bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Patient-centered Care
Authors: Agha Aneeza Z. , Werner Rachel M. , Keddem Shimrit , Huseman Tiffany L. , Long Judith A. , Shea Judy A. 
Published: November 2018

Background:
While patient engagement can be beneficial for patient care, there are barriers to engaging patients. These barriers exist for health care organizations, for health care personnel, and for the patients themselves. Solutions to barriers are not well documented.

Objectives:
Our objective was to explore barriers to patient engagement efforts and their corresponding solutions.

Research Design:
Qualitative interviews and site visits from a national sample of primary care facilities within the Veterans Health Administration were analyzed to understand patient engagement barriers and solutions.

Sampling:
We conducted a total of 155 phone and in-person semistructured interviews with primary care providers, mental health staff, social workers, pharmacists, patient advocates, health behavior coaches, and administrative staff at 27 Veterans Health Administration sites. Participants were asked to describe the obstacles they had to overcome in their efforts to improve patient engagement at their site.

Results:
Barriers to patient engagement are overcome by strategically updating data analytics; enhancing organization-wide processes and procedures; being creative with space design, staff hiring, and time commitments; cultivating staff collaborations; and addressing patient care issues such as access, customer service, and patient education. A key component of successful implementation is to create a culture, supported by leadership that promotes patient engagement.

Conclusions:
Participants understood the patient centered approach, despite experiencing a lack of resources and training and could push through solutions to patient engagement barriers while working within the limits of their settings.
The First Report of Robotic Bilateral Modified Radical Neck Dissection Through the Bilateral Axillo-breast Approach for Papillary Thyroid Carcinoma With Bilateral Lateral Neck Metastasis
Authors: Song Ra-Yeong , Sohn Hee Ju , Paek Se Hyun , Kang Kyung Ho 
Published: November 2018

Background:
Robotic unilateral modified radical neck dissection (MRND) has been reported to be safe and achieves good oncologic results. However, there is no report of successful robotic bilateral MRND to date. We report the first case series of robotic bilateral MRND through the bilateral axillo-breast approach (BABA).

Methods and Results:
We reviewed 4 patients who presented with papillary thyroid cancer and metastasis to both lateral neck compartments. BABA robotic total thyroidectomy with bilateral MRND was performed. There were no incidences of vocal cord palsy, permanent hypoparathyroidism, or chyle leakage. All patients underwent high-dose radioiodine ablation. At last follow-up, imaging tests showed no recurrence and thyroglobulin levels remained low.

Conclusions:
BABA allows complete compartment-oriented neck dissection with outcomes that may be comparable with open bilateral MRND. BABA robotic surgery could be a good alternative for patients with papillary thyroid cancer and bilateral neck metastasis who wish to avoid long neck scar.
Genome-Wide Association Studies of malaria susceptibility and resistance: progress, pitfalls and prospects
Authors: Damena Delesa , Denis Awany , Golassa Lemu , Chimusa Emile R. 
Published: November 2018

AbstractP. falciparum malaria is still among the leading causes of child mortality in sub-Saharan Africa; killing hundreds of thousands of children each year. Malaria has been recognized as one of the prominent evolutionary selective forces of human genome that led to the emergence of multiple host protective polymorphisms associated with minimizing the risk of developing severe malaria in endemic areas. A comprehensive understanding of the genetic bases of malaria resistance can shed light to the molecular mechanisms of host-parasite interactions that can potentially pave ways to the development of new therapeutics and vaccines. Genome-wide association studies (GWASs) have recently been implemented in malaria endemic areas and identified a number of novel association genetic variants. Despite this success, only few variants did replicate across the studies and the underlying biology is yet to be understood for the majority of the novel variants. Besides, there are several open questions around heritability, polygenic effects, epistatic interactions, genetic correlations and associated molecular pathways among others. In this review, we first assess the progress and pitfalls of malaria susceptibility GWASs. We then, provide an overview of the current progress in post-GWAS approaches and discuss how these approaches can potentially be implemented in malaria susceptibility GWASs to extract further functional information. We conclude by highlighting the importance of multi-step and multidimensional integrative studies for unravelling the genetic basis of malaria susceptibility and resistance at systems biology level.
Gkmexplain: Fast and Accurate Interpretation of Nonlinear Gapped k-mer SVMs Using Integrated Gradients
Authors: Shrikumar Avanti , Prakash Eva , Kundaje Anshul 
Published: November 2018

