bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of an in vitro assay to screen for the immunotoxic potential of chemicals to fish
Authors: Rehberger Kristina , Escher Beate I. , Scheidegger Andreas , Werner Inge , Segner Helmut 
Published: February 2021

AbstractA wide variety of environmental contaminants has been shown to disrupt immune functions of fish and may compromise their defense capability against pathogens. Immunotoxic effects, however, are rarely considered in ecotoxicological testing strategies. The aim of this study was to systematically evaluate the suitability of an in vitro immuno-assay using selected fish immune parameters to screen for chemicals with known immunotoxic potential and to differentiate them from non-immunotoxicants. Non-stimulated and lipopolysaccharide-stimulated head kidney leukocytes of rainbow trout (Oncorhynchus mykiss) were exposed for 3 h or 19 h to chemicals with different modes of action. As immune parameters, phagocytosis activity, oxidative burst activity and cytokine transcription (IL-1β, TNFα, IL-10) were examined, accompanied by in silico modelling. The immunotoxicants dexamethasone, benzo(a)pyrene, ethinylestradiol and bisphenol A significantly altered the immune parameters at non-cytotoxic concentrations whereas diclofenac had only weak effects. However, the two baseline chemicals with no known immunotoxic potential, butanol and ethylene glycol, caused significant effects, too. From our results it appears that the in vitro fish leukocyte assay as performed in the present study has only a limited capacity for discriminating between immunotoxicants and non-immunotoxicants.
Development of a Genetic Risk Score to predict the risk of overweight and obesity in European adolescents from the HELENA study
Authors: Seral-Cortes Miguel , Sabroso-Lasa Sergio , De Miguel-Etayo Pilar , Gonzalez-Gross Marcela , Gesteiro Eva , Molina-Hidalgo Cristina , De Henauw Stefaan , Gottrand Frederic , Mavrogianni Christina , Manios Yannis , Plada Maria , Widhalm Kurt , Kafatos Anthony , Erhardt Éva , Meirhaeghe Aline , Salazar-Tortosa Diego , Ruiz Jonatan , Moreno Luis A. , Esteban Luis Mariano , Labayen Idoia 
Published: February 2021

AbstractObesity is the result of interactions between genes and environmental factors. Since monogenic etiology is only known in some obesity-related genes, a genetic risk score (GRS) could be useful to determine the genetic predisposition to obesity. Therefore, the aim of our study was to build a GRS able to predict genetic predisposition to overweight and obesity in European adolescents. A total of 1069 adolescents (51.3% female), aged 11–19 years participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were genotyped. The sample was divided in non-overweight (non-OW) and overweight/obesity (OW/OB). From 611 single nucleotide polymorphisms (SNP) available, a first screening of 104 SNPs univariately associated with obesity (p < 0.20) was established selecting 21 significant SNPs (p < 0.05) in the multivariate model. Unweighted GRS (uGRS) was calculated by summing the number of risk alleles and weighted GRS (wGRS) by multiplying the risk alleles to each estimated coefficient. The area under curve (AUC) was calculated in uGRS (0.723) and wGRS (0.734) using tenfold internal cross-validation. Both uGRS and wGRS were significantly associated with body mass index (BMI) (p < .001). Both GRSs could potentially be considered as useful genetic tools to evaluate individual’s predisposition to overweight/obesity in European adolescents.
Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies
Authors: Carmeli Cristian , Kutalik Zoltán , Mishra Pashupati P. , Porcu Eleonora , Delpierre Cyrille , Delaneau Olivier , Kelly-Irving Michelle , Bochud Murielle , Dhayat Nasser A. , Ponte Belen , Pruijm Menno , Ehret Georg , Kähönen Mika , Lehtimäki Terho , Raitakari Olli T. , Vineis Paolo , Kivimäki Mika , Chadeau-Hyam Marc , Dermitzakis Emmanouil , Vuilleumier Nicolas , Stringhini Silvia 
Published: February 2021

AbstractIndividuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.
Free radical degradation in aqueous solution by blowing hydrogen and carbon dioxide nanobubbles
Authors: Fujita Toyohisa , Kurokawa Hiromi , Han Zhenyao , Zhou Yali , Matsui Hirofumi , Ponou Josiane , Dodbiba Gjergj , He Chunlin , Wei Yuezou 
Published: February 2021

AbstractThe main findings are the hydroxyl radical scavenging and the superoxide anion diminishing by mixing the carbon dioxide (CO2) nanobubbles after hydrogen nanobubble blowing in water and alcohol aqueous solution. The nanobubbles produce the hydroxyl radical by ultrasonic waves, changing the pH and catalyst and so on, while the nanobubble is very reactive to scavenge free radicals. In this research especially hydrogen (4% H2 in argon) and CO2 nanobubbles have been blown into hydrogen peroxide (H2O2) added pure water, ethanol, and ethylene glycol aqueous solution through a porous ceramic sparger from the gas cylinder. The aqueous solutions with H2O2 are irradiated by ultraviolet (UV) light and the produced hydroxyl radical amount is measured with spin trapping reagent and electron spin resonance (ESR). The CO2 nanobubble blowing extremely has reduced the hydroxyl radical in water, ethanol, and ethylene glycol aqueous solution. On the other hand, when H2 nanobubbles are brown after CO2 nanobubble blowing, the hydroxyl radical amount has increased. For the disinfection test, the increase of hydroxyl radicals is useful to reduce the bacteria by the observation in the agar medium. Next, when the superoxide anion solution is mixed with nanobubble containing water, ethanol, and ethylene glycol aqueous solution, H2 nanobubble has reduced the superoxide anion slightly. The water containing both CO2 and H2 nanobubble reduces the superoxide anion. The less than 20% ethanol and the 30% ethylene glycol aqueous solution containing CO2 nanobubbles generated after H2 nanobubble blowing can diminish the superoxide anion much more. While the H2 nanobubble blowing after CO2 nanobubble blowing scavenges the superoxide anion slightly. The experimental results have been considered using a chemical reaction formula.
Predictors for the severe coronavirus disease 2019 (COVID-19) infection in patients with underlying liver disease: a retrospective analytical study in Iran
Authors: Bahardoust Mansour , Heiat Mohammad , Khodabandeh Mehrdad , Karbasi Ashraf , Bagheri-Hosseinabadi Zahra , Ataee Mohammad Hossein , Seidalian Narjes , Babazadeh Amirhossein , Agah Shahram , Abyazi Mohammad Ali 
Published: February 2021

AbstractRisk factors for clinical outcomes of COVID-19 pneumonia have not yet been well established in patients with underlying liver diseases. Our study aimed to describe the clinical characteristics and outcomes of COVID-19 infection among patients with underlying liver diseases and determine the risk factors for severe COVID-19 among them. In a retrospective analytical study, 1002 patients with confirmed COVID-19 pneumonia were divided into two groups: patients with and without underlying liver diseases. The admission period was from 5 March to 14 May 2020. The prevalence of underlying conditions, Demographic data, clinical parameters, laboratory data, and participants' outcomes were evaluated. Logistic regression was used to estimate the predictive factors. Eighty-one (8%) of patients had underlying liver diseases. The frequencies of gastrointestinal symptoms such as diarrhea and vomiting were significantly higher among patients with liver diseases (48% vs. 25% and 46.1% vs. 30% respectively, both P < 0.05). Moreover, ALT and AST were significantly higher among patients with liver diseases (54.5 ± 45.6 vs. 37.1 ± 28.4, P = 0.013 and 41.4 ± 27.2 vs. 29.2 ± 24.3, P = 0.028, respectively). Additionally, the mortality rate was significantly high in patients with liver disease (12.4% vs. 7%, P = 0.018). We also observed that the parameters such as neutrophil to leukocyte ratio [Odds Ratio Adjusted (ORAdj) 1.81, 95% CI 1.21–3.11, P = 0.011] and blood group A (ORAdj 1.59, 95% CI 1.15–2.11, P = 0.001) were associated with progression of symptoms of COVID-19. The presence of underlying liver diseases should be considered one of the poor prognostic factors for worse outcomes in patients with COVID-19.
Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice
Authors: Weisell Jonna , Ruotsalainen Anna-Kaisa , Näpänkangas Juha , Jauhiainen Matti , Rysä Jaana 
Published: February 2021

