bluuebunny/crossref_metadata_2025 huggingface dataset:
A major Role for Nrf2 transcription factors in cell transformation by KSHV encoded oncogenes
Authors: Daiana Sapochnik , Ana Raimondi , Victoria Medina , Julian Naipauer , Enrique Mesri , Omar Coso
Published: June 2019

Kaposi‘s sarcoma (KS) is the most common tumor in AIDS patients and the highly vascularized patient‘s skin lesions are composed of the cells that derive from the endothelial tissue transformed by the KSHV virus. Heme oxygenase-1 (HO-1) is an enzyme upregulated by the Kaposi‘s sarcoma-associated herpesvirus (KSHV) and highly expressed in human Kaposi Sarcoma (KS) lesions. The oncogenic G protein-coupled receptor (KSHV-GPCR or vGPCR) is expressed by the viral genome in infected cells and is involved in KS development, HO-1 expression and vascular endothelial growth factor (VEGF) expression. We have characterized that vGPCR induces HO-1 expression and HO-1 dependent transformation through the Ga13 subunit of heterotrimeric G proteins and the small GTPase RhoA. We have found here several lines of evidence that support a role for Nrf2 transcription factors and family members in the vGPCR,-Ga13,-RhoA signaling pathway that converges on the HO-1 gene promoter. Our current information assigns a major role to Erk1/2 MAPK pathways as intermediate in signaling from vGPCR to Nrf2, influencing Nrf2 translocation to the cell nucleus, Nrf2 transactivation activity and consequently HO-1 expression. Experiments in nude mice show that the tumorigenic effect of vGPCR is dependent on Nrf2 suggesting this transcription factor or its associated proteins as putative pharmacological or therapeutic targets in KS.
CD49f is a novel marker to purify functional human iPSC-derived astrocytes
Authors: Barbar Lilianne , Jain Tanya , Zimmer Matthew , Kruglikov Ilya , Burstein Suzanne R. , Rusielewicz Tomasz , Nijsure Madhura , Croft Gist , Wang Minghui , Zhang Bin , Liddelow Shane , Fossati Valentina
Published: June 2019

Astrocytes play a central role in the central nervous system (CNS), maintaining brain homeostasis, providing metabolic support to neurons, regulating connectivity of neural circuits, and controlling blood flow as an integral part of the blood-brain barrier. They have been increasingly implicated in the mechanisms of neurodegenerative diseases, prompting a greater need for methods that enable their study. The advent of human induced pluripotent stem cell (iPSC) technology has made it possible to generate patient-specific astrocytes and CNS cells using protocols developed by our team and others as valuable disease models. Yet isolating astrocytes from primary specimens or from in vitro mixed cultures for downstream analyses has remained challenging. To address this need, we performed a screen for surface markers that allow FACS sorting of astrocytes. Here we demonstrate that CD49f is an effective marker for sorting functional human astrocytes. We sorted CD49f+ cells from a protocol we previously developed that generates a complex culture of oligodendrocytes, neurons and astrocytes from iPSCs. CD49f+-purified cells express all canonical astrocyte markers and perform characteristic functions, such as neuronal support and glutamate uptake. Of particular relevance to neurodegenerative diseases, CD49f+ astrocytes can be stimulated to take on an A1 neurotoxic phenotype, in which they secrete pro-inflammatory cytokines and show an impaired ability to support neuronal maturation. This study establishes a novel marker for isolating functional astrocytes from complex CNS cell populations, strengthening the use of iPSC-astrocytes for the study of their regulation and dysregulation in neurodegenerative diseases.
Inter- and intra-animal variation of integrative properties of stellate cells in the medial entorhinal cortex
Authors: Pastoll Hugh , Garden Derek , Papastathopoulos Ioannis , Sürmeli Gülşen , Nolan Matthew F.
Published: June 2019

Distinctions between cell types underpin organisational principles for nervous system function. Functional variation also exists between neurons of the same type. This is exemplified by correspondence between grid cell spatial scales and synaptic integrative properties of stellate cells (SCs) in the medial entorhinal cortex. However, we know little about how functional variability is structured either within or between individuals. Using ex-vivo patch-clamp recordings from up to 55 SCs per mouse, we find that integrative properties vary between mice and, in contrast to modularity of grid cell spatial scales, have a continuous dorsoventral organisation. Our results constrain mechanisms for modular grid firing and provide evidence for inter-animal phenotypic variability among neurons of the same type. We suggest that neuron type properties are tuned to circuit level set points that vary within and between animals.
M2IA: a Web Server for Microbiome and Metabolome Integrative Analysis
Authors: Ni Yan , Yu Gang , Chen Huan , Deng Yongqiong , Wells Philippa M , Steves Claire J , Ju Feng , Fu Junfen
Published: June 2019

Background

In the last decade, integrative studies of microbiome and metabolome have experienced exponential growth in understanding their impact on human health and diseases. However, analyzing the resulting multi-omics data and their correlations remains a significant challenge in current studies due to the lack of a comprehensive computational tool to facilitate data integration and interpretation. In this study, we have developed a microbiome and metabolome integrative analysis pipeline (M2IA) to meet the urgent needs for tools that effectively integrate microbiome and metabolome data to derive biological insights.

