bluuebunny/crossref_metadata_2025_split huggingface dataset:
Schizophrenia Polygenic Risk Score and 20-Year Course of Illness in Psychotic Disorders
Authors: Jonas Katherine G. , Lencz Todd , Li Kaiqiao , Malhotra Anil K. , Perlman Greg , Fochtmann Laura J. , Bromet Evelyn J. , Kotov Roman 
Published: March 2019

AbstractUnderstanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnostics and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β= 0.21), lower GAF (β= −0.28), and worse cognition (β= −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a powerful tool for diagnosis and treatment planning.
Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle
Authors: Santos-Lopez Alfonso , Marshall Christopher W. , Scribner Michelle R. , Snyder Daniel , Cooper Vaughn S. 
Published: March 2019

AbstractBacterial populations vary in their stress tolerance and population structure depending upon whether growth occurs in well-mixed or structured environments. We hypothesized that evolution in biofilms would generate greater genetic diversity than well-mixed environments and lead to different pathways of antibiotic resistance. We used experimental evolution and whole genome sequencing to test how the biofilm lifestyle influenced the rate, genetic mechanisms, and pleiotropic effects of resistance to ciprofloxacin inAcinetobacter baumanniipopulations. Both evolutionary dynamics and the identities of mutations differed between lifestyle. Planktonic populations experienced selective sweeps of mutations including the primary topoisomerase drug targets, whereas biofilm-adapted populations acquired mutations in regulators of efflux pumps. An overall trade-off between fitness and resistance level emerged, wherein biofilm-adapted clones were less resistant than planktonic but more fit in the absence of drug. However, biofilm populations developed collateral sensitivity to cephalosporins, demonstrating the clinical relevance of lifestyle on the evolution of resistance.
PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers
Authors: Aakula Anna , Isomursu Aleksi , Rupp Christian , Erickson Andrew , Kauko Otto , Shah Pragya , Padzik Artur , Pokharel Yuba Raj , Kaur Amanpreet , Li Song-Ping , Trotman Lloyd , Taimen Pekka , Rannikko Antti , Lammerding Jan , Paatero Ilkka , Mirtti Tuomas , Ivaska Johanna , Westermarck Jukka 
Published: March 2019

ABSTRACTWhile organ-confined PCa is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities. Here, we discover that PCa tumors with concomitantly compromised function of two tumor suppressor phosphatases, PP2A and PTEN, are particularly aggressive, having less than 50% 5-year secondary-therapy free patient survival. Functionally, overexpression of PME-1, a PP2A inhibitor protein, inhibits anoikis in PTEN-deficient PCa cells. In vivo, PME-1 inhibition increased apoptosis in in ovo PCa tumor xenografts, and attenuated PCa cell survival in zebrafish circulation. Molecularly, PME-1 deficient PCa cells display increased trimethylation at lysines 9 and 27 of histone H3 (H3K9me3 and H3K27me3), a phenotype corresponding to increased apoptosis sensitivity. In summary, we discover that PME-1 overexpression supports anoikis resistance in PTEN-deficient PCa cells. Clinically, the results identify PME-1 as a candidate biomarker for a subset of particularly aggressive PTEN-deficient PCa.
Multiplatform Biomarker Identification using a Data-driven Approach Enables Single-sample Classification
Authors: Zhang Ling , Thapa Ishwor , Haas Christian , Bastola Dhundy 
Published: March 2019

AbstractHigh-throughput gene expression profiles have allowed discovery of potential biomarkers enabling early diagnosis, prognosis and developing individualized treatment. However, it remains a challenge to identify a set of reliable and reproducible biomarkers across various gene expression platforms and laboratories for single sample diagnosis and prognosis. We address this need with our Data-Driven Reference (DDR) approach, which employs stably expressed housekeeping genes as references to eliminate platform-specific biases and non-biological variabilities. Our method identifies biomarkers with “built-in” features, and these features can be interpreted consistently regardless of profiling technology, which enable classification of single-sample independent of platforms. Validation with RNA-seq data of blood platelets shows that DDR achieves the superior performance in classification of six different tumor types as well as molecular target statuses (such asMETorHER2-positive, and mutantKRAS, EGFRorPIK3CA) with smaller sets of biomarkers. We demonstrate on the three microarray datasets that our method is capable of identifying robust biomarkers for subgrouping medulloblastoma samples with data perturbation due to different microarray platforms. In addition to identifying the majority of subgroup-specific biomarkers in Code-Set of nanoString, some potential new biomarkers for subgrouping medulloblastoma were detected by our method. Our results show that the DDR method contributes significantly to single-sample classification of disease and shed light on personalized medicine.
Insight into dynamics of APOBEC3G protein in complexes with DNA assessed by high speed AFM
Authors: Pan Yangang , Shlyakhtenko Luda S. , Lyubchenko Yuri L. 
Published: March 2019

