bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant Functions of the Aryl Hydrocarbon Receptor
Authors: Dietrich Cornelia
Published: October 2016

The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix‐loop‐helix/PER‐ARNT‐SIM family. It is activated by a variety of ligands, such as environmental contaminants like polycyclic aromatic hydrocarbons or dioxins, but also by naturally occurring compounds and endogenous ligands. Binding of the ligand leads to dimerization of the AhR with aryl hydrocarbon receptor nuclear translocator (ARNT) and transcriptional activation of several xenobiotic phase I and phase II metabolizing enzymes. It is generally accepted that the toxic responses of polycyclic aromatic hydrocarbons, dioxins, and structurally related compounds are mediated by activation of the AhR. A multitude of studies indicate that the AhR operates beyond xenobiotic metabolism and exerts pleiotropic functions. Increasing evidence points to a protective role of the AhR against carcinogenesis and oxidative stress. Herein, I will highlight data demonstrating a causal role of the AhR in the antioxidant response and present novel findings on potential AhR‐mediated antioxidative mechanisms.
NRAMP1 Polymorphisms like Susceptibility Marker in Mexican Focus of Cutaneous Leishmaniasis
Authors: Hernández-Rivera Mirsha Pamela , Ramírez-Ramírez Alicia , Chiñas-Pérez Adelaido , Monroy-Ostria Amalia , Cancino-Díaz Mario Eugenio , Hernández-Montes Omar
Published: October 2016

Cutaneous leishmaniasis (CL) is endemic in Campeche state, Mexico. Host and parasite factors are involved in the establishment and development of CL. Host factors include immune response and genetic background. NRAMP1 (Natural Resistance Associated Macrophage Protein 1) is important in innate immunity. Polymorphisms inNRAMP1have been associated with susceptibility or resistance to infectious and autoimmune diseases. To study the association ofNRAMP1mutations with CL in patients from Calakmul, Campeche, samples from 115 CL patients and 69 samples of healthy people from the same area were evaluated. Five regions inNRAMP1were amplified and digested, looking for mutations in the promoter region (−524G/C), exon 3 (274C/T), exon 8 (823 C7T), and exon 15 (G/A) and deletion of 4 bp in the 3′UTR region. We found a statistical association between polymorphisms in 3′UTR region and exon 8 and CL [χ2=13.26;p<0.05; OR = 17.00; IC of 95% (2.24–128.99)]. Some patients who needed more than 40 doses of Glucantime®to heal injuries presented mutations in exons 3, 8, and 15. Multiple or ear lesions were not associated withNRAMP1polymorphism.
Trace Metal Contamination Characteristics and Health Risks Assessment ofCommelina africanaL. and Psammitic Sandflats in the Niger Delta, Nigeria
Authors: Benson Nsikak U. , Enyong Paul A. , Fred-Ahmadu Omowunmi H.
Published: October 2016

The purpose of this study was to investigate and quantify trace metal concentrations inCommelina africanaL. and psammitic sandflats from an intertidal coastal ecosystem in Niger Delta, Nigeria, and to evaluate their spatial distribution, degree of contamination, and source apportionment. The environmental risks associated with soil contamination were elaborately assessed using potential ecological risk index, sediment quality guidelines, and enrichment relative to background levels. The mean concentrations of Cd, Cr, Ni, Pb, and Zn in sandflat soil samples are0.76±9.0×10-2,7.39±8.7×10-1,2.28±0.35,0.024±4.0×10-3, and74.51±2.55 mg/kg, respectively. Metal levels indicate strong variability with sampling sites. The order of trace metal concentrations in theCommelina africanaL. samples isZn>Ni>Cr>Pb>Cd. The concentrations varied with the sample locations; and the levels of Pb (0.05 to 0.08 mg/kg) at all locations are found to be significantly below permissible level of 0.3 mg/kg. Potential sources of metal loadings may be associated with localised or diffused anthropogenic activities. The average carcinogenic risks are below1.0×10-6threshold values, and the sandflat soils are not considered to pose significant health effects to children and adult males and females. However, the carcinogenicity and noncarcinogenicity risks ranking decrease following the orderchildren>adult  males>adult  females. Comparatively, the hazard quotient and hazard index indicate that the psammitic sandflats might pose a health risk to children in future.
Audit ofHelicobacter pyloriTesting in Microbiology Laboratories in England: To Inform Compliance with NICE Guidance and the Feasibility of Routine Antimicrobial Resistance Surveillance
Authors: Allison Rosalie , Lecky Donna M. , Bull Megan , Turner Kim , Godbole Gauri , McNulty Cliodna A. M.
Published: October 2016

Introduction. The National Institute for Health and Clinical Excellence (NICE) guidance recommends that dyspeptic patients are tested forHelicobacter pyloriusing a urea breath test, stool antigen test, or serology. Antibiotic resistance inH. pyloriis globally increasing, but treatment in England is rarely guided by susceptibility testing or surveillance.Aims. To determine compliance of microbiology laboratories in England with NICE guidance and whether laboratories perform culture and antibiotic susceptibility testing (AST).Methods. In 2015, 170 accredited English microbiology laboratories were surveyed, by email.Results. 121/170 (71%) laboratories responded; 96% providedH. pyloritesting (78% on site). 94% providedH. pyloridiagnosis using stool antigen; only four provided serology as their noninvasive test; 3/4 of these encouraged urea breath tests in their acute trusts. Only 22/94 (23%) of the laboratories performedH. pyloricultures from gastric biopsies on site; 9/22 performed AST, but the vast majority processed less than one specimen/week.Conclusions. Only five laboratories in England do not comply with NICE guidance; these will need the guidance reinforced. National surveillance needs to be implemented; culture-based AST would need to be centralised. Moving forward, detection of resistance inH. pylorifrom stool specimens using molecular methods (PCR) needs to be explored.
Adaptive Plasticity in the Healthy Language Network: Implications for Language Recovery after Stroke
Authors: Hartwigsen Gesa
Published: October 2016

