bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent Elevation of Electrical Pain Threshold following Continuous Theta Burst Stimulation over Primary Somatosensory Cortex in Humans
Authors: Rao Nishant , Chen Yen-Ting , Ramirez Regan , Tran John , Li Sheng , Parikh Pranav J. 
Published: August 2019

ABSTRACTBackgroundPrimary somatosensory cortex (S1) is involved in pain processing and thus its suppression using neuromodulatory techniques such as continuous theta burst stimulation (cTBS) might be a potential pain management strategy in patients with neuropathic pain. S1 cTBS is known to elevate pain threshold in young adults. However, the persistence of this effect is unknown.Objective/HypothesisWe hypothesized persistent elevation of pain threshold following cTBS over S1 in healthy, young adults.MethodsWe recruited ten subjects in a sham-controlled crossover design and recorded their electrical pain threshold (EPT) for 40 min following cTBS over S1. We assessed corticospinal excitability (CSE) to rule out the involvement of primary motor cortex due to spread of current.ResultscTBS over S1 elevated EPT without modulating CSE compared to sham stimulation. EPT was elevated for 40 min post-cTBS.ConclusionsS1 can be focally targeted using cTBS for a longer lasting pain relief in patients.
Molecular signature of pruriceptive MrgprA3+ neurons
Authors: Xing Yanyan , Chen Junyu , Hilley Henry , Steele Haley , Yang Jingjing , Han Liang 
Published: August 2019

ABSTRACTItch, initiated by the activation of sensory neurons, is frequently associated with dermatological or systemic diseases and significantly affects patient quality of life. MrgprA3+ sensory neurons have been identified as one of the major itch-sensing neuronal populations. Mounting evidence has demonstrated that peripheral pathological conditions induce physiological regulations of sensory neurons, which is critical for the maintenance of chronic itch sensation. However, the underlying molecular mechanisms are not clear. Here we performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis condition. Our results revealed the unique molecular signature of itch-sensing neurons and the distinct transcriptional profile changes that result in response to dermatitis. We found enrichment of nine Mrgpr family members and two histamine receptors in MrgprA3+ neurons, suggesting that MrgprA3+ neurons are the main, direct neuronal target for histamine and Mrgprs agonists. In addition, Ptpn6 and Pcdh12 were identified as novel and highly selective markers of MrgprA3+ neurons. We also discovered that MrgprA3+ neurons respond to skin dermatitis in a way that is unique from other sensory neurons by regulating a combination of transcriptional factors, ion channels, and key molecules involved in synaptic transmission. These results significantly increase our knowledge of itch transmission and uncover potentially novel targets for combating itch.
Engineering of Chimeric Antigen Receptor T Cells with integrin αEβ7 Results in Augmented Therapeutic Efficacy against E-cadherin positive tumor
Authors: Sun Hongxing , He Shan , Meng Lijun , Wang Ying , Zhang Hanghang , Liu Yongnian , Wang Jian , Tao Min , Barta Stefan K. , Dulaimi Essel , Fung Henry , Issa Jean-Pierre J. , Zheng Lei-Zhen , Zhang Yi 
Published: August 2019

