bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in liver transplantation for primary biliary cholangitis in Europe over the past three decades
Authors: Harms Maren H. , Janssen Quisette P. , Adam Rene , Duvoux Christophe , Mirza Darius , Hidalgo Ernest , Watson Christopher , Wigmore Stephen J. , Pinzani Massimo , Isoniemi Helena , Pratschke Johann , Zieniewicz Krzysztof , Klempnauer Jurgen L. , Bennet William , Karam Vincent , van Buuren Henk R. , Hansen Bettina E. , Metselaar Herold J. ,   the European Liver and Intestine Transplant Association (ELITA)
Published: December 2018

SummaryBackgroundThe importance of primary biliary cholangitis as an indication for liver transplantation has probably been influenced by the introduction of therapies, and changes in selection criteria and disease epidemiology.AimsTo assess the time trends in liver transplantation for primary biliary cholangitis and to evaluate the characteristics of the patient population during the past three decades.MethodsPatients undergoing liver transplantation from 1986 to 2015 in centres reporting to the European Liver Transplantation Registry were included. We excluded combined organ transplantations and patients <18 years. Trends were assessed using linear regression models.ResultsWe included 112 874 patients, of whom 6029 (5.3%) had primary biliary cholangitis. After an initial increase in the first decade, the annual number of liver transplantation for primary biliary cholangitis remained stable at around 200. The proportion of liver transplantations for primary biliary cholangitis decreased from 20% in 1986 to 4% in 2015 (P < 0.001). Primary biliary cholangitis was the only indication showing a consistent proportional decrease throughout all decades. From the first to the third decade, the age at liver transplantation increased from 54 (IQR 47‐59) to 56 years (IQR 48‐62) and the proportion of males increased from 11% to 15% (both P < 0.001).ConclusionsWe have found a proportional decrease in primary biliary cholangitis as indication for liver transplantation. However, despite treatment with ursodeoxycholic acid and improved disease awareness, the absolute annual number of liver transplantations has stabilised.
Nordic symposium on “toxicology and pharmacology without animal experiments—Will it be possible in the next 10 years?”
Authors: Knudsen Lisbeth E. , Smith Adrian , Törnqvist Elin , Forsby Anna , Tähti Hanna 
Published: December 2018

AbstractToxicological and pharmacological information from human cells and tissues provides knowledge readily applicable to human safety assessment and to the efficacy assessment of pharmaceuticals. The 3R principle in animal studies includes the use of human material in the R of Replacement. The Reduction and Refinement Rs are related to animal use. Knowledge of the 3Rs and successful 3R methods are a prerequisite for the Reduction of animal experiments in the future. More collaboration among researchers using experimental animals and those working in vitro is necessary with mutual respect. The OECD Guidelines for the Testing of Chemicals have included the animal‐free part of the 3Rs in guidances for the development and reporting of Adverse Outcome Pathways (AOPs), which is to be part of the Integrated Approaches to Testing and Assessment (IATA). The 3R centres established to help fulfil the Directive 2010/63/EU play an important role to promote the 3Rs and in the development of animal‐free toxicology. Research centres in each Nordic country are founded upon solid research activities in cell and organ toxicity, including major EU programmes to promote 3Rs and implementation of good practices and methods broadly in all stakeholders of industry, regulators and academia. In the light of this, the Nordic Symposium on Toxicology and Pharmacology without Animal Experiments addressed more adopted/modified test guidelines or new test guidelines for new end‐points, or hazard challenges, new in vitro 3D models, speeding up transfer of knowledge from research to regulation to understand AOP and towards IATA.
EMPIRICAL PERFORMANCE OF GARCH MODELS WITH HEAVY‐TAILED INNOVATIONS
Authors: Guo Zi‐Yi 
Published: December 2018