Results

M2IA streamlines the integrative data analysis between metabolome and microbiome, including both univariate analysis and multivariate modeling methods. KEGG-based functional analysis of microbiome and metabolome are provided to explore their biological interactions within specific metabolic pathways. The functionality of M2IA was demonstrated using TwinsUK cohort data with 1116 fecal metabolites and 16s rRNA microbiome from 786 individuals. As a result, we identified two important pathways, i.e., the benzoate degradation and phosphotransferase system, were closely associated with obesity from both metabolome and microbiome.

Conclusions

M2IA is a public available web server (http://m2ia.met-bioinformatics.cn) with the capability to investigate the complex interplay between microbiome and metabolome, and help users to develop mechanistic hypothesis for nutritional and personalized therapies of diseases.
The common message of constraint-based optimization approaches: overflow metabolism is caused by two growth-limiting constraints
Authors: de Groot Daan H. , Lischke Julia , Muolo Riccardo , Planqué Robert , Bruggeman Frank J. , Teusink Bas
Published: June 2019

Living cells can express different metabolic pathways that support growth. The criteria that determine which pathways are selected in which environment remain unclear. One recurrent selection is overflow metabolism: the simultaneous usage of an ATP-efficient and -inefficient pathway, shown for example inEscherichia coli,Saccharomyces cerevisiaeand cancer cells. Many models, based on different assumptions, can reproduce this observation. Therefore, they provide no conclusive evidence which mechanism is causing overflow metabolism. We compare the mathematical structure of these models. Although ranging from Flux Balance Analyses to self-fabricating Metabolism and Expression models, we can rewrite all models into one standard form. We conclude that all models predict overflow metabolism when two, model-specific, growth-limiting constraints are hit. This is consistent with recent theory. Thus, identifying these two constraints is essential for understanding overflow metabolism. We list all imposed constraints by these models, so that they can hopefully be tested in future experiments.
Mismatch of the morphology model is mostly unproblematic in total-evidence dating: insights from an extensive simulation study
Authors: Klopfstein Seraina , Ryer Remo , Coiro Mario , Spasojevic Tamara
Published: June 2019

Calibrating the molecular clock is the most contentious step in every dating analysis, but the emerging total-evidence dating approach promises increased objectivity. It combines molecular and morphological data of extant and fossil taxa in a Bayesian framework. Information about absolute node ages stems from the inferred fossil placements and associated branch lengths, under the assumption of a morphological clock. We here use computer simulations to assess the impact of mismatch of the morphology model, such as misspecification of character states and transition rates, non-stationarity of the evolutionary process, and extensive variation of evolutionary rates among branches. Comparisons with published datasets suggest that, at least for evolutionary rates typically observed in discrete morphological characters, the total-evidence dating framework is surprisingly robust to these factors. We show that even with relatively low numbers of morphological characters sampled, extensive model mismatch is mostly irrelevant for the performance of the method. The only exception we found are cases of highly asymmetric state frequencies and thus transition rates, but these can be accounted for by appropriate morphology models. In contrast, we find that the temporal scope of fossil sampling has a major impact on divergence time estimates, with the time signal quickly eroding if only rather young fossils are included in an analysis. Our results suggest that total-evidence dating might work even without a good understanding of morphological evolution and that study design should instead focus on an adequate sampling of all relevant fossils, even those with highly incomplete preservation.
Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain
Authors: Gutmann Theresia , Schäfer Ingmar , Poojari Chetan , Brankatschk Beate , Vattulainen Ilpo , Strauss Mike , Coskun Ünal
Published: June 2019

Glucose homeostasis and growth essentially depend on the peptide hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current understanding of insulin ligand–receptor interactions. While biochemistry predicts two distinct insulin binding sites, 1 and 2, recent structural analyses have only resolved site 1. Using a combined approach of cryo-EM and atomistic molecular dynamics simulation, we determined the structure of the entire dimeric insulin receptor ectodomain saturated with four insulin molecules. Complementing the previously described insulin–site 1 interaction, we present the first view of insulin bound to the discrete insulin receptor site 2. Insulin binding stabilizes the receptor ectodomain in a T-shaped conformation wherein the membrane-proximal domains converge and contact each other. These findings expand the current models of insulin binding to its receptor and of its regulation. In summary, we provide the structural basis enabling a comprehensive description of ligand–receptor interactions that ultimately will inform new approaches to structure-based drug design.