AbstractSupport Vector Machines with gapped k-mer kernels (gkm-SVMs) have been used to learn predictive models of regulatory DNA sequence. However, interpreting predictive sequence patterns learned by gkm-SVMs can be challenging. Existing interpretation methods such as deltaSVM, in-silico mutagenesis (ISM), or SHAP either do not scale well or make limiting assumptions about the model that can produce misleading results when the gkm kernel is combined with nonlinear kernels. Here, we propose gkmexplain: a novel approach inspired by the method of Integrated Gradients for interpreting gkm-SVM models. Using simulated regulatory DNA sequences, we show that gkmexplain identifies predictive patterns with high accuracy while avoiding pitfalls of deltaSVM and ISM and being orders of magnitude more computationally efficient than SHAP. We use a novel motif discovery method called TF-MoDISco to recover consolidated TF motifs from gkm-SVM models of in vivo TF binding by aggregating predictive patterns identified by gkmexplain. Finally, we find that mutation impact scores derived through gkmexplain using gkm-SVM models of chromatin accessibility in lymphoblastoid cell-lines consistently outperform deltaSVM and ISM at identifying regulatory genetic variants (dsQTLs). Code and example notebooks replicating the workflow are available at https://github.com/kundajelab/gkmexplain. Explanatory videos available at http://bit.ly/gkmexplainvids.
Diverse tuning underlies sparse activity in L2/3 vibrissal cortex of awake mice
Authors: Ranjbar-Slamloo Yadollah , Arabzadeh Ehsan 
Published: November 2018

AbstractIt is widely reported that superficial layers of the somatosensory cortex exhibit sparse firing. This sparseness could reflect weak feedforward sensory inputs that are not sufficient to generate action potentials in these layers. Alternatively, sparseness might reflect tuning to unknown or higher-level complex features that are not fully explored in the stimulus space. Here, we examined these hypotheses by applying a range of vibrotactile and manual vibrissal stimuli in awake, head-fixed mice while performing loose-seal cell-attached recordings from the vibrissal primary somatosensory (vS1) cortex. A high-velocity stimulus delivered by a piezo-electric actuator evoked activity in a small fraction of regular spiking supragranular neurons (29%) in awake condition. However, a majority of the supragranular regular spiking neurons (84%) were driven by manual stimulation of whiskers. Our results suggest that most neurons in the superficial layers of vS1 cortex contribute to coding in awake conditions when neurons may encounter their preferred feature(s) during whisker-object interactions.
Structural and Practical Identifiability of Dual-input Kinetic Modeling in Dynamic PET of Liver Inflammation
Authors: Zuo Yang , Sarkar Souvik , Corwin Michael T. , Olson Kristin , Badawi Ramsey D. , Wang Guobao 
Published: November 2018