ABSTRACTWe introduce a new type of heavy‐tailed distribution, the normal reciprocal inverse Gaussian distribution (NRIG), to the GARCH and Glosten‐Jagannathan‐Runkle (1993) GARCH models, and compare its empirical performance with two other popular types of heavy‐tailed distribution, the Student's t distribution and the normal inverse Gaussian distribution (NIG), using a variety of asset return series. Our results illustrate that there is no overwhelmingly dominant distribution in fitting the data under the GARCH framework, although the NRIG distribution performs slightly better than the other two types of distribution. For market indexes series, it is important to introduce both GJR‐terms and the NRIG distribution to improve the models’ performance, but it is ambiguous for individual stock prices series. Our results also show the GJR‐GARCH NRIG model has practical advantages in quantitative risk management. Finally, the convergence of numerical solutions in maximum‐likelihood estimation of GARCH and GJR‐GARCH models with the three types of heavy‐tailed distribution is investigated.
Identifying de‐NEDDylation inhibitors: Virtual high‐throughput screens targeting SENP8
Authors: Chen Jonathan J. , Schmucker Lyndsey N. , Visco Donald P. 
Published: December 2018

AbstractProtein modification can have far‐reaching effects. NEDDylation, a protein modification process with the protein NEDD8, stabilizes and modifies how the targeted protein interacts with other proteins. Its role in system regulation makes it a prime therapeutic target, and virtual high‐throughput screening has already identified new NEDD8 inhibitors. SENP8 matures the NEDD8 proenzyme into the active form and regulates NEDDylation by removing NEDD8 from over‐NEDDylated proteins. In this work, SENP8 inhibitor candidates were identified in two rounds of virtual high‐throughput screening. Of the ten candidates identified in the first round of screening, four were active in validation experiments to yield an experimental hit rate of 40%. Of the five candidates identified in the second round of screening, one was active in validation experiments to yield an experimental hit rate of 20%. Results indicate virtual high‐throughput screening improved hit rates over traditional high‐throughput screening. The SENP8 inhibitor candidates can be used to interrogate the NEDDylation regulation mechanism.
Prevalence of subtypes of multiple sclerosis and the most common clinical symptoms in Iranian patients: A meta‐analysis
Authors: Kheradmand Motahareh , Afshari Mahdi , Nasehi Mohammad M. , Aghaei Iraj , Shabani Mohammad , Farshidi Fereshteh , Moosazadeh Mahmood 
Published: December 2018

AbstractMultiple sclerosis (MS) is an inflammatory disease defined by damage to the myelin sheaths of neurons. MS is classified into different subtypes including relapsing–remitting MS, secondary progressive MS and primary progressive MS. The present study aimed to estimate the prevalence of different forms and clinical symptoms of MS among Iranian people using meta‐analysis. We searched all available databanks, such as SID, Magiran, PubMed, Google scholar, Scopus and Science, directly to identify relevant evidence. All findings were reviewed and eligible articles were selected. The standard error of prevalence was calculated based on binomial distribution formula. The heterogeneity between the results of primary studies was detected using Cochrane (Q) and I2 indices. The primary results were combined according to a random effects model. The effect of related factors in heterogeneity was investigated using a meta‐regression model. During the primary search, 17 352 articles were identified. After limiting the search strategy, and excluding duplicates and irrelevant papers, finally, 21 primary studies were entered into the final meta‐analysis. The total prevalences of relapsing–remitting MS, primary progressive MS and secondary progressive MS types among Iranian people were estimated to be 69.7% (95% CI 63.7–75.8), 7.01% (95% CI 4.05–9.96) and 17.8% (95% CI 11.7–23.9) respectively. In addition, prevalences of fatigue and motor dysfunction were estimated to be 71.1% (95% CI 60.9–81.3) and 56.3% (95% CI 27.9–84.6), respectively. Our meta‐analysis showed that relapsing–remitting MS is the most common type of MS, and fatigue is the most common clinical manifestation in patients. Motor dysfunction and balance disorder are the other common problems in patients.
Bagged ensembles with tunable parameters
Authors: Pham Hieu , Olafsson Sigurdur 
Published: December 2018

AbstractEnsemble learning is a popular classification method where many individual simple learners contribute to a final prediction. Constructing an ensemble of learners has been shown to often improve prediction accuracy over a single learner. Bagging and boosting are the most common ensemble methods, each with distinct advantages. While boosting methods are typically very tunable with numerous parameters, to date, the type of flexibility this allows has been missing for general bagging ensembles. In this paper, we propose a new tunable weighted bagged ensemble methodology, resulting in a very flexible method for classification. We explore the impact tunable weighting has on the votes of each learner in an ensemble and compare the results with pure bagging and the best known bagged ensemble method, namely, the random forest.
Rise and fall of forest loss and industrial plantations in Borneo (2000–2017)
Authors: Gaveau David L.A. , Locatelli Bruno , Salim Mohammad A. , Yaen Husna , Pacheco Pablo , Sheil Douglas 
Published: December 2018