AbstractAPOBEC3G (A3G) is a single-stranded DNA (ssDNA) binding protein that restricts the HIV virus by deamination of dC to dU during reverse transcription of the viral genome. A3G has two zing-binding domains: the N-terminal domain (NTD), which efficiently binds ssDNA, and the C-terminal catalytic domain (CTD), which supports deaminase activity of A3G. Until now, structural information on A3G has lacked, preventing elucidation of the molecular mechanisms underlying its interaction with ssDNA and deaminase activity. We have recently built computational model for the full-length A3G monomer and validated its structure by data obtained from time-lapse High-Speed Atomic Force Microscopy (HS AFM). Here time-lapse HS AFM was applied to directly visualize the structure and dynamics of A3G in complexes with ssDNA. Our results demonstrate a highly dynamic structure of A3G, where two domains of the protein fluctuate between compact globular and extended dumbbell structures. Quantitative analysis of our data revealed a substantial increase in the number of A3G dumbbell structures in the presence of the DNA substrate, suggesting the interaction of A3G with the ssDNA substrate stabilizes this dumbbell structure. Based on these data, we developed a model explaining the interaction of globular and dumbbell structures of A3G with ssDNA and suggested a possible role of the dumbbell structure in A3G function.
Plasticity at the DNA recognition site of the MeCP2 mCG-binding domain
Authors: Lei Ming , Tempel Wolfram , Liu Ke , Min Jinrong 
Published: March 2019

AbstractMeCP2 is an abundant protein, involved in transcriptional repression by binding to CG and non-CG methylated DNA. However, MeCP2 might also function as a transcription activator as MeCP2 is found bound to sparsely methylated promoters of actively expressed genes. Furthermore, Attachment Region Binding Protein (ARBP), the chicken ortholog of MeCP2, has been reported to bind to Matrix/scaffold attachment regions (MARs/SARs) DNA with an unmethylated 5’-CAC/GTG-3’ consensus sequence. In this study, we investigated how MeCP2 recognizes unmethylated 5’-CAC/GTG-3’ motif containing DNA by binding and structural studies. We found that MeCP2-MBD binds to MARs DNA with a comparable binding affinity to mCG DNA, and the MeCP2-CAC/GTG complex structure revealed that MeCP2 residues R111 and R133 form base-specific interactions with the GTG motif. For comparison, we also determined crystal structures of the MeCP2-MBD bound to mCG and mCAC/GTG DNA, respectively. Together, these crystal structures illustrate the adaptability of the MeCP2-MBD toward the GTG motif as well as the mCG DNA, and also provide structural basis of a biological role of MeCP2 as a transcription activator and its disease implications in Rett syndrome.
An event-related potential study of decision making and feedback utilization in female college students who binge drink
Authors: Na Eun-Chan , Jang Kyoung-Mi , Kim Myung-Sun 
Published: March 2019

AbstractThis study investigated the ability to use feedback for decision making in female college students who binge drink (BD) using the Iowa Gambling Task (IGT) and event-related potentials (ERPs). Twenty-seven binge drinkers and 23 non-binge drinkers (non-BD) were identified based on scores on the Korean version of the Alcohol Use Disorder Test and the Alcohol Use Questionnaire. The IGT consists of four cards, including two cards that result in a net loss, with large immediate gains but greater losses in the long term, and two cards that result in a net gain, with small immediate gains but reduced losses in the long term. Participants were required to choose one card at a time to maximize profit until the end of the task while avoiding losses. The BD group showed a significantly lower total net score than the non-BD group, indicating that the BD group chose more disadvantageous cards. The BD group showed significantly smaller ΔFRN amplitudes (difference in amplitudes of feedback-related negativity [FRN] between gain and loss feedback) except in P3. Additionally, ΔFRN amplitudes in the fronto-central area were positively correlated with the total net score and net scores for sectors 4 and 5. Thus, total net scores and later performance on the IGT increased as ΔFRN amplitudes from the fronto-central area increased. FRN is known to reflect early feedback evaluation employing a bottom-up mechanism, whereas P3 is known to reflect late feedback processing and allocation of attentional resources using a top-down mechanism. These results indicate that college students who binge drink have deficits in early evaluation of positive or negative feedback and that this deficit may be related to decision making deficits.
Anti-disturbance iterative learning tracking control for space manipulators with repetitive reference trajectory
Authors: Qiao Jian Zhong , Wu Hao , Zhu Yukai , Xu Jianwei , Li Wenshuo 
Published: March 2019

