bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL‐VBM study
Authors: Colloby Sean J. , Elder Greg J. , Rabee Riham , O'Brien John T. , Taylor John‐Paul
Published: May 2016

Objectives

Several cholinergic nuclei, and in particular the nucleus basalis of Meynert, are localised to the substantia innominata in the basal forebrain. These nuclei provide major cholinergic innervation to the cerebral cortex and hippocampus, and have an essential role in cognitive function. The aim of this study was to investigate volumetric grey matter (GM) changes in the substantia innominata from structural T1 images in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy older participants using voxel‐based morphometry.

Methods

Participants (41 DLB, 47 AD and 39 controls) underwent 3 T T1 magnetic resonance imaging and cognitive assessments. Voxel‐based morphometry analysis used SPM8 with a substantia innominata brain mask to define the subspace for voxel GM analyses. Group differences, and selected behavioural and clinical correlates, were assessed.

Results

Compared with that in controls, bilateral GM loss in the substantia innominata was apparent in both AD and DLB. Relative to controls, significant bilateral GM loss in the substantia innominata was observed in DLB and AD. In DLB, significant associations were also observed between substantia innominata GM volume loss, and the levels of cognitive impairment and severity of cognitive fluctuations.

Conclusions

Relative to that controls, atrophy of the substantia innominata was apparent in DLB and AD, and is associated with specific clinical manifestations in DLB. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.
Selection of asset investment models by hospitals: examination of influencing factors, using Switzerland as an example
Authors: Eicher Bernhard
Published: May 2016

Hospitals are responsible for a remarkable part of the annual increase in healthcare expenditure. This article examines one of the major cost drivers, the expenditure for investment in hospital assets. The study, conducted in Switzerland, identifies factors that influence hospitals' investment decisions.

A suggestion on how to categorize asset investment models is presented based on the life cycle of an asset, and its influencing factors defined based on transaction cost economics. The influence of five factors (human asset specificity, physical asset specificity, uncertainty, bargaining power, and privacy of ownership) on the selection of an asset investment model is examined using a two‐step fuzzy‐set Qualitative Comparative Analysis.

The research shows that outsourcing‐oriented asset investment models are particularly favored in the presence of two combinations of influencing factors: First, if technological uncertainty is high and both human asset specificity and bargaining power of a hospital are low. Second, if assets are very specific, technological uncertainty is high and there is a private hospital with low bargaining power, outsourcing‐oriented asset investment models are favored too. Using Qualitative Comparative Analysis, it can be demonstrated that investment decisions of hospitals do not depend on isolated influencing factors but on a combination of factors. Copyright © 2016 John Wiley & Sons, Ltd.
Precision Oncology Medicine: The Clinical Relevance of Patient‐Specific Biomarkers Used to Optimize Cancer Treatment
Authors: Schmidt Keith T. , Chau Cindy H. , Price Douglas K. , Figg William D.
Published: May 2016

Precision medicine in oncology is the result of an increasing awareness of patient‐specific clinical features coupled with the development of genomic‐based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug‐target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA‐approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug‐metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression‐based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next‐generation sequencing to detect many potential “actionable” cancer molecular alterations is further shifting the 1 gene–1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI‐MATCH, NCI‐MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI‐MATCH will help determine the clinical utility and future development of the precision‐medicine approach.
Adverse Drug Reactions in Patients Receiving Systemic Antifungal Therapy at a High‐Complexity Hospital
Authors: de Souza Maria Clara Padovani , Santos Andrezza Gouvêa dos , Reis Adriano Max Moreira
Published: May 2016

The aim of the present study was to determine the frequency of adverse drug reactions (ADRs) associated with the use of systemic antifungal drugs in patients hospitalized at a high‐complexity hospital. In addition, factors associated with ADRs were investigated. This cross‐sectional retrospective study involved the investigation of 183 medical records of patients receiving systemic antifungal therapy. Antifungal drugs were classified using the fourth level of the Anatomical Therapeutic Chemical System. ADR causality was classified using the Naranjo algorithm. Drug interactions were assessed using DRUG‐REAX software. Data were analyzed with descriptive statistics and univariate and multivariate logistic regression. A total of 53 patients (29.0%) had at least 1 ADR involving antifungals. Ninety‐six ADRs were detected. The main ADRs observed were an infusion reaction in 24 patients (25.0%), hypokalemia in 22 (22.9%), nephrotoxicity in 18 (18.7%), and hepatotoxicity in 15 (15.6%). Amphotericin B and voriconazole were associated with ADRs of major clinical impact. Eleven of the ADRs (11.4%) were related to drug interactions. The following 3 factors were contributors to the multivariate model for the occurrence of ADRs caused by antifungal drug use: neoplasm diagnosis (odds ratio [OR], 3.9; 1.9–7.9), length of hospital stay (OR, 2.2; 1.1–4.5), and the use of ≥13 drugs (OR, 3.4; 1.6–7.2). Our study revealed positive associations between the occurrence of ADRs and diagnosis of a neoplasm, the length of stay, and the use of multiple drugs concomitant with antifungals. These risk factors should be considered in antifungal stewardship, among other actions, to promote the rational use of antifungal agents.
Jellyfish decomposition at the seafloor rapidly alters biogeochemical cycling and carbon flow through benthic food‐webs
Authors: Sweetman Andrew K. , Chelsky Ariella , Pitt Kylie A. , Andrade Hector , van Oevelen Dick , Renaud Paul E.
Published: May 2016