AbstractDynamic 18F-FDG PET with tracer kinetic modeling has the potential to noninvasively evaluate human liver inflammation using the FDG blood-to-tissue transport rate K1. Accurate kinetic modeling of dynamic liver PET data and K1 quantification requires the knowledge of dual-blood input function from the hepatic artery and portal vein. While the arterial input function can be derived from the aortic region on dynamic PET images, it is difficult to extract the portal vein input function accurately from PET. The optimization-derived dual-input kinetic modeling approach has been proposed to overcome this problem by jointly estimating the portal vein input function and FDG tracer kinetics from time activity curve fitting. In this paper, we further characterize the model properties by analyzing the structural identifiability of the model parameters using the Laplace transform and practical identifiability using Monte Carlo simulation based on fourteen patient datasets. The theoretical analysis has indicated that all the kinetic parameters of the dual-input kinetic model are structurally identifiable, though subject to local solutions. The Monte Carlo simulation results have shown that FDG K1 can be estimated reliably in the whole-liver region of interest with reasonable bias, standard deviation, and high correlation between estimated and original values, indicating of practical identifiability of K1. The result has also demonstrated the correlation between K1 and histological liver inflammation scores is reliable. FDG K1 quantification by the optimization-derived dual-input kinetic model is promising for assessing liver inflammation.
Mesothelioma Interactome with 367 Novel Protein-Protein Interactions
Authors: Karunakaran Kalyani B. , Yanamala Naveena , Boyce Gregory , Ganapathiraju Madhavi K. 
Published: November 2018

AbstractMalignant pleural mesothelioma (MPM) is an aggressive cancer of the thorax with a median survival of one year. We constructed an ‘MPM interactome’ with over 300 computationally predicted PPIs and over 1300 known PPIs of 62 literature-curated genes whose activity affects MPM. Known PPIs of the 62 MPM associated genes were derived from BioGRID and HPRD databases. Novel PPIs were predicted by applying the HiPPIP algorithm, which computes features of protein pairs such as cellular localization, molecular function, biological process membership, genomic location of the gene, gene expression in microarray experiments, protein domains and tissue membership, and classifies the pairwise features asinteractingornon-interactingbased on a random forest model. To our satisfaction, the interactome is significantly enriched with genes differentially expressed in MPM tumors compared with normal pleura, and with other thoracic tumors. The interactome is also significantly enriched with genes whose high expression has been correlated with unfavorable prognosis in lung cancer, and with genes differentially expressed on crocidolite exposure. 28 of the interactors of MPM proteins are targets of 147 FDA-approved drugs. By comparing differential expression profiles induced by drug to profiles induced by MPM, potentially repurposable drugs are identified from this drug list. Development of PPIs of disease-specific set of genes is a powerful approach with high translational impact – the interactome is a vehicle to piece together an integrated view on how genes associated with MPM through various high throughput studies are functionally linked, leading to clinically translatable results such as clinical trials with repurposed drugs. The PPIs are made available on a webserver, calledWiki-Pi MPMathttp://severus.dbmi.pitt.edu/wiki-MPMwith advanced search capabilities.One Sentence SummaryMesothelioma Interactome with 367 novel protein-protein interactions may shed light on the mechanisms of cancer genesis and progression
Genome-wide identification of alternative splicing events that regulate protein transport across the secretory pathway
Authors: Neumann Alexander , Schindler Magdalena , Olofsson Didrik , Wilhelmi Ilka , Schürmann Annette , Heyd Florian 
Published: November 2018

AbstractAlternative splicing (AS) strongly increases proteome diversity and functionality in eukaryotic cells. Protein secretion is a tightly-controlled process, especially in a tissue-specific and differentiation-dependent manner. While previous work has focussed on transcriptional and posttranslational regulatory mechanisms, the impact of AS on the secretory pathway remains largely unexplored. Here we integrate a published screen for modulators of protein transport and RNA-Seq analyses to identify over 200 AS events as secretion regulators. We confirm that splicing events along all stages of the secretory pathway regulate the efficiency of protein transport using Morpholinos and CRISPR/Cas9. We furthermore show that these events are highly tissue-specific and adapt the secretory pathway during T-cell activation and adipocyte differentiation. Our data substantially advance the understanding of AS functionality, add a new regulatory layer to a fundamental cell biological process and provide a resource of alternative isoforms that control the secretory pathway.
A comparison of bivariate frequency domain measures of electrophysiological connectivity
Authors: Pascual-Marqui Roberto D. , Faber Pascal , Kinoshita Toshihiko , Kochi Kieko , Milz Patricia , Keiichiro Nishida , Yoshimura Masafumi 
Published: November 2018

