bluuebunny/crossref_metadata_2025 huggingface dataset:
Closure of Oroantral Fistula With Buccal Fat Pad Flap and Endoscopic Drainage of the Maxillary Sinus
Authors: Abdel-Aziz Mosaad , Fawaz Mohamed , Kamel Mohamed , Kamel Ahmed , Aljeraisi Talal
Published: June 2018

Oroantral fistula (OAF) is a pathologic communication between the oral cavity and the maxillary sinus. It is usually associated with maxillary sinusitis, where drainage of sinus infection is a mandatory step during closure of the fistula. The flap used for closure of OAF should be tension free, broadly based and well vascularized. The aim of this study was to assess the effectiveness of closure of OAF using buccal fat pad (BFP) flap with concomitant endoscopic middle meatal antrostomy for maxillary sinus drainage. Nineteen patients with chronic OAF were included in the study. Closure was performed using BFP with endoscopic middle meatal antrostomy. Preoperative and postoperative assessments were carried out. Patients were followed up for at least 1 year postoperatively. Complete closure of all OAFs was achieved with no recurrence or dehiscence. In conclusion, closure of OAF with BFP flap and concomitant endoscopic drainage of the maxillary sinus through the middle meatus is an effective, easy, and simple method. It has a high success rate with no effect on the vestibular depth or mouth opening.
Integrated breathlessness services for people with chronic conditions
Authors: Bausewein Claudia , Schumacher Philipp , Bolzani Anna
Published: June 2018

Purpose of review

Optimal management of breathlessness requires generally more than one component. Breathlessness services aim to provide specific interventions and support for patients suffering from breathlessness due to any advanced disease and their carers. This review aims to describe recent studies evaluating the effects of breathlessness services for patients with advanced chronic conditions.

Recent findings

Various breathlessness services have been tested and vary regarding structure, duration, frequency and professionals involved. Four randomized controlled trials demonstrated a positive and significant effect on distress due to breathlessness or mastery of breathlessness or breathlessness severity. In the fifth randomized controlled trial, quantitative results were NS, but in the qualitative interviews, patients stressed the positive experience with the breathlessness service and the benefits they gained. The caring, holistic, respectful and integrated approaches were valued by patients.

Breathlessness services combine a variety of evidence-based nonpharmacological interventions and some services also pharmacological interventions when physicians are involved. As the prevalence of breathlessness due to advanced disease is high and increasing, more such services should be provided to support patients throughout the course of their disease.
Central Visual Oscillopsia: Case Report and Review of the Literature
Authors: Jones Wallace , Silkworth William , Dusto Nathaniel , Pelak Victoria S. , Berliner Jean , Buard Isabelle , Kluger Benzi
Published: June 2018

Here we present a patient with persistent central visual oscillopsia, review the literature on this condition, and report results from an experimental intervention using repetitive transcranial magnetic stimulation. A 57-year-old man reported persistent visual oscillopsia after a traumatic brain injury suffered 20 years earlier. Symptoms were presumed to be of cortical origin given his normal eye movements, eye stability, and peripheral vestibular function. Furthermore, he reported oscillopsia with visual imagery during eye closure. Occipital lesions damaging white matter connections identified on magnetic resonance imaging were suspected to be the cause of his symptoms. Repetitive transcranial magnetic stimulation was applied to the left extrastriate visual motion area V5/MT, to bilateral V5/MT, and to bilateral striate visual area V1. The primary outcome measure was dynamic visual acuity. Secondary outcome measures were gaze stabilization testing and subjective improvement as noted by interviews of the patient. Gaze stabilization and dynamic visual acuity testing revealed no difference between pre- and post-intervention with repetitive transcranial magnetic stimulation. The patient reported symptomatic improvement in large-amplitude oscillations that persisted for at least 12 months, but stated that smaller-amplitude oscillations were unchanged. Pathologies associated with central oscillopsia in the literature include neuromyelitis optica spectrum disorder, stroke, migraine without infarction, and psychological trauma. The patient’s reported improvement in large- but not small-amplitude oscillopsia suggests that these symptoms may result from different neurophysiological mechanisms. Repetitive transcranial magnetic stimulation did not result in clinically significant improvement, suggesting a need for other strategies to treat this condition.
Transient Capgras Syndrome Secondary to Bilateral Ischemic Stroke: A Case Report
Authors: Garcha Manveer , Sivakumar Keithan , Leary Megan , Yacoub Hussam A.
Published: June 2018

Capgras syndrome is one of a variety of delusional misidentification syndromes that can be associated with acute ischemic stroke, neurodegenerative disease, or metabolic conditions. Most cases reported in the literature are associated with frontal and/or parietal lobe involvement. Transient Capgras syndrome is rare but has been reported. We present a case of transient Capgras syndrome following bilateral cerebral ischemic infarcts in the frontal, parietal, and temporal regions, and involving the right prefrontal cortex. To our knowledge, transient Capgras syndrome with rapid resolution over a period of days is rare.
Neurofibromatosis Type 2–Related Eye Disease Correlated With Genetic Severity Type
Authors: Painter Sally L. , Sipkova Zuzana , Emmanouil Beatrice , Halliday Dorothy , Parry Allyson , Elston John S.
Published: June 2018

Objective:

Neurofibromatosis type 2 (NF2) is an uncommon but well-recognized disorder characterized by multiple schwannomas and meningiomas. Adults typically present with hearing loss and balance disturbance, and children with ocular, dermatological, and neurological signs. Clinical diagnosis is confirmed by neuroimaging and genetic testing. Although ophthalmic features are present in patients with NF2, there are no reports correlating genetic severity subtypes with ophthalmic involvement.