Jellyfish blooms have increased in magnitude in several locations around the world, including in fjords. While the factors that promote jellyfish blooms and the impacts of live blooms on marine ecosystems are often investigated, the post‐bloom effects from the sinking and accumulation of dead jellyfish at the seafloor remain poorly known. Here, we quantified the effect of jellyfish deposition on short‐term benthic carbon cycling dynamics in benthic cores taken from a cold and deep fjord environment. Respiration was measured and 13C‐labeled algae were used as a tracer to quantify how C‐flow through the benthic food web was affected over 5 d in the presence and absence of jellyfish carcasses. Benthic respiration rates increased rapidly (within 2 h) in the jellyfish‐amended cores, and were significantly higher than cores that were supplied with only labeled phytodetritus between 17 h and 117 h. In the cores that were supplied with only labeled phytodetritus, macrofauna dominated algal‐C uptake over the 5 d study. The addition of jellyfish caused a rapid and significant shift in C‐uptake dynamics: macrofaunal C‐uptake decreased while bacterial C‐uptake increased relative to the cores supplied with only phytodetritus. Our results suggest that the addition of jellyfish detritus to the seafloor can rapidly alter benthic biogeochemical cycling, and substantially modify C‐flow through benthic communities. If our results are representative for other areas, they suggest that jellyfish blooms may have cascading effects for benthic ecosystem functions and services when blooms senesce, such as enhanced bacterial metabolism and reduced energy transfer to upper trophic levels.
Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists
Authors: Maslov Leonid N , Khaliulin Igor , Oeltgen Peter R. , Naryzhnaya Natalia V. , Pei Jian‐Ming , Brown Stephen A. , Lishmanov Yury B. , Downey James M.
Published: May 2016

It has now been demonstrated that the μ, δ1, δ2, and κ1 opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct‐reducing effect with prophylactic administration and prevent reperfusion‐induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia‐induced arrhythmias.
Indocyanine green videoangiography‐assisted prediction of flap necrosis in the rat epigastric flap using the flow® 800 tool
Authors: Mücke Thomas , Fichter Andreas M. , Schmidt Leonard H. , Mitchell David A. , Wolff Klaus‐Dietrich , Ritschl Lucas M.
Published: May 2016

Background

The decision to re‐operate on a potentially ischemic free flap remains challenging. Indocyanine green videoangiography (ICG) with the FLOW® 800 tool is a method which allows an immediate qualitative conclusion about the patency of an anastomosis. Is it also able to predict the outcome of potentially compromised vascular free flaps?

Materials and Methods

An epigastric flap was raised and repositioned in 79 rats. Intraoperative fluorescence angiography was performed using ICG videoangiography and the FLOW® 800 tool was applied. Six regions of interest were positioned systematically over the flap, changes of the ICG fluorescence were color coded with respect to time and 474 measurements were performed. The flap was clinically monitored for one week and the resulting necrotic areas were correlated with the ICG/FLOW® 800 results.

Results

Mean intensity of clinically vital areas was 83.39 ± 50.96 arbitrary units (AU) and 37.33 ± 15.14 AU in necrotic areas. The receiver operating characteristic curve and Youden‐Index analysis revealed that the optimal cutoff for the maximal intensity of ICG after FLOW® 800 analysis was ≤ 61.733 for the prediction of flap necrosis and > 61.733 for the prediction of flap survival (P < 0.0001; 95% CI = 0.85–0.91; Youden‐Index: 0.67). The maximal intensity of ICG angiography had a specificity of 96.1% and sensitivity of 71.4%. The positive predictive value was 97.46% and the corresponding negative predictive value was 61.34%.

Conclusion

This demonstrates the potential additional value of ICG videoangiography including FLOW® 800 analyses in the postoperative monitoring of transplanted flaps. © 2016 Wiley Periodicals, Inc. Microsurgery 37:235–242, 2017.
Explicit integration of a porosity‐dependent hydro‐mechanical model for unsaturated soils
Authors: Zhang Yue , Zhou Annan
Published: May 2016