In brief

A cryo-EM structure of the complete insulin receptor ectodomain saturated with four insulin ligands is reported. The structural model of the insulin–insulin receptor complex adopts a T-shaped conformation, reveals two additional insulin-binding sites potentially involved in the initial interaction of insulin with its receptor, and resolves the membrane proximal region.
Salivary sex hormone levels following oxytocin administration in autistic and typical women
Authors: Procyshyn Tanya L. , Lombardo Michael V. , Lai Meng-Chuan , Auyeung Bonnie , Crockford Sarah K. , Deakin Julia , Soubramanian Sentil , Sule Akeem , Baron-Cohen Simon , Bethlehem Richard A. I.
Published: June 2019

Oxytocin administration, which may be of therapeutic value for social disabilities, likely influences endogenous levels of other socially-relevant hormones. However, to date, the effects of oxytocin administration on endogenous hormones have only been examined in typical males. The need to consider multi-hormone interactions is particularly warranted in oxytocin trials for autism due to evidence of irregularities in both oxytocin and sex steroid systems. Here, as part of a larger trial with a double-blind cross-over design, we assessed salivary testosterone and oestradiol levels in 16 autistic and 29 typical women before and after intranasal administration of 24IU oxytocin or placebo. Distinct patterns of change in testosterone and oestradiol across time were observed between groups, with autistic women showing increases in both hormones 90 min post-administration and typical women showing small decreases (mean %change oestradiol: +12% Autism, −10% Typical, 95%CI of difference: 5.0–39.4%, p=0.01; mean %change testosterone: +8% Autism, −14% Typical, 95%CI of difference: 7.8–35.6%, p=0.002). Under the oxytocin condition, the group difference in %change testosterone was amplified (+14.4% Autism, −15.2% Typical, p=0.018). Although baseline hormone levels did not differ between groups, greater baseline oestradiol relative to testosterone was negatively correlated with autistic-like traits (r= −0.36, p=0.019) and positively correlated (r=0.35, p=0.02) with self-reported empathy in the overall sample. These results provide further evidence that oxytocin influences endogenous testosterone, with autistic women showing increases similar to previous reports in typical men. These findings may help to identify autistic people expected to benefit most from interventions involving oxytocin.
Amyloid pathology disrupts gliotransmitter release in astrocytes
Authors: Pillai Anup G. , Nadkarni Suhita
Published: June 2019

Accumulation of amyloid-β peptide (Aβ), a hallmark of Alzheimer’s disease (AD), is associated with synchronous hyperactivity and dysregulated Ca2+ signaling in hippocampal astrocytes. However, the consequences of altered Ca2+ signaling on the temporal dynamics of Ca2+ and gliotransmitter release events at astrocytic microdomains are not known. We have developed a detailed biophysical model of microdomain signaling at a single astrocytic process that accurately describes key temporal features of Ca2+ events and Ca2+-mediated kiss-and-run and full fusion exocytosis. Using this model, we ask how aberrant plasma-membrane Ca2+ pumps and mGluR activity, molecular hallmarks of Aβ toxicity that are also critically involved in Ca2+ signaling, modify astrocytic feedback at a tripartite synapse. We show that AD related molecular pathologies increase the rate and synchrony of Ca2+ and exocytotic events triggered by neuronal activity. Moreover, temporal precision between Ca2+ and release events, a mechanism indispensable for rapid modulation of synaptic transmission by astrocytes, is lost in AD astrocytic processes. Our results provide important evidence on the link between AD-related molecular pathology, dysregulated calcium signaling and gliotransmitter release at an astrocytic process.
A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics
Authors: Baniulyte Gabriele , Wade Joseph T.
Published: June 2019

Expression of many bacterial genes is regulated bycis- andtrans-acting elements in their 5’ upstream regions (URs).Cis-acting regulatory elements in URs include upstream ORFs (uORF), short ORFs that sense translation stress that manifests as ribosomes stalling at specific codons within the uORF. Here, we show that the transcript encoding theEscherichia coliTopAI-YjhQ toxin-antitoxin system is regulated by a uORF that we name “toiL”. We propose that in the absence of translation stress, a secondary structure in the UR represses translation of thetopAItranscript by occluding the ribosome-binding site. Translation repression oftopAIleads to premature Rho-dependent transcription termination within thetopAIORF. At least five different classes of ribosome-targeting antibiotics relieve repression oftopAI. Our data suggest that these antibiotics function by stalling ribosomes at different positions withintoiL, thereby altering the RNA secondary structure around thetopAIribosome-binding site. Thus,toiLis a multipurpose uORF that can respond to a wide variety of translation stresses.
Social isolation: development and validation of measures
Authors: Ranjan Sushant , Yadav Rama Shankar
Published: June 2019

Purpose

The purpose of this paper is to develop and empirically validate items on social isolation. The comprehensive literature review of existing studies on the measures of social isolation, loneliness and the related construct was conducted. The paper seeks to conceptualize, validate and present items to measure social isolation.

Design/methodology/approach

The paper is based on theoretical and empirical investigation of the measures of social isolation, loneliness and related constructs such as social others, social loneliness and feeling of sociability. The items were generated through theoretical exploration of previous literature and later modified. The author examined the items through exploratory factor analysis, confirmatory factor analysis and further checked for external criterion validity. Data collected from 128 individuals, in India, were examined to design and validate the scale.

Findings

The finding of the paper is a ten-item social isolation scale. Using structural equation modeling, we have found extraversion and well-being significantly associated with final items in the present study, confirming the external quality of the scale.

Practical implications

Organizations may benefit by close examination of the presence of social isolation in employees along with providing support and assistance to employees so as to reduce negative consequences of social isolation and can address the well-being of the employee.