1AbstractThe problem of interest here concerns electrophysiological signals from two cortical sites, acquired as invasive intracranial recordings, or from non-invasive estimates of cortical electric neuronal activity computed from EEG or MEG recordings (see e.g. https://doi.org/10.1101/269753). In the absence of other sources, these measured signals consist of an instantaneous linear mixture of the true, actual, unobserved local signals, due to low spatial resolution and volume conduction. A connectivity measure is unreliable as a true indicator of electrophysiological connectivity if it is not invariant to mixing, or if it reports a significant connection for a mixture of independent signals. In (Vinck et al 2011 Neuroimage 55:1548) it was shown that coherence, imaginary coherence, and phase locking value are not invariant to mixing, while the phase lag index (PLI) and the weighted version (wPLI) are invariant to mixing. Here we show that the lagged coherence (LagCoh) measure (2007, https://arxiv.org/abs/0711.1455), not studied in Vinck et al, is invariant to mixing. Additionally, we present here a new mixture-invariant connectivity statistic: the “standardized imaginary covariance” (sImCov). We also include in the comparisons the directed PLI (dPLI) by Stam et al (2012 Neuroimage 62:1415). Fourier coefficients for “N” trials are generated from a linear unidirectional causal time domain model with electrophysiological delay “k” and regression coefficient “b”. 1000 random data sets of “N” trials are simulated, and for each one, and for each connectivity measure, non-parametric randomization tests are performed. The “true positive detection rate” is calculated as the fraction of 1000 cases that have significant connectivity at p<0.05, 0.1, and 0.2. The connectivity methods were compared in terms of detection rates, under non-mixed and mixed conditions, for small and large sample sizes “N”, with and without jitter for “k”, and for different values of signal to noise. Under mixing, the results show that LagCoh outperforms wPLI, PLI, dPLI, and sImCov. Without mixing, LagCoh and sImCov outperform wPLI, PLI, and dPLI. Finally, it is shown that dPLI is an invalid estimator of flow direction, i.e. it reverses and “goes against the flow” by merely changing the sign of one of the time series, a fact that violates the basic definition of Granger causality. For the sake of reproducible research, the supplementary material includes Delphi Pascal source code and all detailed result files in human readable format.
Contractile acto-myosin network on nuclear envelope remnants positions human chromosomes for mitosis
Authors: Booth Alexander JR , Yue Zuojun , Eykelenboom John K , Stiff Tom , Luxton GW Gant , Hochegger Helfrid , Tanaka Tomoyuki U 
Published: November 2018

AbstractTo ensure proper segregation during mitosis, chromosomes must be efficiently captured by kinetochore microtubules and subsequently aligned on the mitotic spindle. The efficacy of chromosome capture by the mitotic spindle can be influenced by how widely chromosomes are scattered in space. Here, we quantify chromosome-scattering volume (CSV) and find that it is reduced immediately after nuclear envelope breakdown (NEBD) in human cells. The reduction of CSV occurs independently of microtubules and is therefore not an outcome of interactions between chromosomes and the spindle. We find that, prior to NEBD, an acto-myosin network is assembled in a LINC complex-dependent manner on the cytoplasmic surface of the nuclear envelope. This acto-myosin network remains around chromosomes soon after NEBD, and its myosin-II-mediated contraction reduces CSV and facilitates chromosome interaction with spindle microtubules.
A direct selection strategy for isolating aptamers with pH-sensitive binding activity
Authors: Gordon Chelsea K. L. , Eisenstein Michael , Tom Soh Hyongsok 
Published: November 2018

