bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumorigenic Effects of Inhibiting Ephrin Receptor Kinase Signaling by GLPG1790 against Colorectal Cancer Cell Lines In Vitro and In Vivo
Authors: Colapietro Alessandro , Gravina Giovanni Luca , Petragnano Francesco , Fasciani Irene , Scicchitano Bianca Maria , Beirinckx Filip , Pujuguet Philippe , Saniere Laurent , Van der Aar Ellen , Musio Daniela , De Felice Francesca , Mattei Vincenzo , Martellucci Stefano , Maggio Roberto , Tombolini Vincenzo , Festuccia Claudio , Marampon Francesco
Published: February 2020

Erythropoietin-producing hepatocellular receptors (Eph) promote the onset and sustain the progression of cancers such as colorectal cancer (CRC), in which the A2 subtype of Eph receptor expression has been shown to correlate with a poor prognosis and has been identified as a promising therapeutic target. Herein, we investigated, in vitro and in vivo, the effects of treatment with GLPG1790, a potent pan-Eph inhibitor. The small molecule has selective activity against the EphA2 isoform in human HCT116 and HCT15 CRC cell lines expressing a constitutively active form of RAS concurrently with a wild-type or mutant form of p53, respectively. GLPG1790 reduced EPHA2 phosphorylation/activation and induced G1/S cell-cycle growth arrest by downregulating the expression of cyclin E and PCNA, while upregulating p21Waf1/Cip1 and p27Cip/Kip. The inhibition of ephrin signaling induced quiescence in HCT15 and senescence in HCT116 cells. While investigating the role of CRC-related, pro-oncogenic p53 and RAS pathways, we found that GLPG1790 upregulated p53 expression and that silencing p53 or inhibiting RAS (human rat sarcoma)/ERKs (extracellular signal-regulated kinase) signaling restrained the ability of GLPG1790 to induce senescence in HCT116 cells. On the other hand, HCT15 silencing of p53 predisposed cells to GLPG1790-induced senescence, whilst no effects of ERK inhibition were observed. Finally, GLPG1790 hindered the epithelial-mesenchymal transition, reduced the migratory capacities of CRC, and affected tumor formation in xenograft models in vivo more efficiently using HCT116 than HCT15 for xenografts. Taken together, our data suggest the therapeutic potential of GLPG1790 as a signal transduction-based therapeutic strategy in to treat CRC.
Experimental and Theoretical Studies of Wet Snow Accumulation on Inclined Cylindrical Surfaces
Authors: Mohammadian Behrouz , Sarayloo Mehdi , Abdelaal Ahmed , Raiyan Asif , Nims Douglas K. , Sojoudi Hossein
Published: February 2020

Wet snow accumulation on bridge cables and its shedding due to external phenomena such as rise in temperature, wind, and gravity is a serious threat to the safety of cars and pedestrians crossing the bridge. Commonly the accumulated snow on bridge cables is removed by external means such as mechanical removal or heat treatment which are expensive, time-consuming, and high-risk processes and are conducted based on little or no information available regarding the actual size and shape of the accumulated snow. In addition, cleaning of cables using the mechanical methods can potentially lead to erosion of cable materials when applied over years, resulting in enhanced surface roughness and potentially increased wet snow/ice accumulation during future precipitation events, and sometimes might require replacement of cable stays, which is an extremely costly and complicated task. Optimizing the number of mechanical cleaning procedures such as chain release through predicting the shape and thickness of the accumulated snow on the cable stays reduces the cost, time, and risk associated with the process. In this study, wet snow accumulation on torsionally rigid inclined cylinders of high-density polyethylene (HDPE) has been studied experimentally and numerically. A 2-D numerical model has been developed utilizing weather data to predict the thickness and the shape of the accumulated wet snow on inclined cylindrical surfaces. Outdoor experiments were also conducted to measure the density and thickness of accumulated snow, while monitoring the weather data real time. Overall, snow density was found to be linearly increasing with an increase in wind velocity, during snow precipitation. The maximum thickness and shape of the accumulated snow on cables obtained from the numerical model were found to be in good agreement with the outdoor experimental data. This work aims to provide a mean for prediction of snow accumulation on surfaces for optimizing the efficiency of the costly and high-risk snow removal procedures.
Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy
Authors: Tähtinen Siri , Feola Sara , Capasso Cristian , Laustio Netta , Groeneveldt Christianne , Ylösmäki Erkko O. , Ylösmäki Leena , Martins Beatriz , Fusciello Manlio , Medeot Marta , Tagliamonte Maria , Chiaro Jacopo , Hamdan Firas , Peltonen Karita , Ranki Tuuli , Buonaguro Luigi , Cerullo Vincenzo
Published: February 2020

