bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract SY27-02: Tumour heterogeneity and therapy resistance in melanoma
Authors: Wellbrock Claudia
Published: August 2015

Solid tumors are structurally very complex; they consist of heterogeneous cancer cell populations, other non-cancerous cell types and a distinct extracellular matrix. Interactions of cancer cells with non-cancerous cells is well investigated, and our recent work in melanoma has demonstrated that the cellular environment that surrounds cancer cells has a major impact on the way a patient responds to MAP-kinase pathway targeting therapy.

We have shown that intra-tumor signaling within a heterogeneous tumor can have a major impact on the efficacy of BRAF and MEK inhibitors. With the increasing evidence of genetic and phenotypic heterogeneity within tumors, intra-tumor signaling between individual cancer-cell subpopulations is therefore a crucial factor that needs to be considered in future therapy approaches. Our work has identified the ‘melanocyte-lineage survival oncogene’ MITF as an important player in phenotypic heterogeneity (MITFhigh and MITFlow cells) in melanoma, and MITF expression levels are crucial for the response to MAP-kinase pathway targeted therapy. We found that ‘MITF heterogeneity’ can be caused by cell-autonomous mechanisms or by the microenvironment, including the immune-microenvironment.

We have identified various mechanisms underlying MITF action in resistance to BRAF and MEK inhibitors in melanoma. In MITFhigh expressing cells, MITF confers cell-autonomous resistance to MAP-kinase pathway targeted therapy. Moreover, it appears that in melanomas heterogeneous for MITF expression (MITFhigh and MITFlow cells), individual subpopulations of resistant and sensitive cells communicate and MITF can contribute to overall tumor-resistance through intra-tumor signaling. Finally, we have identified a novel approach of interfering with MITF action, which profoundly sensitizes melanoma to MAP-kinase pathway targeted therapy.

Citation Format: Claudia Wellbrock. Tumour heterogeneity and therapy resistance in melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY27-02. doi:10.1158/1538-7445.AM2015-SY27-02
Abstract SY35-04: Arming tumor-targeting antibodies with cytokine payloads: Emerging clinical results
Authors: Neri Dario
Published: August 2015

Antibodies can be used to deliver bioactive molecules (drugs, cytokines, photosensitizers, radionuclides, etc.) to the tumor environment, thus sparing normal tissues. Pharmacodelivery strategies targeting certain modified extracellular matrix components, associated with the tumor neo-vasculature, is particularly attractive, because of: (i) the abundance and stability of these antigens (e.g., splice isoforms of fibronectin and tenascin-C); (ii) the dependence of cancer on new blood vessels; (iii) the accessibility of neo-vascular structures for therapeutic agents coming from the blood-stream; (iv) the fact that some extracellular matrix components are very abundant in many different cancer types, while being virtually undetectable in most normal adult tissues [Refs. 1-8].

In this lecture, I will present our experience (at a preclinical and clinical level) in the development and clinical applications of antibody-cytokine fusion proteins (“immunocytokines”) for cancer therapy applications. In particular, I will focus on pro-inflammatory immunocytokines specific to the alternatively-spliced EDA and EDB domains of fibronectin, or A1 domain of tenascin-C, used either as single agents or in combination. Immunocytokines based on IL2 or TNF as payloads are able to dramatically increase the density of certain leukocytes (e.g., T cells and NK cells) at the neoplastic site in various types of malignancies.

References:

1. Neri, D. & Bicknell, R.. Nature Rev. Cancer. 2005, 5, 436-446

2. Neri, D. & Supuran, C. Nature Rev. Drug Discov., 2011, 10, 767-777

3. Neri, D. & Pasche N. Drug Discov. Today, 2012, 17, 583-590

4. Gutbrodt, K. et al. Sci. Transl. Med., 2013, 5, 201ra118

5. Hemmerle, T. et al. Br. J. Cancer, 2013, 109, 1206-1213

6. Schwager K. et al. J. Invest. Dermatol., 2013, 133, 751-758

7. Schliemann C. et al. Blood, 2009, 113, 2275-2283

8. Halin C. et al. Nat. Biotechnol., 2002, 20, 264-269

Citation Format: Dario Neri. Arming tumor-targeting antibodies with cytokine payloads: Emerging clinical results. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY35-04. doi:10.1158/1538-7445.AM2015-SY35-04
Comparison between Cystatin C- and Creatinine-Estimated Glomerular Filtration Rate in Cardiology Patients
Authors: Åkerblom Axel , Helmersson-Karlqvist Johanna , Flodin Mats , Larsson Anders
Published: August 2015