Across the last three decades, the application of noninvasive brain stimulation (NIBS) has substantially increased the current knowledge of the brain’s potential to undergo rapid short-term reorganization on the systems level. A large number of studies applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in the healthy brain to probe the functional relevance and interaction of specific areas for different cognitive processes. NIBS is also increasingly being used to induce adaptive plasticity in motor and cognitive networks and shape cognitive functions. Recently, NIBS has been combined with electrophysiological techniques to modulate neural oscillations of specific cortical networks. In this review, we will discuss recent advances in the use of NIBS to modulate neural activity and effective connectivity in the healthy language network, with a special focus on the combination of NIBS and neuroimaging or electrophysiological approaches. Moreover, we outline how these results can be transferred to the lesioned brain to unravel the dynamics of reorganization processes in poststroke aphasia. We conclude with a critical discussion on the potential of NIBS to facilitate language recovery after stroke and propose a phase-specific model for the application of NIBS in language rehabilitation.
Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer
Authors: Gibson William J. , Ruan Daniel T. , Paulson Vera A. , Barletta Justine A. , Hanna Glenn J. , Kraft Stefan , Calles Antonio , Nehs Matthew A. , Moore Francis D. , Taylor-Weiner Amaro , Wala Jeremiah A. , Zack Travis I. , Lee Thomas C. , Fennessy Fiona M. , Alexander Erik K. , Thomas Tom , Janne Pasi A. , Garraway Levi A. , Carter Scott L. , Beroukhim Rameen , Lorch Jochen H. , Van Allen Eliezer M.
Published: October 2016

Purpose: Cancers may resist single-agent targeted therapies when the flux of cellular growth signals is shifted from one pathway to another. Blockade of multiple pathways may be necessary for effective inhibition of tumor growth. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR/PI3K or combined RAF/MEK inhibition but experienced a dramatic response when both drug regimens were combined.

Experimental Design: Multi-region whole-exome sequencing of five diagnostic and four autopsy tumor biopsies was performed. Meta-analysis of DNA and RNA sequencing studies of ATC was performed.

Results: Sequencing revealed truncal BRAF and PIK3CA mutations, which are known to activate the MAPK and PI3K/AKT pathways, respectively. Meta-analysis demonstrated 10.3% cooccurrence of MAPK and PI3K pathway alterations in ATC. These tumors display a separate transcriptional profile from other ATCs, consistent with a novel subgroup of ATC.

Conclusions: BRAF and PIK3CA mutations define a distinct subset of ATC. Blockade of the MAPK and PI3K pathways appears necessary for tumor response in this subset of ATC. This identification of synergistic activity between targeted agents may inform clinical trial design in ATC. Clin Cancer Res; 23(9); 2367–73. ©2016 AACR.
Hepatoid Carcinoma of the Pancreas: Case Report, Next-Generation Tumor Profiling, and Literature Review
Authors: Chang James M. , Katariya Nitin N. , Lam-Himlin Dora M. , Haakinson Danielle J. , Ramanathan Ramesh K. , Halfdanarson Thorvardur R. , Borad Mitesh J. , Pannala Rahul , Faigel Douglas , Moss Adyr A. , Mathur Amit K.
Published: October 2016

Fewer than 25 cases of hepatoid carcinoma of the pancreas have been reported in the literature. We present a case in a 61-year-old male with a remote history of Hodgkin’s lymphoma and gastric neuroendocrine cell hyperplasia. On surveillance endoscopic ultrasound, an 8 × 5 mm cystic lesion was seen in the tail of the pancreas. MRI showed a focal pancreatic duct cut-off with mild ductal dilation. Fine needle aspiration was performed, which was concerning for acinar cell carcinoma. The patient underwent distal pancreatectomy and recovered uneventfully. Final pathology demonstrated a 1.3-cm hepatoid carcinoma of the pancreas, with a final clinicopathological stage of T1N0M0. Next-generation nucleic acid sequencing of the tumor did not suggest a viable adjuvant chemotherapeutic agent, and no adjuvant therapy was administered. The patient has no evidence of disease 6 months following resection. A further characterization and description of the outcomes of these rare tumors is warranted to help guide providers and counsel patients.
Long-Gap Esophageal Atresia Is a Unique Entity within the Esophageal Atresia Defect Spectrum
Authors: Bairdain Sigrid , Zurakowski David , Vargas Sara O. , Stenquist Nicole , McDonald Molly , Towne Meghan C. , Miller David T. , Jennings Russell W. , Kantor David B. , Agrawal Pankaj B.
Published: October 2016

