bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐inflammatory agents in the treatment of bipolar depression: a systematic review and meta‐analysis
Authors: Rosenblat Joshua D , Kakar Ron , Berk Michael , Kessing Lars V , Vinberg Maj , Baune Bernhard T , Mansur Rodrigo B , Brietzke Elisa , Goldstein Benjamin I , McIntyre Roger S 
Published: March 2016

ObjectiveInflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti‐inflammatory agents in the treatment of bipolar depression.MethodsCompleted and ongoing clinical trials of anti‐inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti‐inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone.ResultsTen RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti‐inflammatory drugs (n = 53), omega‐3 polyunsaturated fatty acids (n = 140), N‐acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti‐inflammatory agents on depressive symptoms was −0.40 (95% confidence interval −0.14 to −0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment‐emergent adverse events were reported.ConclusionsOverall, a moderate antidepressant effect was observed for adjunctive anti‐inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.
History of psychosis and previous episodes as potential explanatory factors for neurocognitive impairment in first‐treatment bipolar I disorder
Authors: Demmo Christine , Lagerberg Trine Vik , Aminoff Sofie R , Hellvin Tone , Kvitland Levi R , Simonsen Carmen , Andreassen Ole A , Melle Ingrid , Ueland Torill 
Published: March 2016

ObjectivesExplanatory factors for the observed neurocognitive impairment in early‐stage bipolar I disorder (BD‐I) have received little attention. The current study investigated neurocognitive functioning in first‐treatment (FT) BD‐I compared to FT schizophrenia (SCZ), and healthy controls (HCs), and the effect of history of psychosis and previous episodes in the two clinical groups.MethodsA total of 202 FT patients with BD‐I (n = 101) and SCZ spectrum disorder (n = 101), in addition to HCs (n = 101), were included. A comprehensive neurocognitive test battery was used to assess verbal learning and memory, executive functioning, processing speed, and attention and working memory. Neurocognitive functioning and the effect of history of psychosis and number of previous episodes were analyzed using separate multivariate analyses of variance and correlation analysis.ResultsFT patients with BD‐I performed intermediately between FT SCZ spectrum patients and HCs on all measures. Compared to HCs, FT BD‐I showed impaired functioning across all neurocognitive domains. No differences in neurocognitive functioning were observed in psychotic versus nonpsychotic FT patients with BD‐I. With the exception of an association between number of manic episodes and two measures of executive function in FT BD‐I, no associations were found between number of episodes and neurocognitive performance.ConclusionsNeurocognitive impairments were present in FT BD‐I, and were not explained by history of psychosis or number of previous psychotic or depressive episodes. There were indications that executive function could be associated with number of previous manic episodes.
Biased and Unbiased Estimation in Longitudinal Studies with Informative Visit Processes
Authors: McCulloch Charles E. , Neuhaus John M. , Olin Rebecca L. 
Published: March 2016

Summary
The availability of data in longitudinal studies is often driven by features of the characteristics being studied. For example, clinical databases are increasingly being used for research to address longitudinal questions. Because visit times in such data are often driven by patient characteristics that may be related to the outcome being studied, the danger is that this will result in biased estimation compared to designed, prospective studies. We study longitudinal data that follow a generalized linear mixed model and use a log link to relate an informative visit process to random effects in the mixed model. This device allows us to elucidate which parameters are biased under the informative visit process and to what degree. We show that the informative visit process can badly bias estimators of parameters of covariates associated with the random effects, while allowing consistent estimation of other parameters.
Label-Noise Resistant Logistic Regression for Functional Data Classification with an Application to Alzheimer's Disease Study
Authors: Lee Seokho , Shin Hyejin , Lee Sang Han 
Published: March 2016