Objective: Estimation of the glomerular filtration rate (GFR) is essential for identification, evaluation and risk prediction in patients with kidney disease. Estimated GFR (eGFR) is also needed for the correct dosing of drugs eliminated by the kidneys and to identify high-risk individuals in whom coronary angiography or other procedures may lead to kidney failure. Both cystatin C and creatinine are used for the determination of GFR, and we aimed to investigate if eGFR by the two methods differ in cardiology patients. Methods: We compared cystatin C and creatinine (CKD-EPI) eGFR calculated from the same request from a cardiology outpatient unit (n = 2,716), a cardiology ward (n = 980), a coronary care unit (n = 1,464), and an advanced coronary care unit (n = 518) in an observational, cross-sectional study. Results: The median creatinine eGFR results are approximately 10 ml/min/1.73 m2 higher than the median cystatin C eGFR that is up to 90 ml/min/1.73 m2, irrespective of the level of care. Creatinine eGFR resulted in a less advanced eGFR category in the majority of patients with a cystatin C eGFR <60 ml/min/1.73 m2. Conclusions: Our study demonstrates a difference between creatinine and cystatin C eGFR in cardiology patients. It is important to be aware of which marker is used for the reported eGFR to minimize erroneous interpretations of the test results, as this could lead to under- or overmedication. Further studies are needed to determine the best method of estimating the GFR in cardiology units.
Long-Term Maintenance of Complete Response after Sorafenib Treatment for Multiple Lung Metastases from Hepatocellular Carcinoma
Authors: Katafuchi Eisuke , Takami Yuko , Wada Yoshiyuki , Tateishi Masaki , Ryu Tomoki , Mikagi Kazuhiro , Saitsu Hideki , Wada Yoshiyuki
Published: August 2015

Sorafenib is an effective treatment for unresectable hepatocellular carcinoma (HCC) characterized by disease stabilization. However, the response rates are very low (<9%), and a complete response is rarely achieved. We report an extremely rare case of a HCC patient with multiple lung metastases treated with sorafenib who achieved a complete response for a long period. A 77-year-old woman was diagnosed with chronic hepatitis C in 1990. In 2007, a HCC detected in the liver was treated with percutaneous ethanol injection therapy. Subsequently, recurrence of HCC in the liver was treated with microwave coagulonecrotic therapy in 2010. In April 2011, a computed tomography (CT) scan revealed innumerable multiple metastases spread diffusely in both lungs. Tumor marker levels were extremely high [α-fetoprotein (AFP) 76,170 ng/ml, lens culinaris agglutinin-reactive fraction of AFP 7.5%, des-γ-carboxyprothrombin (DCP) 63,400 mAU/ml]. Sorafenib was administered at a reduced dose of 400 mg/day because of old age. Four months after sorafenib treatment, AFP and DCP had decreased to within normal levels, and the multiple lung metastases had disappeared. Currently, sorafenib is administered at a reduced dose of 400 mg/day, and the complete response has been maintained for 48 months.
Prognostic Significance of Short-Term Blood Pressure Variability in Acute Stroke
Authors: Manning Lisa S. , Rothwell Peter M. , Potter John F. , Robinson Thompson G.
Published: August 2015

Background and Purpose—

Blood pressure variability (BPV) may be an important prognostic factor acutely after stroke. This review investigated the existing evidence for the effect of BPV on outcome after stroke, also considering BPV measurement techniques and definitions.

Methods—

A literature search was performed according to a prespecified study protocol. Two reviewers independently assessed study eligibility and quality. Where appropriate, meta-analyses were performed to assess the effect of BPV on poor functional outcome.

Results—

Eighteen studies from 1359 identified citations were included. Seven studies were included in a meta-analysis for the effect of BPV on functional outcome (death or disability). Systolic BPV was significantly associated with poor functional outcome: pooled odds ratio per 10-mm Hg increment, 1.2; confidence interval (1.1–1.3). A descriptive review of included studies also supports these findings, and in addition, it suggests that systolic BPV may be associated with increased risk of intracranial hemorrhage in those treated with thrombolytic therapy.

Conclusions—

This systematic review and meta-analysis suggest that greater systolic BPV, measured early from ischemic stroke or intracerebral hemorrhage onset, is associated with poor longer-term functional outcome. Future prospective studies should investigate how best to measure and define BPV in acute stroke, as well as to determine its prognostic significance.
Rapid Attentional Selection of Non-native Stimuli despite Perceptual Narrowing
Authors: Wu Rachel , Nako Rebecca , Band Jared , Pizzuto Jacquelyne , Ghoreishi Yalda , Scerif Gaia , Aslin Richard
Published: August 2015

Visual experiences increase our ability to discriminate environmentally relevant stimuli (native stimuli, e.g., human faces) at the cost of a reduced sensitivity to irrelevant or infrequent stimuli (non-native stimuli, e.g., monkey/ape faces)—a developmental progression known as perceptual narrowing. One possible source of the reduced sensitivity in distinguishing non-native stimuli (e.g., one ape face vs. another ape face) could be underspecified attentional search templates (i.e., working memory representations). To determine whether perceptual narrowing stems from underspecified attentional templates for non-native exemplars, this study used ERP (the N2pc component) and behavioral measures in a visual search task, where the target was either an exemplar (e.g., a specific ape face) or a category (e.g., any ape face). The N2pc component, an ERP marker of early attentional selection emerging at 200 msec poststimulus, is typically modulated by the specificity of the target and, therefore, by the attentional template—the N2pc is larger for specific items versus categories. In two experiments using both human and ape faces (i.e., native and non-native stimuli), we found that perceptual narrowing affects later response selection (i.e., manual RT and accuracy), but not early attentional selection relying on attentional templates (i.e., the N2pc component). Our ERP results show that adults deploy exemplar level attentional templates for non-native stimuli (as well as native stimuli), despite poor downstream behavioral performance. Our findings suggest that long-term previous experience with reduced exemplar level judgments (i.e., perceptual narrowing) does not appear to eliminate early attentional selection of non-native exemplars.
Semantic Relations between Visual Objects Can Be Unconsciously Processed but Not Reported under Change Blindness
Authors: Ball Felix , Bernasconi Fosco , Busch Niko A.
Published: August 2015