Background: Long-gap esophageal atresia (LGEA) may have clinical and syndromic presentations different from those of esophageal atresia (EA) that affects shorter segments of the esophagus (non-LGEA). This may suggest unique underlying developmental mechanisms. Objectives: We sought to characterize clinical differences between LGEA and non-LGEA by carefully phenotyping a cohort of EA patients, and furthermore to assess molecular genetic findings in a subset of them. Methods: This is a retrospective cohort study to systematically evaluate clinical and genetic findings in EA infants who presented at our institution over a period of 10 years (2005-2015). Results: Two hundred twenty-nine EA patients were identified, 69 (30%) of whom had LGEA. Tracheoesophageal fistula was present in most non-LGEA patients (158 of 160) but in only 30% of LGEA patients. The VACTERL association was more commonly seen with non-LGEA compared to LGEA (70 vs. 25%; p < 0.001). Further, trisomy 21 was more common in LGEA than in non-LGEA. 25% of LGEA patients had an isolated EA diagnosis without other anomalies, compared to <1% for non-LGEA. Chromosomal microarray analysis showed copy number variations (CNV) in 4 of 39 non-LGEA patients and 0 of 3 LGEA patients. A review of the ClinGen database showed that none of those CNV have been previously described with EA. Conclusions: LGEA represents a unique type of EA. Compared to non-LGEA, it is more likely to be an isolated defect and associated with trisomy 21. Further, it is less commonly seen with VACTERL anomalies. Our findings suggest the involvement of unique pathways that may be distinct from those causing non-LGEA.
Intussuscepting Ampullary Adenoma: An Unusual Cause of Gastric Outlet Obstruction Leading to Cavitating Lung Lesions
Authors: McCluney Simon J. , Balarajah Vickna , Giakoustidis Alex , Chin-Aleong Joanne , Lovett Bryony , Kocher Hemant M.
Published: October 2016

Ampullary adenomas are a rare clinical entity, occurring at a rate of 0.04–0.12% in the general population. They are premalignant lesions which have the capability to progress to malignancy, and they should be excised if they are causing immediate symptoms and/or are likely to degenerate to carcinoma. Intestinal intussusception in adults is rare and, unlike in children, is often due to a structural pathology. Intussuscepting duodenal/ampullary adenomas have been reported in the literature on 13 previous occasions, however never before with this presentation. We report the case of a woman who presented with a 1-year history of recurrent chest infections. She was treated with numerous antibiotics, whilst intermittent symptoms of recurrent vomiting and weight loss were initially attributed to her lung infections. A chest CT demonstrated multiple cavitating lung lesions, whilst an obstructing polypoid mass was noted at D2 on dedicated abdominal imaging. Due to ongoing nutritional problems, she had a semi-urgent pancreaticoduodenectomy. Intraoperative findings demonstrated a large mass at D2 with a duodeno-duodenal intussusception. Histological analysis reported a duodenal, ampullary, low-grade tubular adenoma, 75 × 28 × 30 mm in size, with intussusception and complete resection margins. The patient recovered well and was discharged on postoperative day 10, with no complications to date. Ampullary adenomas may present with obstruction of the main gastrointestinal tract and/or biliary/pancreatic ducts. Common presentations include gastric outlet obstruction, gastrointestinal bleeding or acute pancreatitis. This unique presentation should remind clinicians of the need to investigate recurrent chest infections for a possible gastrointestinal cause.
Successful Treatment of Small Intestinal Bleeding in a Crohn’s Patient with Noncirrhotic Portal Hypertension by Transjugular Portosystemic Shunt Placement and Infliximab Treatment
Authors: Heimgartner Benjamin , Dawson Heather , De Gottardi Andrea , Wiest Reiner , Niess Jan Hendrik
Published: October 2016

Small intestinal bleeding in Crohn’s disease patients with noncirrhotic portal hypertension and partial portal and superior mesenteric vein thrombosis is a life-threatening event. Here, a case is reported in which treatment with azathioprine may have resulted in nodular regenerative hyperplasia, portal hypertension and portal vein thrombosis. The 56-year-old patient with Crohn’s disease developed nodular regenerative hyperplasia under treatment with azathioprine. He was admitted with severe bleeding. Gastroscopy showed small esophageal varices without bleeding stigmata. Blood was detected in the terminal ileum. CT scan revealed a partial portal vein thrombosis with extension to the superior mesenteric vein, thickening of the jejunal wall and splenomegaly. Because intestinal bleeding could not be controlled by conservative treatment, the thrombus was aspirated and a transjugular intrahepatic portosystemic shunt (TIPS) was placed. Switching the immunosuppressive medication to infliximab controlled Crohn’s disease activity. Bleeding was stopped, hemoglobin normalized, and thrombocytopenia and bowel movements improved. In summary, small intestinal bleeding in a Crohn’s patient with nodular regenerative hyperplasia, portal hypertension and portal vein thrombosis can be efficiently treated by TIPS. TIPS placement together with infliximab treatment led to the improvement of the blood panel and remission in this patient.
Severe de novo Hepatitis B Recovered from Late-Onset Liver Insufficiency with Prolonged Ascites and Hypoalbuminemia due to Hepatitis B Virus Genotype Bj with Precore Mutation
Authors: Sato Akira , Ishii Toshiya , Sano Fumiaki , Yamada Takayuki , Takahashi Hideaki , Matsumoto Nobuyuki
Published: October 2016