SummaryAlzheimer's disease (AD) is usually diagnosed by clinicians through cognitive and functional performance test with a potential risk of misdiagnosis. Since the progression of AD is known to cause structural changes in the corpus callosum (CC), the CC thickness can be used as a functional covariate in AD classification problem for a diagnosis. However, misclassified class labels negatively impact the classification performance. Motivated by AD–CC association studies, we propose a logistic regression for functional data classification that is robust to misdiagnosis or label noise. Specifically, our logistic regression model is constructed by adopting individual intercepts to functional logistic regression model. This approach enables to indicate which observations are possibly mislabeled and also lead to a robust and efficient classifier. An effective algorithm using MM algorithm provides simple closed-form update formulas. We test our method using synthetic datasets to demonstrate its superiority over an existing method, and apply it to differentiating patients with AD from healthy normals based on CC from MRI.
Circular Piecewise Regression with Applications to Cell-Cycle Data
Authors: Rueda Cristina , Fernández Miguel A. , Barragán Sandra , Mardia Kanti V. , Peddada Shyamal D. 
Published: March 2016

Summary
Applications of circular regression models appear in many different fields such as evolutionary psychology, motor behavior, biology, and, in particular, in the analysis of gene expressions in oscillatory systems. Specifically, for the gene expression problem, a researcher may be interested in modeling the relationship among the phases of cell-cycle genes in two species with differing periods. This challenging problem reduces to the problem of constructing a piecewise circular regression model and, with this objective in mind, we propose a flexible circular regression model which allows different parameter values depending on sectors along the circle. We give a detailed interpretation of the parameters in the model and provide maximum likelihood estimators. We also provide a model selection procedure based on the concept of generalized degrees of freedom. The model is then applied to the analysis of two different cell-cycle data sets and through these examples we highlight the power of our new methodology.
Pedagogy first: Realising technology enhanced learning by focusing on teaching practice
Authors: Glover Ian , Hepplestone Stuart , Parkin Helen J. , Rodger Helen , Irwin Brian 
Published: March 2016

AbstractThis paper explores a “pedagogy first” approach to technology enhanced learning developed by Sheffield Hallam University (SHU) as a method to encourage use of, and experimentation with, technology within teaching practice and to promote the mainstreaming of innovative practice. Through a consultative approach where all staff members were invited to contribute, SHU has created a Teaching Approaches Menu that reflects practice at the institution and can be used to explore teaching practice and appropriate supporting technology either by individuals or as part of a facilitated discussion. Background to the project is provided, along with the design philosophy and approach, including a brief review of other frameworks. The Teaching Approaches Menu is introduced, its development outlined, and some initial feedback is presented.
Who or what contributes to student satisfaction in different blended learning modalities?
Authors: Diep Anh‐Nguyet , Zhu Chang , Struyven Katrien , Blieck Yves 
Published: March 2016

AbstractDifferent blended learning (BL) modalities and the interaction effect between human and technological factors on student satisfaction need adequately researched to shed more light on successful BL implementation. The objective of the present article is three‐fold: (1) to present a model to predict student satisfaction with BL programs, (2) to examine the interaction effect between the instructor expertise and the learning management system (LMS) on student satisfaction in different BL modes, and (3) to investigate if different modes of BL will exert an influence on students’ perceived achievement goals and satisfaction, their evaluation of the instructors, and the LMS quality. Results show that the instructor expertise, students’ perceived task value and achievement goals are the most influential factors, followed by the LMS quality, instructor support, and students’ general self‐efficacy. Contradictory to previous studies, the LMS quality only has an indirect effect on student satisfaction, via perceived achievement goals. In different BL conditions, the LMS quality has significantly different effect on student satisfaction, when interacting with the instructor expertise. The two modalities of BL programs also yield differences in students’ perceived achievement goals and their demand for the LMS's functionality and design, hence crucial implications for pedagogical practices and institutional policy addressed.
PERCEIVED INTENTIONALITY IN 2 × 2 EXPERIMENTAL GAMES
Authors: Chuah Swee‐Hoon , Hoffmann Robert , Larner Jeremy 
Published: March 2016