An adaptive substepping explicit integration scheme is developed for a porosity‐dependent hydro‐mechanical model for unsaturated soils. The model is referred to as the modified σ–Θ model in this paper, which features the employment of the subloading surface plasticity and the stress–saturation approach. On numerical aspects, convex/nonconvex subloading surfaces in the σ–Θ space may result in incorrect loading–unloading decisions during the integration. A new loading–unloading decision method is developed here to solve the problem and then embedded into the explicit integration scheme for the modified σ–Θ model. In addition, to enhance the accuracy of the explicit integration, local errors from both hydraulic and mechanical components are included in the error control for each substep. A drift correction method is also developed to ensure the state point lies on the subloading surface in the σ–Θ space within a set error level. The performance of the loading–unloading decision method for the modified σ–Θ model is discussed through comparing it with the conventional loading–unloading decision method. The importance of involving the hydraulic component in the error control is also demonstrated. The accuracy and efficiency of the proposed adaptive substepping explicit integration scheme for the modified p–Θ model are also studied via several numerical examples. Copyright © 2016 John Wiley & Sons, Ltd.
Large‐scale multiplex absolute protein quantification of drug‐metabolizing enzymes and transporters in human intestine, liver, and kidney microsomes by SWATH‐MS: Comparison with MRM/SRM and HR‐MRM/PRM
Authors: Nakamura Kenji , Hirayama‐Kurogi Mio , Ito Shingo , Kuno Takuya , Yoneyama Toshihiro , Obuchi Wataru , Terasaki Tetsuya , Ohtsuki Sumio
Published: May 2016

The purpose of the present study was to examine simultaneously the absolute protein amounts of 152 membrane and membrane‐associated proteins, including 30 metabolizing enzymes and 107 transporters, in pooled microsomal fractions of human liver, kidney, and intestine by means of SWATH‐MS with stable isotope‐labeled internal standard peptides, and to compare the results with those obtained by MRM/SRM and high resolution (HR)‐MRM/PRM. The protein expression levels of 27 metabolizing enzymes, 54 transporters, and six other membrane proteins were quantitated by SWATH‐MS; other targets were below the lower limits of quantitation. Most of the values determined by SWATH‐MS differed by less than 50% from those obtained by MRM/SRM or HR‐MRM/PRM. Various metabolizing enzymes were expressed in liver microsomes more abundantly than in other microsomes. Ten, 13, and eight transporters listed as important for drugs by International Transporter Consortium were quantified in liver, kidney, and intestinal microsomes, respectively. Our results indicate that SWATH‐MS enables large‐scale multiplex absolute protein quantification while retaining similar quantitative capability to MRM/SRM or HR‐MRM/PRM. SWATH‐MS is expected to be useful methodology in the context of drug development for elucidating the molecular mechanisms of drug absorption, metabolism, and excretion in the human body based on protein profile information.
Whole body MRI (WB‐MRI) assessment of metastatic spread in prostate cancer: Therapeutic perspectives on targeted management of oligometastatic disease
Authors: Larbi Ahmed , Dallaudière Benjamin , Pasoglou Vasiliki , Padhani Anwar , Michoux Nicolas , Vande Berg Bruno C. , Tombal Bertrand , Lecouvet Frédéric E.
Published: May 2016

OBJECTIVES

To determine the proportion of prostate cancer (PCa) patients with oligometastatic disease (≤3 synchronous lesions) using whole body magnetic resonance imaging with diffusion‐weighted imaging (WB‐MRI/DWI). To determine the proportion of patients with nodal disease confined within currently accepted target areas for extended lymph node dissection (eLND) and pelvic external beam radiation therapy (EBRT).

SUBJECTS AND METHODS

Two radiologists reviewed WB‐MRI/DWI studies in 96 consecutive newly diagnosed metastatic PCa patients; 46 patients with newly diagnosed castration naive PCa (mHNPC) and 50 patients with first appearance of metastasis during monitoring for non‐metastatic castration resistant PCa (M0 to mCRPC). The distribution of metastatic deposits was assessed and the proportions of patients with oligometastatic disease and with LN metastases located within eLND and EBRT targets were determined.

RESULTS

Twenty‐eight percent of mHNPC and 50% of mCPRC entered the metastatic disease with ≤3 sites. Bone metastases (BM) were identified in 68.8% patients; 71.7% of mHNPC and 66% mCRPC patients. Most commonly involved areas were iliac bones and lumbar spine. Enlarged lymph nodes (LN) were detected in 68.7% of patients; 69.6% of mHNPC and 68.0% of mCRPC. Most commonly involved areas were para‐aortic, inter‐aortico‐cava, and external iliac areas. BM and LN were detected concomitantly in 41% of mHNPC and 34% of mCRPC. Visceral metastases were detected in 6.7%. Metastatic disease was confined to LN located within the accepted boundaries of eLND or pelvic EBRT target areas in only ≤25% and ≤30% of patients, respectively.