AbstractThe links between plantation expansion and deforestation in Borneo are debated. We used satellite imagery to map annual loss of old‐growth forests, expansion of industrial plantations (oil palm and pulpwood), and their overlap in Borneo from 2001 to 2017. In 17 years, forest area declined by 14% (6.04 Mha), including 3.06 Mha of forest ultimately converted into industrial plantations. Plantations expanded by 170% (6.20 Mha: 88% oil palm; 12% pulpwood). Most forests converted to plantations were cleared and planted in the same year (92%; 2.83 Mha). Annual forest loss generally increased before peaking in 2016 (0.61 Mha) and declining sharply in 2017 (0.25 Mha). After peaks in 2009 and 2012, plantation expansion and associated forest conversion have been declining in Indonesia and Malaysia. Annual plantation expansion is positively correlated with annual forest loss in both countries. The correlation vanishes when we consider plantation expansion versus forests that are cleared but not converted to plantations. The price of crude palm oil is positively correlated with plantation expansion in the following year in Indonesian (not Malaysian) Borneo. Low palm oil prices, wet conditions, and improved fire prevention all likely contributed to reduced 2017 deforestation. Oversight of company conduct requires transparent concession ownership.
Association between fragmented QRS complexes and left ventricular dysfunction in healthy smokers
Authors: Bayramoğlu Adil , Taşolar Hakan , Bektaş Osman , Kaya Ahmet , Günaydın Zeki Yüksel 
Published: December 2018

ObjectiveSmoking is a known risk factor for cardiovascular diseases and may cause myocardial damage independently of coronary artery disease. Fragmented QRS (fQRS) is an important marker of myocardial fibrosis, while speckle‐tracking echocardiography is a method used to show subclinical left ventricle dysfunction.MethodsOur study included 230 healthy individuals aged 18–40 years. The patients included were separated into two groups: those smokers (n = 130) and non‐smokers (n = 100). After that healthy smokers group were divided into two groups: those with fQRS (n = 24) and those without (n = 106). In both groups, the arithmetic mean of three images was used to obtain the left ventricle global longitudinal strain (LV‐GLS). The E/SRe ratio was also calculated and analyzed.ResultsThere were significant differences between the smokers and non‐smokers in terms of, E/SRe (55.7 ± 17.9 vs 50.3 ± 14.8; P = 0.015), LV‐GLS (23.1 ± 1.9 vs 24.0 ± 1.7; P = 0.001), and fQRS (18.5% vs 6%; P = 0.005). As a result of subgroup analysis, pack‐year history was higher in the fQRS positive group (16.7 ± 3.7 vs 11.2 ± 3.7, P < 0.001). While a negative correlation was observed between pack‐year history and LV‐GLS (r = –0.678, P < 0.001), there was a positive correlation between pack‐year history and E/SRe (r = 0.730, P < 0.001).ConclusionIn conclusion, our study demonstrated that fQRS is a parameter that can be used to determine left ventricle subclinical systolic and diastolic dysfunction in smokers, and that left ventricle dysfunction is related to the duration and intensity of smoking.
The combination of apolipoprotein E4, age and Alzheimer's Disease Assessment Scale – Cognitive Subscale improves the prediction of amyloid positron emission tomography status in clinically diagnosed mild cognitive impairment
Authors: Ba M. , Ng K. P. , Gao X. , Kong M. , Guan L. , Yu L. ,   the Alzheimer's Disease Neuroimaging Initiative
Published: December 2018

