bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of cognitive remediation and supported employment for people with mental illness: a randomized controlled trial
Authors: Yamaguchi S. , Sato S. , Horio N. , Yoshida K. , Shimodaira M. , Taneda A. , Ikebuchi E. , Nishio M. , Ito J. 
Published: September 2016

BackgroundLittle is known about the economic benefits of cognitive remediation and supported employment (CR + SE). The present study aimed to investigate the cost-effectiveness of CR + SE compared with traditional vocational services (TVS).MethodIndividuals with mental illness and low cognitive function were recruited at six sites in Japan. A total of 111 participants were randomly allocated to the CR + SE group or the TVS group. Clinical and vocational outcomes were assessed at baseline and 12-month follow-up. Service utilization data were collected monthly. The data on outcomes and costs were combined to examine cost-effectiveness.ResultsThe data were obtained from a total of 92 participants. The CR + SE group resulted in better vocational and clinical outcomes (employment rate, 62.2%; work tenures, 78.6 days; cognitive improvement, 0.5) than the TVS group (19.1%, 24.9 days and 0.2). There was no significant difference in mean total costs between the groups (CR + SE group: $9823, s.d. = $6372, TVS group: $11 063, s.d. = $11 263) with and without adjustment for covariates. However, mean cost for medical services in the CR + SE group was significantly lower than that in the TVS group after adjusting covariates (Β = −$3979, 95% confidence interval −$7816 to −$143, p = 0.042). Cost-effectiveness acceptability curves for vocational outcomes illustrated the high probabilities (approximately 70%) of the CR + SE group being more cost-effective than TVS when society is not willing to pay additional costs.ConclusionsCR + SE appears to be a cost-effective option for people with mental illness who have low cognitive functioning when compared with TVS.
Predictors of psychological improvement on non-professional suicide message boards: content analysis
Authors: Niederkrotenthaler T. , Gould M. , Sonneck G. , Stack S. , Till B. 
Published: September 2016

BackgroundSuicide message boards have been at the core of debates about negative influences of the Internet on suicidality. Nothing is currently known about communication styles that may help users to psychologically improve in these settings.MethodIn all, 1182 archival threads with 20 499 individual postings from seven non-professional suicide message boards supporting an ‘against-suicide’, ‘neutral’ or ‘pro-suicide’ attitude were randomly selected and subject to content analysis. Initial needs of primary posters (i.e. individual who open a thread), their psychological improvement by the end of the thread, their responses received and indicators of suicidality were coded. Differences between ‘pro-suicide’, ‘neutral’ and ‘against suicide’ boards, and correlations between primary posters and respondents in terms of suicidality were assessed. Logistic regression was used to test associations with psychological improvement.Results‘Pro-suicide’ boards (n= 4) differed from ‘neutral’ (n= 1) and ‘against-suicide’ (n= 2) boards in terms of communicated contents. Indicators of suicidality correlated moderately to strongly between primary posters and respondents on ‘pro-suicide’ message boards, but less on other boards. Several communicative strategies were associated with psychological improvement in primary posters, including the provision of constructive advice [adjusted odds ratio (aOR) 4.10, 95% confidence interval (CI) 2.40–7.03], active listening (aOR 1.60, 95% CI 1.12–2.27), sympathy towards the poster (aOR 2.22, 95% CI 1.68–2.95) and provision of alternatives to suicide (aOR 2.30, 95% CI 1.67–3.18).ConclusionsRespondents resemble primary posters with regard to suicidality in ‘pro-suicide’ boards, which may hinder psychological improvement. Still, opportunities to intervene in these settings using simple communication techniques exist and need to be taken and evaluated.
Analyzing Confabulations in Schizophrenia and Healthy Participants
Authors: Shakeel Mohammed K. , Docherty Nancy M. , Rich Patrick R. , Zaragoza Maria S. , Chrobak Quin M. , McCleery Amanda 
Published: September 2016