Because of the high coverage of international vaccination programs, most people worldwide have been vaccinated against common pathogens, leading to acquired pathogen-specific immunity with a robust memory T-cell repertoire. Although CD8+ antitumor cytotoxic T lymphocytes (CTL) are the preferred effectors of cancer immunotherapy, CD4+ T-cell help is also required for an optimal antitumor immune response to occur. Hence, we investigated whether the pathogen-related CD4+ T-cell memory populations could be reengaged to support the CTLs, converting a weak primary antitumor immune response into a stronger secondary one. To this end, we used our PeptiCRAd technology that consists of an oncolytic adenovirus coated with MHC-I–restricted tumor-specific peptides and developed it further by introducing pathogen-specific MHC-II–restricted peptides. Mice preimmunized with tetanus vaccine were challenged with B16.OVA tumors and treated with the newly developed hybrid TT-OVA-PeptiCRAd containing both tetanus toxoid- and tumor-specific peptides. Treatment with the hybrid PeptiCRAd significantly enhanced antitumor efficacy and induced TT-specific, CD40 ligand-expressing CD4+ T helper cells and maturation of antigen-presenting cells. Importantly, this approach could be extended to naturally occurring tumor peptides (both tumor-associated antigens and neoantigens), as well as to other pathogens beyond tetanus, highlighting the usefulness of this technique to take full advantage of CD4+ memory T-cell repertoires when designing immunotherapeutic treatment regimens. Finally, the antitumor effect was even more prominent when combined with the immune checkpoint inhibitor anti–PD-1, strengthening the rationale behind combination therapy with oncolytic viruses.

Significance:

These findings establish a novel technology that enhances oncolytic cancer immunotherapy by capitalizing on pre-acquired immunity to pathogens to convert a weak antitumor immune response into a much stronger one.
Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study
Authors: Kleinstern Geffen , Camp Nicola J. , Berndt Sonja I. , Birmann Brenda M. , Nieters Alexandra , Bracci Paige M. , McKay James D. , Ghesquières Hervé , Lan Qing , Hjalgrim Henrik , Benavente Yolanda , Monnereau Alain , Wang Sophia S. , Zhang Yawei , Purdue Mark P. , Zeleniuch-Jacquotte Anne , Giles Graham G. , Vermeulen Roel , Cocco Pierluigi , Albanes Demetrius , Teras Lauren R. , Brooks-Wilson Angela R. , Vajdic Claire M. , Kane Eleanor , Caporaso Neil E. , Smedby Karin E. , Salles Gilles , Vijai Joseph , Chanock Stephen J. , Skibola Christine F. , Rothman Nathaniel , Slager Susan L. , Cerhan James R.
Published: February 2020

Background:

Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis.

Methods:

Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated (P < 5 × 10−8) with high-density lipoprotein (HDL, n = 164), low-density lipoprotein (LDL, n = 137), total cholesterol (TC, n = 161), and triglycerides (TG, n = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance–weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI).

Results:

HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00–1.30) and MZL (OR = 1.09; 95% CI, 1.01–1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83–0.99), all at nominal significance (P < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99–1.19; P = 0.087). No associations were noteworthy after adjusting for multiple testing.

Conclusions:

We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes.

Impact:

Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.
Patient-Centered Outcomes with Pituitary and Parasellar Disease
Authors: Webb Susan M. , Santos Alicia , Aulinas Anna , Resmini Eugenia , Martel Luciana , Martínez-Momblán María-Antonia , Valassi Elena
Published: February 2020

Over the last 2 decades, advances in the diagnosis and management of pituitary diseases have made it possible to attain an endocrine “cure” in a large proportion of patients. In other words, tumors can be excised or controlled with drugs, mass effects of the lesion on surrounding structures can be solved, and pituitary deficiencies can be substituted with all relevant hormones. While this is considered a satisfactory outcome for health care providers, patients often suffer from an aftermath of prior endocrine dysfunction exposure, with irreversible effects, both physically and psychologically, which have a great impact on their everyday life. Diagnostic delay, often of several years, adds a negative impact on health perception. This affects their social, professional, and family domains and determines their future life. Understanding that this may occur is important, and health care providers should offer information to prepare the patient for this difficult journey, especially in the case of acromegaly, Cushing disease, or hypopituitarism. In order to maintain a good quality of life (QoL) in the long-term, patients need to adapt to this new situation, something that may be difficult, since they often cannot continue with all the activities and rhythm they used to do. Depression is often the consequence of maladaptation to the new situation, leading to impaired QoL.
Myocardial Ischemia in Children With Anomalous Aortic Origin of a Coronary Artery With Intraseptal Course
Authors: Doan Tam T. , Zea-Vera Rodrigo , Agrawal Hitesh , Mery Carlos M. , Masand Prakash , Reaves-O’Neal Dana L. , Noel Cory V. , Qureshi Athar M. , Sexson-Tejtel S. Kristen , Fraser Charles D. , Molossi Silvana
Published: February 2020

Background:

Intraseptal anomalous aortic origin of a coronary artery is considered a benign condition. However, there have been case reports of patients with myocardial ischemia, arrhythmia, and sudden cardiac death. The purpose of this study was to determine the clinical presentation, myocardial perfusion on provocative stress testing, and management of children with anomalous aortic origin of a coronary artery with an intraseptal course in a prospective cohort.

Methods:

Patients with anomalous aortic origin of a coronary artery and intraseptal course were prospectively enrolled from December 2012 to May 2019, evaluated, and managed following a standardized algorithm. Myocardial perfusion was assessed using stress imaging. Fractional flow reserve was performed in patients with myocardial hypoperfusion on noninvasive testing. Exercise restriction, β-blockers, and surgical intervention were discussed with the families.