Originality/value

There is a dearth of developed and validated measures of social isolation in the literature. The study reveals the conceptualization and empirical validation of measures of social isolation in the Indian context so that researchers can move forward to develop theories on social isolation.
Numerical assessment of miniaturized cold spray nozzle for additive manufacturing
Authors: Nasif Gus , Barron R.M. , Balachandar Ram , Villafuerte Julio
Published: June 2019

Purpose

Application of cold spray technology may exhibit significant benefits for the additive manufacturing process, particularly for producing intricate objects. To ascertain the feasibility of such an application, this paper aims to present a numerical investigation of the effect of scaling down a convergent-divergent (de Laval) nozzle, which is typically used in the cold spray industry, on the compressible flow parameters and thermal characteristics.

Design/methodology/approach

The Navier–Stokes equations and energy equation governing compressible flow are numerically solved using a finite volume method with a coupled solver. The conjugate heat transfer technique is used to couple fluid and solid heat transfer domains and predict the local heat transfer coefficient between the solid and fluid. The use of various RANS turbulence models has also been investigated to quantify the effect of the turbulence model on the simulation.

Findings

The numerical results reveal that the flow and thermal characteristics are altered as the convergent-divergent nozzle is scaled down. The static pressure and temperature profiles at any section in the nozzle are shifted toward higher values, while the Mach number profile at any section in the nozzle is shifted toward a lower Mach number. The turbulent kinetic energy at the nozzle exit increases with the scaling down of the nozzle geometry. This study also provides convincing evidence that the adiabatic approach is still suitable even though the temperature of the nozzle wall is extremely high, as required for industrial application. Results indicate that it is feasible to use the available capabilities of the cold spray technology for additive manufacturing after scaling down the nozzle.

Originality/value

The idea of adopting cold spray technology for additive manufacturing is new and innovative. To develop this idea into a viable commercial product, a thorough understanding of the flow physics within a cold spray nozzle is required. The simulation results discussed in this paper demonstrate the effect that scaling down of a convergent-divergent nozzle has on the flow characteristics in the nozzle.
Free convection analysis in a Γ-shaped heat exchanger using lattice Boltzmann method employing second law analysis and heatline visualization
Authors: KhakRah HamidReza , Mohammaei Mehdi , Hooshmand Payam , Bagheri Navid , Hasani Malekshah Emad
Published: June 2019

Purpose

The nanofluid flow and heat transfer within a heat exchanger, with different thermal arrangements of internal active bodies, are investigated.

Design/methodology/approach

For the numerical simulations, the lattice Boltzmann method is utilized. The KKL model is used to predict the dynamic viscosity of CuO-water nanofluid. Furthermore, the Brownian method is taken account using this model. The influence of shapes of nanoparticles on the heat transfer performance is considered.

Findings

The results show that the platelet nanoparticles render higher average Nusselt number showing better heat transfer performance. In order to perform comprehensive analysis, the heatline visualization, local and total entropy generation, local and average Nusselt variation are employed.

Originality/value

The originality of this work is carrying out a comprehensive investigation of nanofluid flow and heat transfer during natural convection using lattice Boltzmann method and employing second law analysis and heatline visualization.
Behavioral intentions of different religions
Authors: Jumani Zulfiqar Ali , Sukhabot Sasiwemon
Published: June 2019

Purpose

The demand for halal products is growing and attracting the attention of producers. In recent years, the importance of halal logo and popularity of halal products has increased. The purpose of this paper was to identify the behavioral intentions among people of different religion in respect of purchasing products bearing halal logo (halal logo products) at convenience stores in Hatyai. 7-Eleven store chain was targeted to collect data in this research because it serves people of different religions.

Design/methodology/approach

The conceptual model adopted for this research work was the theory of reasoned action (TRA). The response of consumers was collected through a structured survey, using the convenience sampling technique. A total of 215 respondents submitted their responses, consisting of 92.8 per cent local respondents and 8.2 per cent international respondents. The purposive sample technique was used to select the locations for collecting data, who was purchasing items from 7-Eleven stores and lives in Hatyai.

Findings

The findings indicate that Muslims strictly follow the halal logo and their attitude is positive in selecting halal logo products. The influence of their subjective norms is stronger because of their families and culture, as they are Muslim which influence their intentions. For non-Muslims, there is no obligation requiring them to select halal logo products, but even so, around 80 per cent of non-Muslims showed a positive attitude toward the halal logo, 54 per cent showed were interest and indicated that they may select products with halal logo in future.

Research limitations/implications

This study was conducted in Hatyai and the results were based on three independent variables, namely, attitude, subjective norms and intention, with religion as the demographic variable. The findings offer an insight into the importance of the halal logo for different religions at convenience stores in Hatyai.

Practical implications

This study is initially beneficial for 7-Eleven stores, other convenience stores, businesses and halal institutes. It offers an insight into the importance of the halal logo and the motives of consumers in choosing halal logo products.