AbstractObjectives: Confabulations occur in schizophrenia and certain severe neuropsychiatric conditions, and to a lesser degree in healthy individuals. The present study used a forced confabulation paradigm to assess differences in confabulation between schizophrenia patients and healthy controls. Methods: Schizophrenia patients (n=60) and healthy control participants (n=19) were shown a video with missing segments, asked to fill in the gaps with speculations, and tested on their memory for the story. Cognitive functions and severity of symptoms were also evaluated. Results: Schizophrenia patients generated significantly more confabulations than healthy control participants and had a greater tendency to generate confabulations that were related to each other. Schizophrenic confabulations were positively associated with temporal context confusions and formal thought disorder, and negatively with delusions. Conclusions: Our findings show that the schizophrenia patients generate more confabulations than healthy controls and schizophrenic confabulations are associated with positive symptoms. (JINS, 2016, 22, 911–919)
Food swamps and food deserts in Baltimore City, MD, USA: associations with dietary behaviours among urban adolescent girls
Authors: Hager Erin R , Cockerham Alexandra , O’Reilly Nicole , Harrington Donna , Harding James , Hurley Kristen M , Black Maureen M 
Published: September 2016

AbstractObjectiveTo determine whether living in a food swamp (≥4 corner stores within 0·40 km (0·25 miles) of home) or a food desert (generally, no supermarket or access to healthy foods) is associated with consumption of snacks/desserts or fruits/vegetables, and if neighbourhood-level socio-economic status (SES) confounds relationships.DesignCross-sectional. Assessments included diet (Youth/Adolescent FFQ, skewed dietary variables normalized) and measured height/weight (BMI-for-age percentiles/Z-scores calculated). A geographic information system geocoded home addresses and mapped food deserts/food swamps. Associations examined using multiple linear regression (MLR) models adjusting for age and BMI-for-ageZ-score.SettingBaltimore City, MD, USA.SubjectsEarly adolescent girls (6th/7th grade,n634; mean age 12·1 years; 90·7 % African American; 52·4 % overweight/obese), recruited from twenty-two urban, low-income schools.ResultsGirls’ consumption of fruit, vegetables and snacks/desserts: 1·2, 1·7 and 3·4 servings/d, respectively. Girls’ food environment: 10·4 % food desert only, 19·1 % food swamp only, 16·1 % both food desert/swamp and 54·4 % neither food desert/swamp. Average median neighbourhood-level household income: $US 35 298. In MLR models, girls living in both food deserts/swamps consumed additional servings of snacks/dessertsv. girls living in neither (β=0·13,P=0·029; 3·8v. 3·2 servings/d). Specifically, girls living in food swamps consumed more snacks/desserts than girls who did not (β=0·16,P=0·003; 3·7v. 3·1 servings/d), with no confounding effect of neighbourhood-level SES. No associations were identified with food deserts or consumption of fruits/vegetables.ConclusionsEarly adolescent girls living in food swamps consumed more snacks/desserts than girls not living in food swamps. Dietary interventions should consider the built environment/food access when addressing adolescent dietary behaviours.
Inhibition of Hedgehog-dependent tumors and cancer stem cells by a newly identified naturally occurring chemotype
Authors: Infante Paola , Alfonsi Romina , Ingallina Cinzia , Quaglio Deborah , Ghirga Francesca , D'Acquarica Ilaria , Bernardi Flavia , Di Magno Laura , Canettieri Gianluca , Screpanti Isabella , Gulino Alberto , Botta Bruno , Mori Mattia , Di Marcotullio Lucia 
Published: September 2016

AbstractHedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma. However, Smo mutations that confer constitutive activity and drug resistance have emerged during treatment with Vismodegib. For this reason, the development of new effective Hh inhibitors represents a major challenge for cancer therapy. Natural products have always represented a unique source of lead structures in drug discovery, and in recent years have been used to modulate the Hh pathway at multiple levels. Here, starting from an in house library of natural compounds and their derivatives, we discovered novel chemotypes of Hh inhibitors by mean of virtual screening against the crystallographic structure of Smo. Hh functional based assay identified the chalcone derivative 12 as the most effective Hh inhibitor within the test set. The chalcone 12 binds the Smo receptor and promotes the displacement of Bodipy-Cyclopamine in both Smo WT and drug-resistant Smo mutant. Our molecule stands as a promising Smo antagonist able to specifically impair the growth of Hh-dependent tumor cells in vitro and in vivo and medulloblastoma stem-like cells and potentially overcome the associated drug resistance.
A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques
Authors: Lee Sujin , Nguyen Minh Trang , Currier Michael G. , Jenkins Joe B. , Strobert Elizabeth A. , Kajon Adriana E. , Madan-Lala Ranjna , Bochkov Yury A. , Gern James E. , Roy Krishnendu , Lu Xiaoyan , Erdman Dean D. , Spearman Paul , Moore Martin L. 
Published: September 2016

AbstractAs the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.
Sizing nanomaterials in bio-fluids by cFRAP enables protein aggregation measurements and diagnosis of bio-barrier permeability
Authors: Xiong Ranhua , Vandenbroucke Roosmarijn E. , Broos Katleen , Brans Toon , Van Wonterghem Elien , Libert Claude , Demeester Jo , De Smedt Stefaan C. , Braeckmans Kevin 
Published: September 2016

AbstractSizing nanomaterials in complex biological fluids, such as blood, remains a great challenge in spite of its importance for a wide range of biomedical applications. In drug delivery, for instance, it is essential that aggregation of protein-based drugs is avoided as it may alter their efficacy or elicit immune responses. Similarly it is of interest to determine which size of molecules can pass through biological barriers in vivo to diagnose pathologies, such as sepsis. Here, we report on continuous fluorescence recovery after photobleaching (cFRAP) as a analytical method enabling size distribution measurements of nanomaterials (1–100 nm) in undiluted biological fluids. We demonstrate that cFRAP allows to measure protein aggregation in human serum and to determine the permeability of intestinal and vascular barriers in vivo. cFRAP is a new analytical technique that paves the way towards exciting new applications that benefit from nanomaterial sizing in bio-fluids.
Third trimester phthalate exposure is associated with DNA methylation of growth-related genes in human placenta
Authors: Zhao Yan , Chen Jiao , Wang Xiu , Song Qi , Xu Hui-Hui , Zhang Yun-Hui 
Published: September 2016

AbstractStrong evidence implicates maternal phthalate exposure during pregnancy in contributing to adverse birth outcomes. Recent research suggests these effects might be mediated through the improper regulation of DNA methylation in offspring tissue. In this study, we examined associations between prenatal phthalate exposure and DNA methylation in human placenta. We recruited 181 mother-newborn pairs (80 fetal growth restriction newborns, 101 normal newborns) in Wenzhou, China and measured third trimester urinary phthalate metabolite concentrations and placental DNA methylation levels of IGF2 and AHRR. We found urinary concentrations of mono (2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were significantly inversely associated with placental IGF2 DNA methylation. The associations were much more evident in fetal growth restriction (FGR) newborns than those in normal newborns. These findings suggest that changes in placental DNA methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth.
Utilization of paramagnetic relaxation enhancements for structural analysis of actin-binding proteins in complex with actin
Authors: Huang Shuxian , Umemoto Ryo , Tamura Yuki , Kofuku Yutaka , Uyeda Taro Q. P. , Nishida Noritaka , Shimada Ichio 
Published: September 2016