De novo hepatitis B is associated with a high risk of hepatic failure often resulting in fatal fulminant hepatitis even when nucleotide analogues are administered. A 77-year-old female developed de novo hepatitis B after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) treatment for diffuse large B-cell lymphoma. Hepatitis B virus (HBV) isolated from the patient was of genotype Bj, with a precore mutation (G1896A) exhibiting an extremely high viral load at the onset of hepatitis. She showed markedly high levels of transaminase with mild jaundice on admission and rapid decrease of prothrombin activity after admission. Although acute liver failure was averted by the administration of entecavir and corticosteroid pulse therapy, liver volume decreased to 860 ml, and marked hypoalbuminemia accompanying massive ascites occurred 2 months after the onset of hepatitis and persisted for 3 months with high levels of HBV DNA and mild abnormal alanine aminotransferase levels. Frequent infusions of albumin solution, nutrition support, and alleviation therapy showed limited effect. However, overall improvement along with HBV DNA reduction was observed after increasing the dose of entecavir and completion of prednisolone that was administered with a minimum dose for adrenal insufficiency. An immediate and sufficient suppression of virus replication with potent antiviral therapy is critical, particularly in patients infected with HBV precore mutation (G1896A) and/or Bj genotype, which may have a high viral replication and direct hepatocellular damage.
Elevated Lipase during Initial Presentation of Ulcerative Colitis in a Pediatric Patient: Do We Check for It
Authors: Ray Piyali , Van Arsdall Melissa R.
Published: October 2016

There are very few reports of elevated lipase in pediatric inflammatory bowel disease (IBD). Symptoms of pancreatitis may be masked by abdominal pain in pediatric IBD. During the initial presentation of IBD in our patient, lipase was elevated to more than 3 times the upper limit of normal. Normalization of values coincided with remission of IBD. This may be due to extraintestinal involvement of the pancreas as part of the inflammatory process or due to leakage of pancreatic enzymes from an inflamed gut or mediated by inflammatory cytokines. Checking pancreatic enzymes during initial presentation of IBD may, therefore, be important to determine if pancreatic involvement has resulted from the inflammation in IBD or as an adverse effect of therapy. If unchecked, recurrent subclinical pancreatitis may be masked by IBD symptoms and missed prior to starting IBD therapy. This may result in chronic pancreatic insufficiency as reported in 50% of adults with IBD. Early detection of elevated pancreatic enzymes in IBD may help direct the management strategy, as treatment of the underlying inflammation in IBD may be the most important management for resolution of pancreatitis instead of cessation of therapy for fear of iatrogenic medication-induced pancreatitis.
Long-Term Risk of Stroke after Transient Ischemic Attack
Authors: Appelros Peter , Háls Berglund Maria , Ström Jakob O.
Published: October 2016

Background: In the absence of active management, the stroke risk after a transient ischemic attack (TIA) may be high. Almost 10 years ago, the results of the EXPRESS and SOS-TIA studies called for a more rapid management of TIA patients. The purpose of this study was to investigate the other stroke risks in the longer term, after the implementation of a more active approach to TIA. We also wanted to assess the predictive value of the ABCD2 score in this context. Methods: Riksstroke is the national stroke registry in Sweden. Data from Riksstroke's TIA module, and the national cause-of-death register, for the years 2011 and 2012 were used in this study. Stroke occurrence was monitored via Riksstroke. Cox's regression was used for risk evaluation. The predictive value of the ABCD2 score was assessed by calculating the area under the receiver operating characteristics curve. Results: A total of 15,068 TIA episodes occurred in 14,102 patients. The follow-up time varied between 0 and 819 days, with an average of 417 days. The mortality for all TIA patients during the follow-up time was 7.1%. Of the unique patients, 545 had one or more strokes (3.9%), corresponding to 34 events per 1,000 person years. Significant risk factors for stroke were: age, previous TIA, atrial fibrillation (AF), oral anticoagulant (OAC) treatment, hypertension treatment, and the ABCD2 items speech impairment, unilateral weakness, and diabetes mellitus. The ABCD2 score correlated with a subsequent stroke, but its predictive value was low. Conclusion: The risk of stroke is low after the acute phase of a TIA, probably lower than in previous studies. This may be due to better secondary prevention in recent years. Several risk factors predict stroke, notably hypertensive treatment, which may be inadequate; and AF, where OACs may be under-used. It is difficult to identify the role of the ABCD2 score in clinical practice.
Endovascular Therapy Demonstrates Benefit over Intravenous Recombinant Tissue Plasminogen Activator Based on Repeatedly Measured National Institutes of Health Stroke Scale
Authors: Fan Liqiong , Yeatts Sharon D. , Foster Lydia D. , Khatri Pooja , Tomsick Thomas , Broderick Joseph P. , Palesch Yuko Y.
Published: October 2016

Background and Purpose: The Interventional Management of Stroke (IMS) III trial was a randomized controlled trial designed to compare the effect of endovascular therapy after intravenous recombinant tissue plasminogen activator (i.v. rt-PA) as compared to i.v. rt-PA alone. The primary outcome was modified Rankin Scale at 90 days. Secondary outcomes included National Institutes of Health Stroke Scale (NIHSS), which was assessed repeatedly through 90 days. The objective of this analysis is to evaluate the treatment effect of endovascular therapy over time on NIHSS. Methods: 656 subjects were enrolled in the IMS III trial, including 434 subjects randomized to endovascular therapy and 222 to i.v. rt-PA only. NIHSS scores evaluated at 40 min, 24 h, Day 5, and Day 90 were included in the analysis. A covariance structure model was used to investigate the treatment effect on NIHSS over time, adjusting for relevant covariates including baseline stroke severity. Model assumptions were valid. Results: Based on the covariance structure model, after adjusting for relevant baseline covariates, a significant time-by-treatment interaction effect (p = 0.0137) was observed. Only NIHSS at Day 90 showed a significant treatment effect (p = 0.0473), with subjects in the endovascular arm having a lower NIHSS (less neurologic deficit) compared to the i.v. rt-PA arm. Conclusions: The IMS III trial demonstrated an endovascular treatment effect based on the secondary outcome of NIHSS. However, the magnitude of this treatment effect varied by the time of assessment. It was only at Day 90 that the endovascular arm had a significantly lower NIHSS compared to that in the i.v. rt-PA arm.
Assessment of the European Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute Myocardial Infarction
Authors: Pickering John W. , Greenslade Jaimi H. , Cullen Louise , Flaws Dylan , Parsonage William , Aldous Sally , George Peter , Worster Andrew , Kavsak Peter A. , Than Martin P.
Published: October 2016

