bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of metformin on glycaemic control in patients with type 1 diabetes: A meta‐analysis of randomized controlled trials
Authors: Meng Haiyang , Zhang Ailing , Liang Yan , Hao Jie , Zhang Xiaojian , Lu Jingli 
Published: January 2018

AbstractBackgroundFor type 1 diabetes (T1D) patients, adding metformin to insulin therapies is thought to improve blood glucose levels, but current evidence does not support this clinical benefit. Additional data from large clinical trials are now available; therefore, we conducted a meta‐analysis of studies on assessing the efficacy and adverse effects of metformin.MethodsWe searched the MEDLINE, EMBASE, and Cochrane Library databases for data from randomized controlled trials. We performed statistical analyses by using Review Manager 5.2.ResultsThirteen randomized controlled trials that compared metformin versus placebo met our inclusion criteria and were included in the study. The final meta‐analysis included a total of 1183 participants with T1D. Metformin was associated with reductions in BMI (−1.14, 95% CI −2.05 to −0.24, P = .01), insulin requirements (−0.47, 95% CI −0.70 to −0.23, P = .0001), total cholesterol (−0.23, 95% CI −0.34 to −0.12, P < .0001), and low‐density lipoprotein cholesterol (−0.20, 95% CI −0.29 to −0.11, P < .0001) in T1D patients. No clear evidence indicated that metformin improved HbA1c, triglyceride, or high‐density lipoprotein cholesterol levels. A safety analysis showed that metformin slightly increased the risk of severe hypoglycaemia (1.23, 95% CI 1.00 to 1.52, P = .05) and mainly gastrointestinal adverse events (2.67, 95% CI 2.06 to 3.45, P < .00001). No evidence showed that metformin increased diabetic ketoacidosis events.ConclusionsCompared with placebo, metformin was not associated with glycaemic control in T1D patients. Although it exhibited other benefits, such as lower BMI and reduced insulin requirements, total cholesterol, and low‐density lipoprotein cholesterol, negative outcomes, such as gastrointestinal adverse effects and severe hypoglycaemia, should also be considered in the use of metformin for T1D patients.
Age‐dependent, negative heterozygosity–fitness correlations and local effects in an endangered Caribbean reptile, Iguana delicatissima
Authors: Judson Jessica L. Martin , Knapp Charles R. , Welch Mark E. 
Published: January 2018

AbstractInbreeding depression can have alarming impacts on threatened species with small population sizes. Assessing inbreeding has therefore become an important focus of conservation research. In this study, heterozygosity–fitness correlations (HFCs) were measured by genotyping 7 loci in 83 adult and 184 hatchling Lesser Antillean Iguanas, Iguana delicatissima, at a communal nesting site in Dominica to assess the role of inbreeding depression on hatchling fitness and recruitment to the adult population in this endangered species. We found insignificant correlations between multilocus heterozygosity and multiple fitness proxies in hatchlings and adults. Further, multilocus heterozygosity did not differ significantly between hatchlings and adults, which suggests that the survivorship of homozygous hatchlings does not differ markedly from that of their heterozygous counterparts. However, genotypes at two individual loci were correlated with hatching date, a finding consistent with the linkage between specific marker loci and segregating deleterious recessive alleles. These results provide only modest evidence that inbreeding depression influences the population dynamics of I. delicatissima on Dominica.
The vaccine adjuvant alum promotes IL‐10 production that suppresses Th1 responses
Authors: Oleszycka Ewa , McCluskey Sean , Sharp Fiona A. , Muñoz‐Wolf Natalia , Hams Emily , Gorman Aoife L. , Fallon Padraic G. , Lavelle Ed C. 
Published: January 2018

AbstractThe effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1‐type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL‐10. Injection of alum primed draining lymph node cells for enhanced IL‐10 secretion ex vivo. Moreover, at the site of injection, macrophages and dendritic cells were key sources of IL‐10 expression. Alum strongly enhanced the transcription and secretion of IL‐10 by macrophages and dendritic cells. The absence of IL‐10 signalling did not compromise alum‐induced cell infiltration into the site of injection, but resulted in enhanced antigen‐specific Th1 responses after vaccination. In contrast to its decisive regulatory role in regulating Th1 responses, there was no significant change in antigen‐specific IgG1 antibody production following vaccination with alum in IL‐10‐deficient mice. Overall, these findings indicate that injection of alum promotes IL‐10, which can block Th1 responses and may explain the poor efficacy of alum as an adjuvant for inducing protective Th1 immunity.
Differential gene expression in trigeminal ganglia of male and female rats following chronic constriction of the infraorbital nerve
Authors: Korczeniewska O.A. , Husain S. , Khan J. , Eliav E. , Soteropoulos P. , Benoliel R. 
Published: January 2018