ABSTRACTIntegrin αEβ7 (CD103) can interact with E-cadherin and promote T cell retention in epithelial tissue. However, whether the expression of CD103 on chimeric antigen receptor (CAR)-T cells may augment T cell anti-tumor activity remains unknown. Using a preclinical model, we demonstrate that CD103 engineering of human CAR-T cells significantly improves their therapeutic effects on eliminating pre-established E-cadherin expressing tumor cells in immune deficient NOD.scid.Il2Rγcnull (NSG) mice. Human T cells that were engineered with CAR containing 4-1BB and CD3zeta intracellular signaling domains (named BBz) expressed reduced level of CD103 in mice model. Ex vivo assays confirmed the effect of 4-1BB on repressing CD103 expression in CAR-T cells. On the other hand, we generated CD103 expressing CAR-T cells by introducing the αE gene into the CAR structure (named CD103-BBz CAR-T cells). As compared to BBz CAR-T cells, CD103-BBz CAR-T cells produced higher levels of IL-2 and underwent greater expansion in cultures and acquired greater capacity to control the growth and metastasis of E-cadherin expressing lymphoma cells in NSG mice. This effect of CD103-BBz CAR-T cells was associated with their increased capacity to infiltrate into the tumor and persist in vivo, leading to significantly improved overall survival of lymphoma mice. Our findings suggest that engineering tumor-reactive T cells with CD103 may represent a novel strategy to improve adoptive T cells anti-tumor efficacy, and this strategy may have broad implication in the epithelial solid tumor treatment.HighlightsCAR-T cells with 4-1BB costimulatory domain express reduced level of CD1034-1BB signaling antagonist TGF-β1 induced CD103 expressionEctopically expression of CD103 on CAR-T cells enhanced their anti-E-cadherin positive tumor capacityGraphical Abstract:Graphic Summary: The co-stimulatory molecule 4-1BB within the CAR protein potently suppresses CD103 expression. Engineering CAR-T cells with CD103 significantly enhances their capacity to proliferate and infiltrate into the solid tumor, leading to augmented anti-tumor immunity.
Vav1 is essential for HIF-1α activation in vascular response to ischemic stress
Authors: Min Yongfen , Hong Jaewoo , Wuest Todd , Lin P. Charles 
Published: August 2019

AbstractVascular response to hypoxia is a major determinant of organ function under stress, which is particularly critical for vital organs such as the heart. This study identifies Vav1 as a key vascular regulator of hypoxia. Vav1 is present in vascular endothelium and is essential for HIF-1 activation under hypoxia. It regulates HIF-1α stabilization through the p38/Siah2/PHD3 pathway. Consequently, Vav1 deficient mice are predisposed to sudden death under cardiac ischemia with increased coronary endothelial apoptosis. Moreover, Vav1 binds to VEGFR1 that carries Vav1 to lysosomes for degradation in normoxia. Hypoxia upregulates Vav1 through inhibition of protein degradation. These findings reveal that regulation of Vav1 by hypoxia is analogous to HIF-1α regulation. Both proteins are constitutively produced allowing for rapid responses when stress occurs, and constantly degraded in normoxia. Hypoxia stabilizes Vav1, which is required for HIF-1α accumulation. Together they mediate the vascular response to hypoxia and maintain tissue homeostasis.
Measuring significant changes in chromatin conformation with ACCOST
Authors: Cook Kate B. , Roch Karine Le , Vert Jean Philippe , Noble William Stafford 
Published: August 2019

AbstractChromatin conformation assays such as Hi-C cannot directly measure differences in 3D architecture between cell types or cell states. For this purpose, two or more Hi-C experiments must be carried out, but direct comparison of the resulting Hi-C matrices is confounded by several features of Hi-C data. Most notably, the genomic distance effect, whereby contacts between pairs of genomic loci that are proximal along the chromosome exhibit many more Hi-C contacts that distal pairs of loci, dominates every Hi-C matrix. Furthermore, the form that this distance effect takes often varies between different Hi-C experiments, even between replicate experiments. Thus, a statistical confidence measure designed to identify differential Hi-C contacts must accurately account for the genomic distance effect or risk being misled by large-scale but artifactual differences. ACCOST (Altered Chromatin Conformation STatistics) accomplishes this goal by extending the statistical model employed by DEseq, re-purposing the “size factors,” which were originally developed to account for differences in read depth between samples, to instead model the genomic distance effect. We show via analysis of simulated and real data that ACCOST provides unbiased statistical confidence estimates that compare favorably with competing methods such as diffHiC, FIND, and HiCcompare. ACCOST is freely available with an Apache license at https://bitbucket.org/noblelab/accost.
Using high-definition transcranial direct current stimulation to investigate the role of the dorsolateral prefrontal cortex in explicit sequence learning
Authors: Ballard Hannah K. , Eakin Sydney M. , Maldonado Ted , Bernard Jessica A. 
Published: August 2019