Background:

The new European Society of Cardiology guidelines to rule-in and rule-out acute myocardial infarction (AMI) in the emergency department include a rapid assessment algorithm based on high-sensitivity cardiac troponin and sampling at 0 and 1 hour. Emergency department physicians require high sensitivity to confidently rule-out AMI, whereas cardiologists aim to minimize false-positive results.

Methods:

High-sensitivity troponin I and T assays were used to measure troponin concentrations in patients presenting with chest-pain symptoms and being investigated for possible acute coronary syndrome at hospitals in New Zealand, Australia, and Canada. AMI outcomes were independently adjudicated by at least 2 physicians. The European Society of Cardiology algorithm performance with each assay was assessed by the sensitivity and proportion with AMI ruled out and the positive predictive value and proportion ruled-in.

Results:

There were 2222 patients with serial high-sensitivity troponin T and high-sensitivity troponin I measurements. The high-sensitivity troponin T algorithm ruled out 1425 (64.1%) with a sensitivity of 97.1% (95% confidence interval [CI], 94.0%–98.8%) and ruled-in 292 (13.1%) with a positive predictive value of 63.4% (95% CI, 57.5%–68.9%).

The high-sensitivity troponin I algorithm ruled out 1205 (54.2%) with a sensitivity of 98.8% (95% CI, 96.4%–99.7%)) and ruled-in 310 (14.0%) with a positive predictive value of 68.1% (95% CI, 62.6%–73.2%).

Conclusions:

The sensitivity of the European Society of Cardiology rapid assessment 0-/1-hour algorithm to rule-out AMI with high-sensitivity troponin may be insufficient for some emergency department physicians to confidently send patients home. These algorithms may prove useful to identify patients requiring expedited management. However, the positive predictive value was modest for both algorithms.
Macrophage Foam Cell–Derived Extracellular Vesicles Promote Vascular Smooth Muscle Cell Migration and Adhesion
Authors: Niu Chenguang , Wang Xu , Zhao Mingming , Cai Tanxi , Liu Peibin , Li Jizhao , Willard Belinda , Zu Lingyun , Zhou Enchen , Li Yufeng , Pan Bing , Yang Fuquan , Zheng Lemin
Published: October 2016

Background

A new mechanism for intercellular communication has recently emerged that involves intercellular transfer of extracellular vesicles (EVs). Several studies have indicated that EVs may play a potential role in cell‐to‐cell communication between macrophage foam cells and vascular smooth muscle cells (VSMCs) in atherosclerotic lesion.

Methods and Results

This study involved the comparison of circulating EVs from atherosclerotic patients and control participants. The results showed that the circulation of the patients contained more leukocyte‐derived EVs and that these EVs promoted more VSMC adhesion and migration than those of healthy participants. We then established a macrophage foam cell model and characterized the EVs from the macrophages. We used flow cytometric analyses and cell migration and adhesion assays and determined that the foam cells generated more EVs than the normal macrophages and that the foam cell–derived EVs were capable of promoting increased levels of VSMC migration and adhesion. Furthermore, we performed a proteomic analysis of the EVs. The data showed that the foam cell–derived EVs may promote VSMC adhesion and migration by regulating the actin cytoskeleton and focal adhesion pathways. In addition, Western blotting revealed that foam cell–derived EVs could promote the phosphorylation of ERK and Akt in VSMCs in a time‐dependent manner. We also found that foam cell–derived EVs could enter the VSMCs and transfer integrins to the surface of these cells.

Conclusions

The data in our present study provide the first evidence that EVs from foam cells could promote VSMC migration and adhesion, which may be mediated by the integration of EVs into VSMCs and the subsequent downstream activation of ERK and Akt.
Nero’s “Solar” Kingship and the Architecture of the Domus Aurea
Authors: Hannah Robert , Magli Giulio , Palmieri Antonella
Published: October 2016

The Domus Aurea, Nero’s last “palace” constructed in the very heart of ancient Rome, is a true masterpiece of Roman architecture. We explore here symbolic aspects of the emperor’s project, analyzing the archaeoastronomy of the best preserved part of the Domus, the Esquiline Wing. In particular, we study the so-called Octagonal Room, the huge vaulted room which is in many respects a predecessor of the Pantheon. The project of the room turns out to be connected with astronomy, as is Hadrian’s Pantheon sixty years later. Indeed, the divinization and “solarization” of the emperor — placed at the equinoxes as a point of balance in the heavens — are shown to be explicitly referred to in the rigorous orientation of the plan and in the peculiar geometry of the design of the dome.
Reconstructing “Religion” from the Bottom Up
Authors: Hanegraaff Wouter J.
Published: October 2016

