bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation on the fracture mechanism of homogenized micro-crack crushing technology for portland cement concrete pavement rehabilitation
Authors: Li Wenjie , Zhang Qunlei , Zhi Zihan , Feng Chun , Cai Yingchun , Yue Jinchao
Published: July 2019

The homogenized micro-crack crushing technology for concrete pavement maintenance has received increased attention in China. To study the fracture mechanism of the homogenized micro-crack crushing technology, a low-velocity impact test system is developed and experiments using concrete slabs of different thicknesses are conducted with different drop heights and hammer weights. Furthermore, the fracture of concrete slabs under impact loading is simulated using the continuous-discontinuous element method. Finally, the fracture mechanism is investigated in a case study. It is concluded that a cylindrical compression–shear fracture surface appears under the impact head while the fractured blocks are still interlocked with each other. The main cracks in the concrete slabs are initiated and propagate parallel to the longer side of the impact head, whereas branch cracks develop perpendicular to the main cracks. These cracks radiate from the center of the impact head. The cracks inside the concrete develop upward from the bottom of the slabs. Because fractured blocks divided by micro-cracks can interlock with themselves and the crack distributions tend to be uniform, it is beneficial for portland cement concrete pavement rehabilitation to be overlaid by a hot-mix asphalt mixture.
Facilitating equitable prevention and management of gout for Māori in Northland, New Zealand, through a collaborative primary care approach
Authors: Lawrence Aniva , Scott Sharon , Saparelli Fabio , Greville Georgina , Miller Andrew , Taylor Andrea , Gow Peter
Published: July 2019

ABSTRACT INTRODUCTIONThe Gout Stop Programme was developed for primary care in Northland, New Zealand, to address inequitable health outcomes for Māori and Pacific people with gout. AIMThe aim of the programme was to make it easier for clinicians to prescribe urate-lowering treatment, facilitate patient adherence through education and support, and reduce barriers to gout prevention and long-term management. METHODSFrom 2015 to 2017, patients with acute gout who met inclusion criteria were prescribed treatment according to a ‘Gout Stop Pack’ option, based on renal function and diabetes status. Patients were monitored by community pharmacists. Gout educators and a Gout Kaiāwhina (community support worker) provided education and support to patients and whānau (families). Patient completion of the programme and outcomes, according to target serum urate level, were recorded. Patient experience was documented using a questionnaire and rating scale. RESULTSIn total, 160 clinicians prescribed therapy at 887 patient presentations; 71% were Māori and Pacific patients. The completion rate was 55% in this group and 84% for the non-Māori and non-Pacific group. In the Māori and Pacific group, 40% reached the target serum urate level (≤0.36 mmol L-1) in 91 days, and 26% required further titration. In the non-Māori/non-Pacific group, these rates were 51% and 19% respectively. Following programme completion, 68% of Māori and Pacific patients and 65% of non-Māori and non-Pacific patients continued to take allopurinol. The 21 patients interviewed rated the programme as excellent or very good. DISCUSSIONCulturally appropriate education and support for patients and the primary care team was essential. Collaboration between prescribers, community pharmacists and support workers reduced barriers to initiating prevention and long-term urate-lowering treatment and urate testing in this high-needs gout population.
Adapting the Auckland Sleep Screening Tool for pharmacy: pharmacists’ experience and feedback
Authors: Gauld Natalie , Braganza Crystal , Arroll Bruce
Published: July 2019

ABSTRACT
INTRODUCTIONInsomnia has negative health effects and may indicate underlying serious conditions, but is underdiagnosed and often not discussed with a doctor.
AIMThis study aimed to explore the utility and workability in New Zealand community pharmacies of a 23-question sleep-screening tool adapted from the Short Auckland Sleep Questionnaire.
METHODSA multidisciplinary advisory group (sleep specialist, general practitioner and pharmacists) discussed the tool, pharmacists’ capability in managing insomnia and training needs for pharmacists, and recommended management strategies, including referral points. Twelve community pharmacists piloted the tool with people with insomnia who presented in pharmacies, recording the time it took to administer the tool. The pharmacists were then surveyed about their experiences with the tool and possible improvements.
RESULTSTen pharmacists took an average of 12.4 min (range 4–35 min) for each use of the screening tool with 62 people with insomnia. Most pharmacists found the screening tool easy to administer, organised and easy to follow and nine of 10 said it provided better information than their usual consultation. Seven of 10 pharmacists would use it again. Time limitations and low recruitment were potential barriers to usage especially for pharmacy owners.
DISCUSSIONThe screening tool could provide a useful addition to pharmacists’ toolkits, aiding information gathering and better than usual practice. The tool was acceptable to most pharmacists, but its use takes time and remuneration needs consideration.
Australian rangeland futures: time now for systemic responses to interconnected challenges
Authors: Foran Barney , Smith Mark Stafford , Burnside Don , Andrew Martin , Blesing Don , Forrest Kate , Taylor John
Published: July 2019