AbstractThough we have a general understanding of the brain areas involved in motor sequence learning, there is more to discover about the neural mechanisms underlying skill acquisition. Skill acquisition may be subserved, in part, by interactions between the cerebellum and prefrontal cortex through a cerebello-thalamo-prefrontal network. In prior work, we investigated this network by targeting the cerebellum; here, we explored the consequence of stimulating the dorsolateral prefrontal cortex using high-definition transcranial direct current stimulation (HD-tDCS) before administering an explicit motor sequence learning paradigm. Using a mixed within- and between-subjects design, we employed anodal (n = 24) and cathodal (n = 25) HD-tDCS (relative to sham) to temporarily alter brain function and examine effects on skill acquisition. The results indicate that both anodal and cathodal prefrontal stimulation impedes motor sequence learning, relative to sham. These findings suggest an overall negative influence of active prefrontal stimulation on the acquisition of a sequential pattern of finger movements. Collectively, this provides novel insight on the role of the dorsolateral prefrontal cortex in initial skill acquisition, when cognitive processes such as working memory are used. Exploring methods that may improve motor learning is important in developing therapeutic strategies for motor-related diseases and rehabilitation.
Gamification of assembly planning in virtual environment
Authors: Garbaya Samir , Romano Daniela M. , Hattar Gunjeet 
Published: August 2019

Purpose
The purpose of this paper is to study the effect of the gamification of virtual assembly planning on the user performance, user experience and engagement.

Design/methodology/approach
A multi-touch table was used to manipulate virtual parts and gamification features were integrated into the virtual assembly environment. An experiment was conducted in two conditions: a gamified and a non-gamified virtual environment. Subjects had to assemble a virtual pump. The user performance was evaluated in terms of the number of errors, the feasibility of the generated assembly sequence and the user feedback.

Findings
The gamification reduced the number of errors and increased the score representing the number of right decisions. The results of the subjective and objective analysis showed that the number of errors decreased with engagement in the gamified assembly. The increase in the overall user experience reduced the number of errors. The subjective evaluation showed a significant difference between the gamified and the non-gamified assembly in terms of the level of engagement, the learning usability and the overall experience.

Research limitations/implications
The effective learning retention after training has not been tested, and longitudinal studies are necessary. The effect of the used gamification elements has been evaluated as a whole; further work could isolate the most beneficial features and add other elements that might be more beneficial for learning.

Originality/value
The research reported in this paper provides valuable insights into the gamification of virtual assembly using a low-cost multi-touch interface. The results are promising for training operators to assemble a product at the design stage.
Assembly variation analysis of compliant mechanisms by combining direct linearization method and Lagrange’s equations
Authors: Niu Zhihua , Li Zhimin , Jin Sun , Liu Tao 
Published: August 2019

Purpose
This paper aims to carry out assembly variation analysis for mechanisms with compliant joints by considering deformations induced by manufactured deviations. Such an analysis procedure extends the application area of direct linearization method (DLM) to compliant mechanisms and also illustrates the dimensional interaction within multi-loop compliant structures.

Design/methodology/approach
By applying DLM to both geometrical equations and Lagrange’s equations of the second kind, an analytical deviation modeling method for mechanisms with compliant joints are proposed and further used for statistical assembly variation analysis. The precision of this method is verified by comparing it with finite element simulation and traditional DLM.

Findings
A new modeling method is proposed to represent kinematic relationships between joint deformations and parts/components deviations. Based on a case evaluation, the computational efficiency is improved greatly while the modeling accuracy is maintained at more than 94% rate comparing with the benchmark finite element simulation.

