bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testosterone deprivation intensifies cognitive decline in obese male rats via glial hyperactivity, increased oxidative stress, and apoptosis in both hippocampus and cortex
Authors: Chunchai Titikorn , Apaijai Nattayaporn , Keawtep Puntarik , Mantor Duangkamol , Arinno Apiwan , Pratchayasakul Wasana , Chattipakorn Nipon , Chattipakorn Siriporn C. 
Published: December 2018

AbstractAimThe study hypothesized that testosterone deprivation aggravates cognitive decline in obesity through increasing oxidative stress, glial activation, and apoptosis.MethodsMale Wistar rats (n = 24) were fed with either normal‐diet (ND) or high‐fat diet (HFD) for 24 weeks. At week 13, ND‐fed rats and HFD‐fed rats were randomly assigned to two subgroups to receive either a sham‐operation or bilateral‐orchiectomy (ORX). Rats were evaluated for metabolic parameters and cognition at 4, 8, and 12 weeks after the operation. At the end of protocol, the reactive oxygen species (ROS), glial morphology, and cell apoptosis were determined in hippocampus and cortex.ResultsBoth HFD‐fed groups developed obese‐insulin resistance, but ND‐fed rats did not. HFD‐fed rats with sham‐operation showed cognitive decline, when compared to ND‐fed rats with sham‐operation at all time points. At 4‐ and 8‐week after ORX, the cognitive impairment of ND‐fed rats and both HFD‐fed groups was not different. However, 12‐week after ORX, cognitive decline and of glial hyperactivity of HFD‐fed rats had the greatest increase among all groups. Hippocampal ROS levels and apoptotic cells in both HFD‐fed groups were equally increased, but the cortical ROS levels and apoptotic cells of HFD‐fed rats with ORX were the highest ones.ConclusionsThese findings suggest that testosterone deprivation aggravates cognitive decline in obesity via increasing oxidative stress, glial activity and apoptosis.
Intrapallidal injection of botulinum toxin A recovers gait deficits in a parkinsonian rodent model
Authors: Tsang Adrianna R. , Rajakumar Nagalingam , Jog Mandar S. 
Published: December 2018

AbstractAimModulation of electrical activity in the subthalamic nucleus has been therapeutically effective in Parkinson's disease. Pharmacological manipulation of glutamate release from subthalamic neurons could also favourably alter basal ganglia activity to improve motor symptoms. This study investigates the efficacy of selective suppression of hyperactive glutamatergic input from the subthalamic nucleus to the globus pallidus internal segment by botulinum toxin A (BoNT‐A) in a parkinsonian model.MethodsUnilateral 6‐hydroxydopamine lesioned parkinsonian rodents and controls received microinfusions of BoNT‐A or vehicle into the ipsilateral internal globus pallidus (n = 8 per group). Changes in gait were measured by the CatWalk apparatus, along with assessment of apomorphine‐induced rotational behaviour prior to and following BoNT‐A injection. Immunofluorescent staining for markers of glutamatergic, GABAergic and total terminals was performed at the internal globus pallidus.ResultsAdministration of a single dose of BoNT‐A (0.5 ng) significantly improved the rotational asymmetry and gait abnormalities. Ameliorations in speed, body speed variation, cadence and walking pattern were comparable to pre‐lesioned animals, and persisted up to 1 month following BoNT‐A injection. These changes are associated to BoNT‐A's ability to selectively target glutamatergic terminals.ConclusionBlockade of subthalamic hyperactivity by BoNT‐A leads to sufficient reorganization in the basal ganglia needed to generate a consistent rhythmic pattern of walking. This suggests the potential use of intracerebral BoNT‐A to produce effective neuromodulation in the parkinsonian brain, as well as expansion into other neurodegenerative disorders linked to excitotoxity.
Serum bile acid patterns are associated with the presence of NAFLD in twins, and dose‐dependent changes with increase in fibrosis stage in patients with biopsy‐proven NAFLD
Authors: Caussy Cyrielle , Hsu Cynthia , Singh Seema , Bassirian Shirin , Kolar James , Faulkner Claire , Sinha Nikhil , Bettencourt Ricki , Gara Naveen , Valasek Mark A. , Schnabl Bernd , Richards Lisa , Brenner David A. , Hofmann Alan F. , Loomba Rohit 
Published: December 2018