Australia’s rangelands contain wildlands, relatively intact biodiversity, widespread Indigenous cultures, pastoral and mining industries all set in past and present events and mythologies. The nature of risks and threats to these rangelands is increasingly global and systemic. Future policy frameworks must acknowledge this and act accordingly. We collate current key information on land tenures and land uses, people and domestic livestock in Australian rangelands, and discuss five perspectives on how the rangelands are changing that should inform the development of integrated policy: climate and environmental change, the southern rangelands, the northern rangelands, Indigenous Australia, and governance and management. From these perspectives we argue that more attention must be paid to: ensuring a social licence to operate across a range of uses, acknowledging and supporting a younger, more Indigenous population, implementing positive aspects of technological innovation, halting capital and governance leakages, and building human capacity. A recommended set of systemic responses should therefore (i) address governance issues consistently and comprehensively, (ii) ensure that new technologies can foster the delivery of sustainable livelihoods, and (iii) focus capacity building on a community of industries where knowledge is built for the long-term, and do all three of these with an eye to the changing demographics of the rangelands.
Introduction.
Authors: Stainton H.
Published: July 2019

This chapter introduces TEFL tourism, a niche form of tourism that involves travelling to teach English as a foreign language. The historical context of niche tourism, the postmodern tourist, and the operators and communities in TEFL tourism are discussed.
TEFL tourism as a form of niche tourism.
Authors: Stainton H.
Published: July 2019

This chapter seeks to identify a number of similarities between TEFL tourism (i.e., tourism that involves teaching English as a foreign language) and various other forms of tourism, placing it firmly in the 'micro-niche' category. The work-leisure binary in TEFL tourism is discussed, as well as TEFL tourism's ties with volunteer tourism. A typology of TEFL tourism is then presented, which includes cultural TEFL tourism, philanthropic TEFL tourism, pro-poor TEFL tourism, educational TEFL tourism, adventure TEFL tourism, and gap-year TEFL tourism.
The education paradox.
Authors: Stainton H.
Published: July 2019

This chapter addresses the issues associated with the convergence of education and tourism in the context of TEFL tourism (i.e., tourism that involves teaching English as a foreign language). Differences in teaching practice between the developed and developing worlds, ethnocentric perceptions of educational provision, the definition of 'teacher', TEFL training and qualifications, and teacher skills and suitability are discussed.
The sustainability of TEFL tourism.
Authors: Stainton H.
Published: July 2019

This chapter provides an overview of sustainability considerations that should be taken into account by operators and academics in TEFL tourism (i.e., tourism that involves teaching English as a foreign language). The chapter discusses: TEFL as a tool for development; TEFL tourism as a tool for poverty reduction; the social, economic, and pedagogic impacts of TEFL tourism; and ethics within TEFL tourism.
The symbolism of sacred space.
Authors: Olsen D. H.
Published: July 2019

This chapter discusses the development and maintenance of sacred spaces and places as defined by institutionalized religion, and how these spaces and places are contested yet also a meeting ground for cross-cultural understanding. The chapter begins by briefly summarizing some of the academic shifts that have taken place over the past few decades regarding the study of sacred space. It then turns to discuss the production and contestation of sacred space with an emphasis on sacred spaces as 'places in motion', before examining how sacred spaces are being used by religious groups for outreach and to promote cross-cultural understanding.
Images as an embodiment of the sacred.
Authors: Ferrer Ventosa R.
Published: July 2019

This chapter focuses on images that allude one way or another to the sacred. Images can be used to express ultimate truths in a more effective way than texts or words, getting round the limitations of texts: illiteracy or the fragmentation in various languages. Through sacred visual art, many metaphysical ideas take shape and can be communicated through symbols and metaphors.
Does a religious tourist need a guide? Interpretation and storytelling in sacred places.
Authors: Duda T.
Published: July 2019

This chapter presents contemporary trends in religious tourism and the role that pilgrimage plays in shaping the knowledge and attitudes related to the religious and spiritual heritage of the region. Based on surveys and direct interviews in the Pomerania region (north-west Poland and north-east Germany), the role of a tourist guide was determined to be an 'interpreter of places and routes, responsible for the provision of an adequate storytelling process'. The chapter also attempts to answer some key questions that trouble contemporary researchers studying the problem of interpretation in tourism, associated with the phenomenon of pilgrimage and/or religious tourism.
Updating a romantic view? Ruskin's Mornings in Florence.
Authors: Crous-Costa N.
Published: July 2019