Results:

Eighteen patients (female 6, 33.3%), who presented with no symptoms (10, 55.6%), nonexertional (4, 22.2%), and exertional symptoms (4, 22.2%), were enrolled at a median age of 12.4 years (0.3–15.9). Perfusion imaging was performed in 14/18 (77.8%) and was abnormal in 7/14 (50%); fractional flow reserve was positive in 5/8 (62.5%). All 4 patients with exertional symptoms and 3/10 (30%) with no or nonexertional symptoms had myocardial hypoperfusion. Coronary artery bypass grafting was performed in a 4-year-old patient; β-blocker and exercise restriction were recommended in 4 patients not suitable for surgery. One patient had nonexertional chest pain and 17 were symptom-free at median follow-up of 2.5 years (0.2–7.1).

Conclusions:

Up to 50% of patients with intraseptal anomalous aortic origin of a coronary artery had inducible myocardial hypoperfusion during noninvasive provocative testing. Long-term follow-up is necessary to understand the natural history of this rare anomaly.
Long‐Term Effects of Transcatheter Aortic Valve Implantation on Coronary Hemodynamics in Patients With Concomitant Coronary Artery Disease and Severe Aortic Stenosis
Authors: Vendrik Jeroen , Ahmad Yousif , Eftekhari Ashkan , Howard James P. , Wijntjens Gilbert W. M. , Stegehuis Valerie E. , Cook Christopher , Terkelsen Christian J. , Christiansen Evald H. , Koch Karel T. , Piek Jan J. , Sen Sayan , Baan Jan
Published: February 2020

Background

As younger patients are being considered for transcatheter aortic valve implantation (TAVI), the assessment and treatment of concomitant coronary artery disease is taking on increased importance.

Methods and Results

Thirteen contemporary lower‐risk patients with TAVI with severe aortic stenosis (AS) and moderate‐severe coronary lesions were included. Patients underwent assessment of coronary hemodynamics in the presence of severe AS (pre‐
TAVI
), in the absence of severe AS (immediately post‐
TAVI
), and at longer‐term follow‐up (6 months post‐
TAVI
). Fractional flow reserve decreased from 0.85 (0.76–0.88) pre‐
TAVI
to 0.79 (0.74–0.83) post‐
TAVI
, and then to 0.71 (0.65–0.77) at 6‐month follow‐up (
P
<0.001 for all comparisons). Conversely, instantaneous wave‐free ratio was not significantly different: 0.82 (0.80–0.90) pre‐
TAVI
, 0.83 (0.77–0.88) post‐
TAVI
, and 0.83 (0.73–0.89) at 6 months (
P
=0.735). These changes are explained by the underlying coronary flow. Hyperemic whole‐cycle coronary flow (fractional flow reserve flow) increased from 26.36 cm/s (23.82–31.82 cm/s) pre‐
TAVI
to 30.78 cm/s (29.70–34.68 cm/s) post‐
TAVI
(
P
=0.012), to 40.20 cm/s (32.14–50.00 cm/s) at 6‐month follow‐up (
P
<0.001 for both comparisons). Resting flow during the wave‐free period of diastole was not significantly different: 25.48 cm/s (21.12–33.65 cm/s) pre‐
TAVI
, 24.54 cm/s (20.74–27.88 cm/s) post‐
TAVI
, and 25.89 cm/s (22.57–28.96 cm/s) at 6 months (
P
=0.500).

Conclusions

TAVI
acutely improves whole‐cycle hyperemic coronary flow, with ongoing sustained improvements at longer‐term follow‐up. This enhanced response to hyperemic stimuli appears to make fractional flow reserve assessment less suitable for patients with severe AS. Conversely, resting diastolic flow is not significantly influenced by the presence of severe AS. Resting indices of coronary stenosis severity, therefore, appear to be more appropriate for this patient population, although large‐scale prospective randomized trials will be required to determine the role of coronary physiology in patients with severe AS.
Soma-Based Nonphysical Instrument Design in Electronic Music Performance
Authors: Mainsbridge Mary
Published: February 2020

Attention to the role of the body and bodily awareness in human-computer interaction is increasing. Broader availability of cost-effective motion sensors in mobile and gaming applications has prompted a shift to body-centered design methods. This article examines the relevance of embodied sketching activities drawn from soma-based and sonic interaction design to digital musical instrument (DMI) development. It focuses specifically on the Telechord, a novel motion-controlled system that promotes methods for exploring connections between movement and sound. By emphasizing the felt aspects of movement-based design and performance, this approach places performer experience at the forefront, complementing technical efforts to enhance nuance and coherence in current DMI design research.
The Computer-Based Generation of Fonts in the Style of Kandinsky
Authors: Zhang Kang , Yu Jinhui
Published: February 2020

This article presents a general framework for programmed automatic generation of artistic fonts. By parameterizing various font attributes, such as color and aspect ratio, the authors are able to generate artistically styled fonts in almost unlimited variations to suit any type of design requirement. The authors demonstrate their experiments on generating fonts in an abstract style similar to Kandinsky's, built on a collection of the artist's styled patterns. The approach generates fonts composed of vector strokes and is thus highly scalable, limited only by the computer hardware.
A new species of the genus Haplotropis Saussure, 1888 (Orthoptera, Acridoidea, Pamphagidae) from Heilongjiang, China
Authors: ZHANG DA-PENG , LI SHAO-HUA , YIN ZHAN
Published: February 2020