SummaryBackgroundThe fasting‐state serum bile acid profile in nonalcoholic fatty liver disease (NAFLD) has been reported to differ when nonalcoholic steatohepatitis is compared to nonalcoholic fatty liver. However, there are few data comparing changes in NAFLD vs non‐NAFLD, or whether the bile acid profile differs according to the degree of fibrosis.AimTo examine the serum bile acid profile across the entire spectrum of NAFLD.MethodsWe performed a cross‐sectional analysis of two complementary cohorts: a Twin and Family cohort of 156 participants, and a biopsy‐proven‐NAFLD cohort of 156 participants with fasting bile acid profiling using liquid chromatography/mass spectrometry.ResultsIn the Twin and Family cohort (mean age 46.3 years and body mass index (BMI) 26.6 kg/m2), 36 (23%) participants had NAFLD (magnetic resonance imaging proton density fat fraction ≥ 5%). Higher chenodeoxycholyl conjugates (9.0% vs 6.5%, P = 0.019) and lower glycohyocholate (1.2% vs 3.6%, P < 0.001) were observed in NAFLD compared to non‐NAFLD‐controls. In the biopsy‐proven‐NAFLD cohort (mean age 49.8 years, BMI 32.0 kg/m2), no differences in total bile acid were seen between nonalcoholic fatty liver vs nonalcoholic steatohepatitis. The total unconjugated bile acid significantly decreased across nonalcoholic steatohepatitis categories (P = 0.044). The distribution of stage of fibrosis was F0: 42.3%, F1: 32.7%, F2: 10.3%, F3: 8.3% and F4: 6.4%. The total serum bile acid increased with increase in fibrosis stage (P < 0.001). The primary conjugated bile acid proportion increased (P < 0.001) whereas unconjugated bile acid (P = 0.006), unconjugated cholyl (P < 0.001) and chenodeoxycholyl conjugates (P < 0.002) significantly decreased with increase in liver fibrosis stage.ConclusionsFasting‐state serum bile acid profile alterations are seen across the entire spectrum of NAFLD. The total serum bile acids did not differ significantly between NAFLD vs non‐NAFLD and nonalcoholic fatty liver vs nonalcoholic steatohepatitis, but were significantly perturbed progressively as liver fibrosis increases.
The effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in paediatric patients with Crohn’s disease: a post hoc analysis
Authors: Hyams Jeffrey S. , Dubinsky Marla , Rosh Joel , Ruemmele Frank M. , Eichner Samantha F. , Maa Jen‐Fue , Lazar Andreas , Alperovich Gabriela , Mostafa Nael M. , Robinson Anne M. 
Published: December 2018