CONCLUSIONS

Non‐invasive mapping of metastatic landing sites in PCa using WB‐MRI/DWI shows that 28% of the mHNPC patients, and 52% of the mCRPC can be classified as oligometastatic, thus challenging the concept of metastatic targeted therapy. More than two thirds of metastatic patients have LN located outside the usually recommended targets of eLND and pelvic EBRT. Prophylactic or salvage treatments of these sole areas in patients with high‐risk prostate cancer may not prevent the emergence of subsequent metastases. Prostate 76:1024–1033, 2016. © 2016 Wiley Periodicals, Inc.
Technical Standards for Nursing Education Programs in the 21st Century
Authors: Ailey Sarah H. , Marks Beth
Published: May 2016

Purpose:

The Institute of Medicine (2000, 2002) exposed serious safety problems in the health system and called for total qualitative system change. The Institute of Medicine (2011, 2015) also calls for improving the education of nurses to provide leadership for a redesigned health system. Intertwined with improving education is the need to recruit and retain diverse highly qualified students. Disability is part of diversity inclusion, but current technical standards (nonacademic requirements) for admission to many nursing programs are a barrier to the entry of persons with disabilities. Rehabilitation nurse leaders are in a unique position to improve disability diversity in nursing. The purpose of this paper is to discuss the importance of disability diversity in nursing.

Design:

The history of existing technical standards used in many nursing programs is reviewed along with examples.

Methods:

On the basis of the concept that disability inclusion is a part of diversity inclusion, we propose a new model of technical standards for nursing education.

Conclusion and Clinical Relevance:

Rehabilitation nurse leaders can lead in eliminating barriers to persons with disabilities entering nursing.
First‐principles calculations of oxygen adsorption on the Ti3Al (0001) surface
Authors: Wei L. J. , Guo J. X. , Dai X. H. , Guan L. , Wang Y. L. , Liu B. T.
Published: May 2016

Adsorption energies and density of states for O atoms adsorption on the Ti3Al (0001) surface have been calculated using first‐principles calculations based on density functional theory. It is found that the order of O atom adsorption on the Ti3Al (0001) surface is associated with the adsorption energy as well as the distance of O atoms because of the interaction. The adsorption energy mainly depends on the bond number and bond strength between O and Ti atoms, and the adsorption site with rich‐Ti surface (HI and HCPAl) is first priority. The adsorption energy decreases with the increase of the oxygen coverage because of the characteristics of the valence d‐orbitals of transition metals surface. Furthermore, the density of states indicates that the hybridization peak of O and Ti atoms is mainly from the contribution of Ti 3d‐ and O 2p‐orbitals, and the hybridization peak of O and Al atoms from the contribution of Al 2p‐ and O 2p‐orbitals. Copyright © 2016 John Wiley & Sons, Ltd.
Skeletal muscle fiber type: using insights from muscle developmental biology to dissect targets for susceptibility and resistance to muscle disease
Authors: Talbot Jared , Maves Lisa
Published: May 2016

Skeletal muscle fibers are classified into fiber types, in particular, slow twitch versus fast twitch. Muscle fiber types are generally defined by the particular myosin heavy chain isoforms that they express, but many other components contribute to a fiber's physiological characteristics. Skeletal muscle fiber type can have a profound impact on muscle diseases, including certain muscular dystrophies and sarcopenia, the aging‐induced loss of muscle mass and strength. These findings suggest that some muscle diseases may be treated by shifting fiber type characteristics either from slow to fast, or fast to slow phenotypes, depending on the disease. Recent studies have begun to address which components of muscle fiber types mediate their susceptibility or resistance to muscle disease. However, for many diseases it remains largely unclear why certain fiber types are affected. A substantial body of work has revealed molecular pathways that regulate muscle fiber type plasticity and early developmental muscle fiber identity. For instance, recent studies have revealed many factors that regulate muscle fiber type through modulating the activity of the muscle regulatory transcription factor MYOD1. Future studies of muscle fiber type development in animal models will continue to enhance our understanding of factors and pathways that may provide therapeutic targets to treat muscle diseases. WIREs Dev Biol 2016, 5:518–534. doi: 10.1002/wdev.230

This article is categorized under:

Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms

Vertebrate Organogenesis > Musculoskeletal and Vascular

Birth Defects > Organ Anomalies
The lattice‐based approaches for mining association rules: a review
Authors: Le Tuong , Vo Bay
Published: May 2016

The traditional methods for mining association rules (ARs) include two phrases: mining frequent itemsets (FIs)/frequent closed itemsets (FCIs)/frequent maximal itemsets (FMIs) and generating ARs from FIs/FCIs/FMIs. Lattice‐based approaches (LBAs) for mining ARs are new approaches including two phrases: frequent itemset lattice (FIL)/frequent closed itemset lattice (FCIL) building and generating ARs from the lattice. Total mining time of LBAs for mining ARs outperforms the traditional methods for mining ARs. Besides, the most important advantage of LBAs for mining ARs is that the algorithms only build the lattice once and mine ARs with many different confidences or many different minimum supports (the thresholds have to be greater than or equal to the threshold used to build lattices) without mining FIs/FCIs again. In this article, we describe a number of existing LBAs for mining ARs on static databases including lattice building and rule generation. In addition, in today's online system, the data often change in several operations such as insert, delete, and update. Hence, a number of LBAs for mining ARs on dynamic databases are mentioned. Finally, complexity analysis of the LBAs for mining ARs is also thoroughly discussed. WIREs Data Mining Knowl Discov 2016, 6:140–151. doi: 10.1002/widm.1181

This article is categorized under:

Algorithmic Development > Association Rules
RNA‐Seq methods for transcriptome analysis
Authors: Hrdlickova Radmila , Toloue Masoud , Tian Bin
Published: May 2016

Deep sequencing has been revolutionizing biology and medicine in recent years, providing single base‐level precision for our understanding of nucleic acid sequences in high throughput fashion. Sequencing of RNA, or RNA‐Seq, is now a common method to analyze gene expression and to uncover novel RNA species. Aspects of RNA biogenesis and metabolism can be interrogated with specialized methods for cDNA library preparation. In this study, we review current RNA‐Seq methods for general analysis of gene expression and several specific applications, including isoform and gene fusion detection, digital gene expression profiling, targeted sequencing and single‐cell analysis. In addition, we discuss approaches to examine aspects of RNA in the cell, technical challenges of existing RNA‐Seq methods, and future directions. WIREs RNA 2017, 8:e1364. doi: 10.1002/wrna.1364

This article is categorized under:

RNA Evolution and Genomics > Ribonomics

RNA Methods > RNA Analyses In Vitro and In Silico
A Positive Node on Ultrasound‐Guided Fine Needle Aspiration Predicts Higher Nodal Burden Than a Positive Sentinel Lymph Node Biopsy in Breast Carcinoma
Authors: Boland M. R. , Ni Cearbhaill R. , Fitzpatrick K. , Walsh S. M. , Evoy D. , Geraghty J. , Rothwell J. , McNally S. , O’Doherty A. , Quinn C. M. , McDermott E. W. , Prichard R. S.
Published: May 2016

Introduction

Axillary status remains an important prognostic indicator in breast cancer. Certain patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Uncertainty remains if this approach could be applied to patients diagnosed with axillary metastases on ultrasound‐guided fine needle aspiration cytology (USFNAC). The aim of this study was to compare nodal burden in patients with positive USFNAC and a positive SLNB.

Methods

A retrospective study was performed involving all BC patients between 2007 and 2014 who had either pre‐operative USFNAC or a SLNB. Patient/tumour characteristics and nodal burden were examined in all patients proceeding to AC.

Results

974 patients were eligible for analysis. 439 patients (45 %) had positive USFNAC and 535 (55 %) had a positive SLNB. USFNAC‐positive patients were more likely to undergo mastectomy (Chi‐square test; p < 0.001), have extra‐nodal extension (p < 0.001), be oestrogen receptor negative (p < 0.001) and be HER2 positive (p < 0.001). The median total number of lymph nodes (LNs) excised during AC was higher in the USFNAC group (Mann–Whitney test; 23 vs. 21; p < 0.001). The median total number of involved LNs was 3 (range 1–47) in FNAC‐positive patients versus 1 (range 1–37) in SLNB‐positive patients (p < 0.001). The median number of involved LNs in level 1 was 3 in FNAC‐positive patients versus 1 in SLNB‐positive patients (p < 0.001). Within the SLN‐positive group, 49 % of the patients had only one involved LN, 28 % had two nodes involved and 23 % had ≥3. In comparison, within the FNAC‐positive group only 13 % of the patients had one involved LN, 12 % had two nodes involved and 74 % had ≥3.

Conclusion

Patients with positive USFNAC have more aggressive clinico‐pathological characteristics and higher nodal burden compared to SLNB‐positive patients. Currently, the authors advocate that patients not receiving neoadjuvant chemotherapy, with a positive USFNAC, should proceed directly to an axillary ALND.
Myristic Acid Enhances Diacylglycerol Kinase δ‐Dependent Glucose Uptake in Myotubes
Authors: Wada Yuko , Sakiyama Shizuka , Sakai Hiromichi , Sakane Fumio
Published: May 2016

Decreased expression of diacylglycerol kinase (DGK) δ in skeletal muscles attenuates glucose uptake and is closely related to the pathogenesis of type 2 diabetes. Therefore, up‐regulation of DGKδ expression is thought to protect and improve glucose homoeostasis in type 2 diabetes. We recently determined that myristic acid (14:0), but not palmitic (16:0) or stearic (18:0) acid, significantly increased DGKδ2 protein expression in mouse C2C12 myotubes. In the current study, we analyzed whether myristic acid indeed enhances glucose uptake in C2C12 myotubes. We observed that myristic acid caused ~1.4‐fold increase in insulin‐independent glucose uptake. However, palmitic and stearic acids failed to enhance glucose uptake. DGKδ‐specific siRNA decreased myristic acid‐dependent increase of glucose uptake. Moreover, overexpression of DGKδ2 enhanced glucose uptake in C2C12 cells in the absence of myristic acid treatment. Taken together, these results strongly suggest that myristic acid enhances basal glucose uptake in myotubes in a DGKδ2 expression‐dependent manner.
The importance of EHD1 in neurite outgrowth contributing to the functional recovery after spinal cord injury
Authors: Wu Chunshuai , Cui Zhiming , Liu Yonghua , Zhang Jinlong , Ding Wensen , Wang Song , Bao Guofeng , Xu Guanhua , Sun Yuyu , Chen Jiajia
Published: May 2016