Originality/value
The Equilibrium Equations of Incremental Forces derived from Lagrange’s equations are proposed to quantitatively represent the relationships between manufactured deviations and assembly deformations. The present method extends the application area of DLM to compliant structures, such as automobile suspension systems and some Micro-Electro-Mechanical-Systems.
Statistical solution of inverse problems using a state reduction
Authors: Neumayer Markus , Suppan Thomas , Bretterklieber Thomas 
Published: August 2019

Purpose
The application of statistical inversion theory provides a powerful approach for solving estimation problems including the ability for uncertainty quantification (UQ) by means of Markov chain Monte Carlo (MCMC) methods and Monte Carlo integration. This paper aims to analyze the application of a state reduction technique within different MCMC techniques to improve the computational efficiency and the tuning process of these algorithms.

Design/methodology/approach
A reduced state representation is constructed from a general prior distribution. For sampling the Metropolis Hastings (MH) Algorithm and the Gibbs sampler are used. Efficient proposal generation techniques and techniques for conditional sampling are proposed and evaluated for an exemplary inverse problem.

Findings
For the MH-algorithm, high acceptance rates can be obtained with a simple proposal kernel. For the Gibbs sampler, an efficient technique for conditional sampling was found. The state reduction scheme stabilizes the ill-posed inverse problem, allowing a solution without a dedicated prior distribution. The state reduction is suitable to represent general material distributions.

Practical implications
The state reduction scheme and the MCMC techniques can be applied in different imaging problems. The stabilizing nature of the state reduction improves the solution of ill-posed problems. The tuning of the MCMC methods is simplified.

Originality/value
The paper presents a method to improve the solution process of inverse problems within the Bayesian framework. The stabilization of the inverse problem due to the state reduction improves the solution. The approach simplifies the tuning of MCMC methods.
Converging resources and co-producing for innovation: evidence from healthcare services
Authors: Sehgal Sanjeewani , Gupta Garima 
Published: August 2019

PurposeThe purpose of this paper is to examine healthcare organizations for the improvements in their existing services (incremental innovation) as well as for the new service developments (radical innovation) initiated through the utilization of resources and co-producing behavior.Design/methodology/approachThe paper uses an SEM approach to analyze the responses obtained from 257 medical administrators of 50 hospitals registered with National Accreditation Board for Hospitals and Healthcare Providers.FindingsThe results reflect a positive and significant impact that is more driven by internal resources and is found to be stronger for incremental innovation in healthcare. The study also posits that resource utilization in conjunction with co-production activities has greater potential to bring innovation that is likely to succeed and stay inimitable.Research limitations/implicationsThe paper outlines scope for future research and suggests inclusion of other service sectors, geographical locations and performance indicators to attain a better understanding of the constructs examined.Practical implicationsThe paper outlines implications for policy makers concerned with healthcare. Providers of health services ought to develop a proactive customer-oriented approach so as to deliver value through service innovations. Integrating customer co-production processes may further augment the overall quality of care.Originality/valueEmpirical studies integrating the resource-oriented view of innovation along with firms’ co-production and collaborative mechanisms are majorly lacking. The study bridges this gap and suggests ways to bring innovation in health services, a pivotal need for health institutions of an emerging economy like India.
The effect of royal family members on the board on firm performance in Saudi Arabia
Authors: AL Nasser Zahra 
Published: August 2019

