bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the Glucocorticoid Receptor Reduces Binge‐Like Drinking in High Drinking in the Dark (HDID‐1) Mice
Authors: Savarese Antonia M. , Ozburn Angela R. , Metten Pamela , Schlumbohm Jason P. , Hack Wyatt R. , LeMoine Kathryn , Hunt Hazel , Hausch Felix , Bauder Michael , Crabbe John C. 
Published: March 2020

BackgroundChronic alcohol exposure can alter glucocorticoid receptor (GR) function in some brain areas that promotes escalated and compulsive‐like alcohol intake. GR antagonism can prevent dependence‐induced escalation in drinking, but very little is known about the role of GR in regulating high‐risk nondependent alcohol intake. Here, we investigate the role of GR in regulating binge‐like drinking and aversive responses to alcohol in the High Drinking in the Dark (HDID‐1) mice, which have been selectively bred for high blood ethanol (EtOH) concentrations (BECs) in the Drinking in the Dark (DID) test, and in their founder line, the HS/NPT.MethodsIn separate experiments, male and female HDID‐1 mice were administered one of several compounds that inhibited GR or its negative regulator, FKBP51 (mifepristone [12.5, 25, 50, 100 mg/kg], CORT113176 [20, 40, 80 mg/kg], and SAFit2 [10, 20, 40 mg/kg]) during a 2‐day DID task. EtOH consumption and BECs were measured. EtOH conditioned taste and place aversion (CTA and CPA, respectively) were measured in separate HDID‐1 mice after mifepristone administration to assess GR’s role in regulating the conditioned aversive effects of EtOH. Lastly, HS/NPT mice were administered CORT113176 during DID to assess whether dissimilar effects from those of HDID‐1 would be observed, which could suggest that selective breeding had altered sensitivity to the effects of GR antagonism on binge‐like drinking.ResultsGR antagonism (with both mifepristone and CORT113176) selectively reduced binge‐like EtOH intake and BECs in the HDID‐1 mice, while inhibition of FKBP51 did not alter intake or BECs. In contrast, GR antagonism had no effect on EtOH intake or BECs in the HS/NPT mice. Although HDID‐1 mice exhibit attenuated EtOH CTA, mifepristone administration did not enhance the aversive effects of EtOH in either a CTA or CPA task.ConclusionThese data suggest that the selection process increased sensitivity to GR antagonism on EtOH intake in the HDID‐1 mice, and support a role for the GR as a genetic risk factor for high‐risk alcohol intake.
Effect of Single‐Dose, Oral Enzymatic Porcine Placental Extract on Pharmacokinetics of Alcohol and Liver Function in Rats
Authors: Kim Hyun‐Jin , Kim Semi , Seo Jin‐Sook , Bae Gun‐Won , Kim Keun‐Nam , Kang Ju‐Seop 
Published: March 2020

BackgroundHuman placenta extract (HPE) has been used to treat a number of liver diseases. Porcine placenta is relatively safe and has been reported to have similar immune effects to HPE and used as its alternative. This study evaluates the effect of enzymatic porcine placental extract (EPPE, Uni‐Placenta®) on alcohol pharmacokinetics in rat.MethodsThis study was designed to determine the effect of single‐dose EPPE on the pharmacokinetics of alcohol and liver function. Results were based on serum alcohol and acetaldehyde concentrations and activities of hepatic and gastric ADH and ALDH in rats.ResultsThe hepatic ADH in alcohol group was significantly increased and it may be enzyme‐induction by alcohol. The hepatic ALDH and gastric ADH were not changed, but gastric ALDH was significantly decreased only in the high‐dose EPPE group. In the alcohol pharmacokinetics parameters, the AUC was 44.5 mM∙h in the alcohol group. Otherwise, AUCs of low, middle, high, and silymarin groups were significantly decreased. Cmax was reached at 1 hour and then gradually decreased to 63% and 43% in the middle and high groups at 3 hours, respectively, and to 92% in the low groups. The pharmacokinetics and serum concentrations of acetaldehyde showed no differences between EPPE groups except the silymarin group. No histologic changes were seen in any group.ConclusionsThe single‐dose EPPE (0.5 to 2.5 g/kg) suppressed absorption of alcohol in the gastrointestinal tract. This may be useful in preventing hangover effects and toxicity after drinking alcohol and may also preserve liver health after alcohol ingestion.
Differential Activation of Unconventional T Cells, Including iNKT Cells, in Alcohol‐Related Liver Disease
Authors: Marrero Idania , Maricic Igor , Morgan Timothy R. , Stolz Andrew A. , Schnabl Bernd , Liu Zhang‐Xu , Tsukamoto Hidekazu , Kumar Vipin 
Published: March 2020