Background and purposeRandomized clinical trials involving anti‐amyloid interventions focus on the early stages of Alzheimer's disease (AD) with proven amyloid pathology, using amyloid positron emission tomography (amyloid‐PET) imaging or cerebrospinal fluid analysis. However, these investigations are either expensive or invasive and are not readily available in resource‐limited centres. Hence, the identification of cost‐effective clinical alternatives to amyloid‐PET is highly desirable. This study aimed to investigate the accuracy of combined clinical markers in predicting amyloid‐PET status in mild cognitive impairment (MCI) individuals.MethodsIn all, 406 MCI participants from the Alzheimer's Disease Neuroimaging Initiative database were dichotomized into amyloid‐PET(+) and amyloid‐PET(−) using a cut‐off of >1.11. The accuracies of single clinical markers [apolipoprotein E4 (ApoE4) genotype, demographics, cognitive measures and cerebrospinal fluid analysis] in predicting amyloid‐PET status were evaluated using receiver operating characteristic curve analysis. A logistic regression model was then used to determine the optimal model with combined clinical markers to predict amyloid‐PET status.ResultsCerebrospinal fluid amyloid‐β (Aβ) showed the best predictive accuracy of amyloid‐PET status [area under the curve (AUC) = 0.927]. Whilst ApoE4 genotype (AUC = 0.737) and Alzheimer's Disease Assessment Scale – Cognitive Subscale (ADAS‐Cog) 13 (AUC = 0.724) independently discriminated amyloid‐PET(+) and amyloid‐PET(−) MCI individuals, the combination of clinical markers (ApoE4 carrier, age >60 years and ADAS‐Cog 13 > 13.5) improved the predictive accuracy of amyloid‐PET status (AUC = 0.827, P < 0.001).ConclusionsCerebrospinal fluid Aβ, which is an invasive procedure, is most accurate in predicting amyloid‐PET status in MCI individuals. The combination of ApoE4, age and ADAS‐Cog 13 also accurately predicts amyloid‐PET status. As this combination of clinical markers is cheap, non‐invasive and readily available, it offers an attractive surrogate assessment for amyloid status amongst MCI individuals in resource‐limited settings.
Association between plasma α‐aminobutyric acid and depressive symptoms in older community‐dwelling adults in Japan
Authors: Adachi Yusuke , Toyoshima Kenji , Nishimoto Rumi , Ueno Satoko , Tanaka Takayuki , Imaizumi Akira , Arashida Naoko , Nakamura Marie , Abe Yasuko , Hakamada Tomomi , Kaneko Eiji , Takahashi Soichiro , Jinzu Hiroko , Shimokado Kentaro 
Published: December 2018

AimTo examine the association between depressive symptoms and plasma amino acid related metaboli in older adults.MethodsA total of 152 older adults aged ≥65 years, residing in Niigata, Japan, were used for analysis. We evaluated depressive symptoms using the Geriatric Depression Scale‐15, which has been validated in older community‐dwelling individuals, and used a cut off score of ≥5 to classify participants as having depressive symptoms. We used high‐performance liquid chromatography‐electrospray ionization mass spectrometry to measure the concentrations of plasma amino acid‐related metabolites, and carried out logistic regression analysis to assess the association between depressive symptoms and plasma amino acid‐related metabolites.ResultsOf the 119 older adults (mean age 76.3 years) included in the analysis, 22 were classified as having depressive symptoms (depressive group). There were no significant differences in physical and cognitive impairments between participants in the depressive and non‐depressive groups. The plasma α‐aminobutyric acid (AABA) level was significantly lower in the depressive group than in the non‐depressive group (P < 0.001). Logistic regression analysis showed the best‐fit model, which included AABA, leucine, threonine, hydroxyl proline and histidine levels (area under the receiver operating characteristic curve 0.8346; 95% confidence interval 0.7365–0.9326). In particular, the plasma AABA level was strongly associated with depressive symptoms.ConclusionsPlasma AABA level is significantly associated with depression symptoms in older community‐dwelling adults in Japan. Thus, plasma AABA might serve as a potential marker of depression in older adults aged ≥65 years. Geriatr Gerontol Int 2019; 19: 254–258.
Chemoprevention by means of soy proteins and peptides – current status and future approaches: a review
Authors: Chen Sheng‐I , Hsieh Chia‐Chien 
Published: December 2018