Methods:

We retrospectively reviewed longitudinal ophthalmological data of 83 patients with NF2, with known genetic severity subtype, to determine visual function over time. We created a scoring system (Oxford NF2 Ophthalmic Score [ONOS]) to quantify visually debilitating pathology.

Results:

The prevalence of optic atrophy, combined hamartomas, cataract, and epiretinal membranes significantly increased with genetic severity. Median age of survival to visual acuity worse than 1.0 logarithm of minimum angle of resolution in one eye significantly decreased with genetic severity and was 38 years in the genetically severe group, 49 years in moderate classics, 64 years in mild classics, and 84 years in the tissue mosaics. In the genetically severe, the visually damaging pathologies were largely untreatable. The ONOS correlated with genetic severity longitudinally and cross-sectionally.

Conclusions:

Mutations associated with severe systemic disease result in greater visual morbidity at an earlier age. Those with tissue mosaicism are unlikely to have visually debilitating pathology secondary to NF2. Potentially treatable sources of damage to vision, however, affect all groups and must be identified early and treated effectively to retain useful vision throughout life.
Sequestration of macroalgal carbon: the elephant in the Blue Carbon room
Authors: Krause-Jensen Dorte , Lavery Paul , Serrano Oscar , Marbà Núria , Masque Pere , Duarte Carlos M.
Published: June 2018

Macroalgae form the most extensive and productive benthic marine vegetated habitats globally but their inclusion in Blue Carbon (BC) strategies remains controversial. We review the arguments offered to reject or include macroalgae in the BC framework, and identify the challenges that have precluded macroalgae from being incorporated so far. Evidence that macroalgae support significant carbon burial is compelling. The carbon they supply to sediment stocks in angiosperm BC habitats is already included in current assessments, so that macroalgae are de facto recognized as important donors of BC. The key challenges are (i) documenting macroalgal carbon sequestered beyond BC habitat, (ii) tracing it back to source habitats, and (iii) showing that management actions at the habitat lead to increased sequestration at the sink site. These challenges apply equally to carbon exported from BC coastal habitats. Because of the large carbon sink they support, incorporation of macroalgae into BC accounting and actions is an imperative. This requires a paradigm shift in accounting procedures as well as developing methods to enable the capacity to trace carbon from donor to sink habitats in the ocean.
Temperature-induced self-sealing capability of
Banksia
follicles
Authors: Huss Jessica C. , Spaeker Oliver , Gierlinger Notburga , Merritt David J. , Miller Ben P. , Neinhuis Christoph , Fratzl Peter , Eder Michaela
Published: June 2018

Many plants in fire-prone regions retain their seeds in woody fruits in the plant canopy until the passage of a fire causes the fruit to open and release the seeds. To enable this function, suitable tissues are required that effectively store and protect seeds until they are released. Here, we show that three different species of the Australian genus
Banksia
incorporate waxes at the interface of the two valves of the follicle enclosing the seeds, which melt between 45°C and 55°C. Since the melting temperature of the waxes is lower than the opening temperatures of the follicles in all investigated species (
B. candolleana
,
B. serrata
,
B. attenuata
), we propose that melting of these waxes allows the sealing of micro-fissures at the interface of the two valves while they are still closed. Such a self-sealing mechanism likely contributes to the structural integrity of the seed pods, and benefits seed viability and persistence during storage on the plants. Furthermore, we show in a simplified, bioinspired model system that temperature treatments seal artificially applied surface cuts and restore the barrier properties.
Analyses of cancer data in the Genomic Data Commons Data Portal with new functionalities in the TCGAbiolinks R/Bioconductor package
Authors: Mounir Mohamed , Silva Tiago C. , Lucchetta Marta , Olsen Catharina , Bontempi Gianluca , Noushmehr Houtan , Colaprico Antonio , Papaleo Elena
Published: June 2018

The advent of Next Generation Sequencing (NGS) technologies has opened new perspectives in deciphering the genetic mechanisms underlying complex diseases. Nowadays, the amount of genomic data is massive and substantial efforts and new tools are required to unveil the information hidden in the data.