BackgroundLiver is enriched in several innate‐like unconventional T cells, but their role in alcohol‐related liver disease (ALD) is not fully understood. Studies in several acute alcohol feeding models but not in chronic alcoholic steatohepatitis (ASH) model have shown that invariant natural killer T (iNKT) cells play a pathogenic role in ALD. Here, we investigated the activation of iNKT cells in an intragastric (iG) infusion model of chronic ASH as well as the frequency and cytokine phenotype of 3 different unconventional T cells: iNKT, mucosal‐associated invariant T (MAIT), and CD8+CD161hiVα7.2− cells in peripheral blood of ALD patients.MethodsHepatic iNKT cells were investigated using the iG model of chronic ASH that combines feeding of high‐cholesterol/high‐fat diet (HCFD) with intragastric feeding of ethanol diet (HCFD + iG Alc). Human iNKT, MAIT, and CD8+CD161hiVα7.2− cells were examined by flow cytometry in peripheral blood of patients with severe alcoholic hepatitis (SAH) and chronic alcoholics (ChA) and compared with healthy controls.ResultsIn the iG model of chronic ASH, IFNγ+ iNKT cells accumulate in their livers compared with pair‐fed control mice and activated hepatic iNKT cells show high expression of Fas and FasL. Notably, IFNγ+ iNKT cells are also significantly increased in peripheral blood of ChA patients compared with SAH patients. MAIT cells are significantly reduced in all ALD patients, but CD8+CD161hiVα7.2− cells are increased in SAH patients. Although MAIT and CD8+CD161hiVα7.2− cells displayed a similar cytokine production profile, the production of IFNγ and TNFα is significantly increased in SAH patients, while significant IL‐17A production is found in ChA patients.ConclusionsWe found that the 3 unconventional T cells are activated in ALD patients showing interesting differences in their frequency and cytokine production profile between SAH and ChA patients. In the iG murine model of chronic ASH, iNKT cells are also activated secreting proinflammatory cytokines suggesting their involvement in liver disease.
Source of dopamine in gastric juice and luminal dopamine‐induced duodenal bicarbonate secretion via apical dopamine D2 receptors
Authors: Feng Xiao‐Yan , Yan Jing‐Ting , Li Guang‐Wen , Liu Jing‐Hua , Fan Rui‐Fang , Li Shi‐Chao , Zheng Li‐Fei , Zhang Yue , Zhu Jin‐Xia 
Published: March 2020

Background and PurposeDopamine protects the duodenal mucosa. Here we have investigated the source of dopamine in gastric juice and the mechanism underlying the effects of luminal dopamine on duodenal bicarbonate secretion (DBS) in rodents.Experimental ApproachImmunofluorescence, UPLC‐MS/MS, gastric incubation and perfusion were used to detect gastric‐derived dopamine. Immunofluorescence and RT‐PCR were used to examine the expression of dopamine receptors in the duodenal mucosa. Real‐time pH titration and pHi measurement were performed to investigate DBS.Key ResultsH+‐K+‐ATPase was co‐localized with tyrosine hydroxylase and dopamine transporters in gastric parietal cells. Dopamine was increased in in vivo gastric perfusate after intravenous infusion of histamine and in gastric mucosa incubated, in vitro, with bethanechol chloride or tyrosine. D2 receptors were the most abundant dopamine receptors in rat duodenum, mainly distributed on the apical membrane of epithelial cells. Luminal dopamine increased DBS in a concentration‐dependent manner, an effect mimicked by a D2 receptor agonist quinpirole and inhibited by the D2 receptor antagonist L741,626, in vivo D2 receptor siRNA and in D2 receptor −/− mice. Dopamine and quinpirole raised the duodenal enterocyte pHi. Quinpirole‐evoked DBS and PI3K/Akt activity were inhibited by calcium chelator BAPTA‐AM or in D2 receptor−/− mice.Conclusion and ImplicationsDopamine in the gastric juice is derived from parietal cells and is secreted along with gastric acid. On arrival in the duodenal lumen, dopamine increased DBS via an apical D2 receptor‐ and calcium‐dependent pathway. Our data provide novel insights into the protective effects of dopamine on the duodenal mucosa.
Improved efficacy, tolerance, safety, and abuse liability profile of the combination of CR4056 and morphine over morphine alone in rodent models
Authors: Sala Emanuele , Ferrari Flora , Lanza Marco , Milia Chiara , Sabatini Chiara , Bonazzi Albino , Comi Eleonora , Borsi Franchini Miriam , Caselli Gianfranco , Rovati Lucio Claudio 
Published: March 2020

