bluuebunny/crossref_metadata_2025 huggingface dataset:
CHOROIDAL NEOVASCULARIZATION IN NORTH CAROLINA MACULAR DYSTROPHY RESPONSIVE TO ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Authors: Bakall Benjamin , Bryan J. Shepard , Stone Edwin M. , Small Kent W.
Published: November 2018

Purpose:

To report a new family with North Carolina macular dystrophy including a patient with choroidal neovascularization (CNV).

Methods:

Diagnostic modalities included fundus imaging, fluorescein angiography, optical coherence tomography, and genetic testing. The CNV was treated with intravitreal anti–vascular endothelial growth factor according to a treat-and-extend protocol in both eyes.

Results:

A 60-year-old man presented with North Carolina macular dystrophy with decreasing vision in the left eye and persistently deceased central vision in the right eye. Optical coherence tomography examination showed intraretinal and subretinal fluid consistent with CNV. Genetic testing was performed. Examination of family members showed no signs of CNV. The visual acuity improved from 20/400 to 20/150 in the right eye and from 20/100 to 20/40 in the left eye after intravitreal bevacizumab treatment for CNV. Molecular analysis of the PRDM13 gene revealed a pathogenic heterozygous point mutation.

Conclusion:

Recognition and treatment of CNV in North Carolina macular dystrophy can result in improved vision. Genetic testing of the PRDM13 gene can confirm a molecular diagnosis for North Carolina macular dystrophy.
Development and Long-Term Evaluation of Ocular Surface Conditions Using Ovariectomized Cynomolgus Monkey
Authors: Li Chang , Zhang Xiaofeng , Wang Yun , Li Mengmeng
Published: November 2018

Objectives:

We aim to use the ovariectomized cynomolgus monkey to observe the effect of long-term changes of sex hormone levels on ocular surface.

Methods:

Six healthy adolescent cynomolgus monkeys were randomly assigned to control and experimental groups (n=3/group). Bilateral ovariectomy was performed in experimental group, and sham operation was performed on control animals with their ovaries reserved. The concentrations of serum estradiol and testosterone in cynomolgus monkeys' lower-limb venous were detected by radioimmunoassay before surgery, and at 6, 12, 18, and 24 months after the surgery. Phenol red cotton thread test, tear osmolarity, corneal fluorescein staining, and conjunctival impression cytology were performed to evaluate the ocular surface conditions before surgery, and at 6, 12, 18, and 24 months after the surgery. The histological examinations of the bulbar conjunctiva and labial glands tissues were performed at 12 and 24 months after the surgery.

Results:

There were no significant differences in the serum level of estradiol and testosterone between the experimental and control groups before surgery, at 6, and 12 months after surgery (P>0.05). Serum level of estradiol and testosterone were significantly less in experimental versus control group at 18 and 24 months after surgery (P<0.05). There was no significant differences in phenol red cotton between the experimental and control groups before surgery, at 6, 12, 18, and 24 months after surgery (P>0.05). Tear osmolarity had no significant differences between experimental and control group before surgery (P>0.05), and it was significantly higher in experimental versus control group at all four time-points after surgery (P<0.05). The number of conjunctival goblet cells had no significant differences between experimental and control group before surgery, at 6 months after surgery (P>0.05), and it was significantly lower in experimental versus control group at 12, 18, and 24 months after surgery (P<0.05). There were no significant differences in the corneal fluorescein staining score between the experimental and control groups before surgery, at 6, 12, and 18 months after surgery (P>0.05), and it was higher in experimental than control group at 24 months after surgery (P<0.05). In addition, inflammatory cell infiltration in bulbar conjunctiva and labial glands tissues was observed in experimental group and was unobserved in control group at 24 months after surgery.

Conclusions:

Ovariectomy led to decreased sex hormone levels in cynomolgus monkey. In turn, tear osmolarity was increased, the number of conjunctival goblet cells were decreased, the corneal fluorescence staining was increased, and the pathological examination of the bulbar conjunctiva and labial glands tissues were abnormal, phenol red cotton thread test did not change significantly.
Predictors of Perinatal HIV Transmission Among Women Without Prior Antiretroviral Therapy in a Resource-Limited Setting
Authors: Ewing Alexander C. , Ellington Sascha R. , Wiener Jeffrey B. , Chasela Charles S. , Tegha Gerald , Nelson Julie A. E. , Jamieson Denise J. , van der Horst Charles , Kourtis Athena P.
Published: November 2018

Background:

To investigate potential risk factors for perinatal (intrauterine and intrapartum) mother-to-child transmission (MTCT) of HIV in women unexposed to antiretroviral therapy (ART) during pregnancy.