The genus Haplotropis Saussure, 1888 belongs to family Pamphagidae, superfamily Acridioidea. It contains five species: Haplotropis brunneriana Saussure, 1888; Haplotropis xiai Ye, Shi & Li 2016; Haplotropis zhuoluensis Ye, Shi & Li 2016; Haplotropis aqiensis Zhang, Lin et Yin, 2018 and Haplotropis shandongensis Zhang, Yin et Liu, 2019 distributed mainly in Amur River region of Asia and China only (Saussure, 1888; Bey-Bienko et Mishchenko, 1951; Otte, 1994; Yin, Shi et Yin, 1996; Storozhenko & Paik, 2011; Yin et al, 2014; Dong et al, 2015; Ye et al, 2016; Zhang et al, 2017; Zhang et al, 2018; Zhang et al, 2019; Cigliano et al, 2019). A new species Haplotropis heiheensis sp. nov. is described in this paper. The new species is similar to Haplotropis aqiensis Zhang, Lin et Yin, 2018, but differs from latter by Krauss’ organ of male without ramified keel; tegmine narrower, length 2.4 times width; cercus of male gently tapering at apical half part; minimum width 1.4 times length in mesosternum and epiphallus with 36 spikes. Type specimens are deposited in the College of Plant Protection, Shandong Agricultural University, Taian, Shandong, China.
On the Oriental leafhopper genus Takagioma Thapa, 1989 (Hemiptera: Cicadellidae: Typhlocybinae: Dikraneurini) with descriptions of six new species
Authors: QIN HUIMIN , KANG JUXIA , HUANG MIN , ZHANG YALIN
Published: February 2020

The leafhopper genus Takagioma Thapa, 1989 is recorded from China for the first time. Six species, T. pagoda Kang and Zhang, T. rostra Qin and Huang, T. gladius Kang and Zhang, T. curvata Kang and Zhang, T. anguis Qin and Huang and T. longicuada Qin and Huang spp. nov, are described and illustrated. A check-list and a key to all species of Takagioma are provided.
New species of genus Hydromanicus Brauer 1865 (Trichoptera: Hydropsychidae) from India
Authors: PANDHER MANPREET SINGH , KAUR SIMARJIT , PAREY SAJAD HUSSAIN
Published: February 2020

We describe three new species of genus Hydromanicus. The newly described species are Hydromanicus digitatus sp. nov., Hy. clavatus sp. nov. (both from Uttarakhand), and Hy. betteni sp. nov. (from Sikkim). With these additions the updated number of Indian species in this genus is 11.
Metaspace, Mobility and Resistance: Understanding Vendors’ Movement Pattern as a Resistive Strategy in Kano, Nigeria
Authors: Balarabe Muhammad Kabir , Sahin Murat
Published: February 2020

The street vendor’s (SV) potential mobility in subverting authorities’ hegemony over public space has been theorised within the contexts of urban informality and resistance. Discussions mainly revolve around movement tactics as resistance strategy while evading arrests and confiscations. This negates SV agency and limits understanding mobility in resistance. Using Bunschoten’s metaspace and Cresswell’s aspects of mobility, this paper employs semi-structured interviews with mobile SV, road users and pedestrians in Kano (Nigeria), to describe vendors’ mobile practices and how they delay hostility from the state. Observing the interplay between vendors, users and environment, this paper identifies four types of vendor movement: focused, targeted, sporadic and self-regulatory; and examines how vendors exploit Cresswell’s speed and rhythm in challenging formal urban practice hegemony through continuous operation. The paper also describes how vendors’ movement affects other actors’ mobilities. Finally, the paper discusses urban design implications for integrating SV within city plans, setting out potential proposals.
Civil–Military Relations and Civil War Recurrence: Security Forces in Postwar Politics
Authors: Berg Louis-Alexandre
Published: February 2020

Does restructuring security forces reduce the risk of civil war recurrence? Prior research has examined effects of military integration in alleviating commitment problems, but the evidence has been inconclusive. Other aspects of civil–military relations have received less attention. This article examines the effects of civil–military relations in the context of postwar struggles to consolidate authority. It outlines three pathways through which security forces contribute to renewed civil war: by excluding rival factions and facilitating insurgent mobilization, by exploiting control over resources to challenge the regime, or by escalating incipient insurgency through repression. Analysis of original, cross-national data on postwar civil–military relations shows that reducing the potential for exclusion and exploitation through diverse officer appointments and robust civilian oversight lowers the risk of civil war. These findings emphasize the distributive effects of restructuring security forces and highlight the value of examining political contests around state institutions to understand why civil wars restart.
Book review: Gita Chadha and Joseph M. T. (Eds.), Re-imagining Sociology in India: Feminist Perspectives
Authors: Rayaprol Aparna
Published: February 2020

Gita Chadha and Joseph M. T. (Eds.), Re-imagining Sociology in India: Feminist Perspectives. London: Routledge, 2018, 348 pp., ₹1,095 (hardback). ISBN: 978-1-138-36365-6.
‘Verdammte Staats-Klugheit / die Treu und Bund heist brechen!’ Reason of state in Lohenstein’s Cleopatra
Authors: Robertson Ritchie
Published: February 2020