PurposeThe purpose of this paper is to empirically examine the effect of royal family members on firm performance of publicly listed companies in Saudi Arabia.Design/methodology/approachUsing 491 firm-year observations of non-financial publicly listed firms in Saudi Arabia’s stock market between 2009 and 2013, the study employs, besides others, the advanced econometric technique GMM-system estimator. This allows the dynamic nature and control of the endogeneity problem to be accounted for in corporate governance and firm performance.FindingsThe main result is that the attendance of royal family members at board meetings negatively influences firm performance but does not have an influence on firm value. The results also show that firms with many independent royal family members on the board of directors have better firm performance and firm value. In addition, firms with a high number of royal family members presenting on the board have better firm performance.Research limitations/implicationsThis study offers guidance to assist the further investigation of the SA Royal Family’s BoD membership either in SA or in other monarchy countries. It is interesting to compare these results in order to further understand the different effects that the Royal Family’s BoD membership have in such countries. This study’s results suggest that independent members of SA’s Royal Family on the BoD have some influence on firm performance in both the short and long term. Thus, policymakers should encourage the members of SA’s Royal Family to become more involved in firms’ BoDs.Practical implicationsThis study offers guidance for further investigation of royal family members in the region or in other monarchy countries. It will be interesting to compare these results. The study suggests that royal family members on the board have a partial influence on firm performance, especially the independent ones. Thus, the policymakers should encourage more involvement of independent royal family members on the board.Social implicationsForeign and minority investors, who invest in SA’s publicly listed firms, should note that when independent members of SA’s Royal Family are on the BoD their investment will benefit from the reduced risks and uncertainty.Originality/valueTo the best of the author’s knowledge, this is the first study undertaken to investigate empirically the influence a royal family’s presence on the board of directors has on firm performance. This study is based on both theories, namely the agency theory and resource dependence theory.
Behind the cloak of competence: brain injury and mental capacity legislation
Authors: Moore Sophie , Wotus Rebecca , Norman Alyson , Holloway Mark , Dean Jackie 
Published: August 2019

Purpose
Brain Injury Case Managers (BICMs) work closely with individuals with Acquired Brain Injury (ABI), assessing needs, structuring rehabilitation interventions and providing support, and have significant experience of clients with impairments to decision making. The purpose of this paper is to explore the application of the Mental Capacity Act (MCA) and its guidance when applied to ABI survivors. This research aimed to: first, highlight potential conflicts or tensions that application of the MCA might pose, and second, identify approaches to mitigate the problems of the MCA and capacity assessments with ABI survivors. It is hoped that this will support improvements in the services offered.

Design/methodology/approach
Using a mixed method approach, 93 BICMs responded to an online questionnaire about decision making following ABI. Of these, 12 BICMs agreed to take part in a follow-up semi-structured telephone interview.

Findings
The data revealed four main themes: disagreements with other professionals, hidden disabilities, vulnerability in the community and implementation of the MCA and capacity assessments.

Practical implications
The findings highlight the need for changes to the way mental capacity assessments are conducted and the need for training for professionals in the hidden effects of ABI.

Originality/value
Limited research exists on potential limitations of the application of the MCA for individuals with an ABI. This paper provides much needed research on the difficulties surrounding mental capacity and ABI.
Information to support strategic campus management in universities
Authors: Curvelo Curvelo Magdaniel Flavia , Den Heijer Alexandra , Arkesteijn Monique 
Published: August 2019

PurposeThis paper aims to underpin the importance of the availability (or absence) of campus management information (CMI) in supporting universities’ goals.Design/methodology/approachFour perspectives of campus management were used to develop a structured survey enquiring campus managers about universities’ goals, finances, users and spaces. Its descriptive analysis distinguishes two domains: campus strategy and CMI.FindingsA total of 14 participant universities in nine countries provided substantial data, increasing the available CMI in each of the four perspectives compared with previous research. Three goal-related patterns driving the strategies of universities and their campuses were identified across competitive, social, economic and environmental performance aspects. Accordingly, particular CMI is discussed.Research limitations/implicationsThe paper’s overarching approach in four perspectives challenged the collection of data, which needed to be retrieved from different departments in the organisation, with different domains (human resources, finance, facilities and organisational strategy), lingo and accountability cultures.Originality/valueThese findings improve the current understanding of university campuses as strategic resources enabling a variety of university goals and missions in today’s knowledge-based economy, society and cities. Moreover, the authors discuss that a more structural approach to collecting CMI may benefit universities to identify critical aspects of campus management supporting their strategies from which performance indicators can be derived and shared among campus managers with similar strategies to make better future decisions.