Change blindness—the failure to detect changes in visual scenes—has often been interpreted as a result of impoverished visual information encoding or as a failure to compare the prechange and postchange scene. In the present electroencephalography study, we investigated whether semantic features of prechange and postchange information are processed unconsciously, even when observers are unaware that a change has occurred. We presented scenes composed of natural objects in which one object changed from one presentation to the next. Object changes were either semantically related (e.g., rail car changed to rail) or unrelated (e.g., rail car changed to sausage). Observers were first asked to detect whether any change had occurred and then to judge the semantic relation of the two objects involved in the change. We found a semantic mismatch ERP effect, that is, a more negative-going ERP for semantically unrelated compared to related changes, originating from a cortical network including the left middle temporal gyrus and occipital cortex and resembling the N400 effect, albeit at longer latencies. Importantly, this semantic mismatch effect persisted even when observers were unaware of the change and the semantic relationship of prechange and postchange object. This finding implies that change blindness does not preclude the encoding of the prechange and postchange objects' identities and possibly even the comparison of their semantic content. Thus, change blindness cannot be interpreted as resulting from impoverished or volatile visual representations or as a failure to process the prechange and postchange object. Instead, change detection appears to be limited at a later, postperceptual stage.
From Metaphor to Theology
Authors: Brisman Leslie
Published: August 2015

Theological change suffers under the obligation to seem—and the danger of seeming—both consistent with what has come before and genuinely new. Where does the idea of the suffering servant in Isaiah 53 come from? Leaving aside those acts of warfare and violence against the innocent, which seem more matters of brute aggression than symbolic atonement, we can find well-acknowledged roots for the doctrine of a suffering servant in the practice of symbolic animal sacrifice and in the figure of the prophet who suffers with, and perhaps for, the people. But there is a third root as well that goes back to the language of the divine attributes and to the ambiguous Hebrew idiom of noseh avon, bearing sin or forgiving sin. If the servant of God bears iniquity, he can be imagined not just to remove sin from the head or shoulders of many but also to carry what he removes; he himself can “bear” it. And when all the people in the Gospel of Matthew call down the blood of Jesus on their heads, they “own” (own up to, but also claim for their own) the rich history of ambiguous responsibility and atonement.
Studies on some pottiaceous mosses from Africa, 3.
Authors: Sollman Philip
Published: August 2015

Didymodon tisserantii P.de la Varde is Barbula bolleana (Müll.Hal) Broth. Didymodon capitatus Dixon is Bryoerythrophyllum campylocarpum (Müll.Hal.) H.A.Crum. Barbula congoana Thér. is Bryoerythrophyllum ferruginascens (Stirt.) Giacom. Barbula dioritica Müll.Hal. is Didymodon acutus (Brid.) K.Saito. Barbula mollis Bruch & Schimp. ex Müll.Hal. is Syntrichia princeps (De Not.) Mitt. Bryoerythrophyllum alpigenum is reported new for Ethiopia. Bryoerythrophyllum rubrum is reported for several central African countries. Comments on several nomina nuda taxa are given.
New Sericosura (Pycnogonida:Ammotheidae) from deep-sea hydrothermal vents in the Southern Ocean
Authors: ARANGO CLAUDIA P. , LINSE KATRIN
Published: August 2015

Three new species of Sericosura (Pycnogonida: Ammotheidae) are described from recently discovered hydrothermal vents in the East Scotia Ridge, Southern Ocean: Sericosura bamberi sp. nov., S. dimorpha sp. nov. and S. curva sp. nov. The eleven species known to date in the genus Sericosura are all inhabitants of chemosynthetic environments in different oceans around the world.        Morphology and preliminary DNA data from the COI locus suggest the East Scotia Ridge pycnogonids have relatively close evolutionary affinities with species known from the East Pacific Rise and the Mid-Atlantic Ridge. This finding highlights the importance of Sericosura as a characteristic taxon of hydrothermal vents and the great potential of this genus for global scale ecological and evolutionary studies of hydrothermal vents fauna.        The use of pycnogonid DNA data combined with recent models explaining biogeographic provinces along the mid-ocean ridge system should prove extremely useful to understanding the patterns of diversification of endemic fauna from chemosynthetic environments and from the deep-sea in general.
Impact of Victim, Offender, and Relationship Characteristics on Frequency and Timing of Intimate Partner Violence using Life History Calendar Data
Authors: Hayes Brittany E.
Published: August 2015

Objectives:

To examine whether victim, offender, and relationship characteristics increase the risk and frequency of intimate partner violence (IPV). The effect of separation length on the risk of IPV is also evaluated.