Although the tragedies of Daniel Casper von Lohenstein (1635–83) are nowadays known mainly to specialists in the Baroque, they amply repay attention. Set in the ancient world or the modern Ottoman Empire, they explore politics in the coolly realistic light of ‘reason of state’, a doctrine prominent in early modern absolutism. They are indebted also to neo-Stoicism. These features are illustrated by a close study of the tense intrigues and double-dealing that dominate the drama Cleopatra (the revised edition of 1680).
‘Painting out’ (and ‘reading in’) the Franco-Prussian War: Politics and art criticism in the 1870s
Authors: Lethbridge Robert
Published: February 2020

Taking the majority of its examples from the Salon of 1872, this article explores the extent to which official intervention was effective in eliminating from the exhibition potentially inopportune representations of the Franco-Prussian War. The withdrawal of a certain number of works deemed to risk offending the Prussians coincided with the very moment the French government was trying to negotiate the departure of occupying enemy troops under the terms of the May 1871 Treaty of Frankfurt. It initiated, or reignited, a debate about censorship during the course of which art criticism was itself politicized. Drawing on information in the Salon catalogue and analysing the reviews of the exhibition which appeared in the Parisian press, the article takes issue with much scholarship to date. In particular, it demonstrates how the interpretation of artistic works on display is inflected by polemical and ideological determinants. What emerges from this is precisely the incipient revanchard discourse which the government had hoped to suppress.
Describing the psychosocial profile and unmet support needs of parents caring for a child with a life-limiting condition: A cross-sectional study of caregiver-reported outcomes
Authors: Collins Anna , Burchell Jodie , Remedios Cheryl , Thomas Kristina
Published: February 2020

Background:

There is a lack of studies examining the prevalence and severity of psychosocial distress in parents caring for a child with life-limiting condition. More research is also needed to better understand the experience, support needs and quality-of-life of this population.

Aim:

To describe the experience and support needs of caring for children with life-limiting conditions and examine the level of distress and quality-of-life experienced by parents.

Design:

Cross-sectional, prospective, quantitative study guided by an advisory group. Participants completed a survey that included demographics and self-report outcome measures of unmet support needs, appraisal of caregiving, psychological distress and quality-of-life. Bivariate correlation analyses were performed to examine for associations between measures.

Setting/participants:

Parents currently caring for one or more children (⩽18 years) with a life-limiting condition and registered with a paediatric palliative care service (Australia).

Results:

In total, 143 parents (88% female) completed the questionnaire (36% RR). Compared with population norms, participants reported low quality-of-life, high carer burden and high psychological distress. Almost half (47%) of the sample met the criteria for one or more diagnoses of clinically elevated stress, anxiety or depression. There were significant associations between the psychosocial outcome variables; carer strain and depression had the strongest correlations with quality-of-life ( r = –.63, p < .001, for both). Participants also reported multiple unmet needs related to emotional and practical support.

Conclusions:

This study contributes to the growing body of evidence on paediatric palliative care, specifically that parents caring for a child with a life-limiting condition report high levels of distress and burden, low quality-of-life and need more emotional and practical support targeted at their unmet needs. Paediatric palliative care services should routinely assess parent mental health and provide appropriate support.
White, Male, and Bartending in Detroit: Masculinity Work in a Hipster Scene
Authors: Murray Margaret Anne
Published: February 2020

The hipster scene in Detroit, Michigan, is explored via participant observation and in-depth interviews. Participants used hipster norms as a resource for masculinity dilemmas, including a lack of white- or blue-collar jobs and stable female partners. The analysis examines how these men successfully enacted their progressive values in some arenas (read: gender) but not in others (race relations). More specifically, their emphasis on the creative class, the bicycle as an attainable status symbol, and “bro-mances” served as masculinity balms. These strategies are examples of how homophobia and violence are not always the response to “threatened” masculinity. At the same time, participants enacted a definition of community and specific spatial practices that resulted in a subculture with a white majority within a city with a black majority. This work demonstrates how ethnography is a powerful tool for studying the intersectionality of race, gender, and class in subcultures.
Ongoing Cognitive Processing Influences Precise Eye-Movement Targets in Reading
Authors: Bicknell Klinton , Levy Roger , Rayner Keith
Published: February 2020

Reading is a highly complex learned skill in which humans move their eyes three to four times every second in response to visual and cognitive processing. The consensus view is that the details of these rapid eye-movement decisions—which part of a word to target with a saccade—are determined solely by low-level oculomotor heuristics. But maximally efficient saccade targeting would be sensitive to ongoing word identification, sending the eyes farther into a word the farther its identification has already progressed. Here, using a covert text-shifting paradigm, we showed just such a statistical relationship between saccade targeting in reading and trial-to-trial variability in cognitive processing. This result suggests that, rather than relying purely on heuristics, the human brain has learned to optimize eye movements in reading even at the fine-grained level of character-position targeting, reflecting efficiency-based sensitivity to ongoing cognitive processing.
The Ubiquity of State Fragility: Fault Lines in the Categorisation and Conceptualisation of Failed and Fragile States
Authors: Saeed Raza
Published: February 2020