Background and PurposeProlonged use of opioids causes analgesic tolerance and adverse effects including constipation and dependence. Compounds targeting imidazoline I2 receptors are known to potentiate opioid analgesia in rodents. We investigated whether combination with the I2 receptor ligand CR4056 could improve efficacy and safety of morphine and explored the mechanisms of the CR4056–opioid interaction.Experimental ApproachWe used the complete Freund's adjuvant (CFA) model in rats to study the effects of treatments on hyperalgesia, morphine tolerance and microglia activation as measured by immunofluorescence. Opioid‐induced adverse effects were assessed in rodent models of morphine‐induced constipation, sedation (open field, sedation rating scale, and rotarod), physical dependence (naloxone‐induced withdrawal), and abuse (conditioned place preference‐associated reward). Chemiluminescence assays tested CR4056 as allosteric modulator of μ‐opioid receptors.Key ResultsCR4056 (ED50 = 4.88 mg·kg−1) and morphine (ED50 = 2.07 mg·kg−1) synergized in reducing CFA‐induced hyperalgesia (ED50 = 0.52 mg·kg−1; 1:1 combination). Consistently, low doses of CR4056 (1 mg·kg−1) spared one third of the cumulative morphine dose administered during 4 days and prevented/reversed the development of tolerance to morphine anti‐hyperalgesia. These opioid‐sparing effects were associated with decreased activation of microglia, independent of CR4056 interactions on μ‐opioid receptors. Importantly, the low doses of CR4056 and morphine that synergize in analgesia did not induce constipation, sedation, physical dependence, or place preference.Conclusion and ImplicationsWe showed selective synergism between CR4056 and morphine as analgesics. Their combination showed an improved safety and abuse liability profile over morphine alone. CR4056 could be developed as an opioid‐sparing drug in multimodal analgesia.
The ecological importance of crocodylians: towards evidence‐based justification for their conservation
Authors: Somaweera Ruchira , Nifong James , Rosenblatt Adam , Brien Mathew L. , Combrink Xander , Elsey Ruth M. , Grigg Gordon , Magnusson William E. , Mazzotti Frank J. , Pearcy Ashley , Platt Steven G. , Shirley Matthew H. , Tellez Marisa , van der Ploeg Jan , Webb Grahame , Whitaker Rom , Webber Bruce L. 
Published: March 2020

ABSTRACTLarge‐bodied predators are well represented among the world's threatened and endangered species. A significant body of literature shows that in terrestrial and marine ecosystems large predators can play important roles in ecosystem structure and functioning. By contrast, the ecological roles and importance of large predators within freshwater ecosystems are poorly understood, constraining the design and implementation of optimal conservation strategies for freshwater ecosystems. Conservationists and environmentalists frequently promulgate ecological roles that crocodylians are assumed to fulfil, but often with limited evidence supporting those claims.Here, we review the available information on the ecological importance of crocodylians, a widely distributed group of predominantly freshwater‐dwelling, large‐bodied predators. We synthesise information regarding the role of crocodylians under five criteria within the context of modern ecological concepts: as indicators of ecological health, as ecosystem engineers, apex predators, keystone species, and as contributors to nutrient and energy translocation across ecosystems. Some crocodylians play a role as indicators of ecosystem health, but this is largely untested across the order Crocodylia. By contrast, the role of crocodylian activities in ecosystem engineering is largely anecdotal, and information supporting their assumed role as apex predators is currently limited to only a few species. Whether crocodylians contribute significantly to nutrient and energy translocation through cross‐ecosystem movements is unknown.We conclude that most claims regarding the importance of crocodylians as apex predators, keystone species, ecosystem engineers, and as contributors to nutrient and energy translocation across ecosystems are mostly unsubstantiated speculation, drawn from anecdotal observations made during research carried out primarily for other purposes. There is a paucity of biological research targeted directly at: understanding population dynamics; trophic interactions within their ecological communities; and quantifying the short‐ and long‐term ecological impacts of crocodylian population declines, extirpations, and recoveries. Conservation practices ideally need evidence‐based planning, decision making and justification. Addressing the knowledge gaps identified here will be important for achieving effective conservation of crocodylians.
Welfare to work and subjective well‐being: Evidence from a randomized control trial
Authors: Riddell Chris 
Published: March 2020