Originality/value

This paper seeks to explicate consumers’ intentions to buy halal logo products in convenience stores.
Categories in emergency decision-making: prototype-based classification
Authors: Cai Mei , Wei Guo , Cao Jie
Published: June 2019

Purpose

This paper aims to demonstrate how to make emergency decision when decision makers face a complex and turbulent environment that needs quite different decision-making processes from conventional ones. Traditional decision techniques cannot meet the demands of today’s social stability and security.

Design/methodology/approach

The main work is to develop an instance-driven classifier for the emergency categories based upon three fuzzy measures: features for an instance, solution for the instance and effect evaluation of the outcome. First, the information collected from the past emergency events is encodes into a prototype model. Second, a three-dimensional space that describes the locations and mutual distance relationships of the emergency events in different emergency prototypes is formulated. Third, for any new emergency event to be classified, the nearest emergency prototype is identified in the three-dimensional space and is classified into that category.

Findings

An instance-driven classifier based on prototype theory helps decision makers to describe emergency concept more clearly. The maximizing deviation model is constructed to determine the optimal relative weights of features according to the characteristics of the new instance, such that every customized feature space maximizes the influence of features shared by members of the category. Comparisons and discusses of the proposed method with other existing methods are given.

Practical implications

To reduce the affection to economic development, more and more countries have recognized the importance of emergency response solutions as an indispensable activity. In a new emergency instance, it is very challengeable for a decision maker to form a rational and feasible humanitarian aids scheme under the time pressure. After selecting a most suitable prototype, decision makers can learn most relevant experience and lessons in the emergency profile database and generate plan for the new instance. The proposed approach is to effectively make full use of inhomogeneous information in different types of resources and optimize resource allocation.

Originality/value

The combination of instances can reflect different aspects of a prototype. This feature solves the problem of insufficient learning data, which is a significant characteristic of emergency decision-making. It can be seen as a customized classification mechanism, while the previous classifiers always assume key features of a category.
The impact of corruption on travelers’ perceptions and preferences
Authors: Papathanassis Alexis
Published: June 2019

Purpose

This paper aims to explore and model tourists’ perceptions of corruption-related holiday incidents and their impact on travel preferences and behavior.

Design/methodology/approach

This research methodology reflects an exploratory-sequential, mixed-method design, comprising a content analysis of 205 online reviews, followed by a survey of 268 respondents.

Findings

According to the data collected and analyzed, exposure to corruption appears to be more than an exception for holidaymakers. Moreover, tourists often associate corruption with a wide spectrum of incident types; those ranging from personal integrity threats to service delivery failures and heritage/attraction mismanagement. The impact of such incidents on travel preferences and behavior of tourists is highly dependent on the perceived competence, effectiveness and professionalism of local (destination) public services and authorities.

Practical implications

Recommendations for destination stakeholders include the need to enable and take ownership of tourists’ complaints and the importance of recognizing the role of heritage attractions as corruption-related symbols and destination image carriers.

Originality/value

This paper attempts to establish the connection between corruption and tourism externalities within the context of the recent “over-tourism” debate. In exploring tourism-corruption, the authors adopt a “micro-behavioral” perspective, which represents a novelty in the related macro/systemic-level approach, characterizing the predominant research in this area. Moreover, in terms of research methodology, both qualitative and quantitative methods are combined. This is an ambitious and challenging research design, demonstrating the synergies between the two paradigms and contributing to the completeness of the paper.
Does the form of venous thromboembolism prophylaxis following primary total knee arthroplasty alter the rate of early reoperation or revision surgery?
Authors: Kerr David L. , Butler Stephen , Read Andrew C. , Harris Ian A.
Published: June 2019

Background

Currently there is significant variation in the management of venous thromboembolism prophylaxis following total knee arthroplasty (TKA). Excessive wound ooze and bleeding is thought to increase a patient's risk of haematoma formation and possible infection. We evaluated the rate of unexpected reoperation in the perioperative period in patients who received aspirin, rivaroxaban or enoxaparin following primary TKA.

Method

A systematic literature search was conducted in MEDLINE, CENTRAL and Embase to identify patients who underwent primary TKA. Two researchers independently reviewed the references identified in the literature search. The final 11 studies included for review were published between 1996 and 2016.

Results

There was a higher rate of reoperation in patients treated with aspirin following TKA when compared to enoxaparin and rivaroxaban in the perioperative period. Of the 5141 patients treated with enoxaparin, 11 (0.21%) required reoperation; of the 2764 patients treated with rivaroxaban, 12 (0.43%) required reoperation; and of the 228 patients treated with aspirin, seven (3.07%) required reoperation. The average time to follow‐up in the 11 studies was 55 days, ranging from 30 to 180 days post‐operatively.