ABSTRACTWe test experimentally whether decisions in 2 × 2 games with mixed equilibria depend on the co‐player being nature or a human agent. Controlling for social preferences, we find differences in decisions in the chicken game and battle of the sexes but not for stag hunt and matching pennies. We attribute these to subjects' perception of the other's intentionality and disapproval avoidance in particular.
Ozanimod (RPC1063) is a potent sphingosine‐1‐phosphate receptor‐1 (S1P1) and receptor‐5 (S1P5) agonist with autoimmune disease‐modifying activity
Authors: Scott F L , Clemons B , Brooks J , Brahmachary E , Powell R , Dedman H , Desale H G , Timony G A , Martinborough E , Rosen H , Roberts E , Boehm M F , Peach R J 
Published: March 2016

Background and PurposeSphingosine1‐phosphate (S1P) receptors mediate multiple events including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Stimulation of S1P1 receptors sequesters lymphocyte subsets in peripheral lymphoid organs, preventing their trafficking to inflamed tissue sites, modulating immunity. Targeting S1P receptors for treating autoimmune disease has been established in clinical studies with the non‐selective S1P modulator, FTY720 (fingolimod, Gilenya™). The purpose of this study was to assess RPC1063 for its therapeutic utility in autoimmune diseases.Experimental ApproachThe specificity and potency of RPC1063 (ozanimod) was evaluated for all five S1P receptors, and its effect on cell surface S1P1 receptor expression, was characterized in vitro. The oral pharmacokinetic (PK) parameters and pharmacodynamic effects were established in rodents, and its activity in three models of autoimmune disease (experimental autoimmune encephalitis, 2,4,6‐trinitrobenzenesulfonic acid colitis and CD4+CD45RBhi T cell adoptive transfer colitis) was assessed.Key ResultsRPC1063 was specific for S1P1 and S1P5 receptors, induced S1P1 receptor internalization and induced a reversible reduction in circulating B and CCR7+ T lymphocytes in vivo. RPC1063 showed high oral bioavailability and volume of distribution, and a circulatory half‐life that supports once daily dosing. Oral RPC1063 reduced inflammation and disease parameters in all three autoimmune disease models.Conclusions and ImplicationsS1P receptor selectivity, favourable PK properties and efficacy in three distinct disease models supports the clinical development of RPC1063 for the treatment of relapsing multiple sclerosis and inflammatory bowel disease, differentiates RPC1063 from other S1P receptor agonists, and could result in improved safety outcomes in the clinic.
Identification of a selective glucocorticoid receptor modulator that prevents both diet‐induced obesity and inflammation
Authors: van den Heuvel José K , Boon Mariëtte R , van Hengel Ingmar , Peschier‐van der Put Emma , van Beek Lianne , van Harmelen Vanessa , van Dijk Ko Willems , Pereira Alberto M , Hunt Hazel , Belanoff Joseph K , Rensen Patrick C N , Meijer Onno C 
Published: March 2016

Background and PurposeHigh‐fat diet consumption results in obesity and chronic low‐grade inflammation in adipose tissue. Whereas glucocorticoid receptor (GR) antagonism reduces diet‐induced obesity, GR agonism reduces inflammation, the combination of which would be desired in a strategy to combat the metabolic syndrome. The purpose of this study was to assess the beneficial effects of the selective GR modulator C108297 on both diet‐induced weight gain and inflammation in mice and to elucidate underlying mechanisms.Experimental ApproachTen‐week‐old C57Bl/6 J mice were fed a high‐fat diet for 4 weeks while being treated with the selective GR modulator C108297, a full GR antagonist (RU486/mifepristone) or vehicle.Key ResultsC108297 and, to a lesser extent, mifepristone reduced body weight gain and fat mass. C108297 decreased food and fructose intake and increased lipolysis in white adipose tissue (WAT) and free fatty acid levels in plasma, resulting in decreased fat cell size and increased fatty acid oxidation. Furthermore, C108297 reduced macrophage infiltration and pro‐inflammatory cytokine expression in WAT, as well as in vitro LPS‐stimulated TNF‐α secretion in macrophage RAW 264.7 cells. However, mifepristone also increased energy expenditure, as measured by fully automatic metabolic cages, and enhanced expression of thermogenic markers in energy‐combusting brown adipose tissue (BAT) but did not affect inflammation.Conclusions and ImplicationsC108297 attenuates obesity by reducing caloric intake and increasing lipolysis and fat oxidation, and in addition attenuates inflammation. These data suggest that selective GR modulation may be a viable strategy for the reduction of diet‐induced obesity and inflammation.
A novel protein tyrosine phosphatase 1B inhibitor with therapeutic potential for insulin resistance
Authors: Zhang Xiaolin , Tian Jinying , Li Juan , Huang Liwei , Wu Song , Liang Wei , Zhong Liangwei , Ye Jianping , Ye Fei 
Published: March 2016

