estimate SOC change. We briefly consider models that can be used to simulate and project change in SOC and examine the MRV platforms for SOC change already in use in various countries/regions. In the final section, we bring together the various components described in this review, to describe a new vision for a global framework for MRV of SOC change, to support national and international initiatives seeking to effect change in the way we manage our soils.