AbstractBackgroundThe mechanisms underlying sex‐based differences in pain and analgesia are poorly understood. In this study, we investigated gene expression changes in trigeminal ganglia (TG) of male and female rats exposed to infraorbital nerve chronic constriction injury (IoN‐CCI).MethodsSomatosensory assessments were performed prior to IoN‐CCI and at selected time points postsurgery. Selected gene expression changes were examined with real‐time quantitative polymerase chain reaction (RT‐PCR) in ipsilateral TG at 21 days postsurgery.ResultsRats exposed to IoN‐CCI developed significant mechanical allodynia and hyperalgesia on days 19 and 21 postsurgery. During this period, females developed significantly more allodynia but not hyperalgesia compared to males. At 21 days postsurgery, expression levels of 44 of the 84 investigated pain‐related genes in ipsilateral TG were significantly regulated relative to naïve rats in either sex. Csf1 and Cx3cr1 were up‐regulated in both sexes, but the magnitude of regulation was significantly higher in females (p = 0.02 and p = 0.001, respectively). Htr1a and Scn9a were down‐regulated in both sexes, but the down‐regulation was significantly more pronounced in males (p = 0.04 and p = 0.02, respectively). Additionally, Cck, Il1a, Pla2g1b and Tnf genes were significantly regulated in females but not in males, and Chrna4 gene was significantly down‐regulated in males but not in females.ConclusionsOur findings suggest sex‐dependent gene regulation in response to nerve injury, which may contribute to sex dimorphism of trigeminal neuropathic pain. Further studies are needed to establish gene expression changes over time and correlate these with hormonal and other physiological parameters in male and female.SignificanceWe present novel sex‐specific transcriptional regulation in trigeminal ganglia that may contribute to male‐/female‐based differences in trigeminal neuropathic pain. These findings are expected to open new research horizons, particularly in male versus female targeted therapeutic regimens.
Meta-analysis of fish early life stage tests—Association of toxic ratios and acute-to-chronic ratios with modes of action
Authors: Scholz Stefan , Schreiber Rene , Armitage James , Mayer Philipp , Escher Beate I. , Lidzba Annegret , Léonard Marc , Altenburger Rolf 
Published: January 2018

Abstract

Fish early life stage (ELS) tests (Organisation for Economic Co-operation and Development test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stages. To analyze whether certain modes of action are related to high toxic ratios (i.e., ratios between baseline toxicity and experimental effect) and/or acute-to-chronic ratios (ACRs) in the fish ELS test, effect concentrations (ECs) for 183 compounds were extracted from the US Environmental Protection Agency's ecotoxicity database. Analysis of ECs of narcotic compounds indicated that baseline toxicity could be observed in the fish ELS test at similar concentrations as in the acute fish toxicity test. All nonnarcotic modes of action were associated with higher toxic ratios, with median values ranging from 4 to 9.3 × 104 (uncoupling &lt; reactivity &lt; neuromuscular toxicity &lt; methemoglobin formation &lt; endocrine disruption &lt; extracellular matrix formation inhibition). Four modes of action were also found to be associated with high ACRs: 1) lysyl oxidase inhibition leading to notochord distortion, 2) putative methemoglobin formation or hemolytic anemia, 3) endocrine disruption, and 4) compounds with neuromuscular toxicity. For the prediction of ECs in the fish ELS test with alternative test systems, endpoints targeted to the modes of action of compounds with enhanced toxic ratios or ACRs could be used to trigger fish ELS tests or even replace these tests. Environ Toxicol Chem 2018;37:955–969. © 2018 SETAC
Abstract
Modes of action in the fish early life stage test that lead to median toxic ratios and acute-to-chronic ratios (ACRs) ≥10. The ACR was calculated using acute toxicity in juvenile/adult fish (AFT) or zebrafish embryos (ZFET) as reference values.
On the impact of sample size on median lethal concentration estimation in acute fish toxicity testing: Is n = 7/group enough?
Authors: Carr Gregory J. , Bailer A. John , Rawlings Jane M. , Belanger Scott E. 
Published: January 2018