Methods:

Using abuse incident data ( N = 4,960) from IPV victims ( n = 497), who accessed a health-care facility over a one-year period, between-individual differences in the frequency and timing of abuse were assessed. Dependence of event times within respondents was accounted for with conditional risk set “gap time” models, which stratified participants across event number and failure order.

Results:

Employment of both partners and only the victim decreased the risk and frequency. Employment of only the abuser and length of separation decreased frequency but was not significantly associated with timing of abuse. Separated and non-separated respondents were not significantly different in frequency (incident risk ratio = 1.06, p > .05) and timing of abuse, (exp ( b) = 0.95, p > .05).

Conclusions:

By capturing the timing between abuse incidents, insight into the long-term risk of abuse is provided and accounts for selection effects. Findings call for an improvement in measuring relationship status indicators, including relationship length and time since separation. Future research should examine within-individual changes in separation and IPV risk.
Well-being, austerity and policing
Authors: Hesketh Ian , Cooper Cary L. , Ivy Jonathan
Published: August 2015

The purpose of this paper is to deepen conceptual understanding of workplace well-being in policing, particularly personal resilience. This is a conceptual paper reviewing and discussing contemporary literature with a focus on themes congruent with personal resilience in a police setting. This paper considers well-being in the context of police work in the UK, how resilience factors impact on an individual’s working life and the implications for policing generally.

People can be trained to improve their resilience by a host of activities and approaches. These skills can be used to assess their own levels of resilience, and inform how to manage others through a variety of techniques.

Some resilience factors are completely out of an individual’s locus of control; but many are not. Organisations can contribute by providing training and creating environments where individuals can practice these approaches as part and parcel of their daily activity, and flourish from doing so.
A Gay-Friendly Public Service
Authors: Stanisevski Dragan
Published: August 2015

The article examines whether intrinsic psychological orientations influence the attitudes of public servants toward homosexuality. Using Schwartz’s typology of psychological orientations, and based on data from 24 countries, collected in two waves by the World Values Survey, the article develops two models: an individual and an aggregate cross-country model. The article finds support in the individual model for the argument that intrinsic psychological orientations that facilitate openness to change (self-direction, hedonism) and self-transcendence (universalism) have positive impact, while psychological orientations that emphasize conservation (security, conformity, tradition) and self-enhancement (achievement, economic power) have negative impact, on attitudes toward homosexuality. Extrinsic factors show to be significant influences on attitudes toward homosexuality in both models, but particularly on the aggregate level. The study concludes that to improve the attitudes of public servants toward homosexuality, public personnel administrators should encourage cultural openness and familiarity-building practices that reduce existential anxieties.
Rising Residency Applications
Authors: Chang C. W. David , Erhardt Benjamin F.
Published: August 2015

Otolaryngology is viewed as a competitive residency program, and as a result, a high number of applications are submitted by each applicant. A look at the data quantifies the cost and the challenges.
Transverse Retropalatal Collapsibility Is Associated with Obstructive Sleep Apnea Severity and Outcome of Relocation Pharyngoplasty
Authors: Chen Hung‐Chin , Lee Li‐Ang , Hsin Li‐Jen , Lin Wan‐Ni , Fang Tuan‐Jen , Huang Chung‐Guei , Li Hsueh‐Yu
Published: August 2015

Objective

The aim of this study was to investigate whether the retropalatal airway shape and collapsibility defined by awake nasopharyngoscopy with Müller’s maneuver were associated with apnea‐hypopnea index (AHI), positional dependency, and surgical outcome of relocation pharyngoplasty in patients with obstructive sleep apnea.

Study Design

Case series with planned data collection.

Setting

Tertiary referral center.

Subjects and Methods

A total of 45 obstructive sleep apnea patients were included who underwent conservative treatment (n = 13) or relocation pharyngoplasty (n = 32), and their baseline and postoperative polysomnographies and awake nasopharyngoscopies with Müller’s maneuver were reviewed. Shape ratio (transverse diameter [TD] / longitudinal diameter [LD]) in the stationary and Müller’s phases and collapsibility (ColTD and ColLD) of the airway at the level of the uvular base were measured with a picture archiving and communication system. Intra‐ and interrater reliabilities were assessed. Associations among nasopharyngoscopic measurements, AHI, positional dependency, and surgical success (defined as a reduction of AHI ≥50% and a postoperative AHI ≤20/h) were statistically analyzed.

Results

Reliability tests indicated substantial agreements of all nasopharyngoscopic measurements between raters and within raters. A higher baseline ColTD was significantly associated with an elevated AHI (r = 0.49, P =. 001), whereas a lower postoperative ColTD was significantly related to surgical success (r = −0.38, P =. 034). Nasopharyngoscopic findings were not statistically significantly correlated with positional dependency.

Conclusion

Transverse retropalatal collapsibility measured by awake nasopharyngoscopy with Müller’s maneuver helps to predict individuals with moderate to severe sleep apnea and surgical outcome.
Role of Maternal Allergy on Immune Markers in Colostrum and Secretory Immunoglobulin A in Stools of Breastfed Infants
Authors: Hua Man-Chin , Chen Chien-Chang , Yao Tsung-Chieh , Tsai Ming-Han , Liao Sui-Ling , Lai Shen-Hao , Chiu Chih-Yung , Yeh Kuo-Wei , Huang Jing-Long
Published: August 2015

Background:

Although protection against infectious diseases has been observed among breastfed infants as compared to formula-fed infants, possible benefits of breastfeeding by allergic mothers for allergy prevention remain controversial.