Traumatic spinal cord injury is one of the most common and severe problems for using NGF to promote the neurite outgrowth of survival neurons. EHD1 regulates and controls the endocytosis and transportation of neurotrophins and transmembrane cargo via recycling endosome for neurite outgrowth. TrkA is particularly considered to be a functional specific recepter in the cell membrane for NGF and is activated upon NGF binding. The transcytosis of TrkA is dependent on Rab11 recycling endosomes and is promoted by NGF signaling itself at the axon terminal. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of EHD1 during the pathological process of SCI. Western blot analysis suggested that EHD1 expression was low in the sham‐operated adult rat spinal cords and was significantly up‐regulated 1d after injury. Immunohistochemical staining detected the general distribution of EHD1 protein in both the gray and white matter of adult rat spinal cords. Double immunofluorescent staining indicated that EHD1 was expressed in neurons, astrocytes and microglias in the adult rat spinal cord, and obvious changes of EHD1 expression occurred in neurons during SCI pathological process. Significant up‐regulation of EHD1 expression was observed in MAP2 positive neurons at 1 day after SCI, in comparison with the sham‐operated control, which indicated that EHD1 might play a vital role in neurite outgrowth. Our data indicated that EHD1 could interact with TrkA, and is in the upstream of TrkA. EHD1 up‐regulated the expression of TrkA in the glutamate stimulated primary neurons. Based on our experimental data, we boldly conclude that EHD1 regulates the recycling of TrkA back to cell membrane, improving the utilization efficiency of the NGF, which is vital for neurite outgrowth and functional recovery after spinal cord injury.
Low complete transverse vaginal septum, vesico-ureteric reflux and low anorectal malformation
Authors: Tiwari Charu , Shah Hemanshi , Singhavi Sudhir
Published: May 2016

The complete, imperforate transverse vaginal septum is one of the rare anomalies of the female reproductive tract. This anomaly is a disorder of vertical fusion of the Mullerian ducts and can present with or without obstruction. It has been classified as Type IIAas per the American Fertility Society (AFS) classification. Its thickness and site varies in the vaginal canal; the upper and middle third septa are common. The diagnosis can be made in newborns, infants, and adolescent girls. It is found associated with urological anomalies, anorectal malformation (ARM), and bicornuate uterus. We present a case of a 13-year-old girl with hematometrocolpos due to an imperforate complete low vaginal septum, left-sided vesico-ureteric reflux (VUR), and ectopic anus (low ARM).
Who issues Sukuk and when?: An analysis of the determinants of Islamic bond issuance
Authors: Nagano Mamoru
Published: May 2016

Using security issuer data from Malaysia, Indonesia, Saudi Arabia, and the United Arab Emirates from the 2001–2013 period, this study investigates how Islamic bond (Sukuk) issuers differ from conventional debt and equity issuers. An international comparative analysis of these three types of security issuers yields three key insights. First, accessibility to the Sukuk market is essential in choosing Sukuk issuance; other determinants will not promote the use of Sukuk, unless this requirement is first satisfied. Second, the low degree of financial constraints on a firm promotes Sukuk issuance, once the required condition of issuer accessibility to the Sukuk market is satisfied. Third, undervaluation of a firm in the pre‐issuance period also encourages Sukuk issuance, once the issuer's Sukuk market accessibility condition is satisfied. Taken together, we conclude that Sukuk issuance is preferred along with market timing, once the pecking‐order conditions of market accessibility are satisfied.
WOMEN CHANGE EVERYTHING
Authors: YEAGER MARY A.
Published: May 2016

This address urges a more self-aware business history. It uses autobiographical details and select biographies of literary figures and women professionals to shed light on the subtle and not-so subtle inequalities associated with business and capitalism. The deliberate tease in the title—WOMEN CHANGE EVERYTHING—is intended to convey the power of word placement to change interpretive meaning and significance, and the power of history to modify understanding. Modifiers are key to an appreciation of the constraints and opportunities that have framed the lives and experiences of women in economies and societies. Even footnotes function in this address as modifiers, uncannily revealing sources of authorial intent and inspiration and throwing light on literary and historiographical hierarchies.
Effects of Supportive Feedback Messages on Exergame	Experiences
Authors: Kim Jihyun , Timmerman C. Erik
Published: May 2016

Abstract. Since their inception, the popularity of exercise-based video games, or exergames, has continued to grow. Acknowledging the rapid growth of exergames, scholars have investigated exergame play experiences with a focus on the feedback a player receives about performance (e.g., progress bar, score) and how this information can influence game play experiences. To extend the existing exergame research, this study has two primary goals: (a) to test how the supportiveness of verbal feedback messages from an exergame can influence players’ exergame experiences and (b) to evaluate the way that a player’s sense of social presence may serve as a mechanism for understanding the link between feedback and experiences. An experiment (N = 47) was conducted using a between-subjects design. Two groups were compared: highly supportive versus lowly supportive feedback condition. The findings reveal that players who receive highly supportive feedback report greater exergame experience (e.g., enjoyment) than players who receive lowly supportive feedback. Further, social presence is a key variable that mediates the relationship between feedback and exergame experiences. Although the current research findings are important, they are limited to explaining short-term, immediate responses after exergame play among college students. The current research provides implications for research and practice. In particular, the study contributes to an extended understanding of feedback in exergame research and social presence research. At a practical level, the findings suggest that exergame designers should consider incorporating more supportive social feedback messages into a game.
Commitment to the Team
Authors: McLaughlin Bryan
Published: May 2016