The Genomic Data Commons (GDC) Data Portal is a large data collection platform that includes different genomic studies included the ones from The Cancer Genome Atlas (TCGA) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiatives, accounting for more than 40 tumor types originating from nearly 30000 patients. Such platforms, although very attractive, must make sure the stored data are easily accessible and adequately harmonized. Moreover, they have the primary focus on the data storage in a unique place, and they do not provide a comprehensive toolkit for analyses and interpretation of the data. To fulfill this urgent need, comprehensive but easily accessible computational methods for integrative analyses of genomic data without renouncing a robust statistical and theoretical framework are needed. In this context, the R/Bioconductor package TCGAbiolinks was developed, offering a variety of bioinformatics functionalities. Here we introduce new features and enhancements of TCGAbiolinks in terms of i) more accurate and flexible pipelines for differential expression analyses, ii) different methods for tumor purity estimation and filtering, iii) integration of normal samples from the Genotype-Tissue-Expression (GTEx) platform iv) support for other genomics datasets, here exemplified by the TARGET data.

Evidence has shown that accounting for tumor purity is essential in the study of tumorigenesis, as these factors promote confounding behavior regarding differential expression analysis. Henceforth, we implemented these filtering procedures in TCGAbiolinks. Moreover, a limitation of some of the TCGA datasets is the unavailability or paucity of corresponding normal samples. We thus integrated into TCGAbiolinks the possibility to use normal samples from the Genotype-Tissue Expression (GTEx) project, which is another large-scale repository cataloging gene expression from healthy individuals. The new functionalities are available in the TCGABiolinks v 2.8 and higher released in Bioconductor version 3.7.
Risk of hypoglycemia induced by pivalate-conjugated antibiotics in young children: a population-based retrospective study in Japan
Authors: Yasuhisa Tatebe , Koyama Toshihiro , Mikami Naoko , Kitamura Yoshihisa , Sendo Toshiaki , Hinotsu Shiro
Published: June 2018

Infection is a common cause for an outpatient visit for young children. Pivalate-conjugated antibiotics (PCAs) are often used for these patients in Japan. However, a few case reports have shown that PCAs can provoke hypoglycemia in children, but no larger study has shown that PCAs increase the risk of hypoglycemia. The current study was performed as a retrospective review of children aged 1 month to 5 years old with at least once prescription of PCAs or other beta-lactam antibiotics from January 2011 to December 2013, using a medical and pharmacy claims database. Hypoglycemia was defined based on the International Statistical Classification of Diseases and Related Health Problems 10th Revision code or prescription of 10% or 20% glucose injection, and the incidence of hypoglycemic events was investigated. Logistic regression analysis was performed to examine the risk of hypoglycemia with PCAs compared with control antibiotics. The study cohort contained 179,594 eligible patients (male: 52.2%, mean age: 3.2 years). The numbers of prescriptions were 454,153 and 417,287 for PCAs and control antibiotics, respectively. Multivariate analysis showed that PCAs were associated with hypoglycemia (adjusted OR 1.18, 95% CI 1.12 to 1.24, P < 0.01), and the risk of hypoglycemia was also significantly increased with use of PCAs for ≤7 days (adjusted OR 1.17, 95% CI 1.11 to 1.24, P < 0.01). These results suggest that prescription of PCAs to young children should be avoided, even for a short time period.
Petrobactin protects against oxidative stress and enhances sporulation efficiency inBacillus anthracisSterne
Authors: Hagan Ada K. , Plotnick Yael M. , Dingle Ryan E. , Mendel Zachary I. , Cendrowski Stephen R. , Sherman David H. , Tripathi Ashootosh , Hanna Philip C.
Published: June 2018

Bacillus anthracisis a gram-positive bacillus that under conditions of environmental stress, such as low nutrients, can convert from a vegetative bacillus to a highly durable spore that enables long-term survival. The sporulation process is regulated by a sequential cascade of dedicated transcription factors but requires key nutrients to complete, one of which is iron. Iron acquisition by the iron-scavenging siderophore petrobactin is the only such system known to be required for vegetative growth ofB. anthracisin iron-depleted conditions,e.g., in the host. However, the extent to which petrobactin is involved in spore formation is unknown. This work shows that efficientin vitrosporulation ofB. anthracisrequires petrobactin, that the petrobactin biosynthesis operon (asbA-F) is induced prior to sporulation, and that petrobactin itself is associated with spores. Petrobactin is also required for both oxidative stress protection during late stage growth and wild-type levels of sporulation in sporulation medium. When considered with the petrobactin-dependent sporulation in bovine blood also described in this work, these effects onin vitrogrowth and sporulation suggest that petrobactin is required forB. anthracistransmission via the spore during natural infections in addition to its key functions during active anthrax infections.