This article claims to uncover the core problematics that have made the debate on defining and conceptualizing “religion” so difficult and argues that this makes it possible to move beyond radical deconstruction towardsreconstructing the concept for scholarly purposes. The argument has four main steps. Step 1 consists of establishing the nature of the entity “religion” as areified imaginative formation. Step 2 consists of identifyingthe basic dilemmawith which scholars have been struggling: the fact that, on the one hand, definitions and conceptualizations do not seem to work unless they stay sufficiently close to commonly held prototypes, while yet, on the other hand, those prototypes are grounded in monotheistic, more specifically Christian, even more specifically Protestant, theological biases about “true” religion. The first line of argument leads to crypto-theological definitions and conceptualizations, the second to a radical deconstruction of the very concept of “religion.” Step 3 resolves the dilemma by identifying anunexamined assumption, orproblematic“blind spot,” that the two lines of argument have in common: they both think that “religion” stands against “the secular.” However, the historical record shows that these two defined themselves not just against one another but, simultaneously, against athirddomain (referred to by such terms as “magic” or “superstition”). The structure is therefore not dualistic but triadic. Step 4 consists of replacing common assumptions about how “religion” emerged in the early modern period by an interpretation that explains not just its emergence but its logicalnecessity, at that time, for dealing with the crisis of comparison caused by colonialist expansion. “Religion” emerged as thetertium comparationis— or, in technically more precise language, the “pre-comparativetertium” — that enabled comparison between familiar (monotheist, Christian, Protestant) forms of belief and modes of worship and unfamiliar ones (associated with “pagan” superstition or magic). If we restore the term to its original function, this allows us to reconstruct “religion” as a scholarly concept that not just avoids butpreventsany slippage back to Christian theology or ethnocentric bias.
Foreign Investors and the Colombian Peace Process
Authors: Gomez-Suarez Andrei , Perrone Nicolás M. , Prieto Ríos Enrique
Published: October 2016

The International Investment Regime (iir) materialises in international arbitral tribunals that protect the rights of foreign investors. Could these tribunals hamper the implementation of exceptional measures agreed to end armed conflicts? The principle of proportionality, usually employed to balance competing demands such as the interests of international investors and the right of states to self-determination, could fall short when it comes to the concept of a nation and a society’s right to peace. Focusing on the Colombian peace process, this article argues that the agreement on land redistribution, a cornerstone of the peace agreements, benefits the whole society, including foreign investors. However, the colonialist nature of the iir could lead foreign investors, who see their investments and expected profits affected, to demand compensation for governmental land acquisition. The Colombian case suggests powerful lessons for the willingness of transitional states to defend their people’s right to peace in international tribunals.
International Law and Foreign Investment in Hydroelectric Industry: A Multidimensional Analysis
Authors: Tanzi Attila
Published: October 2016

The main focus of the present article is on the entanglement between four bodies of international law sensitive to foreign investment in the creation and/or operation hydroelectric industry: i.e. international investment law, human rights law, international water law and private international law to the extent that public international law rules on conflict of laws on civil liability for transboundary damage are concerned. This horizontal approach to the analysis is supplemented by a vertical one looking at the interactions between international and domestic law. Consideration of the different bodies of international law in question is associated to that of the adjudicative, and non-adjudicative, means of dispute settlement available under each such bodies of law. On that score, the role of the foreign investor in a litigation scenery will be considered, primarily as claimant, but also, prospectively, in relation to the situation in the State hosting the investment is, or may become, respondent in inter-State litigation.
Are Public Commemorations in Contemporary Japan Post-secular?
Authors: Nishimura Akira
Published: October 2016

This paper asks whether public commemorations in contemporary Japan are post-secular or not. More precisely, it investigates the postwar history of the relationship between such commemorations and the principle of keeping religion and government separate, as embodied in the constitution. Referring to several contemporary cases, I provide an overview of the discourses and actual conditions of the separation of religion and state at Chidorigafuchi National Cemetery (Chidorigafuchi Kokuritsu Senbotsusha Boen 千鳥ヶ淵国立戦没者墓苑) and Yasukuni Shrine (Yasukuni Jinja 靖国神社). In conclusion, I point out on one hand that the non-denominational expressions seen in Chidorigafuchi and other facilities show a distinctive kind of religious expression. On the other hand, I underscore that the excessive avoidance of religious participation by government officials derives from the Yasukuni issue and related legal trials. I explain the relationship of those phenomena in terms of two types of secularization: natural secularization and artificial secularization.
Introduction
Authors: Fujiwara Satoko
Published: October 2016

Japanese universities are currently facing significant challenges that affect the study of religion in Japan in various ways. Against this backdrop, this special issue is a response from a group of Japanese scholars to the inaugural issue of this journal on “Religion and the Secular in the Japanese Context.” Contributors of this issue have chosen concrete, recent cases that appear to be “post-secular”—if based on the conventional (i.e., modern Western) concept of religion—and attempt to explicate the multifaceted dynamics of these cases through further analysis and broader contextualization. This Introduction clarifies their arguments by comparing them with debates on the same topic, in particular the contested border between religion and politics, given by representative Japanese scholars of religion during the 1980s and the 1990s.
Phallus haitangensis, a new species of stinkhorn from Yunnan Province, China
Authors: LI HUILI , MA XUELAN , MORTIMER PETER E. , KARUNARATHNA SAMANTHA C. , XU JIANCHU , HYDE KEVIN D.
Published: October 2016