AbstractI examine the effect of transitioning from welfare to full‐time employment on a variety of measures of subjective well‐being for a sample of long‐term welfare recipients in British Columbia and New Brunswick who participated in the Self‐Sufficiency Project (SSP). Individuals randomly assigned to the treatment group could receive a generous time‐limited earnings supplement if they found full‐time work. I use random assignment to estimate the local average treatment effect of working full time on well‐being. For the complier subpopulation, I find large, positive effects on subjective well‐being that persist over the longer run for New Brunswick and through roughly three years for British Columbia. Policy changes made during the experiment may explain the provincial differences.
Circulating Epstein‐Barr virus microRNAs BART7‐3p and BART13‐3p as novel biomarkers in nasopharyngeal carcinoma
Authors: Lu Tianzhu , Guo Qiaojuan , Lin Keyu , Chen Honglin , Chen Yixin , Xu Yuanji , Lin Cheng , Su Ying , Chen Yan , Chen Mengyuan , Zheng Yuhong , Ye Yunbin , Lin Shaojun , Zong Jingfeng , Pan Jianji 
Published: March 2020

AbstractEpstein‐Barr virus (EBV) BamHI A rightward transcripts (BART) encoded microRNAs (EBV‐miR‐BARTs) are abnormally highly expressed in nasopharyngeal carcinoma (NPC). This study aims to investigate the diagnostic and prognostic performance of miR‐BART7‐3p and miR‐BART13‐3p. Plasma levels of EBV DNA, miR‐BART7‐3p, and miR‐BART13‐3p were examined by quantitative PCR in 483 treatment‐naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow‐up. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for plasma miR‐BART7‐3p, 0.973 for miR‐BART13‐3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above‐median miR‐BART7‐3p and EBV DNA were independent risk for shorter distant metastasis‐free survival (DMFS) (hazard ratio [HR] = 2.94, 95% confidence interval [CI], 1.44‐5.97, P = .003; HR = 2.27, 95% CI, 1.26‐4.10, P = .006) in multivariate Cox regression. Epstein‐Barr virus DNA, miR‐BART7‐3p, and miR‐BART13‐3p after radiotherapy were detectable in 28.6%, 17.6%, and 54.7% of patients, respectively. In multivariate Cox regression, detectable miR‐BART7‐3p and EBV DNA were independent risks for shorter DMFS (HR = 4.13, 95% CI, 1.89‐9.01, P < .001; HR = 2.14, 95% CI, 1.04‐4.42, P = .039). The 4‐year DMFS rate was 92.0% in subjects (n = 156) with neither detectable miR‐BART7‐3p nor EBV DNA, 80.0% in subjects (n = 65) with either detectable miR‐BART7‐3p or EBV DNA, and 52.9% in subjects (n = 24) with both detectable miR‐BART7‐3p and EBV DNA after radiotherapy (P < .001). Circulating levels of miR‐BART7‐3p and miR‐BART13‐3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR‐BART7‐3p and EBV DNA at diagnosis and after radiotherapy could help stratify patients by risk of poor DMFS.
Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke
Authors: Nishi H , Hosomi N , Ohta K , Aoki S , Nakamori M , Nezu T , Shigeishi H , Shintani T , Obayashi T , Ishikawa K , Kinoshita N , Shiga Y , Sugiyama M , Ohge H , Maruyama H , Kawaguchi H , Kurihara H 
Published: March 2020

Summary
Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2–6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18–1·31, P &lt; 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10–1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55–6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.
Lossless data transmission for Internet of things application over wireless multimedia sensor networks using enhanced and optimal path scheduling approach to maximizing the quality of service
Authors: Alqahtani Abdulrahman S. 
Published: March 2020