SummaryEpidemiological studies have shown that soy consumption is associated with lower incidence of various diseases, such as cancer. Over the past decades, soy proteins and derived peptides have been considered as potential preventive agents against the initiation, promotion and progression of cancer. Additionally, soybeans provide essential nutrients and abundant peptides and proteins with multiple bioactivities. Here, we specifically emphasise the chemoprevention property of several soy proteins/peptides, such as lectins, lunasin and protease inhibitors. Moreover, their anti‐inflammatory and antioxidant properties, which have been demonstrated to be associated with chemopreventive properties, are addressed here. Furthermore, computational methods applied in this field are reviewed. Researchers navigate a large volume of data to understand the interactions among the genome, cellular molecules, dietary interventions, medical treatments and diseases. Numerous powerful tools have been recommended for designing an optimal strategy for future anti‐cancer treatments with precise diagnosis and individualised approaches.
Characterization of a novel MICB variant in an individual from the Chinese Uyghur population, MICB*005:09, by cloning and sequencing
Authors: Tursun Mikrban , Wang ZhenFang , Guo WenTao , Hasim Ayshamgul , Tian Wei 
Published: December 2018

SummaryA new allelic variant in MICB*005 lineage, MICB*005:09, has been identified in a male Uyghur individual recruited from Xinjiang Uyghur Autonomous Region, China by PCR‐sequence‐based typing (Sanger sequencing) and confirmed by cloning and sequencing. Aligned with MICB*005:03, this new allelic variant shows a synonymous T substitution at nucleotide position 8 in exon 2, corresponding to codon 3 (CAC→CAT) of the mature MICB mRNA transcript.
Determinants of caregiver burden of patients with haemorrhagic stroke in China
Authors: Zhu Wei , Jiang Yan 
Published: December 2018

AbstractAimThe aim of this study was to assess the caregiver burden over time of patients with haemorrhagic stroke and the determinants of this.BackgroundIdentification of the predictors for caregiver burden can be used to improve the outcomes of stroke survivors and caregivers. Few studies focus on the caregiver burden of patients with haemorrhagic stroke and how this changes over time.DesignThis was a prospective longitudinal study.MethodsA convenience sample of 202 stroke survivor/caregiver pairs were recruited in the neurosurgery unit from March 2015 to March 2016. The participants were assessed at three different times by face to face or telephone interview. Caregiver burden was assessed using the Bakas Caregiver Outcomes Scale. Sociodemographic data and other characteristics of the pairs were also collected. Multiple linear regression was performed to identify the determinants.ResultsCaregiver burden decreased from T1 to T3 significantly. The physical function, depression of stroke survivors, and self‐rated burden of caregivers were the most important determinants for overall caregiver burden. The factors identified explained 41.6% to 67.4% of overall burden.ConclusionCaregiver burden decreased over time, affected by factors from patients and caregivers. More professional caregivers are needed to support informal carers.
Efficacy of novel β3‐adrenoreceptor agonist vibegron on nocturia in patients with overactive bladder: A post‐hoc analysis of a randomized, double‐blind, placebo‐controlled phase 3 study
Authors: Yoshida Masaki , Takeda Masayuki , Gotoh Momokazu , Yokoyama Osamu , Kakizaki Hidehiro , Takahashi Satoru , Masumori Naoya , Nagai Shinji , Hashimoto Keita , Minemura Kazuyoshi 
Published: December 2018

ObjectivesTo investigate the efficacy of vibegron on nocturia in patients with overactive bladder.MethodsAmong the Japanese overactive bladder patients enrolled in the placebo‐controlled, multicenter, randomized, double‐blind phase 3 study of vibegron, a total of 669 patients with nocturia (≥1 nocturnal void) were included. Changes from baseline in micturition parameters were compared for vibegron treatment (50 and 100 mg/day) versus placebo. Correlations of hours of undisturbed sleep with the frequency of nocturnal voiding and the volume of the first nocturnal voiding were examined. Demographics and baseline characteristics contributing to reduction in the frequency of nocturnal voiding were also analyzed.ResultsAt week 12, the frequency of nocturnal voiding was reduced from baseline by 0.74 and 0.78, respectively, for the vibegron 50 and 100 mg groups; the reductions were significant when compared with the placebo group (P < 0.05 and P < 0.001, respectively). The mean volume of nocturnal voids and the volume of the first nocturnal voiding were significantly greater in the vibegron groups than in the placebo group. The vibegron groups showed significant correlations of hours of undisturbed sleep with the changes in the frequency of nocturnal voiding and in the volume of the first nocturnal voiding. Vibegron treatment, no previous treatment with anticholinergics, ≥12 voids per day and hours of undisturbed sleep <180 min significantly contributed to a reduction in the frequency of nocturnal voiding.ConclusionsVibegron is a useful therapeutic option for improving nocturia in patients with overactive bladder.