Objectives:

The aims of this study were to determine whether maternal allergy would influence immune markers (secretory immunoglobulin A [sIgA], interleukin-8 [IL-8], soluble CD14 [sCD14]) in colostrum and the associations between maternal allergy and fecal sIgA levels in breastfed infants.

Methods:

Study subjects were enrolled from the Prediction of Allergies in Taiwanese Children (PATCH) birth cohort study. Colostrum samples were obtained from 98 lactating mothers. Stool samples were collected from 108 infants within 5 days after birth and at 2 and 4 months of age. We compared concentrations of sIgA, IL-8, and sCD14 in colostrum between mothers with and without a history of allergic disease and allergic sensitization. We also compared fecal sIgA levels between breastfed and formula-fed infants and between infants with allergic and nonallergic mothers.

Results:

The sIgA concentrations were significantly higher in colostrum from allergic mothers than from nonallergic mothers ( P = .01) and from allergic mothers who were immunoglobulin E (IgE) sensitized compared to nonallergic mothers who were not IgE sensitized ( P = .023). Breastfed infants had significantly higher fecal sIgA levels as compared to formula-fed infants, regardless of whether their lactating mothers had an allergy ( P < .05).

Conclusion:

We found that breastfeeding is associated with increased infants’ fecal sIgA levels and may have potential protective effects to the infants during the first 4 months of life, regardless of whether their lactating mothers have allergies.
In Response
Authors: Biggar Nigel
Published: August 2015

The author of In Defence of War responds to each commentator in turn, discussing the following issues, among others: the Christian specification of just war, its punitive form, the virtue of callousness, love for the enemy, the intention to kill, proportionality, empire, international law, human fatedness, and the First World War.
The formalized framework for decision-making in child protection care orders: A cross-country analysis
Authors: Berrick Jill D , Peckover Sue , Pösö Tarja , Skivenes Marit
Published: August 2015

Care orders within the child protection system are some of the most invasive interventions a state can make. This article examines the discretionary space governments set out for child protection workers when they prepare care orders. We analyse the formalized framework for these decisions in England, Finland, Norway and the United States. We focus on knowledge, timelines, how children and parents are involved and accountability. We find that Norway and Finland have highly de-regulated systems with wide discretionary space, whereas England and the United States are highly regulated systems with narrow discretionary space. The United States differentiates itself with relatively little parent and/or child involvement in decision-making. England and Finland do not have defined deadlines for terminating the process, and Norway has few directives on what information to collect. Such differences will influence the quality of decisions as well as the principles of the rule of law.
Why call it ‘equality’ when it should be ‘achievement’? A proposal to un-correct the ‘corrected gender gaps’ in the EU Gender Equality Index
Authors: Permanyer Iñaki
Published: August 2015

This study critically reviews the new Gender Equality Index (GEI) proposed by the European Institute for Gender Equality (EIGE) in 2013, arguing that the way in which it has been defined can be misleading for its potential users. The GEI is defined to ensure that good scores in the index are reflective of both low gender gaps and high levels of overall achievement. The study finds that the GEI values are largely driven by differences in overall achievement levels between countries rather than by gender differences within them, a disturbing issue that unduly penalizes low-income countries for factors that are not related to gender norms or discriminatory practices and which might lead to the elaboration of ill-targeted policies. In order to overcome this problem, we introduce a new version of the GEI that gets rid of its achievement component and which is much simpler to interpret.
Ectopic anterior cerebellum (ala lobule centralis)
Authors: Algin Oktay , Ozmen Evrim
Published: August 2015

In this case report we present an adolescent girl who was referred to our radiology department for assessment with advanced magnetic resonance (MR) imaging on suspicion of low-grade quadrigeminal cistern neoplasm on 1.5 Tesla MR examination. We were able to evaluate detailed cerebellar anatomy more clearly, and detected that the lesion was compatible with ectopic cerebellar tissue (a very rare developmental variation) on submillimetric 3-dimensional (3D) images from a 3 Tesla MR unit which has a 32-channel head coil. Our findings were further supported by diffusion tensor imaging which clearly indicated that the lesion was a part of the cerebellum. Furthermore, MR spectroscopic metabolite ratios were in accordance with the characteristics of normal neuronal tissue. As far we know there is no published report that contains similar findings to those of our patient. In conclusion, cranial MR images, if possible in 3D format (with very small isotropic voxels) should be obtained for the precise diagnosis of the lesions located in this region; in addition, the differential diagnostic list should be well known and advanced imaging techniques should be used when necessary.
A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa
Authors: Mohanty Tirthankar , Sjögren Jonathan , Kahn Fredrik , Abu-Humaidan Anas H. A. , Fisker Niels , Assing Kristian , Mörgelin Matthias , Bengtsson Anders A. , Borregaard Niels , Sørensen Ole E.
Published: August 2015