Importance

Bacillus anthraciscauses the disease anthrax, which is transmitted via its dormant, spore phase. However, converting from bacilli to spore is a complex, energetically costly process that requires many nutrients including iron.B. anthracisrequires the siderophore petrobactin to scavenge iron from host environments. We show that in the Sterne strain, petrobactin is required also for efficient sporulation, even when ample iron is available. The petrobactin biosynthesis operon is expressed during sporulation, and petrobactin is biosynthesized during growth in high iron sporulation medium but instead of being exported, the petrobactin remains intracellular to protect against oxidative stress and improve sporulation. It is also required for full growth and sporulation in blood (bovine), an essential step for anthrax transmission between mammalian hosts.
Understanding RNP remodelling uncovers RBPs functionally required for viral replication
Authors: Garcia-Moreno Manuel , Noerenberg Marko , Ni Shuai , Jarvelin Aino I , Gonzalez-Almela Esther , Lenz Caroline , Bach-Pages Marcel , Cox Victoria , Avolio Rosario , Davis Thomas , Hester Svenja , Sohier Thibault JM , Li Bingnan , Sanz Miguel Angel , Carrasco Luis , Ricci Emiliano P , Pelechano Vicent , Fischer Bernd , Mohammed Shabaz , Castello Alfredo
Published: June 2018

The compendium of RNA-binding proteins (RBPome) has been greatly expanded by the development of RNA-interactome capture (RNA-IC). However, it remains unknown how responsive is the RBPome and whether these responses are biologically relevant. To answer these questions, we created "comparative RNA-IC" to analyse cells challenged with an RNA virus, called sindbis (SINV). Strikingly, the virus altered the activity of 245 RBPs, many of which were newly discovered by RNA-IC. Mechanistically, alterations in RNA binding upon SINV infection are caused by changes in the subcellular localisation of RBPs and RNA availability. Moreover, "RBPome" responses are crucial, as perturbation of dynamic RBPs modulates the capacity of the virus to infect the cell. For example, ablation of XRN1 causes cells to be refractory to infection, while GEMIN5 moonlights as a novel antiviral factor. Therefore, RBPome remodelling provides a mechanism by which cells can extensively rewire gene expression in response to physiological cues.
Radiogenomics-based Risk Prediction of Glioblastoma Multiforme with Clinical Relevance
Authors: Qian Xiaohua , Tan Hua , Chen Wei , Zhao Weiling , Chan Michael D. , Zhou Xiaobo
Published: June 2018

GBM is the most common and aggressive primary brain tumor. Although the TMZ-based radiochemotherapy improves overall GBM patients’ survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudoprogression is a treatment-related reaction with an increase in contrast-enhancing lesion size at the tumor site or resection margins which mimics tumor recurrence on MRI. Accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed to develop a prognostic model to evaluate tumor progression potential of GBM patients following standard therapies. We applied a dictionary learning scheme to obtain imaging features of GBM patients with PsP or TTP from the Wake dataset. Based on these radiographic features, we then conducted radiogenomics analysis to identify the significantly associated genes. These significantly associated genes were then used as features to construct a 2YS logistic regression model. GBM patients were classified into low-and high-survival risk groups based on the individual 2YS scores derived from this model. We tested our model using an independent TCGA dataset and found that 2YS scores were significantly associated with the patients’ overall survival. We further used two cohorts of the TCGA data to train and test our model. Our results show that 2YS scores-based classification results from the training and testing TGCA datasets were significantly associated with the overall survival of patients. We also analyzed the survival prediction ability of other clinical factors (gender, age, KPS, normal cell ratio) and found that these factors were not related or weakly correlated with patients’ survival. Overall, our studies have demonstrated the effectiveness and robustness of the 2YS model in predicting clinical outcomes of GBM patients after standard therapies.
Microtubule Probe for Correlative Super-Resolution Fluorescence and Electron Microscopy
Authors: Tian Xiaohe , De Pace Cesare , Ruiz-Perez Lorena , Chen Bo , Su Rina , Zhang Mingzhu , Zhang Ruilong , Zhang Qiong , Wang Qin , Zhou Hongping , Wu Jieying , Xiang Pan , Fang Bin , Tian Yupeng , Zhang Zhongping , Battaglia Giuseppe
Published: June 2018

We report a versatile cyclometalated Iridium (III) complex probe that achieves synchronous fluorescence-electron microscopy correlation to reveal microtubule ultrastructure in cells. The selective insertion of probe between repeatedαandβunits of microtubule triggers remarkable fluorescent enhancement, and high TEM contrast due to the presence of heavy Ir ions. The highly photostable probe allows live cell imaging of tubulin localization and motion during cell division with an resolution of 20 nm, and under TEM imaging reveals theαβunit interspace of 45Å of microtubule in cells.
DeepAffinity: Interpretable Deep Learning of Compound-Protein Affinity through Unified Recurrent and Convolutional Neural Networks
Authors: Karimi Mostafa , Wu Di , Wang Zhangyang , shen Yang
Published: June 2018

Motivation

Drug discovery demands rapid quantification of compound-protein interaction (CPI). However, there is a lack of methods that can predict compound-protein affinity from sequences alone with high applicability, accuracy, and interpretability.