Four specimens of Phallus were collected during surveys in a Pinus armandii forest in Baoshan, Yunnan Province, China. Macro- and micro-characteristics, together with Internal Transcribed Spacer (ITS) sequence data, showed that the four specimens belong to a new species, here named Phallus haitangensis. The ITS phylogenetic analyses, morphological descriptions, color photographs, and line drawings are provided, and compared with closely related species in the genus.
New species and phylogenetic relationships of the spider genus Coptoprepes using morphological and sequence data (Araneae: Anyphaenidae)
Authors: BARONE MARIANA L. , WERENKRAUT VICTORIA , RAMÍREZ MARTÍN J.
Published: October 2016

We present evidence from the standard cytochrome c oxidase subunit I (COI) barcoding marker and from new collections, showing that the males and females of C. ecotono Werenkraut & Ramírez were mismatched, and describe the female of that species for the first time. An undescribed male from Chile is assigned to the new species Coptoprepes laudani, together with the female that was previously thought as C. ecotono. The matching of sexes is justified after a dual cladistics analysis of morphological and sequence data in combination. New locality data and barcoding sequences are provided for other species of Coptoprepes, all endemic of the temperate forests of Chile and adjacent Argentina. Although morphology and sequences are not conclusive on the relationships of Coptoprepes species, the sequence data suggests that the species without a retrolateral tibial apophysis may belong to an independent lineage.
Mesene Doubleday (Lepidoptera: Riodinidae) from Parque Nacional da Serra do Divisor, Acre, Brazil, with taxonomic notes and the description of a new species
Authors: DOLIBAINA DIEGO RODRIGO , DIAS FERNANDO MAIA SILVA , SIEWERT RICARDO RUSSO , MIELKE OLAF HERMANN HENDRIK , CASAGRANDE MIRNA MARTINS
Published: October 2016

The species of Mesene Doubleday, 1847 collected at the Parque Nacional da Serra do Divisor, Acre, Brazil (PNSD) are listed and supplemented by taxonomic and behavioral notes. In total, 30 specimens were collected, representing seven species including one new: M. monostigma monostigma (Erichson, [1849]), M. nepticula stigmosa Stichel, 1910, M. eupteryx Bates, 1868 stat. rest., M. paraena Bates, 1868, M. epaphus pyrrha Bates, 1868, M. leucophrys Bates, 1868, and M. gracielae sp. nov. The following notes on the taxonomy of Mesene are proposed: M. eupteryx Bates, 1868 stat. rest. is recognized as a valid species, M. epaphus sertata Stichel, 1910 syn. nov. is a new synonym of M. epaphus pyrrha Bates, 1868, and M. lecointrei P. Jauffret & J. Jauffret, 2008 syn. nov. is a new synonym of M. philonis Hewitson, 1874. Mesene margaretta (White, 1843), M. philonis and M. nola are recognized as closely related. Species encountered at the PNSD are illustrated, including the genitalia of males and females, when available.
New species of Tenebrionidae Latreille, 1802 (Coleoptera: Tenebrionoidea) from the Philippines
Authors: ANDO KIYOSHI , RUZZIER ENRICO
Published: October 2016

In the present paper Androsus philippinus sp. nov. from Mt. Halcon (Mindoro), Euhemicera smeraldina sp. nov. from Aurora (Luzon) and Thesilea cyaneothorax sp. nov. from Nueva Viscaya (Luzon) are described, diagnosed and illustrated. Thesilea varicolor var. unicolor Kulzer 1951 is recognised as valid subspecies.
A New species and records of Gripopterygidae (Plecoptera) from Rio Grande do Sul State, Southern Brazil
Authors: NOVAES MARCOS CARNEIRO , DA CONCEIÇÃO BISPO PITÁGORAS
Published: October 2016

Specimens of Gripopterygidae (Plecoptera) from Rio Grande do Sul State, southern Brazil were studied. A new species, Tupiperla sepeensis n. sp. is described. Tupiperla misionera Froehlich 2002 is a new record for Brazil and Gripopteryx reticulata Brauer 1866 and Tupiperla tessellata Brauer 1866 are new records for southern Brazil.
More transcontinental mislabeling in the genus Onthophagus: d’Orbigny’s “African” Group 27 (Coleoptera: Scarabaeidae: Scarabaeinae)
Authors: ROSSINI M. , VAZ-DE-MELLO F. Z. , ZUNINO M.
Published: October 2016

With more than 2300 species, Onthophagus Latreille, 1802 is a mega diverse genus within the subfamily Scarabaeinae. Recent revisions have yielded an over-abundance of redundant species names accumulated over the years as results of bad and inappropriate taxonomic practices. Indeed, the difficulty of access to public entomological collections, the usage of outdated bibliographic references, as well as the description of new species based on a few specimens, and often accompanied by diagnoses largely vague, has resulted thus far in a very large number of synonyms.
Barotropic and Baroclinic Eddy Feedbacks in the Midlatitude Jet Variability and Responses to Climate Change–Like Thermal Forcings
Authors: Burrows D. Alex , Chen Gang , Sun Lantao
Published: October 2016

Studies have suggested that the persistence in the meridional vacillation of the midlatitude jet (i.e., annular mode time scale) in comprehensive climate models is related to the model biases in climatological jet latitude, with important implications for projections of future climates and midlatitude weather events. Through the use of the recently developed finite-amplitude wave activity formalism and feedback quantifying techniques, this paper has quantified the role of barotropic and baroclinic eddy feedbacks in annular mode time scales using an idealized dry atmospheric model.