Key Points

Saliva induces bactericidal and DNase resistant NETs in the oral cavity via sialyl LewisX- L-selectin signaling. Disordered homeostasis in the oral cavity may lead to deficient saliva-mediated NETosis.
Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors
Authors: Wang Wei , Cortes Jorge E. , Lin Pei , Beaty Michael W. , Ai Di , Amin Hesham M. , McDonnell Timothy J. , Ok Chi Young , Kantarjian Hagop M. , Medeiros L. Jeffrey , Hu Shimin
Published: August 2015

Key Points

The emergence of 3q26.2 rearrangements in CML is associated with resistance to TKI treatment and poor prognosis. 3q26.2 rearrangements play a predominant role in determining prognosis, irrelevant to the presence or absence of other additional chromosomal abnormalities in CML.
OrthoFinder: solving fundamental biases in whole genome comparisons dramatically improves orthogroup inference accuracy
Authors: Emms David M. , Kelly Steven
Published: August 2015

Identifying homology relationships between sequences is fundamental to biological research. Here we provide a novel orthogroup inference algorithm called OrthoFinder that solves a previously undetected gene length bias in orthogroup inference, resulting in significant improvements in accuracy. Using real benchmark datasets we demonstrate that OrthoFinder is more accurate than other orthogroup inference methods by between 8 % and 33 %. Furthermore, we demonstrate the utility of OrthoFinder by providing a complete classification of transcription factor gene families in plants revealing 6.9 million previously unobserved relationships.
The Role of Bone Marrow Fat in Skeletal Health: Usefulness and Perspectives for Clinicians
Authors: Paccou Julien , Hardouin Pierre , Cotten Anne , Penel Guillaume , Cortet Bernard
Published: August 2015

Context:

There is growing interest in the relationship between bone marrow fat (BMF), bone mineral density (BMD), and fractures. Moreover, BMF might be influenced by metabolic diseases associated with bone loss and fractures, such as type 2 diabetes mellitus (T2DM), anorexia nervosa (AN), and obesity.

Methods:

The primary-source literature for this review was acquired using a PubMed search for articles published between January 2000 and April 2015. Search terms included BMF, BMD, fractures, T2DM, AN, and obesity. The titles and abstracts of all articles were reviewed for relevant subjects.

Results:

Magnetic resonance imaging, with or without spectroscopy, was used to noninvasively quantify BMF in humans. A negative relationship was found between BMD and BMF in both healthy and osteopenic/osteoporotic populations. Data are lacking on the relationship between BMF and fractures. Studies in populations of individuals with metabolic diseases such as T2DM, AN, and obesity have shown BMF abnormalities.

Conclusions:

We conclude that most human data demonstrate an inverse relationship between BMF and BMD, but data on the relationship with fractures are inconsistent and need further study. In daily practice, the usefulness for clinicians of assessing BMF using magnetic resonance imaging is still limited. However, the perspectives are exciting, particularly in terms of improving the diagnosis and management of osteoporosis.
PSFC: a Pathway Signal Flow Calculator App for Cytoscape
Authors: Nersisyan Lilit , Johnson Graham , Riel-Mehan Megan , Pico Alexander R , Arakelyan Arsen
Published: August 2015

Cell signaling pathways are sequences of biochemical reactions that propagate an input signal, such as a hormone binding to a cell-surface receptor, into the cell to trigger a reactive process. Assessment of pathway activities is crucial for determining which pathways play roles in disease versus normal conditions. To date various pathway flow/perturbation assessment tools are available, however they are constrained to specific algorithms and specific data types. There are no accepted standards for evaluation of pathway activities or simulation of flow propagation events in pathways, and the results of different software are difficult to compare. Here we present Pathway Signal Flow Calculator (PSFC), a Cytoscape app for calculation of a pathway signal flow based on the pathway topology and node input data. The app provides a rich framework for customization of different signal flow algorithms to allow users to apply various approaches within a single computational framework.
Social Network: a Cytoscape app for visualizing co-publication networks
Authors: Kofia Victor , Isserlin Ruth , Buchan Alison M.J. , Bader Gary D.
Published: August 2015

Networks that represent connections between individuals can be valuable analytic tools. The Social Network Cytoscape app is capable of creating a visual summary of connected individuals automatically. It does this by representing relationships as networks where each node denotes an individual and an edge linking two individuals represents a connection. The app focuses on creating visual summaries of individuals connected by co-publication links in academia, created from bibliographic databases like PubMed, Scopus and InCites. The resulting co-publication networks can be visualized and analyzed to better understand collaborative research networks or to communicate the extent of collaboration and publication productivity among a group of researchers, like in a grant application or departmental review report. It can also be useful as a research tool to identify important research topics, researchers and papers in a subject area.
Coming with Baggage: Past Rejections and the Evolution of Market Relationships
Authors: Fernandez-Mateo Isabel , Coh Marko
Published: August 2015