AbstractThe congestion of packet forwarding between a source and destination is challenging on downlink transmission in the entire file (ex. Audio and Video). Whenever file is been uploaded to the server, a user requests for file where server transmits it without knowledge of user's bandwidth, which is a major, cause of packet loss or time duration in the receiver end. To accumulate the better solution, Enhanced and Optimal Path Scheduling Approach (EOPSA) designs to find optimal path scheduling for multimedia data transmission in multimedia sensor network over cloud server using IoT devices. EOPSA studied the multisource video‐on‐demand streaming in multimedia sensor networks. The method introduced a heuristic distributed protocol to find optimal route for multimedia data transmissions. Efficient way to identify the bandwidth before the transmission ensures link establishment between sender and receiver. Here, the capture of bandwidth helps to check user's system capability to forward requested media data. Based on experiment evaluation, EOPSA improves 0.20 packet delivery ratio, 130 throughput, 0.20 second average delay and 14 communication overhead for 15, 25, 50, 75, and 100 nodes compared than conventional methods.
Global experience and perspective on anonymous nondirected live donation in living donor liver transplantation
Authors: Raza Muhammad H. , Aziz Hassan , Kaur Navpreet , Lo Mary , Sher Linda , Genyk Yuri , Emamaullee Juliet 
Published: March 2020

AbstractAnonymous nondirected living liver donation (ANLLD), sometimes referred to as “altruistic” donation, occurs when a biologically unrelated person comes forward to donate a portion of his/her liver to a transplant candidate who is unknown to the donor. Here, we explore the current status of ANLLD with special consideration of published reports; US experience; impact on donor psychosocial outcomes; barriers to donation; and current global trends with respect to ethical considerations. Between 1998 and 2019, 105 anonymous nondirected living liver donor (ND‐LLD) transplants have been documented in the US Scientific Registry of Transplant Recipients. Sixteen donors (15%) were reported to experience a postoperative complication. Currently, 89 donors remain alive (85%), 16 (15%) have unknown status, and none are confirmed deceased. Although there are only a handful of case series, these data suggest that ANLLD is a feasible option. While there are no liver‐specific data, studies involving anonymous nondirected kidney donors suggest that anonymous donation does not adversely impact psychosocial outcomes in donors or recipients. There are substantial financial burdens and ethical considerations related to ANLLD. Further studies are required to assess donor demographics, psychosocial motivations, long‐term health‐related quality of life, and financial impact of ANLLD.
Rapid and strong population genetic differentiation and genomic signatures of climatic adaptation in an invasive mealybug
Authors: Ma Ling , Cao Li‐Jun , Hoffmann Ary A. , Gong Ya‐Jun , Chen Jin‐Cui , Chen Hong‐Song , Wang Xu‐Bo , Zeng Ai‐Ping , Wei Shu‐Jun , Zhou Zhong‐Shi 
Published: March 2020

AbstractAimA growing number of studies suggest that adaptation of invasive species plays key roles in their successful establishment in novel environments. However, adaptation of invasive species to climatic conditions remains poorly characterized. This study aimed to understand the population genetic structure produced by the cotton mealybug Phenacoccus solenopsis invasion and to identify preliminary signals of selection during its range expansion.LocationChina.MethodsWe examined genetic structure of 11 populations across China using SNPs, microsatellites and a segment of mitochondrial cox1 gene. ADMIXTURE, STRUCTURE and DAPC were used to infer population genetic structure; the dispersal routes were reconstructed by the DIYABC; SNPs potentially related to climate adaptation were identified by using four populations differentiation methods and three environmental association methods.ResultsStrong genetic differentiation was found among populations with FST values ranging from 0.097 to 0.640 based on SNPs. Populations located at the northern expansion edge exhibited the highest genetic differentiation and the lowest genetic diversity. Demographic analyses indicated that all populations were introduced from a single source population with small effective size and low recent gene flow. RDA analysis showed that climatic variables explained a higher proportion of genetic variance (43%) compared to population structure variables (15%). The top climatic variables associated with genetic differentiation were precipitation of the mean temperature of warmest quarter, mean temperature of driest quarter and isothermality. Genes related to climate candidate SNPs were mainly enriched to pathways of development, energy and xenobiotic metabolisms.Main conclusionsWe found that extremely rapid and strong population genetic differentiation among populations appears to have developed after introduction in the cotton mealybug. Our study points to rapid neutral evolution and suggests possible climatic adaptation despite low genetic diversity in this invasive species.