Conclusion

There was a higher rate of reoperation in patients treated with aspirin following TKA when compared to enoxaparin and rivaroxaban in the perioperative period. While there is extensive data on the safety and efficacy of these medications following joint arthroplasty, improved reporting of surgically relevant outcomes are needed to assist both the surgeon and patient in clinical decision‐making.
Site‐specific absence of microfibrillar‐associated protein 4 (MFAP4) from the internal elastic membrane of arterioles in the rheumatoid arthritis synovial membrane: an immunohistochemical study in patients with advanced rheumatoid arthritis versus osteoarthritis
Authors: Christensen Anne Friesgaard , Sorensen Grith Lykke , Junker Kirsten , Revald Peter , Varnum Claus , Issa Saida Farah , Junker Peter , Sorensen Flemming Brandt
Published: June 2019

Microfibrillar‐associated protein 4 (MFAP4) is a non‐structural matrix protein with cell regulatory activities and a potential as seromarker for fibrosis. We aimed to study the occurrence of MFAP4 in the synovial membrane from patients with rheumatoid arthritis (RA) vs osteoarthritis (OA). Formaldehyde‐fixed synovial tissue sections, from patients with RA (N = 6) and OA (N = 6) undergoing total hip arthroplasty, were deparaffinized and immunostained with monoclonal antibodies against MFAP4. Elastin was detected using ElastiKit. MFAP4 in serum (sMFAP4) and synovial fluid was measured by an immunoassay. MFAP4 was present in synovial biopsies from both RA and OA patients, particularly prominent in deep arterioles where it colocalized with elastin. Notably however, MFAP4 was absent from the internal elastic lamina in RA arterioles irrespective of disease duration and synovitis activity, while present although with irregular staining patterns in OA specimens. sMFAP4 was increased in RA and OA serum vs healthy controls: median (interquartile range) 29.8 (25.3–39.1) and 25.5 U/L (18.1–43.3) vs 17.7 U/L (13.7–21.2), p = 0.006 and p = 0.02, respectively The concentration of synovial fluid was lower than in serum in both RA and OA. These findings may suggest that MFAP4 is involved in adaptive vessel wall remodeling associated with chronic joint disease.
Change management reduces antibiotic use on pig farms
Authors: McKenzie P , Carter R
Published: June 2019

A clostridial ‘syndrome’ in suckling and weaner pigs, with risk factors of high injectable ceftiofur use and poor hygiene, presented an opportunity to engage in management change to improve pig health and reduce ceftiofur use on four farms. Management changes included all‐in‐all‐out pig flow, batch disinfection with biofilm control, reduced protein starter diets, appropriate stocking density and the use of an anti‐clostridial probiotic. Assessment of the program was obtained from a questionnaire. The health and production changes were positive across all farms and were associated with reduced use of antibiotics, together with cost and labour savings. Provided there is a good relationship between a committed, competent veterinarian, and a committed, competent manager, change management programs can be successfully implemented over 6–12 months.
Early clinical outcomes of helical tomotherapy/intensity‐modulated proton therapy combination in nasopharynx cancer
Authors: Park Seung Gyu , Ahn Yong Chan , Oh Dongryul , Noh Jae Myoung , Ju Sang Gyu , Kwon Dongyeol , Jo Kwanghyun , Chung Kwangzoo , Chung Eunah , Lee Woojin , Park Seyjoon
Published: June 2019

This study aimed to evaluate the feasibility of combining helical tomotherapy (HT) and intensity‐modulated proton therapy (IMPT) in treating patients with nasopharynx cancer (NPC). From January 2016 to March 2018, 98 patients received definitive radiation therapy (RT) with concurrent chemotherapy (CCRT). Using simultaneous integrated boost and adaptive re‐plan, 3 different dose levels were prescribed: 68.4 Gy in 30 parts to gross tumor volume (GTV), 60 Gy in 30 parts to high‐risk clinical target volume (CTV), and 36 Gy in 18 parts to low‐risk CTV. In all patients, the initial 18 fractions were delivered by HT, and, after rival plan evaluation on the adaptive re‐plan, the later 12 fractions were delivered either by HT in 63 patients (64.3%, HT only) or IMPT in 35 patients (35.7%, HT/IMPT combination), respectively. Propensity‐score matching was conducted to control differences in patient characteristics. In all patients, grade ≥ 2 mucositis (69.8% vs 45.7%, P = .019) and grade ≥ 2 analgesic usage (54% vs 37.1%, P = .110) were found to be less frequent in HT/IMPT group. In matched patients, grade ≥ 2 mucositis were still less frequent numerically in HT/IMPT group (62.9% vs 45.7%, P = .150). In univariate analysis, stage IV disease and larger GTV volume were associated with increased grade ≥ 2 mucositis. There was no significant factor in multivariate analysis. With the median 14 month follow‐up, locoregional and distant failures occurred in 9 (9.2%) and 12 (12.2%) patients without difference by RT modality. In conclusion, comparable early oncologic outcomes with more favorable acute toxicity profiles were achievable by HT/IMPT combination in treating NPC patients.
Managing soils for resolving the conflict between agriculture and nature: The hard talk
Authors: Lal Rattan
Published: June 2019

Among soil‐centric options for addressing global issues being intensely debated by soil scientists, ecologists and earth scientists regarding their effectiveness and applicability are: (a) harnessing soil carbon (C) sink capacity for adaptation and mitigation of climate change; (b) reducing soil erosion as a source of greenhouse gases and the need to include it in the global C budget; (c) enhancing use efficiency of inputs to agroecosystems and returning land, water and other resources back to nature; (d) using global drylands, saline culture, halomorphic plants and brackish water for provisioning of ecosystem services; and (e) adopting a system‐based conservation agriculture for eco‐intensification of agroecosystems as a strategy of “producing more from less”. Not only should agriculture be made a solution for addressing global issues, but it is also essential to reconciling the need for advancing food and nutritional security with the absolute necessity of enhancing the environment, restoring degraded soils and desertified ecosystems, and advancing Sustainable Development Goals or the Agenda 2030.