Results

We present a seamless integration of domain knowledges and learning-based approaches. Under novel representations of structurally-annotatedprotein sequences, a semi-supervised deep learning model that unifies recurrent and convolutional neural networks has been proposed to exploit both unlabeled and labeled data, for jointly encoding molecular representations and predicting affinities. Our representations and models outperform conventional options in achieving relative error in IC50 within 5-fold for test cases and 20-fold for protein classes not included for training. Performances for new protein classes with few labeled data are further improved by transfer learning. Furthermore, separate and joint attention mechanisms are developed and embedded to our model to add to its interpretability, as illustrated in case studies for predicting and explaining selective drug-target interactions. Lastly, alternative representations using protein sequences or compound graphs and a unified RNN/GCNN-CNN model using graph CNN (GCNN) are also explored to reveal algorithmic challenges ahead.

Availability

Data and source codes are available at https://github.com/Shen-Lab/DeepAffinity

Contact

yshen@tamu.edu

Supplementary information

Supplementary data are available at http://shen-lab.github.io/deep-affinity-bioinf18-supp-rev.pdf.
An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus
Authors: Shen Wen-Fan , Ucat Galula Jedhan , Liu Jyung-Hurng , Liao Mei-Ying , Huang Chang-Hao , Wang Yu-Chun , Wu Han-Chung , Liang Jian-Jong , Lin Yi-Ling , Whitney Matthew T. , Chang Gwong-Jen J. , Chen Sheng-Ren , Wu Shang-Rung , Chao Day-Yu
Published: June 2018

Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein we show for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction. Mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher cross reactive (CR) neutralization antibodies (NtAbs) and were protected against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. Our results revealed that a “epitope-resurfaced” mature-form dengue VLP has the potential to induce quaternary structure-recognizing broad CR NtAbs.
Target localization across saccades and at fixation: Nontargets both facilitate and bias responses
Authors: Zhang Xiaoli , Golomb Julie D.
Published: June 2018

The image on our retina changes every time we make an eye movement. To maintain visual stability across saccades, specifically to locate visual targets, we may use nontarget objects as “landmarks”. In the current study, we compared how the presence of nontargets affects target localization across saccades and during sustained fixation. Participants fixated a target object, which either maintained its location on the screen (sustained-fixation trials), or displaced to trigger a saccade (saccade trials). After the target disappeared, participants reported the most recent target location with a mouse click. We found that the presence of nontargets decreased response error magnitude and variability. However, this nontarget facilitation effect was not larger for saccade trials than sustained-fixation trials, indicating that nontarget facilitation might be a general effect for target localization, rather than of particular importance to saccadic stability. Additionally, participants’ responses were biased towards the nontarget locations, particularly when the nontarget-target relationships were preserved in relative coordinates across the saccade. This nontarget bias interacted with biases from other spatial references, e.g. eye movement paths, possibly in a way that emphasized non-redundant information. In summary, the presence of nontargets is one of several sources of reference that combine to influence (both facilitate and bias) target localization.
The MS4A gene cluster is a key regulator of soluble TREM2 and Alzheimer disease risk
Authors: Deming Yuetiva , Filipello Fabia , Cignarella Francesca , Cantoni Claudia , Hsu Simon , Mikesell Robert , Li Zeran , Del-Aguila Jorge L , Dube Umber , Farias Fabiana Geraldo , Bradley Joseph , Benitez Bruno , Budde John , Ibanez Laura , Fernandez Maria Victoria ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI),   Dominantly Inherited Alzheimer Network (DIAN), Blennow Kaj , Zetterberg Henrik , Heslegrave Amanda , Johansson Per M , Svensson Johan , Nellgård Bengt , Lleo Alberto , Alcolea Daniel , Clarimon Jordi , Rami Lorena , Molinuevo José Luis , Suarez-Calvet Marc , Morenas-Rodríguez Estrella , Kleinberger Gernot , Ewers Michael , Harari Oscar , Haass Christian , Brett Thomas J , Karch Celeste M. , Piccio Laura , Cruchaga Carlos
Published: June 2018

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF) have been associated with Alzheimer disease (AD) status. TREM2 plays a critical role in microglial activation, survival, and phagocytosis; however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may help reveal biological mechanisms underlying AD and identify novel therapeutic targets. We performed a genome-wide association study (GWAS) to identify genetic modifiers of CSF sTREM2 levels. Common variants in the membrane-spanning 4-domains subfamily A (MS4A) gene region were associated with higher CSF sTREM2 levels (rs1582763; P = 1.15×10−15) and replicated in independent datasets. The variants associated with increased levels of sTREM2 are also associated with reduced AD risk and delayed age-at-onset. Rs1582763 influences expression of MS4A4A and MS4A6A in multiple tissues, suggesting that one or both of these genes are important for regulating sTREM2. MS4A genes encode transmembrane proteins that may play a role in intracellular protein trafficking in microglia. We used human macrophages to begin to test the relationship between MS4A4A and TREM2 and found that they co-localize intracellularly and that antibody-mediated targeting of MS4A4A reduces sTREM2. Thus, genetic, molecular, and cellular findings suggest that MS4A4A regulates sTREM2. These findings also provide a mechanistic explanation of the original GWAS signal in the MS4A locus for AD risk and indicate that TREM2 is involved in sporadic AD risk in general, not only in TREM2 risk-variant carriers.
Robust genome editing with short single-stranded and long, partially single-stranded DNA donors in C. elegans
Authors: Dokshin Gregoriy A. , Ghanta Krishna S. , Piscopo Katherine M. , Mello Craig C.
Published: June 2018