SummaryBackgroundIn the IMAgINE 1 study, adalimumab induced and maintained remission of moderate‐to‐severe Crohn's disease in children.AimTo assess the efficacy, pharmacokinetics, immunogenicity and safety of immunomodulator and adalimumab combination therapy vs adalimumab monotherapy in paediatric patients with Crohn's disease.MethodsPatients 6‐17 years old with moderate‐to‐severe Crohn's disease (n = 192) received weight‐based adalimumab induction at baseline and week 2. At week 4, 188 patients were randomised to high‐dose or low‐dose adalimumab. Patients receiving immunomodulators (investigator's decision) at baseline maintained a stable dose until week 26; patients could then discontinue immunomodulators. Adalimumab serum concentrations were measured at weeks 4, 26 and 52. Safety was evaluated at each study visit. Data were analysed using non‐responder imputation (NRI; week 4) or modified NRI (weeks 26; 52).ResultsAt week 4, patients with (n = 117) and without (n = 71) baseline immunomodulator use had similar response (79%; 87%; P = 0.235) and remission (26%; 30%; P = 0.737) rates. At week 26, patients with and without baseline immunomodulators had no significant difference in response (68%; 55%; P = 0.086) or remission (41%; 30%; P = 0.122). At week 52, patients with (n = 82) and without (n = 106) immunomodulator use had no significant difference in response (56%; 46%; P = 0.189) or remission (38%; 33%; P = 0.539). Adalimumab serum trough concentrations and serious infection rates (7%; 6%) were not significantly different between groups.ConclusionsAnalyses found no statistically significant difference in response or remission between patients receiving adalimumab monotherapy vs immunomodulator and adalimumab combination therapy. Serious and infectious adverse event rates were similar between groups.
Systematic review with meta‐analysis: the risk of gastrointestinal bleeding in patients taking third‐generation P2Y12 inhibitors compared with clopidogrel
Authors: Guo Chuan‐Guo , Chen Lijia , Chan Esther W. , Cheung Ka Shing , Isshiki Takaaki , Wong Ian C. K. , Leung Wai K. 
Published: December 2018

SummaryBackgroundTicagrelor and prasugrel are third‐generation oral P2Y12 receptor antagonists with rapid onset and pronounced platelet inhibition. However, higher overall bleeding rates have been reported for these agents when compared with clopidogrel.AimTo compare the risk of gastrointestinal bleeding (GIB) among users of third‐generation P2Y12 inhibitors with clopidogrel.MethodsWe systematically searched for published randomised controlled trials of ticagrelor or prasugrel versus clopidogrel until September 2018. The primary outcome was the risk of GIB among users of third‐generation P2Y12 inhibitors when compared to clopidogrel, expressed as risk ratio (RR) and 95% confidence interval (CI). The rates of non‐coronary artery bypass graft (CABG) major bleeding, life‐threatening bleeding, fatal bleeding, and intracranial bleeding were analysed as secondary outcomes.ResultsForty‐one studies were included in the analysis of non‐CABG major bleeding, of which 12 were included in the analysis of GIB including 58 678 patients. Third‐generation P2Y12 inhibitors were associated with higher risk of GIB as compared with clopidogrel (RR 1.28, 95% CI 1.13‐1.46). The findings were consistent for upper (RR 1.32, 95% CI 1.05‐1.67) and unspecified GIB (RR 1.25, 95% CI 1.01‐1.53), but not lower GIB (RR 1.25, 95% CI 0.95‐1.65). Subgroup analysis showed higher GIB risk in prasugrel studies (RR 1.40, 95% CI 1.10‐1.77) than in ticagrelor studies (RR 1.15, 95% CI 0.94‐1.39). Third‐generation P2Y12 inhibitors also increased the risk of non‐CABG major bleeding (RR 1.18, 95% CI 1.08‐1.28).ConclusionThird‐generation P2Y12 inhibitors were associated with increased risk of GIB and non‐CABG major bleeding when compared with clopidogrel.
Real‐world study of tenofovir disoproxil fumarate to prevent hepatitis B transmission in mothers with high viral load
Authors: Wang Ming , Bian Qian , Zhu Yunxia , Pang Qiumei , Chang Lingzhi , Li Ran , Tiongson Benjamin C. , Zhang Hua , Pan Calvin Q. 
Published: December 2018