Methods:

We compared factors according to perinatal MTCT outcome among 2275 ART-naive (until the onset of labor) HIV-infected women in the Breastfeeding, Antiretrovirals and Nutrition study (2004–2010) in Lilongwe, Malawi. Factors included HIV viral load during pregnancy, food security, demographic characteristics, hematologic and blood chemistry measures, medical history and physical factors. Associations with perinatal MTCT and interactions with maternal viral load were assessed using simple and multivariable logistic regression.

Results:

There were 119 (115 intrauterine and 4 intrapartum) cases of perinatal MTCT, only one to a mother with <1000 HIV copies/mL. Maternal viral loads >10,000 copies/mL were common (63.1%). Lower maternal viral load (<1000 copies/mL and 1000.1–10,000 copies/mL) was associated with reduced odds of perinatal MTCT [adjusted odds ratio (aOR), 0.1; 95% confidence interval (CI): 0.01–0.4 and aOR, 0.2; 95% CI: 0.1–0.4, respectively), compared with maternal viral load >10,000 copies/mL. Low CD4+ T cell count (≤350 cells/μL) was only associated with perinatal MTCT in unadjusted models. Food shortage (aOR, 1.8; 95% CI: 1.2–2.6), sexually transmitted infection (STI) (past year; aOR, 1.9; 95% CI: 1.0–3.7), histories of herpes zoster (aOR, 3.0; 95% CI: 1.6–5.6) and tuberculosis (aOR, 2.5; 95% CI: 1.1–5.7) were associated with increased odds of perinatal MTCT.

Conclusions:

These findings confirm that lowering maternal HIV viral load is most important in preventing perinatal MTCT and support efforts to address food shortage, STI and tuberculosis prevention, while informing programs to improve ART coverage in pregnancy.
Using a Text Mining Approach to Explore the Recording Quality of a Nursing Record System
Authors: CHANG Hsiu-Mei , HUANG Ean-Weng , HOU I-Ching , LIU Hsiu-Yun , LI Fang-Shan , CHIOU Shwu-Fen
Published: November 2018

Background:

Most nursing records in Taiwan have been computerized, resulting in a large amount of unstructured text data. The quality of these records has rarely been discussed.

Purpose:

This study used a text mining method to analyze the quality of a nursing record system to establish an auditing model and associated tools for nursing records, with the ultimate objective of improving the quality of electronic nursing records.

Methods:

This study utilized a retrospective method to collect the electronic nursing records of 6,277 patients who had been discharged from the internal medicine departments of a medical center in northern Taiwan from January to June 2014. SAS Enterprise Guide Version 6.1 and SAS Text Miner Version 13.2 software were used to perform text mining. Nursing experts were invited to examine the electronic nursing records. The text mining results were compared against a benchmark that was developed by the experts, and the efficiency of SAS Text Miner was examined using the criteria of specificity, sensitivity, and accuracy.

Results:

In this study, 27,356 nurse-formulated events were used in the analysis. The results of the nurse-formulated events showed an 8.08% similar error with system-formulated events, 29.72% were identified as necessary and appropriate names, 17.53% were retained, 10.15% involved error event names, and 34.52% were not classified. In this study, the sensitivity of SAS text mining in the training (testing) data set was 96% (95%), and the specificity and accuracy were both 99% (99%).

Conclusions:

The results of this study show that text mining is an effective approach to auditing the quality of electronic nursing records. SAS Text Miner software was shown to identify inappropriate nursing record content quickly and efficiently. Furthermore, the results of this study may be included in in-service education teaching materials to promote the writing of better nursing records to improve the quality of electronic nursing records.
Surgery in Tendinopathies
Authors: Aicale Rocco , Tarantino Domiziano , Maffulli Nicola
Published: November 2018

Tendinopathies are challenging. The term “tendinopathy” refers to clinical condition characterized by pain, swelling, and functional limitations of tendons and nearby structures. Tendinopathies give rise to significant morbidity, and, at present, only limited scientifically proven management modalities exist. Achilles and patellar tendons are among the most vulnerable tendons, and among the most frequent lower extremity overuse injuries. Achilles and patellar tendinopathies can be managed conservatively and surgically. Several surgical procedures have been described for both conditions, and, if performed well, they lead to a relatively higher rate of success with low complication.
Diagnosis and treatment of migraine in the patient with depression
Authors: Cook Calli L. , Shedd Glenn C.
Published: November 2018

Background and purpose:

Migraine headache is an enormous health care burden resulting in billions of dollars in workforce revenue lost and millions of lost workdays per year. Migraine headaches and depression are common comorbidities and require expertise in treatment and prevention.