CRISPR-based genome editing using ribonucleoprotein (RNP) complexes and synthetic single stranded oligodeoxynucleotide (ssODN) donors can be highly effective. However, reproducibility can vary, and precise, targeted integration of longer constructs – such as green fluorescent protein (GFP) tags remains challenging in many systems. Here we describe a streamlined and optimized editing protocol for the nematode C. elegans. We demonstrate its efficacy, flexibility, and cost-effectiveness by affinity-tagging all twelve of the Worm-specific Argonaute (WAGO) proteins in C. elegans using ssODN donors. In addition, we describe a novel PCR-based partially single-stranded “hybrid” donor design that yields high efficiency editing with large (kilobase-scale) constructs. We use these hybrid donors to introduce fluorescent protein tags into multiple loci achieving editing efficiencies that approach those previously obtained only with much shorter ssODN donors. The principals and strategies described here are likely to translate to other systems and should allow researchers to reproducibly and efficiently obtain both long and short precision genome edits.
A highly predictive signature of cognition and brain atrophy for progression to Alzheimer’s dementia
Authors: Tam Angela , Dansereau Christian , Itturia-Medina Yasser , Urchs Sebastian , Orban Pierre , Sharmarke Hanad , Breitner John , Bellec Pierre ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2018

Clinical trials in Alzheimer’s disease need to enroll patients whose cognition will decline over time, if left untreated, in order to demonstrate the efficacy of an intervention. Machine learning models used to screen for patients at risk of progression to dementia should therefore favor specificity (detecting only progressors) over sensitivity (detecting all progressors), especially when the prevalence of progressors is low. Here, we explore whether such high-risk patients can be identified using cognitive assessments and structural neuroimaging, by training machine learning tools in a high specificity regime. A multimodal signature of Alzheimer’s dementia was first extracted from ADNI1. We then validated the predictive value of this signature on ADNI1 patients with mild cognitive impairment (N=235). The signature was optimized to predict progression to dementia over three years with low sensitivity (55.1%) but high specificity (95.6%), resulting in only moderate accuracy (69.3%) but high positive predictive value (80.4%, adjusted for a “typical” 33% prevalence rate of true progressors). These results were replicated in ADNI2 (N=235), with 87.8% adjusted positive predictive value (96.7% specificity, 47.3% sensitivity, 85.1% accuracy). We found that cognitive measures alone could identify high-risk individuals, with structural measurements providing a slight improvement. The signature had comparable receiver operating characteristics to standard machine learning tools, yet a marked improvement in positive predictive value was achieved over the literature by selecting a high specificity operating point. The multimodal signature can be readily applied for the enrichment of clinical trials.
Happy home at Adform – corporate culture as a tool to attract and retain talent
Authors: Augutyte-Kvedaraviciene Ieva
Published: June 2018

Subject area

Social science, Organizational behaviour.

Study level/applicability

The case is intended for bachelor or master level students as a part of HRM and OB curriculum and in particular organizational culture and change management topics as well as talent selection and innovation issues in the organization.

Case overview

Adform, a fast-growing global ad-tech company, is well-known in the market as a workplace that nurtures creativity and innovation. Recently recognized as the Aon Employer of the Year 2016 in the Baltic States by OVC, the company strives to maintain the position and remain an attractive place to work at. However, when both the sector and the company is growing fast, it becomes a challenge to sustain corporate culture and implement shared values in daily activities. Creative and innovative employees are in high demanded in the whole ad-tech sector and competition for the best professionals is inevitable. The key issues Anna, head of HR Strategic initiatives, is facing to present are as follows: How to attract and retain the best talent in a highly competitive labour market? How to maintain corporate culture that promotes innovative thinking when the company is growing fast and the sector is developing even faster? How to manage conflicts between personal and corporate values when employees are in high demand in the market? The case is structured from three different perspectives – newly employed professional Simon, experienced Adformers Ingrid and Martin, and Human Resources department specialists Anna and Sandra – everyone has different challenges and issues to solve; however, they share common values and beliefs, which form a sound base for decision-making and prove the importance of corporate culture as a strong management tool at Adform.

Expected learning outcomes

Expected learning outcomes are as follows: to understand major components of corporate culture and its role in an organisation, to gain practice in assessing corporate culture and its types; to understand the role of corporate culture in attracting and retaining talented employees to help company grow and develop; and to recognize challenges a company may encounter sustaining a strong corporate culture in a fast-growing sector and to analyse means of strong culture maintenance.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS: 6: Human Resource Management.
The impact of supply chain relationship quality on performance in the maritime logistics industry in light of firm characteristics
Authors: Shin Youngran , Thai Vinh , Yuen Kum Fai
Published: June 2018

Purpose

Anchoring on configuration theory, the purpose of this paper is to evaluate how supply chain relationship quality (SCRQ) differs across firm characteristics (FC) in the maritime logistics industry. In addition, it utilises transactional cost theory to establish the relationship between SCRQ and supply chain performance (SCP).