SummaryBackgroundData on tenofovir disoproxil fumarate (TDF) therapy for preventing vertical transmission of hepatitis B virus (HBV) in the real‐world setting are limited.AimTo investigate TDF for preventing vertical transmission of HBV in real‐world practice.MethodsHepatitis B e‐antigen (HBeAg)‐positive mothers with HBV‐DNA >6 log10 IU/mL to receive TDF between gestational weeks 24‐33 and delivery were prospectively enrolled and followed until post‐partum week 28. All infants received immunoprophylaxis. Primary endpoints were safety of TDF use and mother‐to‐child transmission rates. Secondary outcomes were maternal HBV‐DNA level suppression (<200 000 IU/mL) at delivery and HBeAg and hepatitis B surface antigen (HBsAg) serologic changes during the study.ResultsAmong 147 mothers enrolled, 143 started TDF and 143/144 infants completed the study. At delivery, 93.7% (134/143) of the mothers achieved HBV‐DNA<200 000 IU/L. On‐treatment, alanine aminotransferase (ALT) flares were observed in 8.4% (12/143) of mothers. After TDF cessation, ALT increased in 7.7% (11/143) of the mothers and 2.8% (4/143) achieved HBeAg negativity, but none had HBsAg loss. At birth, HBsAg was detected in 13.9% (20/144) of newborns and none at post‐partum week 28. Vertical transmission rates among infants were 0.7% (1/144, intention‐to‐treat) and 0% (per‐protocol). No infants had birth defects. No serious adverse effects were reported in either mothers or infants. Breastfeeding did not increase the HBV infection rate among infants although mothers had viral rebound after TDF cessation.ConclusionsTDF for highly viraemic mothers was well tolerated and reduced vertical transmission of HBV in a real‐world setting. There were no safety concerns during the postpartum 28‐week follow‐up.Registry number: Chinese Clinical Trial Registration No. ChiCTR‐OIC‐17010869
A modified staging of early and intermediate hepatocellular carcinoma based on single tumour >7 cm and multiple tumours beyond up‐to‐seven criteria
Authors: Wang Yan‐Yan , Zhong Jian‐Hong , Xu Hai‐Feng , Xu Gang , Wang Li‐Jun , Xu Da , Wang Hong‐Wei , Wang Kun , Xiang Bang‐De , Mao Yi‐Lei , Li Le‐Qun , Xing Bao‐Cai 
Published: December 2018

SummaryBackgroundThe Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used staging system for hepatocellular carcinoma (HCC). However, the classifications of early (BCLC‐A) and intermediate (BCLC‐B) stage HCC remain controversial.AimTo refine the staging of BCLC‐A and ‐B.MethodsA total of 986 patients with HCC undergoing liver resection from two institutions formed the training cohort, and 694 from another institution were the validation cohort. Time‐dependent receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of tumour size in predicting overall survival (OS), and determined the optimised cut‐off. Discriminatory performance was evaluated using Harrell's concordance index (C‐index).ResultsPatients with multiple tumours exceeding Milan criteria but within up‐to‐seven criteria had similar OS and disease‐free survival (DFS) to those with multiple tumours meeting Milan criteria, and were assigned to the modified BCLC‐A stage. The area under the ROC curve of tumour size for predicting OS was 0.778, and the diameter of 7 cm was the optimal cut‐off to identify patients with single tumours who had higher OS than BCLC‐B stage patients. Due to the similar OS, patients with single HCCs >7 cm were assigned to the modified BCLC‐B stage. The C‐indexes of the modified BCLC classification for OS and DFS were higher compared to the original version. The findings were supported by the validation cohort.ConclusionsThe modified staging of BCLC‐A and ‐B, based on single tumour >7 cm and multiple tumours beyond up‐to‐seven criteria, could be more accurate to predict the prognosis of HCC patients. Liver resection could benefit patients with resectable multifocal HCCs beyond the Milan criteria.
Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis
Authors: Brown Jennifer R. , Moslehi Javid , Ewer Michael S. , O'Brien Susan M. , Ghia Paolo , Cymbalista Florence , Shanafelt Tait D. , Fraser Graeme , Rule Simon , Coutre Steven E. , Dilhuydy Marie‐Sarah , Cramer Paula , Jaeger Ulrich , Dreyling Martin , Byrd John C. , Treon Steven , Liu Emily Y. , Chang Stephen , Bista Amulya , Vempati Rama , Boornazian Lisa , Valentino Rudolph , Reddy Vijay , Mahler Michelle , Yang Huiying , Graef Thorsten , Burger Jan A. 
Published: December 2018

SummaryIbrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B‐cell malignancies. In ibrutinib clinical studies, low‐grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N = 1768), including 4 randomised controlled trials (RCTs). Rates of any‐grade bleeding were similar for single‐agent ibrutinib and ibrutinib combinations (39% and 40%). Low‐grade bleeding was more common in ibrutinib‐treated than comparator‐treated patients (35% and 15%), and early low‐grade bleeding was not associated with MH. The proportion of MH in RCTs was higher with ibrutinib than comparators (4.4% vs. 2.8%), but after adjusting for longer exposure with ibrutinib (median 13 months vs. 6 months), the incidence of MH was similar (3.2 vs. 3.1 per 1000 person‐months). MH led to treatment discontinuation in 1% of all ibrutinib‐treated patients. Use of anticoagulants and/or antiplatelets (AC/AP) during the study was common (~50% of patients) and had an increased exposure‐adjusted relative risk for MH in both the total ibrutinib‐treated population (1.9; 95% confidence interval, 1.2–3.0) and RCT comparator‐treated patients (2.4; 95% confidence interval, 1.0–5.6), indicating that ibrutinib may not alter the effect of AC/AP on the risk of MH in B‐cell malignancies.
EXPORT DIVERSIFICATION AND EXPORT PERFORMANCE BY DESTINATION COUNTRY
Authors: del Rosal Ignacio 
Published: December 2018

ABSTRACTThe main focus of this paper is the relationship between export diversification and export performance. The key difference with respect to the previous literature is that export diversification is measured and related to export volume by destination country. The approach is empirical and an aggregate export demand setting is adopted to test the significance and influence of export diversification, measured via the Herfindahl index, on export performance by destination country. The econometric estimation is performed using export data for Spain to its partner countries for the period 1999–2011. The main finding is the positive relationship between Spanish export concentration and export performance by destination market. This finding is shown to be robust to several econometric specifications.
Commentary: The complexity of family dynamics in child anxiety disorders — a commentary on Breinholst et al. (2018)
Authors: Domoney Jill , Nath Selina 
Published: December 2018

Breinholst et al. explore the impact of parental behaviour and parent–child attachment on child anxiety disorders. They show that maternal variables did not predict child anxiety, while insecure attachment to the father was a significant contributor. But can we really say it's down to dad? The importance of including fathers in both research and clinical work on child anxiety disorders certainly needs to be highlighted, but family dynamics are complex, and we need careful study designs which can capture some of this complexity in order to shed light on the most important targets for intervention.
Dental caries in South American Indigenous peoples: A systematic review
Authors: Soares Gustavo Hermes , Pereira Nayara Fernanda , Biazevic Maria Gabriela Haye , Braga Mariana Minatel , Michel‐Crosato Edgard 
Published: December 2018

AbstractObjectivesTo determine the severity of dental caries in South American Indigenous peoples.MethodsA systematic review was conducted regarding the severity of dental caries in South American Indigenous peoples using the following electronic databases: MEDLINE/PubMed, SCOPUS, SciELO, LILACS and grey literature up to March 2018. Literature search was conducted up to March 2018. No restrictions on language or year of publication were applied. Descriptive analysis and meta‐analysis of studies were performed to determine mean dmft/DMFT index (decayed, missing and filled teeth) and temporal trends for selected age brackets.ResultsThe search strategy retrieved 698 studies, of which 70 full‐text articles were assessed for eligibility and 28 were included in the qualitative analysis. Finally, 18 papers were included in the meta‐analysis. Publication year ranged from 1964 to 2018. Mean dmft for 5‐year‐old children was 5.73 (95% CI 4.67‐6.79), and mean DMFT for 12‐year‐olds was 3.14 (95% CI 1.88‐4.40). Estimated DMFT for 15‐19 years, 35‐44 years and 65‐74 years was 5.53 (95% CI 2.97‐8.09), 19.41 (95% CI 11.88‐26.93) and 28.19 (24.83‐31.55), respectively. DMFT was higher than that reported in general population surveys in Brazil, Chile, Uruguay and Venezuela for all age brackets with available data. Heterogeneity was observed in all age brackets, ranging from 79.7 to 99.7%.ConclusionDental caries remains a significant public health problem for South American Indigenous peoples. Prevention and treatment strategies that consider cultural specificities are needed.
Circ_0078767 suppresses non‐small‐cell lung cancer by protecting RASSF1A expression via sponging miR‐330‐3p
Authors: Chen Ting , Yang Zuozhang , Liu Chao , Wang Li , Yang Jun , Chen Long , Li Wenhui 
Published: December 2018