Highlights

Sustainable soil management, degraded soil restoration abridging agronomic yield gap and improving the environment are important to achieve world peace.

Sustainable eco‐intensification of agro‐ecosystems reduces inputs and enhances use efficiency by restoring soil health.

Harnessing soil carbon sink capacity includes reducing accelerated soil erosion for adaptation and mitigation of climate change.

System‐based conservation agriculture sustains agronomic productivity and minimizes soil degradation and environmental pollution.
Prevalence of adverse events and their effect on completion of high speed treadmill exercise tests at a single institution (2000–2015)
Authors: Brown K. , Stefanovski D. , Davidson E.
Published: June 2019

Background

Decline in high speed treadmill (HSTM) exercise testing may be attributed to the rise of over‐ground endoscopy and telemetric electrocardiography, in addition to concerns of adverse events during treadmill exercise resulting in injury or inadequate testing.

Objectives

To describe adverse events occurring during HSTM exercise tests at a single institution and determine their effect on likelihood of completing diagnostic HSTM exercise testing.

Study design

Retrospective cohort study.

Methods

Pearson’s chi‐square test was used to determine if a significant difference in frequencies of adverse events existed between complete and incomplete HSTM exercise tests. Two Firth logistic regression models were used to determine likelihood of exercise test completion given the presence of any adverse event, and the likelihood of exercise test completion for each type of adverse event.

Results

The majority of horses presenting for HSTM evaluation underwent exercise testing (900/1003; 90%). Eight‐hundred and seven (90%) exercise tests were completed. Adverse events occurred in 136 (15%) HSTM exercise tests of which 97 (71%) did not impact ability to complete HSTM testing. Adverse events significantly but variably decreased the likelihood of HSTM exercise test completion. Sixty‐six percent of incomplete exercise tests were prematurely terminated due to poor performance abnormalities during which diagnosis of poor performance cause(s) was still achieved.

Main limitations

Variable personnel recorded data over the study period. Per‐test rather than per‐horse evaluation does not account for the effect of multiple training and testing episodes performed in the same horse.

Conclusions

This study supports the continued usage of HSTM exercise testing for examination of horses with poor performance, with adverse events occurring infrequently. Adverse events reduced the likelihood of completing HSTM exercise testing although not all adverse events affected likelihood of completion similarly. In many cases, a performance limiting problem was identified for horses in which an exercise test was considered incomplete.

The Summary is available in Spanish – see Supporting information
Uneasy passages between neoliberalism and feminism: Social inclusion and financialization in Israel's empowerment microfinance
Authors: Kemp Adriana , Berkovitch Nitza
Published: June 2019

This article focuses on feminist non‐governmental organizations advocating for economic empowerment of women (EEW) through microfinance, using Israel as a case study. Through fieldwork, interviews and documents, we investigate the institutional practices, cultural discourses and struggles that EEWs develop in order to expose the particular ways in which feminist organizations interact with the world of finance and state institutions. Our analysis points to the complex power dynamics of mediation, suggesting that there are ‘uneasy passages' between neoliberalism and feminism, ones that help re‐signify the meaning of financial discourses while re‐politicizing women's social and economic exclusions. Simultaneously, however, this relation induces a series of compromises, whereby EEWs adopt neoliberal modes of governance. Rejecting the notion that contemporary feminism has simply been co‐opted by neoliberalism or the perception of EEW microfinance as a mere expansion of neoliberal rationalities, we reveal new sites and ways in which feminism both colludes and collides with neoliberalism.
At Pains Following and Serving God: A Contemporary Theology of Joy in Suffering
Authors: Fortin Jean‐Pierre
Published: June 2019

Building on the thought and life of Jürgen Moltmann, Hans Urs von Balthasar, Simone Weil and Teresa of Calcutta, this article demonstrates that it is possible for Christians to find joy in the context of suffering. This joy is the joy of being intimate with Christ, of experiencing Christ’s redeeming power at work effectively transforming one’s whole person. In Christ, spiritual darkness and suffering can become a most effective manifestation of the recreating communion of the human with the divine. Perfect discipleship identifies with the complete offer of Jesus Christ, the suffering God, received within one’s heart, so that invincible light might be brought into the night of the world.
The development of Nursing Quality Care Process Metrics and Indicators for use in Older Persons Care Settings: A Delphi‐Consensus Study
Authors: Murphy Fiona , Doody Owen , Lyons Rosemary , Gallen Anne , Nolan Mary , Killeen Angela , Kavanagh Paula , Donegan Joan , Sezgin Duygu
Published: June 2019

Aim

To develop a suite of nursing quality care process metrics and indicators for older persons care settings in Ireland.