AbstractActin cytoskeleton dynamics are controlled by various actin binding proteins (ABPs) that modulate the polymerization of the monomeric G-actin and the depolymerization of filamentous F-actin. Although revealing the structures of the actin/ABP complexes is crucial to understand how the ABPs regulate actin dynamics, the X-ray crystallography and cryoEM methods are inadequate to apply for the ABPs that interact with G- or F-actin with lower affinity or multiple binding modes. In this study, we aimed to establish the alternative method to build a structural model of G-actin/ABP complexes, utilizing the paramagnetic relaxation enhancement (PRE) experiments. Thymosin β4 (Tβ4) was used as a test case for validation, since its structure in complex with G-actin was reported recently. Recombinantly expressed G-actin, containing a cysteine mutation, was conjugated with a nitroxyl spin label at the specific site. Based on the intensity ratio of the 1H-15N HSQC spectra of Tβ4 in the complex with G-actin in the paramagnetic and diamagnetic states, the distances between the amide groups of Tβ4 and the spin label of G-actin were estimated. Using the PRE-derived distance constraints, we were able to compute a well-converged docking structure of the G-actin/Tβ4 complex that shows great accordance with the reference structure.
Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model
Authors: Fong Sheng , Teo Emelyne , Ng Li Fang , Chen Ce-Belle , Lakshmanan Lakshmi Narayanan , Tsoi Sau Yee , Moore Philip Keith , Inoue Takao , Halliwell Barry , Gruber Jan 
Published: September 2016

AbstractAlzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ1–42 form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ1–42 expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances.
A conjugate of methotrexate and an analog of luteinizing hormone releasing hormone shows increased efficacy against prostate cancer
Authors: Zhu Shengsheng , Wang Qinxia , Jiang Juan , Luo Yongwei , Sun Zuyue 
Published: September 2016

AbstractLHRH receptor, is over-expressed in a variety of human tumors and, is a potential binding site for targeted metastatic prostate cancer therapy. The objectives of our study were to synthesize a bioconjugate of the LHRH analog [DLys6]-LHRH and the anti-tumor agent methotrexate and test the hypothesis that [DLys6]-LHRH-MTX targets and inhibits prostate cancer cell growth in vitro and in vivo. The results of in vitro studies, showed that both [DLys6]-LHRH-MTX and MTX displayed superior cytotoxicity against prostate cancer cells in a concentration-dependent manners, with IC50 concentrations for PC-3 cells of, 1.02 ± 0.18 μmol/L and 6.34 ± 1.01 μmol/L; for DU-145 cells, 1.53 ± 0.27 μmol/L and 8.03 ± 1.29 μmol/L; and for LNCaP cells, 1.93 ± 0.19 μmol/L and 9.68 ± 1.24 μmol/L, respectively. The IC50 values of [DLys6]-LHRH-MTX and MTX were 110.77 ± 15.31 μmol/L and 42.33 ± 7.25 μmol/L, respectively. Finally, [DLys6]-LHRH-MTX significantly improved the anti-tumor activity of MTX in nude mice bearing PC-3 tumor xenografts. The inhibition ratios of tumor volume and tumor weight in the [DLys6]-LHRH-MTX treated group were significantly higher than those in the MTX-treated group. Tumor volume doubling time was also significantly extended from 6.13 days in control animals to 9.67 days in mice treated with [DLys6]-LHRH-MTX. In conclusion, [DLys6]-LHRH -MTX may be useful in treating prostate cancer.
NOR-1/NR4A3 regulates the cellular inhibitor of apoptosis 2 (cIAP2) in vascular cells: role in the survival response to hypoxic stress
Authors: Alonso Judith , Galán María , Martí-Pàmies Ingrid , Romero José María , Camacho Mercedes , Rodríguez Cristina , Martínez-González José 
Published: September 2016