Methods:

The aim of this article is to update the nurse practitioner (NP) on best clinical practices for managing the patient with migraine and previously diagnosed depression. This will include an overview of the pathophysiology of migraine, as well as criteria for diagnosis, treatment, prevention, and patient teaching.

Conclusions:

Migraine and depression are commonly linked and require expertise in treatment to achieve the best patient outcomes.

Implications for Practice:

Patients with migraine are more likely to have depression than the general population. Both conditions require optimal treatment and patient education to reduce overall disease burden. A better understanding of the relationship between depression and migraine will enable the NP to better manage patients with migraine and comorbid depression.
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.
Evaluating an Initiative to Promote Entry-Level Competence in Palliative and End-of-Life Care for Registered Nurses in Canada
Authors: Rietze Lori L. , Tschanz Coby L. , Richardson Holly R.L.
Published: November 2018

Numerous competency statements have been developed for the purpose of guiding nurse educators and clinicians. Rarely, though, are there evaluations of the use of these competency statements in practice. In this cross-sectional descriptive study, nurse educators were surveyed to determine how the Canadian Association of Schools of Nursing (CASN) Palliative and End-of-Life Care Entry-to-Practice Competencies and Indicators are used in schools of nursing in Canada. Twenty-four respondents consented to participating in this study. Findings supported that some version of palliative and end-of-life care (PEOLC) education was offered at each school of nursing in Canada, and it was most commonly threaded throughout existing undergraduate courses. Data also suggested that if nurse educators were interested in PEOLC and had existing knowledge or expertise in PEOLC, the CASN Palliative and End-of-Life Care competency document was used to integrate content into curricula. This study provides some initial insights into the use of the CASN Palliative and End-of-Life Care competency document in Canadian schools of nursing. Implications for additional research, policy, education, and practice are discussed.
Home-Care Nurses’ Experience With Medication Kit in Palliative Care
Authors: Staats Katrine , Tranvåg Oscar , Grov Ellen Karine
Published: November 2018

Home-care nurses assist many advanced cancer patients desiring to live in the familiar surroundings of their own home until the day they die. The purpose of this study was to increase the understanding concerning home-care nurse experience with the Norwegian version of the medication kit as a tool in symptom management for the terminally ill. The study had a qualitative, descriptive, and explorative design, based on hermeneutic methodology. Two focus group interviews with 4 subsequent in-depth interviews helped generate data. The nurses reported how thorough planning and clear instructions on medication kit usage gave security and facilitated proper application. Good collaboration with primaryphysicians, including accessibility and clarifying meetings in particular, was necessary. In the past, infrequent use of the medication kit hindered its relevance for symptom management. Home-care nurses were often alone with the responsibility for assessing the patient and administering medications, leading to unjustifiable professional conditions, particularly during night shifts. Thus, clear guidelines, planning and clarifying meetings with primary physicians, helped to facilitate the use of the medication kit.
Potential Diagnostic Pitfalls in Evaluating Immunohistochemistry for Cervical Myofibroblastomas
Authors: Song Sharon , Ziober Amy , Cooper Kumarasen
Published: November 2018

Cervicovaginal myofibroblastoma (CVM) is a rare benign mesenchymal tumor of the lower female genital tract that shows chromosomal loss of 13q14 (RB1 gene located in this region). The aim of this study was to investigate the utility of immunohistochemistry (IHC) for desmin, CD34, and Rb in diagnosing CVM. All cervical polyps diagnosed from July 2016 to July 2017 were retrospectively reviewed. Cases showing morphologic myofibroblastic differentiation were evaluated by IHC for desmin, CD34, and Rb. Desmin and CD34 staining was recorded as positive or negative. Rb nuclear staining was graded as follows: 0 (<10%), 1 (10%–25%), 2 (>25%–50%), 3 (>50%–75%), or 4 (>75%). Intact nuclear expression of Rb in endothelial cells served as an internal positive control. IHC was performed on 76 cases with 14 excluded from the final cohort due to poor Rb internal control. A total of 61/62 (98.4%) cases were positive for desmin and CD34 with the following Rb distribution: grade 0 (n=53, 86.9%), grade 1 (n=5, 8.2%), grade 2 (n=2, 3.3%), and grade 3 (n=1, 1.6%). One case negative for desmin and CD34 showed grade 3 Rb staining. Upon rereview of the histology, 7/175 cases (4%) were morphologically and immunohistochemically compatible with CVM (desmin and CD34+ grade 0 Rb staining). CVM is a rare and under-recognized entity (4% of cervical polyps) for which morphology remains the mainstay of diagnosis. IHC reliance serves as a potential diagnostic pitfall as 86.9% of cases showing myofibroblastic differentiation demonstrated the staining pattern of desmin and CD34 positivity and Rb deficiency.
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.
Training Implicit Learning of Spelling in Italian Children With Developmental Dyslexia
Authors: Arfé Barbara , Cona Elisa , Merella Anne
Published: November 2018