AbstractIn calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the effect of menaquinone 4 (MK4/vitamin K2) on valvular calcification in the hypercholesterolemic mouse model of CAVD.LDLr−/−ApoB100/100male mice were fed with a Western diet for 5 months, with (n = 10) or without (n = 10) added 0.2 mg/g MK4. Body weight gain was followed weekly. Morphology of aortic valves and liver was assessed with immunohistochemistry. Plasma cholesterol levels and cytokines from hepatic tissue were assessed in the end of the study. Hepatic gene expression of lipid metabolism regulating genes were assessed after 18 h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemicLDLr−/−ApoB100/100mice. The MK4-containing WD diet increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of genes required for triglyceride and cholesterol synthesis. MK4 diminished levels of several cytokines and chemokines in liver, including IL-6, TNFα and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.
The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects
Authors: Vázquez-Moreno Miguel , Locia-Morales Daniel , Valladares-Salgado Adan , Sharma Tanmay , Perez-Herrera Aleyda , Gonzalez-Dzib Roxana , Rodríguez-Ruíz Francisco , Wacher-Rodarte Niels , Cruz Miguel , Meyre David 
Published: February 2021

AbstractWe investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35–2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13–2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14–3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10–6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10–5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.
Mating system evolution and genetic structure of diploid sexual populations of Cyrtomium falcatum in Japan
Authors: Imai Ryosuke , Tsuda Yoshiaki , Ebihara Atsushi , Matsumoto Sadamu , Tezuka Ayumi , Nagano Atsushi J. , Ootsuki Ryo , Watano Yasuyuki 
Published: February 2021

AbstractEvolution of mating systems has become one of the most important research areas in evolutionary biology. Cyrtomium falcatum is a homosporous fern species native to eastern Asia. Two subspecies belonging to a sexual diploid race of C. falcatum are recognized: subsp. littorale and subsp. australe. Subspecies littorale shows intermediate selfing rates, while subsp. australe is an obligate outcrosser. We aimed to evaluate the process of mating system evolution and divergence for the two subspecies using restriction site associated DNA sequencing (RAD-seq). The results showed that subsp. littorale had lower genetic diversity and stronger genetic drift than subsp. australe. Fluctuations in the effective population size over time were evaluated by extended Bayesian skyline plot and Stairway plot analyses, both of which revealed a severe population bottleneck about 20,000 years ago in subsp. littorale. This bottleneck and the subsequent range expansion after the LGM appear to have played an important role in the divergence of the two subspecies and the evolution of selfing in subsp. littorale. These results shed new light on the relationship between mating system evolution and past demographic change in fern species.
Comparison of treatment outcomes for native tissue repair and sacrocolpopexy as apical suspension procedures at the time of hysterectomy for uterine prolapse
Authors: Oh Sumin , Shin E. Kyung , Hyun Sowoon , Jeon Myung Jae 
Published: February 2021