Abstract

The fish acute toxicity test method is foundational to aquatic toxicity testing strategies, yet the literature lacks a concise sample size assessment. Although various sources address sample size, historical precedent seems to play a larger role than objective measures. We present a novel and comprehensive quantification of the effect of sample size on estimation of the median lethal concentration (LC50), covering a wide range of scenarios. The results put into perspective the practical differences across a range of sample sizes, from n = 5/concentration up to n = 23/concentration. We also provide a framework for setting sample size guidance illustrating ways to quantify the performance of LC50 estimation, which can be used to set sample size guidance given reasonably difficult (or worst-case) scenarios. There is a clear benefit to larger sample size studies: they reduce error in the determination of LC50s, and lead to more robust safe environmental concentration determinations, particularly in cases likely to be called worst-case (shallow slope and true LC50 near the edges of the concentration range). Given that the use of well-justified sample sizes is crucial to reducing uncertainty in toxicity estimates, these results lead us to recommend a reconsideration of the current de minimis 7/concentration sample size for critical studies (e.g., studies needed for a chemical registration, which are being tested for the first time, or involving difficult test substances). Environ Toxicol Chem 2018;37:1565–1578. © 2018 SETAC
Potency of polycyclic aromatic hydrocarbons in chicken and Japanese quail embryos
Authors: Franci Cynthia D. , Aleksieva Angelika , Boulanger Emily , Brandenburg Jonas , Johnston Theresa , Malinova Asya , Head Jessica A. 
Published: January 2018

Abstract

Birds are receptors of concern for polycyclic aromatic hydrocarbons (PAHs), yet limited data describing the relative potency of PAH congeners are available for avian species. In the present study, we determined embryonic median lethal dose (LD50) values for 5 PAH congeners in chicken (Gallus gallus) and one PAH congener in Japanese quail (Coturnix japonica). Graded concentrations of each test compound were injected into the air cell of chicken or quail eggs before incubation. Embryos were monitored through development (quail) or hatching (chicken). All PAHs tested caused dose-dependent increases in embryo mortality, but few other effects (e.g., weight changes, deformities) were observed. In chicken, windows of developmental sensitivity were identified between embryonic days 4 and 9 and between embryonic days 20 and 22. The rank order potency of benzo[k]fluoranthene (BkF; 76 μg/kg) ≈ dibenz[ah]anthracene (83 μg/kg) &gt; indeno[1,2,3-cd]pyrene (325 μg/kg) &gt; benzo[a]pyrene (461 μg/kg) &gt; benz[a]anthracene (529 μg/kg) corresponded well with previous in vitro estimates in birds. Previously published ethoxyresorufin-O-deethylase median effect concentrations from cultured chicken embryo hepatocytes were highly predictive of our LD50s (p &lt; 0.001, r2 = 0.99). To explore differences in sensitivity between species, Japanese quail eggs were injected with BkF, the most potent PAH. We found that chicken and quail were nearly equally sensitive to BkF. The present results contribute to our developing understanding of variability in responses to PAHs among congeners and species. Environ Toxicol Chem 2018;37:1556–1564. © 2018 SETAC
Construction of a network describing asparagine metabolism in plants and its application to the identification of genes affecting asparagine metabolism in wheat under drought and nutritional stress
Authors: Curtis Tanya Y. , Bo Valeria , Tucker Allan , Halford Nigel G. 
Published: January 2018

AbstractA detailed network describing asparagine metabolism in plants was constructed using published data from Arabidopsis (Arabidopsis thaliana) maize (Zea mays), wheat (Triticum aestivum), pea (Pisum sativum), soybean (Glycine max), lupin (Lupus albus), and other species, including animals. Asparagine synthesis and degradation is a major part of amino acid and nitrogen metabolism in plants. The complexity of its metabolism, including limiting and regulatory factors, was represented in a logical sequence in a pathway diagram built usingyEDgraph editor software. The network was used with a Unique Network Identification Pipeline in the analysis of data from 18 publicly available transcriptomic data studies. This identified links between genes involved in asparagine metabolism in wheat roots under drought stress, wheat leaves under drought stress, and wheat leaves under conditions of sulfur and nitrogen deficiency. The network represents a powerful aid for interpreting the interactions not only between the genes in the pathway but also among enzymes, metabolites and smaller molecules. It provides a concise, clear understanding of the complexity of asparagine metabolism that could aid the interpretation of data relating to wider amino acid metabolism and other metabolic processes.
DSP30 and interleukin‐2 as a mitotic stimulant in B‐cell disorders including those with a low disease burden
Authors: Dun Karen A. , Riley Louise A. , Diano Giuseppe , Adams Leanne B. , Chiu Eleanor , Sharma Archna 
Published: January 2018

AbstractChromosome abnormalities detected during cytogenetic investigations for B‐cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B‐cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B‐cell malignancies. Here, we describe the comparison of two B‐cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B‐cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B‐cell disorders, revealing abnormal cytogenetic results in a range of B‐cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B‐cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B‐cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease.
The morphometric co‐atrophy networking of schizophrenia, autistic and obsessive spectrum disorders
Authors: Cauda Franco , Nani Andrea , Costa Tommaso , Palermo Sara , Tatu Karina , Manuello Jordi , Duca Sergio , Fox Peter T. , Keller Roberto 
Published: January 2018