In the last three decades, the categories of fragile and failed states have gained significant importance in the fields of law, development, political science and international relations. The wider discourse plays a key role in guiding the policies of international community and multilateral institutions and has also led to the emergence of a plethora of indices and rankings to measure and classify state fragility. A critical and theoretical analysis of these matrices brings to light three crucial aspects that the current study takes as its departure point. First, the formulas and conceptual paradigms show that fragility of states is far more ubiquitous than is generally recognised, and that the so-called successful and stable states are a historical, political and geographical anomaly. Second, in the absence of an agreed definition of a successful state or even that of a failed or fragile state, the indicators generally rely on negative definitions to delineate the failed and fragile state. They generally suggest that their reading is built on a Weberian ideal–typical state, which takes the idea of monopoly over legitimate violence as its starting point. The third and final point suggests that the indicators and rankings, misconstruing the Weberian ideal–typical state, actually end up comparing fragile states against an ideal–mythical state. The article argues that this notional state is not only ahistorical and apolitical, but it also carries the same undertones that have been the hallmark of theories of linear development, colonialism and imperialism.
Supporting Dialogue and Analysis on Trade-Offs in Climate Adaptation Research With the Maladaptation Game
Authors: Neset Tina-Simone , Juhola Sirkku , Wiréhn Lotten , Käyhkö Janina , Navarra Carlo , Asplund Therese , Glaas Erik , Wibeck Victoria , Linnér Björn-Ola
Published: February 2020

Background. Serious games are gaining increasing prominence in environmental communication research, but their potential to form an integrated part of participatory research approaches is still strikingly understudied. This is particularly the case for applications of interactive digital formats in research on environmental challenges of high complexity, such as climate adaptation, which is a specifically suitable case as it involves complex interaction between climate systems and society, but where the response also involves trade-offs with potentially negative – maladaptive – outcomes.

Intervention. This article presents the Maladaptation Game, which was designed to facilitate dialogue about potential negative outcomes of agricultural climate adaptation.

Methods. We conducted test sessions with agricultural stakeholders in Finland and Sweden, and analysed quantitative and qualitative, audio-recorded and transcribed, material for opportunities and challenges related to dialogues, engagement, interactivity and experienced relevance.

Results. The qualitative analysis of recorded dialogues shows that the Maladaptation Game has potential to support dialogue by challenging players to negotiate between options with negative outcomes. The gameplay itself presents opportunities in terms of creating engagement with options that provoke disagreement and debates between players, as well as interactivity, that players reflected upon as quick and easy, while challenges were related to the experienced relevance, in particular the options provided in the game, and its general framing.

Conclusions. The results indicate a need for complementary approaches to this type of game but also suggest the importance of moderation when the game design is aimed at creating dialogue around a complex environmental challenge such as agricultural climate adaptation.
Expectations and Needs of Families in Nursing Homes: An Integrative Review
Authors: Havreng-Théry Charlotte , Giner-Perot Julie , Zawieja Philippe , Bertin-Hugault François , Belmin Joël , Rothan-Tondeur Monique
Published: February 2020

A better understanding of the expectations and needs of the families of nursing home residents is needed for a constructive and sustainable relationship of mutual trust. The objective of this study was to understand the expectations of families of nursing home residents described in the literature. A systematic integrative review of the literature was conducted. After a rigorous selection made by two researchers, independently, 53 articles were selected out of 1,094 results. The expectations of families are quality care, consideration complying with human dignity of the resident, collaboration, honesty, and mutual confidence that ties together families, staff, and physicians. This study reveals that families consider themselves as a strength for a resident’s support services, in line with Gottlieb’s strength-based approach. This approach offers promising implications for practice and for a new type of management in nursing homes based on strong values.
Early echocardiographic modifications after flow reduction by proximal radial artery ligation in patients with high-output heart failure due to high-flow forearm arteriovenous fistula
Authors: Maresca Barbara , Filice Fausta Barbara , Orlando Sara , Ciavarella Giuseppino Massimo , Scrivano Jacopo , Volpe Massimo , Pirozzi Nicola
Published: February 2020

Background:

Arteriovenous fistula (AVF) for haemodialysis (HD) induces a volume/pressure overload which impairs bi-ventricular function and increases systolic pulmonary arterial pressure (PAPS) and left ventricular mass (LVM). In the presence of high blood flow (Qa) AVF (> 1.5 L/min/1.73 m2) and cardio-pulmonary recirculation (>20%), high-output congestive heart failure (CHF) may occur and AVF flow reduction is recommended. Proximal Radial Artery Ligation (PRAL) is an effective technique for distal radio-cephalic (RC) AVF flow reduction.

Methods:

we evaluated six HD and four transplant patients with high-flow RC AVF and symptoms of CHF who underwent PRAL. We compared echocardiographic (ECHO) findings before (T0) and 1 and 6 months (T1,T6) after PRAL. Preoperative ECHO was performed before (T0b) and after AVF anastomosis manual compression (T0c).

Results:

At T1 AVF flow reduction rate was 58.4% ± 13% and 80% of patients reported improved CHF symptoms. ECHO data showed an improvement of tricuspid annular plane systolic excursion (TAPSE) at T1 (p = 0.03) and a reduction of PAPS at T6 (p = 0.04). TAPSE improved after AVF anastomosis compression during preoperative ECHO (p = 0.03). Delta of TAPSE at the dynamic manoeuvre at T0 directly correlated with early (1 month after PRAL, p = 0.01) and late (6 months after PRAL, p = 0.04) deltas of TAPSE.