It had been hypothesized that, in developmental dyslexia (DD), an implicit learning deficit explains children's problems in encoding the phoneme–grapheme correspondences underlying the writing system and thus the development of spelling skills. The present study tested the efficacy of an intervention to facilitate implicit learning of context-sensitive spelling rules with Italian children with DD. Mapping of phonological and orthographic information during spelling was implicitly modeled during 6 sessions of intervention. Thirty-eight elementary-aged children with DD were assigned either to this (phonological–orthographic mapping) condition (n = 19) or to a comparison condition (n = 19) in which phonological spelling procedures and spelling from dictation were used to train word spelling. The two groups were matched on intelligence, vocabulary, and their spelling skills at pretest. The experimental group showed significant improvements in spelling the words trained during the intervention and generalized their acquired spelling knowledge to untrained words. The comparison group also showed improvements, but these were in most cases not significant. Moreover, this group did not show generalization to untrained words. The results seem to confirm that the core problem in DD is inaccurate mappings between phonological and orthographic spelling units and that phonological–orthographic mapping in written word encoding can be modeled for children with DD to facilitate implicit learning.
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

P. 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

Support 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

It 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

Dynamic 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

Malignant 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 Summary

Mesothelioma 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

Alternative 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

1

The 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

To 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

An 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.
Embryonic Immunostaining for the Tardigrade Hypsibius exemplaris
Authors: Smith Frank W. , Gabriel Willow N.
Published: November 2018

Immunostaining is a method used to visualize the localization of proteins in fixed tissue. Many antibodies are available that recognize specific proteins in a wide diversity of organisms, which makes this method ideal for investigating gene expression patterns in nonmodel animal systems. This protocol describes immunostaining for studies of embryogenesis in the tardigrade Hypsibius exemplaris.
ECHIDNA: a decade of high-resolution neutron powder diffraction at OPAL
Authors: Avdeev Maxim , Hester James R.
Published: November 2018

The ECHIDNA high-resolution neutron powder diffractometer at the 20 MW OPAL research reactor in Australia produces high-quality data for a broad spectrum of crystal and magnetic structural studies. The paper presents an overview of the current status of the hardware, latest developments in data-reduction software, statistics on instrument usage and the user programme, and instrument limitations.
X-ray topo-tomography studies of linear dislocations in silicon single crystals
Authors: Asadchikov Victor , Buzmakov Alexey , Chukhovskii Felix , Dyachkova Irina , Zolotov Denis , Danilewsky Andreas , Baumbach Tilo , Bode Simon , Haaga Simon , Hänschke Daniel , Kabukcuoglu Merve , Balzer Matthias , Caselle Michele , Suvorov Ernest
Published: November 2018

This article describes complete characterization of the polygonal dislocation half-loops (PDHLs) introduced by scratching and subsequent bending of an Si(111) crystal. The study is based on the X-ray topo-tomography technique using both a conventional laboratory setup and the high-resolution X-ray image-detecting systems at the synchrotron facilities at KIT (Germany) and ESRF (France). Numerical analysis of PDHL images is performed using the Takagi–Taupin equations and the simultaneous algebraic reconstruction technique (SART) tomographic algorithm.
Significant therapy events with clients with intellectual disabilities
Authors: Wills Sarah , Robbins Lorna , Ward Tony , Christopher Gary
Published: November 2018

Purpose

The purpose of this paper is to explore significant events in psychotherapy with clients with intellectual disabilities (IDs).

Design/methodology/approach

Four 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.