Abstract. Scholars have increasingly employed social identity theory to explain how and why political polarization occurs. This study aims to build off of this work by proposing that perception of intergroup conflict serves as a mechanism that mediates the effect of news media coverage on political polarization. Specifically, I argue that the news media’s emphasis on political animosity can cultivate partisans’ perception that the parties are in conflict, which provides a context that makes partisan identity salient and, ultimately, leads to higher levels of affective and ideological polarization. This hypothesis is tested with an experiment using an American national sample of Democrats and Republicans (N = 300). Participants read a news story in which the public believes the parties are in a state of either high or low conflict (or they did not receive a news story). Using mediation analysis, the results of the study provide evidence that news media coverage of political conflict leads to increased perception of intergroup conflict, which then leads to higher levels of (a) partisan identification, (b) affective polarization, and (c) ideological polarization.
A fully human IgG1 anti‐PD‐L1 MAb in an in vitro assay enhances antigen‐specific T‐cell responses
Authors: Grenga Italia , Donahue Renee N , Lepone Lauren M , Richards Jacob , Schlom Jeffrey
Published: May 2016

Monoclonal antibodies (MAbs) that interfere with checkpoint molecules are being investigated for the treatment of infectious diseases and cancer, with the aim of enhancing the function of an impaired immune system. Avelumab (MSB0010718C) is a fully human IgG1 MAb targeting programmed death‐ligand 1 (PD‐L1), which differs from other checkpoint‐blocking antibodies in its ability to mediate antibody‐dependent cell‐mediated cytotoxicity. These studies were conducted to define whether avelumab could enhance the detection of antigen‐specific immune response in in vitro assays. Peripheral blood mononuclear cells from 17 healthy donors were stimulated in vitro, with and without avelumab, with peptide pools encoding for cytomegalovirus, Epstein–Barr virus, influenza and tetanus toxin or the negative peptide control encoding for human leukocyte antigen. These studies show for the first time that the addition of avelumab to an antigen‐specific IVS assay (a) increased the frequency of activated antigen‐specific CD8+ T lymphocytes, and did so to a greater extent than that seen with commercially available PD‐L1‐blocking antibodies, (b) reduced CD4+ T‐cell proliferation and (c) induced a switch in the production of Th2 to Th1 cytokines. Moreover, there was an inverse correlation between the enhancement of CD8+ T‐cell activation and reduction in CD4+ T‐cell proliferation induced by avelumab. These findings provide the rationale for the use of avelumab anti‐PD‐L1 in in vitro assays to monitor patient immune responses to immunotherapies.
Splicing factors control C. elegans behavioural learning in a single neuron by producing DAF-2c receptor
Authors: Tomioka Masahiro , Naito Yasuki , Kuroyanagi Hidehito , Iino Yuichi
Published: May 2016

Alternative splicing generates protein diversity essential for neuronal properties. However, the precise mechanisms underlying this process and its relevance to physiological and behavioural functions are poorly understood. To address these issues, we focused on a cassette exon of the Caenorhabditis elegans insulin receptor gene daf-2, whose proper variant expression in the taste receptor neuron ASER is critical for taste-avoidance learning. We show that inclusion of daf-2 exon 11.5 is restricted to specific neuron types, including ASER, and is controlled by a combinatorial action of evolutionarily conserved alternative splicing factors, RBFOX, CELF and PTB families of proteins. Mutations of these factors cause a learning defect, and this defect is relieved by DAF-2c (exon 11.5+) isoform expression only in a single neuron ASER. Our results provide evidence that alternative splicing regulation of a single critical gene in a single critical neuron is essential for learning ability in an organism.
Numerical approach for unstructured quantum key distribution
Authors: Coles Patrick J. , Metodiev Eric M. , Lütkenhaus Norbert
Published: May 2016

Quantum key distribution (QKD) allows for communication with security guaranteed by quantum theory. The main theoretical problem in QKD is to calculate the secret key rate for a given protocol. Analytical formulas are known for protocols with symmetries, since symmetry simplifies the analysis. However, experimental imperfections break symmetries, hence the effect of imperfections on key rates is difficult to estimate. Furthermore, it is an interesting question whether (intentionally) asymmetric protocols could outperform symmetric ones. Here we develop a robust numerical approach for calculating the key rate for arbitrary discrete-variable QKD protocols. Ultimately this will allow researchers to study ‘unstructured’ protocols, that is, those that lack symmetry. Our approach relies on transforming the key rate calculation to the dual optimization problem, which markedly reduces the number of parameters and hence the calculation time. We illustrate our method by investigating some unstructured protocols for which the key rate was previously unknown.
Separating hydrogen and oxygen evolution in alkaline water electrolysis using nickel hydroxide
Authors: Chen Long , Dong Xiaoli , Wang Yonggang , Xia Yongyao
Published: May 2016