Background

Regulatory investigations of health system failures highlight non‐adherence to clinical guidelines and standards resulting in deficiencies in nursing care delivery. Limited attention has been paid to measuring nursing care processes particularly in the care of older people. Quality care process metrics can facilitate measurement of nurse‐sensitive measures of care.

Design

A scoping literature review and modified Delphi‐Consensus Technique.

Methods

A scoping review of literature published between January 2007 – January 2017 was conducted to identify nursing process metrics and indicators. The Delphi Consensus phase incorporated a four‐round electronic survey of 404 nurses and a consensus meeting with 13 stakeholders working in Older Persons Care Settings in Ireland.

Findings

From the review, 33 potential metrics were identified. After all Delphi survey rounds, 20 metrics and 90 associated indicators were selected by the nurses. Following the consensus meeting, 19 metrics and 80 indicators were included in the final suite of nursing quality care process metrics and indicators.

Conclusion

Developing this suite of nursing quality care process metrics and indicators for use in older persons care settings provided consensus on what nursing processes should be measured to improve the quality and safety of care delivery.

Impact

The nursing processes identified, provide a framework for future research and educational programmes in the care of older persons. Although conducted in the Irish healthcare system, there is potential for adoption or adaption in other healthcare settings.
Effectiveness of the application of massage therapy and kinesitherapy by parents on premature neonates: A research protocol
Authors: Álvarez‐Álvarez María José , Fernández‐García Daniel , Gómez‐Salgado Juan , Ordás Beatriz , Rodríguez‐González María Dolores , Martínez‐Isasi Santiago
Published: June 2019

Aim

The study aims to analyse the efficacy of massage therapy and kinesitherapy applied by parents of premature infants admitted to hospital.

Background

Premature newborns suffer early somatic deprivation that has adverse effects on their growth and development and that also has a negative impact on the emotional state of their parents. Massage therapy and kinesitherapy is beneficial in alleviating somatic deficit and facilitates the bond between parents and newborns.

Design

A quasi‐experimental community intervention trial will be conducted in a neonatology unit.

Methods

This study will compare the benefits of a 15‐min massage protocol applied by parents with the usual medical and nursing care given by neonatal units for premature babies. The evaluation of neuromotor development will take place through the Spanish Premie‐Neuro scale. The determination of weight, size, and head circumference will be based on the unit's usual procedures.

Discussion

If the implementation of a massage therapy and kinesitherapy protocol is effective in promoting the growth and development of hospitalized premature infants, the results of this study could give an impetus for the inclusion of somatic stimulation in the usual nursing care given for preterm infants.

Impact

Prematurity and its associated morbidity pose a major global public health problem. Somatic and kinaesthetic stimulation has beneficial effects on anthropometric and neuromotor development in preterm infants. The results will have a positive impact on premature neonates and their families, both during the hospitalization, and a positive socio‐economic effect throughout their lives (education, work, disability).

Trial registration: NCT03704012.
Assessing historical and future habitat models for four conservation‐priority Mojave Desert species
Authors: Guida Ross J. , Abella Scott R. , Roberts Chris L. , Norman Carrie M. , Smith William J.
Published: June 2019

Aim

Modelling and quantifying habitat changes using three historical field surveys for four Mojave Desert species and projecting future scenarios.

Location

Newberry Mountains, southern Nevada, USA.

Methods

Three vegetation field surveys were conducted, ending in 1979, 2008 and 2016, respectively. Field data collection across three time steps resulted in a unique dataset with 100 re‐surveyed 0.06‐ha plots. Using Maxent ecological niche modelling and 800‐m resolution Parameter Elevation Regressions on Independent Slopes Model (PRISM) temperature and precipitation data, habitat was assessed for four high‐elevation species. Recognizing that missing location data is a common challenge in species distribution modelling, sensitivity analysis was conducted utilizing three high‐elevation plots that species inhabited during the first two field surveys but that were unable to be sampled in 2016. Area under the curve for three species’ model runs exceeded 0.95, while one wider‐distributed species exceeded 0.79 for all runs. Future scenarios were also modelled under temperature increases and 16% and 0% reductions in precipitation.

Results

The number of presence locations and densities for Juniperus californica, Pinus monophylla, Quercus turbinella and Yucca schidigera decreased from 1979 to 2016, while their average elevational distribution increased. Using the 100 plots measured each of the three study years, models for all four species indicated decreases in potential suitable habitat ranging from 10% to 45%. When including the three highest elevation plots not re‐sampled in 2016, but likely still containing the modelled species, modelled habitat loss ranged from 0% to 29%. Future model projections show drastic reductions in the suitable habitat of all four modelled species.

Main conclusions

While many Maxent ecological modelling studies have been conducted, few have incorporated repeat surveys of identical plots as in our study. Model projections using a unique 100‐plot dataset suggest that suitable habitat area is contracting for the species studied, and this correlated with climatic warming and drying in the Mojave Desert. Despite model projections that show nearly complete loss of suitable habitat in 2053, care should be taken given uncertain estimates of the velocity of climate change and the slower pace of habitat contractions measured in the field.