This chapter focuses on John Ruskin's guidebook Mornings in Florence (1877). The goal of the chapter is to discuss the feasibility of Ruskin's itinerary in this guidebook today. This exploration not only considers the existence of the sights referred to, most of which are still prominent tourist landmarks today, but additionally the chapter reflects on the interest of using this understanding of the city again from the perspective of different stakeholders.
Collagen-derived dipeptide prolyl hydroxyproline directly binds to Foxg1 to change its conformation and inhibit the interaction with Runx2
Authors: Nomura Kaho , Kimira Yoshifumi , Osawa Yoshihiro , Shimizu Jun , Kataoka-Matsushita Aya , Mano Hiroshi
Published: July 2019

Collagen-derived dipeptide prolyl hydroxyproline (Pro-Hyp) is involved in the proliferation and differentiation of various types of cultured cells. To elucidate the mechanism underlying Pro-Hyp actions during osteoblast differentiation, we hypothesized that proteins binding to Pro-Hyp serve to mediate cellular signaling, affecting Runx2 expression. Recently, we performed the characterization of Foxg1, that it enhances Runx2 expression in the presence of Pro-Hyp. Our findings indicate that Pro-Hyp directly binds to the Foxg1 recombinant protein, which leads to the structural alteration of the Foxg1 protein. In addition, Foxg1 appears to interact with Runx2 in the absence of Pro-Hyp, with Pro-Hyp disrupting the interaction between Foxg1 and Runx2. Collectively, our results indicate that the Pro-Hyp bound Foxg1 alters the structured conformation of Foxg1, resulting in conformational changes that lead to dissociation from Runx2. These novel findings suggest that during osteoblast differentiation, Pro-Hyp mediates Runx2 activity though directly binding to Foxg1 and increases Runx2 expression.

Abbreviations: CPT: collagen peptide; GST: Glutathione S-transferase; PAGE: Polyacrylamide gel electrophoresis; PCR: Polymerase chain reaction; prolyl hydroxyproline: Pro-Hyp
Rehabilitating “Disease”: Function, Value, and Objectivity in Medicine
Authors: Powell Russell , Scarffe Eric
Published: July 2019

The concept of disease remains hotly contested. In light of problems with existing accounts, some theorists argue that the disease concept ought to be eliminated. We answer this skeptical challenge by reframing the discussion in terms of the role that the disease concept plays in the complex network of health care institutions in which it is deployed. We argue that while prevailing accounts do not suffer from the particular defects that critics have identified, they do suffer from other deficits, and this leads us to propose a new account that satisfies the desiderata for a concept of disease in human medicine.
Scientific/Intellectual Movements Remedying Epistemic Injustice: The Case of Indigenous Studies
Authors: Koskinen Inkeri , Rolin Kristina
Published: July 2019

Whereas much of the literature in the social epistemology of scientific knowledge has focused either on scientific communities or research groups, we examine the epistemic significance of scientific/intellectual movements (SIMs). We argue that certain types of SIMs can play an important epistemic role in science: they can remedy epistemic injustices in scientific practices. SIMs can counteract epistemic injustices effectively because many forms of epistemic injustice require structural and not merely individual remedies. To illustrate our argument, we discuss the case of indigenous studies.
Magnetocaloric Mn5Si3 and MnFe4Si3 at variable pressure and temperature
Authors: Eich Andreas , Grzechnik Andrzej , Caron Luana , Cheng Yao , Wilden Johanna , Deng Hao , Hutanu Vladimir , Meven Martin , Hanfland Michael , Glazyrin Konstantin , Hering Paul , Herrmann Markus Guido , Ait Haddouch Mohammed , Friese Karen
Published: July 2019

The influence of hydrostatic high pressure on the crystal structures and magnetic properties of magnetocaloric Mn5Si3 and MnFe4Si3 was studied with temperature dependent synchrotron powder diffraction, neutron single-crystal diffraction and magnetization measurements. Mn5Si3 shows no indication for any pressure-induced structural phase transition up to 24.2 GPa at room temperature. MnFe4Si3 exhibits no clear indication for any phase transition at high temperatures (296 K–373 K) and high pressures. Anomalies in the lattice parameter at low temperatures indicate a structural response to magnetic ordering. The gradient of decreasing magnetic transition temperature with increasing pressure is dT
C/dP ≈ −15 K GPa−1. The transition temperature in MnFe4Si3 can be tuned by pressure in the temperature range relevant for applications, while pressure has hardly any detrimental influence on other key features relevant to magnetocaloric applications (the width of hysteresis, saturation magnetization, magnetocrystalline anisotropy).
Canada sets up independent panel to shake up science support
Authors: Gwynne Peter
Published: July 2019