AbstractVascular cell survival is compromised under pathological conditions such as abdominal aortic aneurysm (AAA). We have previously shown that the nuclear receptor NOR-1 is involved in the survival response of vascular cells to hypoxia. Here, we identify the anti-apoptotic protein cIAP2 as a downstream effector of NOR-1. NOR-1 and cIAP2 were up-regulated in human AAA samples, colocalizing in vascular smooth muscle cells (VSMC). While NOR-1 silencing reduced cIAP2 expression in vascular cells, lentiviral over-expression of this receptor increased cIAP2 mRNA and protein levels. The transcriptional regulation of the human cIAP2 promoter was analyzed in cells over-expressing NOR-1 by luciferase reporter assays, electrophoretic mobility shift analysis and chromatin immunoprecipitation, identifying a NGFI-B site (NBRE-358/-351) essential for NOR-1 responsiveness. NOR-1 and cIAP2 were up-regulated by hypoxia and by a hypoxia mimetic showing a similar time-dependent pattern. Deletion and site-directed mutagenesis studies show that NOR-1 mediates the hypoxia-induced cIAP2 expression. While NOR-1 over-expression up-regulated cIAP2 and limited VSMC apoptosis induced by hypoxic stress, cIAP2 silencing partially prevented this NOR-1 pro-survival effect. These results indicate that cIAP2 is a target of NOR-1 and suggest that this anti-apoptotic protein is involved in the survival response to hypoxic stress mediated by NOR-1 in vascular cells.
Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus
Authors: Mifsud Karen R. , Reul Johannes M. H. M. 
Published: September 2016

Significance
Glucocorticoid hormones are important mediators of the stress response and implicated in the etiology of stress-related psychiatric disorders. Glucocorticoids act via mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus, resulting in altered transcription of target genes. Currently, however, little information is available about how they interact with the genome after stress in vivo. Here, we show that an acute stressful challenge results in an increased interaction of both MRs and GRs with their genomic recognition sites. Moreover, they may interact with these sites not just as homodimers but also, as heterodimers, the extent of which is highly gene-dependent. These findings provide insight into how MRs and GRs interact with the hippocampal genome after stress in vivo.
Records of Inspiration
Authors: Hyland Anne M. , Litschauer Walburga 
Published: September 2016

Abstract
The perception of Schubert as an undisciplined, spontaneous composer who was disinclined to revise is challenged by the existence of extensive continuity drafts and autograph scores for the Piano Sonatas D 958, D 959 and D 960. These drafts represent the most important documents of their kind and offer a means by which to reappraise Schubert’s methods of composition for the piano sonata, particularly of what are arguably his greatest examples of the genre. This chapter charts the compositional evolution of the sketches and autographs, before examining the disparities between the continuity drafts and the final versions of the last three Sonatas. This examination permits a more detailed study of the Piano Sonata in B ♭, D 960, in which a number of key features of Schubert’s customary revisions are analysed from the perspective of thematic construction, phrase structure, hypermetre and performance practice.
Musical Causality and Schubert’s Piano Sonata in A Major, D 959, First Movement
Authors: Caskel Julian 
Published: September 2016

Abstract
The first movement of Schubert’s A major Sonata could be connected to Beethoven’s Sonata Op. 31 No. 2, on account of Schubert’s formal intention to mediate between improvisatory structural moments and a genuine ordering of events in sonata form. This parallelisation provides a clue to why Schubert’s final sonatas can—on the grounds of stylistic typology—be accepted as works written in a ‘late style’. In historical discussions the parameters which define the concept ‘late style’ are derived from Beethovenian models and are conceptualised as a departure from his ‘heroic style’. But in the first movement of D 959 Schubert composed precisely a departure from that model. Adorno’s dichotomy between extensive and intensive types of musical time helps to define Schubert’s specific modes of departure: the first movement of the Sonata D 959 composes a metamorphosis of the intensive into the extensive type, the realisation of which lends the movement a narrative dimension.
Schubert, Social Music and Melancholy
Authors: Plantinga Leon 
Published: September 2016

Abstract
If we have inherited unlike competing visions of post-Congress Vienna, the same seems to be true of her native son Schubert. There is the guileless composer of lilting songs and ingenuous instrumental music whose rhythms and textures echoed the sounds of Old Vienna and, more recently, a man who suffered from a venereal disease. The actual Schubert clearly embodied something of each of these visions. His music constantly echoes the sounds heard in Vienna’s taverns and ballrooms, and his later works plumbed new depths of tragedy and despair. In some of Schubert’s most impressive late music these two themes are mingled, such that dances take on the aura of tragedy. Examples from Schubert’s last year are the first movement of the Fantasy in F minor and the slow movements of the final two Piano Sonatas, D 959 and 960, both of the deutsche/Ländler type.