We examine the role of past rejections in the evolution of market relationships. We identify a theoretical tension between the informational benefits and the negative affect resulting from interactions in which one actor rejected another. Rejection can help select future mutually beneficial transactions, but it can also trigger negative affect and lead rejected actors to decline exchange opportunities with those who rejected them in the past. We test this theory with longitudinal data on candidates considered by an executive search firm, using insights from fieldwork and interviews to understand better what motivates the parties’ reactions to being rejected. This paper contributes to research on relationship evolution and highlights the importance of handling rejection in market interactions.
Canine diabetes mellitus: what is new?
Authors: Niessen Stijn
Published: August 2015

Recent developments in genetic research have increased our understanding of the most common form of diabetes affecting pet dogs. This research starts to explain why certain breeds seem more susceptible to developing diabetes; in the long run it could lead to revolutionary screening and prevention strategies. Nevertheless, the genetics do not completely explain the ultimate establishment of the diabetic state, therefore the search continues for other (epigenetic and environmental) factors involved in this process. Clinicians should remain open-minded for the existence of a variety of different types of canine diabetes mellitus. Knowing the aetiology is important, since this will enable development of superior treatment strategies. An entire female diabetic dog usually benefits from prompt neutering, since diabetic remission is possible in a subset of cases and achieving diabetic control will prove easier even if remission is not achieved. Currently, routine treatment of diabetic dogs is based on matching insulin activity, usually provided by twice-daily insulin injections, with post-prandial hyperglycaemia. Being strategic in the timing of injection versus feeding can prove beneficial. Studies with relatively novel drugs such as GLP-1 agonists are currently ongoing and seem promising. In the future, canine diabetes mellitus will probably best be treated through complete pancreatic beta-cell replacement, either by transplantation, regenerative medicine or the use of an artificial pancreas. Gene therapy could play a distinct role and has already been implemented in small trials. Development of a veterinary practice-based diabetes team working closely with dog owners will enable individualisation and optimisation of diabetic pet care whichever shape it takes in the future. Veterinary nurses should play a crucial role in such a team, mirroring the situation in human diabetic care. Where possible, clinic-wide diabetes protocols should be adapted and made flexible, paying particular attention to co-morbidities and their impact on glycaemic control, as well as on the quality of life of the diabetic dog and owner. The use of available quality of life measurement tools should be actively encouraged by any clinic taking individualised diabetic care seriously.
CPD article: General approach to the poisoned patient
Authors: Bates Nicola
Published: August 2015

Numerous potential toxic hazards are present in and around the home, and potential poisoning is not an uncommon presentation. Stabilisation is the priority in a critically ill animal, but in many cases animals present before the onset of signs, so a risk assessment is required to determine if decontamination is appropriate and which method (e.g. emesis, gastric lavage or activated charcoal) is best in the specific circumstances. Thereafter, further treatment is supportive, based on clinical signs, the particular risks associated with whatever substance the animal has been exposed to, and the estimated quantity involved. Management may involve laboratory monitoring, and the use of specific treatments and antidotes. If these drugs are not stocked, it is important to know where to obtain them in an emergency. A poisons information centre can provide specific advice on clinical signs and treatment recommendations if required, particularly if the substance involved is unfamiliar.
Skunks: general care and health concerns
Authors: Chitty John
Published: August 2015

Striped skunks (Mephitis mephitis) are being kept more commonly as pets in the UK, and may therefore be presented to veterinary surgeons in small animal practice. Appropriate husbandry should be encouraged, including an adequate omnivorous diet and plenty of environmental enrichment. Hand-tame skunks are generally not difficult to handle, but care is important to avoid distressing the skunk and triggering discharge of the noxioussmelling anal sac contents. Common presenting conditions include obesity, metabolic bone disease and dental disease, which may be associated with incorrect feeding; cardiac disease; and parasitic diseases, including endoparasites, ectoparasites and toxoplasmosis. The possibility of zoonotic Baylisascaris spp. infections in imported skunks must also be considered.
Science and the media
Authors: Naumann Thomas
Published: August 2015

Science seeks and needs the attention of the public and the media, and the media are eager for news from the world of research. This sometimes seduces scientists to communicate their results in early stages of their work and may bring them into the situation of the sorcerer's apprentice – they can’t get rid of the ghosts they called. We give some recent examples of early or doubtful communication in physics and ask for a responsible cooperation of science and the media which takes care of the peculiarities of the scientific process.
Spectral rigidity for primitive elements of FN
Authors: Horbez Camille
Published: August 2015

Two trees in the boundary of outer space are said to be primitive-equivalent whenever their translation length functions are equal in restriction to the set of primitive elements of FN
. We give an explicit description of this equivalence relation, showing in particular that it is nontrivial. This question is motivated by our description of the horoboundary of outer space for the Lipschitz metric in [`The horoboundary of outer space, and growth under random
automorphisms', preprint (2014)]. In proving this, we extend a theorem due to White about the Lipschitz metric on outer space to trees in the boundary, showing that the infimal Lipschitz constant of an FN
-equivariant map between the metric completion of any two minimal, very small FN
-trees is equal to the supremal ratio between the translation lengths of the elements of FN
in these trees. We also provide approximation results for trees in the boundary of outer space.
An unusual case of hereditary nephrogenic diabetes insipidus (HNDI) affecting mother and daughter
Authors: Giri Dinesh , Hart Rachel , Jones Caroline , Ellis Ian , Ramakrishnan Renuka
Published: August 2015