AbstractAn aptamer reagent that can switch its binding affinity in a pH-responsive manner would be highly valuable for many biomedical applications including imaging and drug delivery. Unfortunately, the discovery of such aptamers is difficult and only a few have been reported to date. Here we report the first experimental strategy for generating pH-responsive aptamers through direct selection. As an exemplar, we report streptavidin-binding aptamers that retain nanomolar affinity at pH 7.4 but exhibit a ~100-fold decrease in affinity at pH 5.2. These aptamers were generated by incorporating a known streptavidin-binding DNA motif into an aptamer library and performing FACS-based screening at multiple pH conditions. Upon structural analysis, we found that one aptamer’s affinity-switching behavior is driven by a non-canonical G-A base-pair that controls its folding in a highly pH-dependent manner. We believe our strategy could be readily extended to other aptamer-target systems because it does not require a priori structural knowledge of the aptamer or the target.
Significant therapy events with clients with intellectual disabilities
Authors: Wills Sarah , Robbins Lorna , Ward Tony , Christopher Gary 
Published: November 2018

PurposeThe purpose of this paper is to explore significant events in psychotherapy with clients with intellectual disabilities (IDs).Design/methodology/approachFour therapy dyads, each consisting of one client and one therapist, were recruited. Following the brief structured recall procedure (Elliott and Shapiro, 1988), semi-structured interviews focused on helpful events in psychotherapy, using video of particular sessions as a stimulus to help prompt recall of that session.FindingsUsing interpretative phenomenological analysis, five super-ordinate themes were identified: “The Uniqueness of the Therapeutic Relationship”; “Using adaptations to Express Emotions”; “Client Behaviour/Therapist Behaviour”; “Hope and Paternalism”; and “Meaning-Making”. The results provide additional evidence that significant therapy events occur for clients with IDs. Furthermore, the research enabled insights to be gained about the process of therapy for this client group and for exploration of therapeutic factors that may be involved in facilitating a significant therapy event.Research limitations/implicationsThis study highlights the need for therapists to work in such a way as to facilitate significant events in therapy. Whilst this study was a necessary first step, owing to the non-existence of research in this area, the sample size and qualitative design may limit any wider generalisation of the findings.Originality/valueSignificant events have not previously been explored in psychotherapy with clients with IDs. This research could therefore make an important contribution to our understanding of the process of psychotherapy for this client group.
Materialism and compulsive buying behaviour
Authors: Pradhan Debasis , Israel D. , Jena Amit Kumar 
Published: November 2018

Purpose
The purpose of this paper is to study the impact of materialism on credit card (CC) use and impulsive buying (IB) and compulsive buying (CB) behaviour. Furthermore, it assesses whether CC use and IB behaviour mediate the relationship between materialism and CB behaviour.

Design/methodology/approach
Data were collected from adult consumers with CCs via an online survey. For model assessment, a two-step approach was followed. First, a measurement model was created and tested using maximum likelihood estimation and validity of the study constructs was assessed. This was followed by structural equation modelling to test the hypotheses.

Findings
Materialism influences CC use and increases the propensity for IB (IB), which then precipitates CB habits. Reduction in CC use can decrease both IB and CB. Out of the six hypotheses assessed, only the one linking CC use to CB was not supported, requiring further investigation. Mediation relationships were identified, where CC use and IB act as mediators between materialism and CB.

Research limitations/implications
The paper captured responses from adult consumers of India. Hence, the findings may not be generalised across geographies and age groups. The study contributes to the debate on the impulsive–CB paradigm by showing that impulsive and CB are not distinct constructs. In fact, the former could lead to the latter.

Practical implications
CC use in itself need not necessarily lead to CB. The only way CC could cause CB is through IB. Hence, firms must promote responsible buying habits, as there has been an increase in IB, which, if not controlled, could lead to debt trap resulting from CB. The findings of this paper will help both retailers and CC institutions to better understand the spending pattern of consumers. Those will also help the policymakers to chalk out ways to the curb indiscriminate issuance of CCs without educating users.

Originality/value
The findings confirm that IB and CB exist on two ends of a continuum, and not as two distinct theoretical constructs. IB acts as a mediator between CC use and CB as well as between materialism and CB.