Purpose
This paper is concerned with the repetitive trajectory tracking control for space manipulators under model uncertainties and vibration disturbances.

Design/methodology/approach
The model uncertainties and link vibration of manipulators will degrade the tracking performance of space manipulators; in this paper, a new hybrid control scheme that consists of a composite hierarchical anti-disturbance controller and an iterative learning controller is developed to solve this problem.

Findings
The composite hierarchical controller can effectively attenuate model uncertainties and reject vibration disturbances, whereas the iterative learning controller is able to improve the tracking accuracy for repetitive reference trajectory.

Originality/value
The proposed scheme compensates for the shortcomings of iterative learning control which can only deal with repetitive disturbances, ensuring the accuracy and repeatability of space manipulators under model uncertainties and random disturbances.
Distributed adaptive fuzzy tracking algorithms for multiple uncertain mechanical systems
Authors: Sun Yanchao , Chen Liangliang , Qin Hongde 
Published: March 2019

Purpose
This paper aims to investigate the distributed coordinated fuzzy tracking problems for multiple mechanical systems with nonlinear model uncertainties under a directed communication topology.

Design/methodology/approach
The dynamic leader case is considered while only a subset of the follower mechanical systems can obtain the leader information. First, this paper approximates the system uncertainties with finite fuzzy rules and proposes a distributed adaptive tracking control scheme. Then, this paper makes a detailed classification of the system uncertainties and uses different fuzzy systems to approximate different kinds of uncertainties. Further, an improved distributed tracking strategy is proposed. Closed-loop systems are investigated using graph theory and Lyapunov theory. Numerical simulations are performed to verify the effectiveness of the proposed methods.

Findings
Based on fuzzy control and adaptive control theories, the desired distributed coordinated tracking control strategies for multiple uncertain mechanical systems are developed.

Originality/value
Compared with most existing literature, the proposed distributed tracking algorithms use fuzzy control and adaptive control techniques to cope with system nonlinear uncertainties of multiple mechanical systems. Moreover, the improved control strategy not only reduces fuzzy rules but also has higher control accuracy.
E-university delivery model: handling the evaluation process
Authors: Ismail Rasha , Safieddine Fadi , Jaradat Ashraf 
Published: March 2019

PurposeThe setting up of e-university has been slow-going. Much of e-university slow progress has been attributed to poor business models, branding, disruptive technologies, lack of organisational structure that accommodates such challenges, and failure to integrate a blended approach. One of the stumbling blocks, among many, is the handling of evaluation process. E-university models do not provide much automation compared to the original brick-and-mortar classroom model of delivery. The underlining technologies may not have been supportive; however, the conditions are changing, and more evaluation tools are becoming available for academics. The paper aims to discuss these issues.Design/methodology/approachThis paper identifies the extent of current online evaluation processes. In this process, the team reviews the case study of a UK E-University using Adobe Connect learning model that mirrors much of the physical processes as well as online exams and evaluation tools. Using the Riva model, the paper compares the physical with the online evaluation processes for e-universities to identify differences in these processes to evaluate the benefits of e-learning. As a result, the models can help us to identify the processes where improvements can take place for automating the process and evaluate the impact of this change.FindingsThe paper concludes that this process can be significantly shortened and provide a fairer outcome but there remain some challenges for e-university processes to overcome.Originality/valueThis paper examines the vital quality assurance processes in academia as more universities move towards process automation, blended or e-university business models. Using the case study of Arden University online distance learning, the paper demonstrates, through modelling and analysis that the process of online automation of the evaluation process is achieved with significant efficiency.
The mediating role of overall fairness perception: a structural equation modelling assessment
Authors: Mohammad Jihad , Quoquab Farzana , Idris Fazli , Al Jabari Mohammad , Wishah Raed 
Published: March 2019