Design/methodology/approach

The data were obtained from a survey with 205 maritime logistics service players (shipping firms, shippers and freight forwarders) in Singapore. MANOVA andt-test analyses are used to examine the difference in SCRQ (i.e. trust and commitment) across FC which includes firm types and ownership types. Thereafter, structural equation modelling is employed to examine the influence of SCRQ on SCP.

Findings

The results indicate that the effects of trust and commitment on SCRQ vary significantly. It was also found that trust as an aspect of SCRQ has a significant impact on SCP, whereas commitment does not.

Research limitations/implications

As the field data were obtained from only one industry, future replication of the findings to other industries should consider industry-specific factors, if applicable.

Practical implications

It is suggested that maritime logistics service players should carefully manage trust and commitment to simultaneously enable SCP. By identifying the various aspects of FC that contribute to SCRQ, maritime logistics service providers could devise appropriate strategies for different customer segments more effectively.

Originality/value

This study expands current supply chain research by linking two dimensions of SCRQ in relationship marketing with SCP in supply chain management. It is also one of the first empirical attempts to explore the role of FC in the linkage between SCRQ and SCP in the maritime logistics industry.
Stories and metaphors in retail selling
Authors: Gilliam David A. , Rockwell Casey C.
Published: June 2018

Purpose

The purpose of this paper is to propose future directions for research into stories and metaphors as concise communication tools that are particularly salient for the fast pace of today’s retail sales environment.

Design/methodology/approach

A cross disciplinary approach is taken to propose new avenues for sales communication research.

Findings

This work highlights research possibilities into the contextually sensitive constructs of stories and metaphors with associated theoretical approaches. This could improve research into stories and metaphors as communication techniques for retail selling.

Research limitations/implications

The findings indicate that stories and metaphors are highly engaging sensemaking tools that salespeople can use in retail sales encounters. The lack of existing literature within the sales domain suggests a significant learning curve in demarcating the use of these tools.

Practical implications

Stories and metaphors are presently used by salespeople but without the benefit of extensive scientific understanding. This paper builds a foundation for research that could bring clarity to the use of these tools in retail selling.

Originality/value

Researchers will benefit from a finer grained conceptualization with which to examine sales communication. The proposed research should get sales practitioners a clearer understanding of using stories and metaphors in sales encounters.
Indexing Arabic texts using association rule data mining
Authors: Haraty Ramzi A. , Nasrallah Rouba
Published: June 2018

Purpose

The purpose of this paper is to propose a new model to enhance auto-indexing Arabic texts. The model denotes extracting new relevant words by relating those chosen by previous classical methods to new words using data mining rules.

Design/methodology/approach

The proposed model uses an association rule algorithm for extracting frequent sets containing related items – to extract relationships between words in the texts to be indexed with words from texts that belong to the same category. The associations of words extracted are illustrated as sets of words that appear frequently together.

Findings

The proposed methodology shows significant enhancement in terms of accuracy, efficiency and reliability when compared to previous works.

Research limitations/implications

The stemming algorithm can be further enhanced. In the Arabic language, we have many grammatical rules. The more we integrate rules to the stemming algorithm, the better the stemming will be. Other enhancements can be done to the stop-list. This is by adding more words to it that should not be taken into consideration in the indexing mechanism. Also, numbers should be added to the list as well as using the thesaurus system because it links different phrases or words with the same meaning to each other, which improves the indexing mechanism. The authors also invite researchers to add more pre-requisite texts to have better results.

Originality/value

In this paper, the authors present a full text-based auto-indexing method for Arabic text documents. The auto-indexing method extracts new relevant words by using data mining rules, which has not been investigated before. The method uses an association rule mining algorithm for extracting frequent sets containing related items to extract relationships between words in the texts to be indexed with words from texts that belong to the same category. The benefits of the method are demonstrated using empirical work involving several Arabic texts.
Two cases of dabrafenib and trametinib therapy‐failed advanced melanoma successfully controlled by nivolumab monotherapy
Authors: Sato Yota , Fujimura Taku , Kambayashi Yumi , Tanita Kayo , Tono Hisayuki , Hashimoto Akira , Aiba Setsuya
Published: June 2018

Although therapies for advanced melanoma have been greatly improved by the development of immune checkpoint inhibitors and BRAF/mitogen‐activated protein kinase kinase inhibitors, there are still many concerns about the administration of these novel drugs. Therefore, to combine these therapies sequentially at appropriate time points of the disease is important. In this report, we report two cases in which dabrafenib and trametinib therapy for advanced melanoma failed but were successfully controlled by nivolumab monotherapy, and investigated the sera sCD163, CCL22 and CXCL10 as biomarkers for tumor progression. Interestingly, the sera levels of sCD163, CXCL10 and CCL22, both of which are produced by activated tumor‐associated macrophages, were increased in parallel with the tumor progression in each case. Because this report presents only two cases, further data will need to be accumulated to provide more fundamental insights into the usefulness of these biomarkers for predicting disease progression in melanoma.
Inducible nitric oxide synthase inhibitor 1400W increases Na+,K+‐ATPase levels and activity and ameliorates mitochondrial dysfunction in Ctns null kidney proximal tubular epithelial cells
Authors: Sumayao Rodolfo , Newsholme Philip , McMorrow Tara
Published: June 2018