Hereditary nephrogenic diabetes iInsipidus (HNDI) is an uncommon disorder due to a resistance to anti-diuretic hormone leading to a reduced urinary concentrating ability. The X-linked form is fully expressed in hemizygous male patients, but diabetes insipidus may also present in heterozygous females where it must be distinguished from autosomal and other secondary causes. We report a mother and daughter in the same family with HNDI due to a heterozygous deletion in exon 1 of the
Anti-Cancer and Immunostimulatory Activity of Chromones
and Other Constituents from Cassia petersiana
Authors: Gamal-Eldeen Amira M. , Djemgou Pierre C. , Tchuendem Marguérite , Ngadjui Bonaventure T. , Tane Pierre , Toshifumi Hirata
Published: August 2015

Phytochemical investigation of Cassia petersiana Bolle leaves afforded four new compounds,
including two chromone derivatives, 7-acetonyl-5-hydroxy-2-methylchromone (petersinone
1, 1) and 7-(propan-2ʹ-ol-1ʹ-yl)-5-hydroxy-2-methylchromone (petersinone 2, 2),
two benzoic acid derivatives, 5-methyl-3-(propan-2ʹ-on-1ʹ-yl) benzoic acid (petersinone 3, 3)
and 5-(methoxymethyl)-3-(propan-2ʹ-ol-1ʹ-yl) benzoic acid (petersinone 4, 4), and glyceryl-
1-tetracosanoate (6), in addition to the known compound sistosterol-3-β-ᴅ-glycoside (5). The
structures of these compounds were determined by comprehensive NMR studies, including
DEPT, COSY, HMQC, HMBC, MS and IR.

Compounds 1, 2, 5 and 6 were tested for antioxidant, anti-cancer and immunostimulatory
properties. The biological investigations indicated that compound 6, among others, possessed
the highest anti-cancer activity against hepatocellular carcinoma, immunoproliferative activity
via induction of T-lymphocytes and macrophage proliferation, anti-inflammatory activity
as indicated by NO inhibition, and antioxidant activity against DPPH radicals. Moreover,
compound 5 was the most effective cytotoxic compound against breast carcinoma and stimulated
a consistent immunoproliferative effect on lymphocytes and macrophages combined
with strong NO inhibitory activity, while compound 1 was promising as immunoproliferative
agent and may act as anti-inflammatory agent as a consequence of its NO inhibitory activity.
Playing Victorian
Authors: Rutherford-Morrison Lara
Published: August 2015

The British heritage industry has long been a subject for debate in the UK, with critics arguing that heritage invests history with a nostalgic idealism that sanitizes and simplifies the nation’s past. This article examines Blists Hill Victorian Town, a British living history museum that purports to re-create everyday industrial life of the 1890s, within the context of these debates, arguing that Blists Hill portrays the late-Victorian period with more complexity than many critics would allow. Shifting the lens of how such sites have typically been evaluated—away from questions of authenticity, to instead focus on how living history museums engage visitors in meaningful play—I consider the ways that Blists Hill promotes creative learning through an imaginative, visceral engagement with history.
An algorithm for identifying the best current friend in a social network
Authors: Moreno Francisco Javier , Hernández Santiago
Published: August 2015

A research field in the area of social networks (SNs) is the identification of some types of users and groups. To facilitate this process, a SN is usually represented by a graph. The centrality measures, which identify the most important vertices in a graph according to some criterion, are usual tools to analyze a graph. One of these measures is the PageRank (a measure originally designed to classify web pages). Informally, in the context of a SN, the PageRank of a user i represents the probability that another user of the SN is seeing the page of i after a considerable time of navigation in the SN. In this paper, we define a new type of user in a SN: the best current friend. The idea is to identify, among the friends of a user i, who is the friend k that would generate the highest decrease in the PageRank of i if k stops being his/her friend. This may be useful to identify the users/customers whose friendship/relationship should be a priority to keep. We provide formal definitions, algorithms and some experiments for this subject. Our experiments showed that the best current friend of a user is not necessarily the one who has the highest PageRank in the SN nor the one who has more friends.
Ultra-Low-Energy Straintronics Using Multiferroic Composites
Authors: Roy Kuntal
Published: August 2015

The primary impediment to continued improvement of charge-based electronics is the excessive energy dissipation incurred in switching a bit of information. With suitable choice of materials, devices made of multiferroic composites, i.e., strain-coupled piezoelectric-magnetostrictive heterostructures, dissipate miniscule amount of energy of ∼1 attojoule at room-temperature, while switching in sub-nanosecond delay. Apart from devising memory bits, such devices can be also utilized for building logic, so that they can be deemed suitable for computing purposes as well. Here, we first review the current state of the art for building nanoelectronics using multiferroic composites. On a recent development, it is shown that these multiferroic straintronic devices can be also utilized for analog signal processing, with suitable choice of materials. By solving stochastic Landau-Lifshitz-Gilbert equation of magnetization dynamics at room-temperature, it is shown that we can achieve a voltage gain, i.e., these straintronic devices can act as voltage amplifiers.