The eddy–mean flow interaction that characterizes the persistent anomalous state of the midlatitude jet depends on processes associated with the lower-tropospheric source of vertically propagating Rossby waves, baroclinic mechanisms, and processes associated with upper-tropospheric wave propagation and breaking, barotropic mechanisms. A variety of climate change–like thermal forcings are used to generate a range of meridional shifts in the midlatitude eddy-driven jet. The idealized model shows a reduction in annular mode time scale associated with an increase in jet latitude, similar to comprehensive climate models. This decrease in time scale can be attributed to a similar decrease in the strength of the barotropic eddy feedback, which, in the positive phase of the annular mode, is characterized by anomalous potential vorticity (PV) mixing on the equatorward flank of the climatological jet. The decrease in subtropical PV mixing is, in turn, associated with a stronger subtropical jet as the eddy-driven jet is more distant from the subtropics. These results highlight the importance of subtropical eddy–mean flow interactions for the persistence of an eddy-driven jet.
Hybrid 4DVAR with a Local Ensemble Tangent Linear Model: Application to the Shallow-Water Model
Authors: Allen Douglas R. , Bishop Craig H. , Frolov Sergey , Hoppel Karl W. , Kuhl David D. , Nedoluha Gerald E.
Published: October 2016

An ensemble-based tangent linear model (TLM) is described and tested in data assimilation experiments using a global shallow-water model (SWM). A hybrid variational data assimilation system was developed with a 4D variational (4DVAR) solver that could be run either with a conventional TLM or a local ensemble TLM (LETLM) that propagates analysis corrections using only ensemble statistics. An offline ensemble Kalman filter (EnKF) is used to generate and maintain the ensemble. The LETLM uses data within a local influence volume, similar to the local ensemble transform Kalman filter, to linearly propagate the state variables at the central grid point. After tuning the LETLM with offline 6-h forecasts of analysis corrections, cycling experiments were performed that assimilated randomly located SWM height observations, based on a truth run with forced bottom topography. The performance using the LETLM is similar to that of the conventional TLM, suggesting that a well-constructed LETLM could free 4D variational methods from dependence on conventional TLMs. This is a first demonstration of the LETLM application within a context of a hybrid-4DVAR system applied to a complex two-dimensional fluid dynamics problem. Sensitivity tests are included that examine LETLM dependence on several factors including length of cycling window, size of analysis correction, spread of initial ensemble perturbations, ensemble size, and model error. LETLM errors are shown to increase linearly with correction size in the linear regime, while TLM errors increase quadratically. As nonlinearity (or forecast model error) increases, the two schemes asymptote to the same solution.
The Royal Air Force, Bomber Command and the Use of Benzedrine Sulphate: An Examination of Policy and Practice During the Second World War
Authors: Pugh James
Published: October 2016

This article explores the development of policy in the Royal Air Force (RAF) relating to the use of Benzedrine, a potent amphetamine, by aircrews during the Second World War. This policy evolved from total prohibition in September 1939 to cautious approval for the use of the drug on operations in November 1942. Such caution reflected the subjective evidence available about Benzedrine, the media profile of the substance, and wider social and cultural factors relating to the use of drugs during this period. This challenges our understanding of drug history, demonstrating that while amphetamines were framed as a ‘miracle drug’, more nuanced, functional interpretations of the substance were in evidence.

In turn, the article examines evidence from the operational context, including new data gathered from questionnaires and interviews with former Bomber Command aircrew and existing oral history material held by the Imperial War Museum. Both policy discussions and operational evidence allows for a re-evaluation of the arguments of Nicholas Rasmussen, who suggests the RAF made use of Benzedrine as a frontline ‘psychiatric medicine’. Such conclusions downplay the significance the RAF attached to the drug’s effects on wakefulness and concerns about the drug’s effects on wellbeing.
Ultimate ugly
Authors: Bown Nicola
Published: October 2016

Ugliness is an elusive concept and has been little discussed in theological aesthetics. This article argues that contemporary culture often regards ugliness as being more authentic than beauty and prizes ugliness in contemporary art. Through a discussion of works by the contemporary British artists Jake and Dinos Chapman that rework Goya’s Disasters of War, this article suggests that ugliness is connected to nihilism, and that it should be seen as not the opposite of, but the negation of beauty. The works by the Chapman brothers embody the aesthetic and affective qualities of ugliness, and thus a consideration of these works can help to formulate a theology of ugliness.
Is There an Estimation Bias in Occupational Health and Safety Surveys? The Mode of Administration and Informants as a Source of Error
Authors: Fondevila-McDonald Yvonne , Molinero-Ruiz Emília , Vergara-Duarte Montse , Guillén Montserrat , Ollé-Espluga Laia , Menéndez María , Benach Joan
Published: October 2016

Information quality deficiencies have been detected in occupational safety and health surveys in Europe, which typically gather self-reported data responded by employers or their representatives. For instance, their low response rates and informant profiles make estimations on establishments with safety representatives (SRs) unreliable. We tested the mode of administration and informants as sources of error regarding establishments with SRs in Catalonia, Spain. Two sources of information were compared: the Second Catalan Survey of Working Conditions 2011 (IICSWC)—with a methodology similar to surveys conducted at the state and European level—and the Progam on Prevention of Risks Management in Companies (PPRMC)—in which the labor authority collected data using a documentary verification in another sample of establishments. Percentage of establishments with SRs was estimated using the data from the PPRMC and also the differences in percentage between sources and informant profiles (with 95 percent confidence interval). Results show that the IICSWC overestimates the percentage of establishments with SRs.