ObjectivesThis study was designed to investigate the role of circ_0078767/miR‐330‐3p/RASSF1A in non‐small‐cell lung cancer (NSCLC). Bioinformatic analysis was performed to screen for the differentially expressed genes in NSCLC tissues from adjacent lung tissues.Materials and MethodsqRT‐PCR was used to detect the RNA expression of genes in cells and tissues, and Western blot was conducted to determine the protein levels of RASSF1A in tissues and cells. A miRanda algorithm was used to predict the targeted relationship among RNAs. A dual‐luciferase reporter gene assay was conducted to verify the targeted relationship. Flow cytometry was performed to investigate the effects of circ_0078767/miR‐330‐3p/RASSF1A on cell cycle progression and apoptosis. A CCK‐8 assay was conducted to explore the effects of circ_0078767/miR‐330‐3p/RASSF1A on cell proliferation. A transwell invasion assay was completed to study the effects of circ_0078767/miR‐330‐3p/RASSF1A on cell invasion. Lastly, an in vivo assay was conducted to investigate the effects of circ_0078767/miR‐330‐3p/RASSF1A on tumour development.ResultsCirc_0078767 and RASSF1A were downregulated, while miR‐330‐3p was upregulated in NSCLC tissues than that in adjacent tissues. miR‐330‐3p had a binding relationship with circ_0078767 and RASSF1A. The overexpression of circ_0078767 and RASSF1A or the underexpression of miR‐330‐3p significantly suppressed NSCLC cell viability, cell cycle progression and invasion while also significantly promoting cell apoptosis. Additionally, these modulations significantly suppressed in vivo tumour growth.ConclusionsCirc_0078767 could suppress NSCLC progression by inhibiting miR‐330‐3p, which thereby increased RASSF1 levels.
PER‐SIMPER—A new tool for inferring community assembly processes from taxon occurrences
Authors: Gibert Corentin , Escarguel Gilles 
Published: December 2018

AbstractAimUnderstanding how ecosystem functioning and evolution shape taxonomic assemblages is a lively debate basically involving two major opposite views: the niche‐ and dispersal‐assembly hypotheses. Here, we introduce a new method allowing for the identification of the first‐order process of assembly underlying a set of taxonomic assemblages.MethodsBuilding on Clarke’s SIMPER (for “similarity percentage”) analysis of a taxon/locality occurrence data set, we develop a permutation‐based algorithm named PER‐SIMPER, allowing for the identification of the first‐order process—either niche‐ or dispersal‐assembly—that drives species distribution within two or more groups of assemblages. We demonstrate the reliability and robustness of the method through cellular automaton‐like simulations generating niche‐assembled and/or dispersal‐assembled species occurrence data sets. Sensitivity analysis further allows evaluation of its accuracy and robustness to sampling effort, including reduced numbers of sampled localities and/or species.Main conclusionsNiche‐ and/or dispersal‐assembled communities generate very different SIMPER profiles, which, in turn, allow for the accurate and consistent identification of the first‐order process of assembly operating within two or more groups of species assemblages through a threefold randomization procedure named PER‐SIMPER. The PER‐SIMPER method appears robust to varying sampling efforts that may affect the number of sampled localities and/or species, especially when one of the two processes of assembly dominates the other. The PER‐SIMPER analysis can be achieved on any empirical occurrence data set using a dedicated R function available as Supporting Information.