PurposeMost of the past studies related to organisational justice focussed on different types of justice, such as procedural justice, distributive justice and interactional justice either separately or collectively. Still, further investigation on the overall concept of fairness is required to extend theoretical generalisability. Moreover, researchers argued that overall fairness rather than a specific type represents more concrete situation about employees’ perception of fairness within an organisation. Considering this, the purpose of this paper is to examine the mediating effect of overall fairness perception (OFP) in relation to workplace outcome as well as its predictive ability on employees’ attitude and behaviour in term of psychological ownership and citizenship behaviour.Design/methodology/approachA total of 250 questionnaires were distributed among the employees of financial institutions in Malaysia, which yielded 150 completed usable responses. Smart PLS (version 3) software and SPSS were utilised in order to analyse the data.FindingsThe results revealed that overall fairness plays a crucial role as a mediator as well as a predictor. Limitations and future research directions are also discussed.Practical implicationsThis study provides useful insights for the mangers of financial institutions. It also suggests strategies about how to manage justice and workplace outcomes at workplace.Originality/valueThis paper is among the pioneers to address the mediating role of OFP in relations to workplace attitude and behaviour in non-western context.
Training effects on subsistence entrepreneurs’ hope and goal attainment
Authors: Barrios Andres , Reficco Ezequiel , Taborda Rodrigo 
Published: March 2019

Purpose
The purpose of this paper is to explore the extent to which hope and perceived goal attainment can be developed in subsistence entrepreneurs through the right training tools.

Design/methodology/approach
A longitudinal study of a subsistence entrepreneurship training program in three Central American countries was carried out. Participants were divided on the basis of their exposure to training (yes, no), and of the type of training received (none, business plan, business model). The authors carried out three assessments (just before the program, six months and one year after the program) of participants’ business goals and their hope of attaining them. Information was analyzed using linear regression.

Findings
Participants exposed to training reported significant increases in perceived goal attainment and in their hope levels. Training based on the business plan affected hope agency in the short term, as predicted by the logic of causation theory. Training based on the business canvas affected hope pathways, as predicted by the logic of effectuation theory.

Research limitations/implications
Given the data collection process (a non-random sample and selection of participants), the findings are not generalizable without stringent procedures and further replication.

Practical implications
If hope is a reliable predictor of goal attainment, it should be promoted and measured. Given the limited means of gathering data and making reliable projections that most entrepreneurs endure, the business canvas’ contribution to entrepreneurs’ “emotional equipment” ceteris paribus should be more valuable for subsistence entrepreneurs.

Originality/value
This is the first study comparing the short- and long-term effects of two entrepreneurial learning devices on entrepreneurs’ hope and business goal attainment.
An inherent differentiation and system level assessment approach to inventory management
Authors: Jonsson Patrik , Mattsson Stig-Arne 
Published: March 2019

PurposeThe purpose of this paper is to explain the effects of inherent differentiation and system level performance assessment in inventory management. This is done by comparing the performance of two common safety stock methods, by considering the methods’ inherent differentiation and item group-level performance effects.Design/methodology/approachDue to the lack of analytical relationships between the two methods, the analysis is based on event-driven simulations. Data are collected from eight different case companies. Findings explain the importance of assessing safety stock performance for groups of items and not for individual items, as is common in academic studies. It explains how the methods’ inherent differentiation and planning environment characteristics affect the relative performances of the two safety stock methods.FindingsThe study explains the importance of assessing performance of safety stock methods on a system-level, rather than on item-level measures. It explains why the demand fill-rate method has a negative impact on the performance for groups of items, while the number-of-days method has a positive impact. The study also explains how the group-level safety stock performance is affected by five demand data characteristics.Research limitations/implicationsThe study explains the importance of assessing performance of safety stock methods on a system-level, rather than on item-level measures. It explains why the demand fill-rate method has a negative impact on the performance for groups of items, while the number-of-days method has a positive impact. The study also explains how the group-level safety stock performance is affected by five demand data characteristics.Practical implicationsUnderstanding the necessity of system level assessment of safety stock performance, how methods inherently differentiate service levels, and how demand characteristics affect methods’ performance can guide the choice of safety stock methods in companies.Originality/valueNo research on the characteristics of the number-of-days safety stock method, any assessment of differentiation characteristics of and comparison with the demand fill-rate method, has been published. The variable “inherent differentiation” is also introduced and defined.