Background and PurposeInsulin‐sensitizing drugs are currently limited, and identifying new candidates is a challenge. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling, and its inhibition is anticipated to improve insulin resistance. Here, the pharmacological properties of CX08005, a novel PTP1B inhibitor, were investigated.Experimental ApproachRecombinant hPTP1B protein was used to study enzyme activity and mode of inhibition. Docking simulation explored the interactions between CX08005 and PTP1B. Insulin sensitivity was evaluated by glucose tolerance test (GTT) in diet‐induced obese (DIO) and KKAy mice; glucose‐stimulated insulin secretion (GSIS), homeostasis model assessment of insulin resistance index (HOMA‐IR) and whole‐body insulin sensitivity (ISWB) were also determined. A hyperinsulinaemic–euglycaemic clamp was performed to evaluate insulin‐stimulated glucose disposal in both whole‐body and insulin‐sensitive tissues. Furthermore, CX08005's effects on muscle, fat and liver cells were determined in vitro.Key ResultsCX08005 competitively inhibited PTP1B by binding to the catalytic P‐loop through hydrogen bonds. In DIO mice, CX08005 ameliorated glucose intolerance dose‐dependently (50–200 mg·kg−1·day−1) and decreased the HOMA‐IR. In KKAy mice, CX08005 (50 mg·kg−1·day−1) improved glucose intolerance, GSIS, ISWB and hyperglycaemia. CX08005 also enhanced insulin‐stimulated glucose disposal, increased glucose infusion rate and glucose uptake in muscle and fat in DIO mice (hyperinsulinaemic–euglycaemic clamp test). CX08005 enhanced insulin‐induced glucose uptake in 3T3‐L1 adipocytes and C2C12 myotubes, and increased phosphorylation of IRβ/IRS1 and downstream molecules in hepatocytes in a dose‐ and insulin‐dependent manner respectively.Conclusions and ImplicationsOur results strongly suggest that CX08005 directly enhances insulin action in vitro and in vivo through competitive inhibition of PTP1B.
Tectonic evolution of an intraplate basin: the Lower Tagus Cenozoic Basin, Portugal
Authors: Carvalho João , Pinto Carlos , Dias Ruben , Rabeh Taha , Torres Luis , Borges José , Torres Ricardo , Duarte Henrique 
Published: March 2016