AbstractBy means of a novel methodology that can statistically derive patterns of co‐alterations distribution from voxel‐based morphological data, this study analyzes the patterns of brain alterations of three important psychiatric spectra—that is, schizophrenia spectrum disorder (SCZD), autistic spectrum disorder (ASD), and obsessive‐compulsive spectrum disorder (OCSD). Our analysis provides five important results. First, in SCZD, ASD, and OCSD brain alterations do not distribute randomly but, rather, follow network‐like patterns of co‐alteration. Second, the clusters of co‐altered areas form a net of alterations that can be defined as morphometric co‐alteration network or co‐atrophy network (in the case of gray matter decreases). Third, within this network certain cerebral areas can be identified as pathoconnectivity hubs, the alteration of which is supposed to enhance the development of neuronal abnormalities. Fourth, within the morphometric co‐atrophy network of SCZD, ASD, and OCSD, a subnetwork composed of eleven highly connected nodes can be distinguished. This subnetwork encompasses the anterior insulae, inferior frontal areas, left superior temporal areas, left parahippocampal regions, left thalamus and right precentral gyri. Fifth, the co‐altered areas also exhibit a normal structural covariance pattern which overlaps, for some of these areas (like the insulae), the co‐alteration pattern. These findings reveal that, similarly to neurodegenerative diseases, psychiatric disorders are characterized by anatomical alterations that distribute according to connectivity constraints so as to form identifiable morphometric co‐atrophy patterns.
Effect of titanium dioxide nanoparticles on glucose homeostasis after oral administration
Authors: Chen Zhangjian , Wang Yun , Wang Xiang , Zhuo Lin , Chen Shi , Tang Shichuan , Zhao Lin , Luan Xianguo , Jia Guang 
Published: January 2018

AbstractAs food additives, titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various products that are usually simultaneously consumed with a high content of sugar, thus necessitating research on the effect of TiO2 NPs on glucose homeostasis. We conducted an animal study to explore the effect of orally administrated TiO2 NPs on glucose absorption and metabolism in rats at 0, 2, 10 and 50 mg kg–1 body weight day–1 for 30 and 90 days. The results showed that oral exposure to TiO2 NPs caused a slight and temporary hypoglycemic effect in rats at 30 days post‐exposure but recovered at 90 days post‐exposure. Decreased levels of intestinal glucose absorption and increased levels of hepatic glucose metabolism may be responsible for the hypoglycemic effect. Remodeling of the villi in the small intestine that decreased the surface area available for glucose absorption and increased levels of hepatic glucose uptake, utilization and storage related to hepatocellular injury are supposed to be the mechanisms. Our results demonstrated that dietary intake of TiO2 NPs as food additives could affect the absorption and metabolism of glucose.
Reproductive toxic impact of subchronic treatment with combined butylparaben and triclosan in weanling male rats
Authors: Riad Madeha A. , Abd‐Rabo Marwa M. , Abd El Aziz Samy A. , El Behairy Adel M. , Badawy Mohamed M. 
Published: January 2018

AbstractThe effect of treatment with combined butylparaben and triclosan on male gonadal toxicity in weanling rats was investigated. All treated groups experienced atrophy in the ventral prostate and seminal vesicle, likewise significant depletion in the number and motility of sperm. Given individually or combined butylparaben and triclosan, significantly decreased testosterone, luteinizing hormone, and follicle‐stimulating hormone levels. Individual treatment with tested compounds caused significant elevation in the E2 level, whereas combined treatment did not alter the E2 level. Testicular DNA damage was recorded in all treated groups. Moreover, the testicular malondialdehyde level was significantly elevated, along with a significant decrease in catalase enzyme activity in all treated groups. Superoxide dismutase enzyme activity was significantly decreased in the butylparaben‐treated group, increased in the triclosan‐treated group, and nonsignificantly changed the butylparaben‐triclosan‐treated group. The combined treatment produced an endocrine disturbance with a concomitant induction of testicular oxidative stress, which may represent a common mechanism of endocrine disruptor‐mediated dysfunction.
Feeling insulted? Examining end‐of‐work anger as a mediator in the relationship between daily illegitimate tasks and next‐day CWB
Authors: Zhou Zhiqing E. , Eatough Erin M. , Wald Danielle R. 
Published: January 2018

SummaryIn this daily diary study, we investigated the within‐person relationship between daily illegitimate tasks and next‐day counterproductive work behavior (CWB). We explored a moderated mediation model where the link between illegitimate tasks and CWB is mediated by daily end‐of‐work anger, with daily time pressure moderating the relationship between illegitimate tasks and end‐of‐work anger. We collected data from 114 full‐time employees across 10 consecutive working days. Results showed that within individuals, daily illegitimate tasks positively predicted next‐day CWB, and the relationship was mediated by daily end‐of‐work anger. Further, daily time pressure moderated the relationship between daily illegitimate tasks and daily end‐of‐work anger with the relationship being stronger when daily time pressure was high.