Conclusions:

AVF flow reduction after PRAL induces immediate regression of CHF symptoms, early improvement of TAPSE and late improvement of PAPS, suggesting a prevalent right sections involvement in CHF. Preoperative TAPSE modification after AVF anastomosis compression could represent a useful evaluation tool to determine which patients would benefit of PRAL.
Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella Species in Pediatric Patients Visiting International Friendship Children’s Hospital, Kathmandu, Nepal
Authors: Kayastha Karuna , Dhungel Binod , Karki Shovana , Adhikari Bipin , Banjara Megha Raj , Rijal Komal Raj , Ghimire Prakash
Published: February 2020

Introduction:

Emergence and spread of antimicrobial resistance (AMR) is a global threat and significantly affects the treatment options for common infectious diseases. Inappropriate use of antibiotics, particularly third-generation cephalosporins, has contributed to the development of AMR. This study aims to determine the prevalence of extended-spectrum β-lactamase (ESBL) production in Escherichia coli and Klebsiella species isolated from various clinical samples.

Methods:

This cross-sectional study was conducted at International Friendship Children’s Hospital, Kathmandu, Nepal, from August 2017 to January 2018. A total of 1443 samples that included urine, pus, wound swab, endotracheal tip, catheter tip, and blood were collected from pediatric patients below 15 years and processed by standard microbiological methods. Following sufficient incubation, isolates were identified by colony morphology, gram staining, and necessary biochemical tests. Identified bacterial isolates were then tested for antibiotic susceptibility test by modified Kirby-Bauer disk diffusion method and were subjected to ESBL screening by using 30 µg cefotaxime and ceftazidime. The ESBL production was confirmed by combination disk method.

Results:

From a total of 103 nonduplicated clinical isolates, E. coli (n = 79), Klebsiella pneumoniae (n = 18), and Klebsiella oxytoca (n = 6) were isolated from different clinical specimens. Of which, 64 (62.1%) exhibited multidrug resistance, and 29 (28.2%) were ESBL producers. All ESBL-producing isolates were resistant toward ampicillin, cefotaxime, ceftriaxone, and ceftazidime. Most ESBL producers were susceptible toward imipenem (89.7%; 26/29), nitrofurantoin (82.8%; 24/29), piperacillin/tazobactam (79.3%; 23/29), and amikacin (72.4%; 21/29).

Conclusions:

A high prevalence of multidrug-resistant ESBL organisms was found in this study among pediatric patients. Treatment based on their routine identification and susceptibility to specific antibiotics is critical to halt the spread of AMR and ESBL.
To love or not to love, that is the question: Examining the intersection of love, care, and education
Authors: Shin Minsun
Published: February 2020

This colloquium discusses the intersection of love, care, and education in the field of early childhood education and care. While the name of the field reflects the belief that both care and education are seen as legitimate elements of the field’s professional discourse, love is still unspoken, undefined, and taken for granted. The author argues that love is professional yet very personal, involving the feelings and strong emotional connection that exist in a complex relationship in professional early childhood classrooms. This colloquium urges us to realize and legitimatize both love and care in the field of early childhood education and care, rather than conflating love and care.
Vibro-acoustic modulation and data fusion for localizing alkali–silica reaction–induced damage in concrete
Authors: Karve Pranav , Miele Sarah , Neal Kyle , Mahadevan Sankaran , Agarwal Vivek , Giannini Eric R , Kyslinger Patricia
Published: February 2020

This article investigates the application of vibro-acoustic modulation testing for diagnosing damage in concrete structures. The vibro-acoustic modulation technique employs two excitation frequencies on a structure. The interaction of these excitations in the measured response indicates damage through the presence of sidebands in the frequency spectra. Past studies using this technique have mostly focused on metals and composites (thin plates or laminates). Our research focuses on concrete, which is a highly heterogeneous material susceptible to a variety of chemical, physical, and mechanical damage processes. In particular, this article investigates diagnosing cracking in concrete from an expansive gel produced by an alkali–silica reaction in the presence of moisture. Past studies have been limited to damage detection using vibro-acoustic modulation testing, whereas this article extends the technique to damage localization. A cement slab with pockets of reactive aggregate is used to investigate the diagnosis technique. The effects of different testing parameters, such as locations, magnitudes, and frequencies of the two excitations, are analyzed and incorporated in the damage localization methodology. A Bayesian probabilistic methodology is developed to fuse the information from multiple test configurations in order to construct damage probability maps for the test specimen. The results of vibro-acoustic modulation–based damage localization are validated by petrographic study of cores taken from the slab.
A Conceptual Framework for Developing Women Social Entrepreneurs in Japan
Authors: Nakamura Yoshie Tomozumi , Horimoto Mayuko
Published: February 2020

The Problem

Limited systematic frameworks exist regarding how women develop social entrepreneurship in Japan and what leads Japanese women to change the way they view the world to do something different by becoming social entrepreneurs. The purpose of this article was to develop a theoretical framework for the development of women social entrepreneurs in Japan. There were two guiding questions in this study: How and in what ways women social entrepreneurship are developed in Japan? and What life events affect the values and beliefs that drive them to take authentic entrepreneurial careers for social change?

The Solution

We explored the connection between women social entrepreneurship, authentic leadership, and transformative learning theories in the context of Japan through an extensive literature review. The proposed theoretical framework could be used to show the role of critical reflection in face of triggering life events and factors that support or hinder in becoming women social entrepreneurs.