Low-cost alkaline water electrolysis has been considered a sustainable approach to producing hydrogen using renewable energy inputs, but preventing hydrogen/oxygen mixing and efficiently using the instable renewable energy are challenging. Here, using nickel hydroxide as a redox mediator, we decouple the hydrogen and oxygen production in alkaline water electrolysis, which overcomes the gas-mixing issue and may increase the use of renewable energy. In this architecture, the hydrogen production occurs at the cathode by water reduction, and the anodic Ni(OH)2 is simultaneously oxidized into NiOOH. The subsequent oxygen production involves a cathodic NiOOH reduction (NiOOH→Ni(OH)2) and an anodic OH− oxidization. Alternatively, the NiOOH formed during hydrogen production can be coupled with a zinc anode to form a NiOOH-Zn battery, and its discharge product (that is, Ni(OH)2) can be used to produce hydrogen again. This architecture brings a potential solution to facilitate renewables-to-hydrogen conversion.
Correction: Corrigendum: Length of intact plasma membrane determines the diffusion properties of cellular water
Authors: Eida Sato , Van Cauteren Marc , Hotokezaka Yuka , Katayama Ikuo , Sasaki Miho , Obara Makoto , Okuaki Tomoyuki , Sumi Misa , Nakamura Takashi
Published: May 2016

Scientific Reports 6: Article number: 19051; published online: 11 January 2016; updated: 20 May 2016. This Article contains errors. In Figure 1j, the x-axis ‘CPL(×103 μm)’ was incorrectly given as ‘CPL(μm/mm2). The corresponding Figure legend, “(j) Graph showing a linear correlation between the ADC values and the cell perimeter length per pellet area (CPL; μm/μm2) of HeLa S3, HL-60, and CV-1 cells.
Memristive Sisyphus circuit for clock signal generation
Authors: Pershin Yuriy V. , Shevchenko Sergey N. , Nori Franco
Published: May 2016

Frequency generators are widely used in electronics. Here, we report the design and experimental realization of a memristive frequency generator employing a unique combination of only digital logic gates, a single-supply voltage and a realistic thresholdtype memristive device. In our circuit, the oscillator frequency and duty cycle are defined by the switching characteristics of the memristive device and external resistors. We demonstrate the circuit operation both experimentally, using a memristor emulator, and theoretically, using a model memristive device with threshold. Importantly, nanoscale realizations of memristive devices offer small-size alternatives to conventional quartz-based oscillators. In addition, the suggested approach can be used for mimicking some cyclic (Sisyphus) processes in nature, such as “dripping ants” or drops from leaky faucets.
Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands
Authors: Guo Zhengyu , González Jorge Francisco , Hernandez Julia N. , McNeilly Tom N. , Corripio-Miyar Yolanda , Frew David , Morrison Tyler , Yu Peng , Li Robert W.
Published: May 2016

Haemonchus contortusappears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response toHaemonchusinfection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 × 10−4). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed.
Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations
Authors: Mangum Joshua E. , Hardee Justin P. , Fix Dennis K. , Puppa Melissa J. , Elkes Johnathon , Altomare Diego , Bykhovskaya Yelena , Campagna Dean R. , Schmidt Paul J. , Sendamarai Anoop K. , Lidov Hart G. W. , Barlow Shayne C. , Fischel-Ghodsian Nathan , Fleming Mark D. , Carson James A. , Patton Jeffrey R.
Published: May 2016

Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) is an oxidative phosphorylation disorder, with primary clinical manifestations of myopathic exercise intolerance and a macrocytic sideroblastic anemia. One cause of MLASA is recessive mutations in PUS1, which encodes pseudouridine (Ψ) synthase 1 (Pus1p). Here we describe a mouse model of MLASA due to mutations in PUS1. As expected, certain Ψ modifications were missing in cytoplasmic and mitochondrial tRNAs from Pus1−/− animals. Pus1−/− mice were born at the expected Mendelian frequency and were non-dysmorphic. At 14 weeks the mutants displayed reduced exercise capacity. Examination of tibialis anterior (TA) muscle morphology and histochemistry demonstrated an increase in the cross sectional area and proportion of myosin heavy chain (MHC) IIB and low succinate dehydrogenase (SDH) expressing myofibers, without a change in the size of MHC IIA positive or high SDH myofibers. Cytochrome c oxidase activity was significantly reduced in extracts from red gastrocnemius muscle from Pus1−/− mice. Transmission electron microscopy on red gastrocnemius muscle demonstrated that Pus1−/− mice also had lower intermyofibrillar mitochondrial density and smaller mitochondria. Collectively, these results suggest that alterations in muscle metabolism related to mitochondrial content and oxidative capacity may account for the reduced exercise capacity in Pus1−/− mice.