Nitric oxide (NO) has been shown to play an important role in renal physiology and pathophysiology partly through its influence on various transport systems in the kidney proximal tubule. The role of NO in kidney dysfunction associated with lysosomal storage disorder, cystinosis, is largely unknown. In the present study, the effects of inducible nitric oxide synthase (iNOS)‐specific inhibitor, 1400W, on Na+,K+‐ATPase activity and expression, mitochondrial integrity and function, nutrient metabolism, and apoptosis were investigated in Ctns null proximal tubular epithelial cells (PTECs). Ctns null PTECs exhibited an increase in iNOS expression, augmented NO and nitrite/nitrate production, and reduced Na+,K+‐ATPase expression and activity. In addition, these cells displayed depolarized mitochondria, reduced adenosine triphosphate content, altered nutrient metabolism, and elevated apoptosis. Treatment of Ctns null PTECs with 1400W abolished these effects which culminated in the mitigation of apoptosis in these cells. These findings indicate that uncontrolled NO production may constitute the upstream event that leads to the molecular and biochemical alterations observed in Ctns null PTECs and may explain, at least in part, the generalized proximal tubular dysfunction associated with cystinosis. Further studies are needed to realize the potential benefits of anti‐nitrosative therapies in improving renal function and/or attenuating renal injury in cystinosis.
Mutable environments and permeable human bodies★
Authors: Lock Margaret
Published: June 2018

Geologists have declared an epochal transition to the Anthropocene, formally recognizing humans as the driving force of destructive global change; a distinction can no longer be made between human history and natural history. Certain commentators argue that Capitalocene better characterizes the situation, given that the effects of planetary decimation and global warming are not equally distributed among humans. A second conceptual change has recently taken place in which genomes are recognized as reactive to environmental stimuli both external and internal to the human body. In the post‐genomic era, genes neither initiate life nor drive human development. The science of the bourgeoning field of behavioural epigenetics is introduced, followed by illustrative examples of environmentally caused epigenetic changes that impact negatively on health. Epigeneticists routinely delimit their attention to detecting measurable changes at the molecular level. It is argued that anthropological contributions that incorporate subjective accounts of embodiment involving past and present events are crucial in order to better situate and account for biological differences and health outcomes historically, ecologically, and politically. Discussion of the microbiome provides a cautionary reminder that microbes are the ultimate driving force of health and illness. In conclusion, the Earth Optimism movement is briefly introduced, as is the concept of resilience, but alone these positive moves will not curb unremitting global warming.
Filming sea‐level rise: media encounters and memory work in the Indian Sundarbans
Authors: Harms Arne
Published: June 2018

In this article, I discuss social consequences of the visualization of climate change. I focus on encounters between film crews and displaced islanders on rapidly eroding islands at the sea‐facing edge of the Indian Sundarbans. As these islands have become the epitome of global environmental damage and dystopian futures, film crews regularly travel here to produce captivating footage on degradation and displacement. I first situate the ensuing encounters in global regimes of visibility and infrastructural possibilities. Building on that, I argue that these encounters set forth what I call unintentional memory work. By virtue of being a spectacle, by enabling a return to the film subjects’ former homes, and by staging acts of remembering, film teams unintentionally induce a reworking of memories and, at times, the production of new memories. In both instances, particular pasts are prioritized and imbued with a sense of urgency and relevance to foreign film teams and global audiences. I frame these media encounters as interfaces through which global anxieties about Anthropocene futures become implicated in the fashioning of selves on remote shores.
The Role of Tacit Knowledge in Auditor Expertise and Human Capital Development
Authors: BOL JASMIJN C. , ESTEP CASSANDRA , MOERS FRANK , PEECHER MARK E.
Published: June 2018

Two critical aspects of the model of auditor expertise development in Tan and Libby [1997] are that audit firms do not value tacit knowledge in inexperienced auditors but do value it in experienced auditors. We update the former and extend the latter. Our paper predicts and finds that audit firms now do value tacit knowledge in inexperienced auditors, especially when their supervisors have higher tacit knowledge. Our proxies of value include higher promotability assessments, annual evaluations, and cash bonuses. Our paper also extends Tan and Libby [1997] by positing that enhanced development of expertise and audit firm human capital are two reasons audit firms value tacit knowledge in experienced auditors. As predicted, higher tacit knowledge in experienced auditors is positively associated with higher tacit knowledge acquisition by their inexperienced subordinates and with stronger firm commitment of inexperienced subordinates having higher tacit knowledge.