AbstractConcomitant apical suspension should be performed at the time of hysterectomy for uterine prolapse to reduce the risk of recurrent prolapse. Native tissue repair (NTR) and sacrocolpopexy (SCP) are commonly used apical suspension procedures; however, it remains unclear which one is preferred. This study aimed to compare the treatment outcomes of NTR and SCP in terms of surgical failure, complication and reoperation rates. Surgical failure was defined as the presence of vaginal bulge symptoms, any prolapse beyond the hymen, or retreatment for prolapse. This retrospective cohort study included 523 patients who had undergone NTR (n = 272) or SCP (n = 251) along with hysterectomy for uterine prolapse and who had at least 4-month follow-up visits. During the median 3-year follow-up period, the surgical failure rate was higher in the NTR group (21.3% vs 6.4%, P < 0.01), with a low rate of retreatment in both groups. Overall complication rates were similar, but complications requiring surgical correction under anesthesia were more common in the SCP group (7.2% vs 0.4%, P < 0.01). As a result, the total reoperation rate was significantly higher in the SCP group (8.0% vs 2.6%, P = 0.02). Taken together, NTR may be a preferred option for apical suspension when hysterectomy is performed for uterine prolapse.
Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
Authors: Youssef Lina , Miranda Jezid , Blasco Miquel , Paules Cristina , Crovetto Francesca , Palomo Marta , Torramade-Moix Sergi , García-Calderó Héctor , Tura-Ceide Olga , Dantas Ana Paula , Hernandez-Gea Virginia , Herrero Pol , Canela Nuria , Campistol Josep Maria , Garcia-Pagan Joan Carles , Diaz-Ricart Maribel , Gratacos Eduard , Crispi Fatima 
Published: February 2021

AbstractPreeclampsia is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality. The exact pathogenesis of this multifactorial disease remains poorly defined. We applied proteomics analysis on maternal blood samples collected from 14 singleton pregnancies with early-onset severe preeclampsia and 6 uncomplicated pregnancies to investigate the pathophysiological pathways involved in this specific subgroup of preeclampsia. Maternal blood was drawn at diagnosis for cases and at matched gestational age for controls. LC–MS/MS proteomics analysis was conducted, and data were analyzed by multivariate and univariate statistical approaches with the identification of differential pathways by exploring the global human protein–protein interaction network. The unsupervised multivariate analysis (the principal component analysis) showed a clear difference between preeclamptic and uncomplicated pregnancies. The supervised multivariate analysis using orthogonal partial least square discriminant analysis resulted in a model with goodness of fit (R2X = 0.99, p < 0.001) and a strong predictive ability (Q2Y = 0.8, p < 0.001). By univariate analysis, we found 17 proteins statistically different after 5% FDR correction (q-value < 0.05). Pathway enrichment analysis revealed 5 significantly enriched pathways whereby the activation of the complement and coagulation cascades was on top (p = 3.17e−07). To validate these results, we assessed the deposits of C5b-9 complement complex and on endothelial cells that were exposed to activated plasma from an independent set of 4 cases of early-onset severe preeclampsia and 4 uncomplicated pregnancies. C5b-9 and Von Willbrand factor deposits were significantly higher in early-onset severe preeclampsia. Future studies are warranted to investigate potential therapeutic targets for early-onset severe preeclampsia within the complement and coagulation pathway.
Coinfection of porcine deltacoronavirus and porcine epidemic diarrhea virus increases disease severity, cell trophism and earlier upregulation of IFN-α and IL12
Authors: Saeng-chuto Kepalee , Madapong Adthakorn , Kaeoket Kampon , Piñeyro Pablo Enrique , Tantituvanont Angkana , Nilubol Dachrit 
Published: February 2021

AbstractPorcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) cause an enteric disease characterized by diarrhea clinically indistinguishable. Both viruses are simultaneously detected in clinical cases, but a study involving the co-infection has not been reported. The study was therefore conducted to investigate the disease severity following a co-infection with PEDV and PDCoV. In the study, 4-day-old pigs were orally inoculated with PEDV and PDCoV, either alone or in combination. Following challenge, fecal score was monitored on a daily basis. Fecal swabs were collected and assayed for the presence of viruses. Three pigs per group were necropsied at 3 and 5 days post inoculation (dpi). Microscopic lesions and villous height to crypt depth (VH:CD) ratio, together with the presence of PEDV and PDCoV antigens, were evaluated in small intestinal tissues. Expressions of interferon alpha (IFN-α) and interleukin 12 (IL12) were investigated in small intestinal mucosa. The findings indicated that coinoculation increased the disease severity, demonstrated by significantly prolonged fecal score and virus shedding and decreasing VH:CD ratio in the jejunum compared with pigs inoculated with either PEDV or PDCoV alone. Notably, in single-inoculated groups, PEDV and PDCoV antigens were detected only in villous enterocytes wile in the coinoculated group, PDCoV antigen was detected in both villous enterocytes and crypts. IFN-α and IL12 were significantly up-regulated in coinoculated groups in comparison with single-inoculated groups. In conclusion, co-infection with PEDV and PDCoV exacerbate clinical signs and have a synergetic on the regulatory effect inflammatory cytokines compared to a single infection with either virus.
Foxes fertilize the subarctic forest and modify vegetation through denning
Authors: Lang Jessica A. , Roth James D. , Markham John H. 
Published: February 2021

AbstractEcosystem engineers modify habitats through processes other than trophic interactions, such as by regulating soil nutrients, and can influence resource availability and quality for other organisms. Predator-mediated elemental cycling may be especially important in determining plant diversity and growth in ecosystems where soil fertility and primary productivity are low. Red foxes (Vulpes vulpesL.), top predators in the Subarctic, could engineer local ecosystems through denning, which could create biogeochemical hotspots of nutrients due to continual input of feces, urine and prey remains. We examined soil and vegetation characteristics on red fox dens and paired control sites in woodland habitats near the Arctic treeline in Manitoba, Canada. The organic soil layer on den sites had 81% more inorganic nitrogen and 250% more extractable phosphorus than in control areas. Denning also increased soil respiration and pH in the organic layer, suggesting improved soil quality and nutrient availability for plants. By enriching nutrients and disturbing soils through digging, den sites had a higher plant species ß-diversity and a greater cover of erect woody shrubs (Salixspp.), grasses (Leymus mollis(Trinius) Pilger) and weedy ephemerals compared to control sites, resulting in a regional increase in plant species richness. Our research highlights the importance of considering impacts of predators other than through their consumption of prey, and provides insight into the role of red foxes in modifying plant diversity and productivity in the Subarctic.
The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients
Authors: Kovacevic Katarina D. , Greisenegger Stefan , Langer Agnes , Gelbenegger Georg , Buchtele Nina , Pabinger Ingrid , Petroczi Karin , Zhu Shuhao , Gilbert James C. , Jilma Bernd 
Published: February 2021

AbstractThe effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of stenotic extracranial/intracranial arteries. A third generation anti-VWF aptamer (BT200) has been generated which could be useful for secondary stroke prevention. To characterize the effects of BT200 in blood of patients with large artery atherosclerosis stroke (LAA). Blood samples were obtained from 33 patients with acute stroke or transient ischemic attack to measure inhibition of VWF activity and VWF-dependent platelet function. Patients who received clopidogrel or dual antiplatelet therapy did not differ in VWF dependent platelet function tests from aspirin treated patients. Of 18 patients receiving clopidogrel with or without aspirin, only 3 had a prolonged collagen adenosine diphosphate closure time, and none of the patients had ristocetin induced aggregation in the target range. BT200 concentration-dependently reduced median VWF activity from 178 to < 3%, ristocetin induced platelet aggregation from 40U to < 10U and prolonged collagen adenosine diphosphate closure times from 93 s to > 300 s. Baseline VWF activity correlated (r = 0.86, p < 0.001) with concentrations needed to reduce VWF activity to < 20% of normal, indicating that BT200 acts in a target concentration-dependent manner. Together with a long half-life supporting once weekly administration, the safety and tolerability observed in an ongoing phase I trial, and the existence of a reversal agent, BT200 is an interesting drug candidate.