Findings

Using 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/implications

This 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/value

Significant 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.
Revealing the impact of operational logistics service quality on omni-channel capability
Authors: Yumurtacı Hüseyinoğlu Işık Özge , Sorkun Metehan Feridun , Börühan Gülmüş
Published: November 2018

Purpose

This paper introduces the term “omni-channel capability” and tests its validity. The purpose of this paper is to investigate the impact of logistics service quality (LSQ) on omni-channel capability.

Design/methodology/approach

An online survey was used to evaluate the new concept of “omni-channel capability” and LSQ from the consumer’s perception. A two split sample technique was used to validate omni-channel capability and test the impact of LSQ on it through structural equation modeling. Factor analysis and structural equation modeling were performed to introduce, test and validate omni-channel capability, and test the study’s hypotheses. Consumers who had previously shopped from both the online and physical stores of a particular retailer completed a self-administered survey.

Findings

The findings supported the use of the term “omni-channel capability,” which has three elements: channel consistency, cross-channel and social media. The results also revealed the positive impact of operational LSQ on omni-channel capability.

Practical implications

Taking consumer perceptions as a reference point, this study reveals major issues that retailers should focus on while pursuing an omni-channel strategy. The findings also highlight the need for retailers to ensure operational LSQ to implement an omni-channel management strategy.

Originality/value

To improve on the limited theoretical understanding and empirical grounding of omni-channel management, this study described the three elements of omni-channel capability. The impact of operational LSQ on omni-channel capability gives empirical support for the theorized hierarchy of dynamic capabilities (zero- and first-order capabilities).
Digital literacies through an intersectional lens: the case of Javier
Authors: Pandya Jessica Zacher , Hansuvadha Nat , Pagdilao Kathleah Allene Consul
Published: November 2018

Purpose

The purpose of this paper is to examine, through an intersectional lens, how digital video composing can be an act of redistributive social justice for students with learning disabilities.

Design/methodology/approach

The authors draw on two years’ worth of observation, interview, survey and digital video data to present a case study of Javier (all names are pseudonyms), a Latinx English Learner with several learning disabilities. The authors worked with him, making digital videos in a general education classroom as part of a larger design-based study. The authors describe how he made meaning in various modes, across modes, and how his intersectional identities inflected his meaning-making and were visible in his video artifacts.

Findings

Javier was an able digital composer, made meaning across modes and was attentive to audience. His videos offer a portrait of a child with learning disabilities navigating his complex cultural worlds.

Research limitations/implications

This is a single case study built to bridge multiple theoretical and disciplinary backgrounds. Javier was able to compose semiotically powerful messages with socially powerful digital tools.

Originality/value

The authors argue that the use of such tools is a chance for redistributive social justice. Children traditionally underserved by innovations in digital making should not be left out.
The future of the management of projects in the 2030s
Authors: Walker Derek , Lloyd-Walker Beverley
Published: November 2018

Purpose

The purpose of this paper is to explore recent literature on the impact of changes in the workplace environment and projected trends through to the year 2030. This allows the authors to identify and discuss what key trends are changing the nature of project organising work. The authors aim to identify what knowledge and which skills, attributes and experiences will be most likely valued and needed in 2030.

Design/methodology/approach

This paper is essentially a reflective review and is explorative in nature. The authors focus on several recent reports published in the UK and Australia that discuss the way that the future workforce will adapt and prepare for radical changes in the workplace environment. The authors focus on project organising work and the changing workplace knowledge, skills, attributes and experience (KSAE) needs of those working in project teams in 2030 and beyond. The authors draw upon existing KSAE literature including findings from a study undertaken into the KSAEs of project alliance managers working in a highly collaborative form of project delivery.

Findings

The analysis suggests that there is good and bad news about project workers prospects in 2030. The good news is that for those working in non-routine roles their work will be more interesting and rewarding than is the case for today. The bad news is that for workers in routine work roles, they will be replaced by advanced digital technology.

Research limitations/implications

Few, if any, papers published in the project organising literature speculate about what this discipline may look like or what KSAEs will be valued and needed.

Practical implications

This paper opens up a debate about how project management/project organising work will be undertaken in future and what skills and expertise will be required. It also prompts project managers to think about how they will craft their careers in 2030 in response to expected work environment demands. This will have professional and learning implications.

Social implications

The issue of the future workplace environment is highly relevant to the social context.

Originality/value

This paper is about a projected future some 12 years onward from today. It bridges a gap in any future debate about how project organising jobs may change and how they will be delivered in the 2030s.