AbstractThis article focuses on the reinterpretation of well, seismic reflection, magnetic, gravimetric, surface wave and geological surface data, together with the acquisition of seismic noise data to study the Lower Tagus Cenozoic Basin tectono‐sedimentary evolution. For the first time, the structure of the base of the basin in its distal and intermediate sectors is unravelled, which was previously only known in the areas covered by seismic reflection data (distal and small part of intermediate sectors). A complex geometry was found, with three subbasins delimited by NNE‐SSW faults and separated by WNW‐ESE to NW‐SE oriented horsts. In the area covered by seismic reflection data, four horizons were studied: top of the Upper Miocene, Lower to Middle Miocene top, the top of the Palaeogene and the base of Cenozoic. Seismic data show that the major filling of the basin occurred during Upper Miocene. The fault pattern affecting Neogene and Palaeogene units derived here points to that of a polyphasic basin. In the Palaeogene, the Vila Franca de Xira (VFX) and a NNE‐SSW trending previously unknown structure (ABC fault zone) probably acted as the major strike‐slip fault zones of the releasing bend of a pull‐apart basin, which produced a WNW‐ESE to NW‐SE fault system with transtensional kinematic. During the Neogene, as the stress regime rotated anticlockwise to the present NW‐SE to WNW‐ESE orientation, the VFX and Azambuja fault zones acted as the major transpressive fault zones and Mesozoic rocks overthrusted Miocene sediments. The reactivation of WNW‐ESE to NW‐SE fault systems with a dextral strike‐slip component generated a series of horsts and grabens and the partitioning of the basin into several subbasins. Therefore, we propose a polyphasic model for the area, with the formation of an early pull‐apart basin during the Palaeogene caused by an Iberia–Eurasia plates collision that later evolved into an incipient foreland basin along the Neogene due to a NW‐SE to WNE‐ESE oriented Iberia–Nubia convergence. This convergence is producing uplift in the area since the Quaternary except for the Tagus estuary subbasin around the VFX fault, where subsidence is observed. This may be due to the locking or the development of a larger component of strike‐slip movement of the NNE‐SSW to N‐S thrust fault system with the exception of the VFX fault, which is more favourably oriented to the maximum compressive stress.
Replanting reduces frog diversity in oil palm
Authors: Kurz David J. , Turner Edgar C. , Aryawan Agung A. , Barkley Hannah C. , Caliman Jean‐Pierre , Konopik Oliver , Ps. Sudharto , Foster William A. 
Published: March 2016

AbstractA growing body of literature has demonstrated significant biodiversity losses for many taxa when forest is converted to oil palm. However, no studies have directly investigated changes to biodiversity throughout the oil palm life cycle, in which oil palm matures for 25–30 yr before replanting. This process leads to major changes in the oil palm landscape that likely influence species assemblages and ecosystem function. We compare frog assemblages between mature (21–27‐yr old) and recently replanted (1–2‐yr old) oil palm in Sumatra, Indonesia. Across eighteen 2.25‐ha oil palm plots, we found 719 frogs from 14 species. Frog richness was 31 percent lower in replanted oil palm (nine species) than mature oil palm (13 species). Total frog abundance was 47 percent lower in replanted oil palm, and frog assemblage composition differed significantly between the two ages of oil palm. The majority of frog species were disturbance‐tolerant, although we encountered four forest‐associated frog species within mature oil palm despite a distance of 28 km between our study sites and the nearest extensive tract of forest. Although it is clear that protection of forest is of paramount importance for the conservation of tropical fauna, our results indicate that management decisions within tropical agricultural landscapes also have a profound impact on biodiversity. Practices such as staggered replanting or maintenance of connectivity among mature oil palm patches could help maintain frog diversity in the oil palm landscape.
Can wing morphology inform conservation priorities for Southeast Asian cave bats?
Authors: Furey Neil M. , Racey Paul A. 
Published: March 2016

AbstractAdaptations for foraging in the complex airspaces of forest interiors may make bat species in the Asian tropics particularly susceptible to forest loss. However, ecomorphological analysis of Vietnamese bat assemblages challenges the hypothesis that, due to their greater vagility, cave‐roosting bats are less vulnerable to habitat fragmentation than foliage‐roosting species. Of the 13 most highly adapted forest‐interior species in our study, eight were cave‐roosting members of the Rhinolophidae and Hipposideridae and had wing morphologies closely resembling five foliage‐roosting members of the Murininae and Kerivoulinae—species typically thought to have low vagility. Overall, both cave‐roosting and foliage‐roosting bats exhibited a wide range of flight indices and species' wing designs corresponded with preferred foraging habitats, suggesting that foraging strategy may outweigh roost preference as a determinant of bat wing morphology and flight performance. Consequently, where such variation occurs, cave‐roosting bat ensembles are likely to include species with low vagility and similar sensitivity to habitat fragmentation. This could have important conservation implications as Asian karst formations support high cave densities and important bat diversity yet increasingly represent forest refugia in anthropogenic landscapes. We, therefore, advocate greater consideration of species vagility in determining conservation priorities for the region's bat fauna.