The Stakeholders

We focused on Japanese women whose social enterprises aim for social benefits operating through a variety of forms including not-for-profits (NPOs), small businesses, cooperative organizations, and worker collectives.
Long non-coding RNA TIRY promotes tumor metastasis by enhancing epithelial-to-mesenchymal transition in oral cancer
Authors: Jin Nuo , Jin Nianqiang , Bu Wenhuan , Li Xing , Liu Lili , Wang Zilin , Tong Jin , Li Dechao
Published: February 2020

Long non-coding RNAs (lncRNAs) modulate a variety of cancerous biological processes, including the promotion of tumorigenicity in tumor parenchymal cells. However, there is a lack of studies assessing the regulation of lncRNAs in cancer-associated fibroblasts. In the present study, a novel lncRNA, TIRY, was found to act as a miRNA sponge and to downregulate miR-14 expression in oral squamous cell carcinoma (OSCC). Fluorescence in situ hybridization assay was used to evaluate TIRY expression in OSCC tissues. Survival analysis in a prospective cohort revealed a correlation between high TIRY expression and short progression-free survival. Subsequently, TIRY expression in cancer-associated fibroblasts and primary fibroblasts from adjacent normal (para-carcinoma) tissues was assessed using quantitative reverse transcription polymerase chain reaction. TIRY overexpression in cancer-associated fibroblasts isolated from OSCC tissues was induced by overexpressing the TIRY plasmid, and candidate microRNA expressions were assessed using quantitative real-time polymerase chain reaction. Moreover, the expression of proteins related to epithelial-to-mesenchymal transition (EMT) was determined; the proliferation, metastasis, and invasion of cancer cells co-cultured with TIRY-overexpressing cancer-associated fibroblasts were determined. We found significantly decreased miR-14 expression in cancer-associated fibroblast-derived exosomes and increased expression of EMT markers including transcription factors (Snail and FOXC2) and cellular scaffolding proteins (α-SMA, β-catenin, and FSP1). TIRY overexpression in cancer-associated fibroblasts activated the Wnt/β-catenin signaling pathway and promoted the invasion and metastasis of OSCC cells through miR-14 sponging based on cancer-associated exosome secretion. Our findings provide a novel molecular mechanism underlying the role of TIRY in cancer-associated fibroblasts in tumor biology; moreover, TIRY is a potential therapeutic target in OSCC.

Impact statement

This study demonstrated the novel lncRNA, TIRY, enhances epithelial-to-mesenchymal transition in cancer-associated fibroblasts and promotes the metastasis of tumor via miR-14 sponging in oral squamous cell carcinoma, and thus provide a novel molecular mechanism underlying the role of TIRY in CAFs in tumor biology and a potential target in OSCC. Further, the data showed that TIRY expression was negatively correlated with miR-14 transcription levels and was associated with poor prognosis in OSCC specimens. Therefore, TIRY may be a potential prognostic biomarker of overall survival and progression-free survival in OSCC. Moreover, TIRY adds to the understanding of regulatory mechanisms involved in CAFs and epithelial cancer cells in OSCC and may provide novel insights for further understanding tumor biology.
Targeting cancer stem cells from a metabolic perspective
Authors: Shen Yao-An , Pan Siao-Cian , Chu I , Lai Ruo-Yun , Wei Yau-Huei
Published: February 2020

The process of cancer development and progression is driven by distinct subsets of cancer stem cells (CSCs) that contribute the self-renewal capacity as the major impetus to the metastatic dissemination and main impediments in cancer treatment. Given that CSCs are so scarce in the tumor mass, there are debatable points on the metabolic signatures of CSCs. As opposed to differentiated tumor progenies, CSCs display exquisite patterns of metabolism that, depending on the type of cancer, predominately rely on glycolysis, oxidative metabolism of glutamine, fatty acids, or amino acids for ATP production. Metabolic heterogeneity of CSCs, which attributes to differences in type and microenvironment of tumors, confers CSCs to have the plasticity to cope with the endogenous mitochondrial stress and exogenous microenvironment. In essence, CSCs and normal stem cells are like mirror images of each other in terms of metabolism. To achieve reprogramming, CSCs not only need to upregulate their metabolic engine for self-renewal and defense mechanism, but also expedite the antioxidant defense to sustain the redox homeostasis. In the context of these pathways, this review portrays the connection between the metabolic features of CSCs and cancer stemness. Identification of the metabolic features in conferring resistance to anticancer treatment dictated by CSCs can enhance the opportunity to open up a new therapeutic dimension, which might not only improve the effectiveness of cancer therapies but also annihilate the whole tumor without recurrence. Henceforth, we highlight current findings of potential therapeutic targets for the design of alternative strategies to compromise the growth, drug resistance, and metastasis of CSCs by altering their metabolic phenotypes. Perturbing the versatile skills of CSCs by barricading metabolic signaling might bring about plentiful approaches to discover novel therapeutic targets for clinical application in cancer treatments.

Impact statement

This minireview highlights the current evidence on the mechanisms of pivotal metabolic pathways that attribute to cancer stem cells (CSCs) with a special focus on developing metabolic strategies of anticancer treatment that can be exploited in preclinical and clinical settings. Specific metabolic inhibitors that can overwhelm the properties of CSCs may impede tumor recurrence and metastasis, and potentially achieve a permanent cure of cancer patients.