The Canadian government has announced a new fund to stop research cash being awarded via lobbying or political interference.
A 3D view on 2D materials
Authors: Demming Anna
Published: July 2019

Nobel laureate Kostya Novoselov from the University of Manchester, UK, talks to Anna Demming about moving on from graphene and going back into 3D materials
Seeing the unseeable
Authors: Durrani Matin
Published: July 2019

The first images of a black hole – released last month – are inspirational and amazing
Coupled practices
Authors: Demming Anna
Published: July 2019

Physics and Dance by Emily Coates and Sarah Demers is not the only book seeking to explore common ground between these two disciplines. What sets it apart is the breadth drawn on in both areas.
Physicist in the making
Authors: Wright Peter
Published: July 2019

Isn’t it strange how small things can shape your life? I recently found myself recalling past experiences, aspirations and failures – how was it that I spent my life in physics
Billion-volt thunderstorm studied using muons
Authors: Jarman Sam
Published: July 2019

A thundercloud with a record-breaking voltage of 1.3 GV has been observed by physicists in India and Japan.
Analysis of magnetic flux in magneto-rheological damper
Authors: Purandare Snehal , Zambare Hrishikesh , Razban Ali
Published: July 2019

Magnetorheological materials are a class of smart substances whose rheological properties can rapidly be varied by application of a magnetic field. The proposed damper consists of an electromagnet and a piston immersed in MR fluid. When current is applied to the electromagnet, the MR fluid solidifies as its yield stress varies in response to the applied magnetic field. Hence, the generation of a magnetic field is an important phenomenon in MR damper. In this research, the magnetic field generated in the damper was analyzed by applying finite element method using COMSOL Multiphysics and was validated using magnetic circuit theory. A quasi-static, 2D—Axisymmetric model was developed using parametric study by varying current from 0–3 A and the magnetic flux density change generated in the fluid flow gap of MR fluid due to external applied current was evaluated. According to the analytical calculations magnetic flux density generated at MR fluid gap was 0.64 Tesla and when calculated using FEA magnetic flux density generated was 0.61 Tesla for 1A current. There is a difference of 4.8% in the simulated results and analytically calculated results of automotive MR damper due to non linear BH curve consideration in Finite element analysis over linear consideration of BH relation in magnetic circuit theory.
Case report of simultaneous transcatheter mitral valve-in-valve implantation and percutaneous closure of two paravalvular leaks
Authors: Asami Masahiko , Pilgrim Thomas , Windecker Stephan , Praz Fabien
Published: July 2019

Background

Concomitant structural degeneration of surgical mitral bioprostheses and paravalvular leak (PVL) is rare but potentially fatal. Data pertaining to simultaneous transcatheter mitral valve implantation (TMVI) and percutaneous PVL closure are limited, and the optimal treatment strategy remains undetermined. We report a case of simultaneous TMVI and double percutaneous PVL closure in a patient with a degenerated bioprosthetic mitral valve and associated medial and lateral PVLs.

Case summary

A 75-year-old woman who underwent combined aortic (Edwards Perimount Magna 19 mm) and mitral (Edwards Perimount Magna 25 mm) surgical valve replacement 6 years ago was referred for treatment of new-onset orthopnoea and severely reduced exercise capacity. Transoesophageal echocardiography revealed severe mitral stenosis and concomitant moderate to severe mitral regurgitation, originating from two PVLs located medial and lateral from the surgical bioprosthesis. Due to high surgical risk, we performed successful transseptal mitral valve-in-valve (ViV) implantation combined with the closure of two PVLs during the same procedure.

Discussion

Although surgery should be considered as a first-line treatment in this setting, most patients have extremely high or prohibitive surgical risk inherent to repeat open heart surgery. Mitral ViV implantation appears a reasonable treatment option for patients with failed mitral bioprostheses. Furthermore, a recent study of percutaneous PVL closure showed no significant difference in long-term all-cause mortality compared with redo open-heart surgery. Simultaneous TMVI and percutaneous PVL closure appears feasible in selected high-risk patients.
Genes, pathways and risk prediction in Alzheimer’s disease
Authors: Hardy John , Escott-Price Valentina
Published: July 2019

The failure of recent clinical trials in Alzheimer's disease has highlighted the need for the development of a more complete understanding of the pathogenesis of the disorder and also a belief that therapies may only work if given very early in the disease process before overt symptoms occur. The rare, early onset forms of the disease are all caused by mutations which make amyloid deposition a more likely event. Here we discuss the recent data showing that, in contrast, much of the risk of late onset disease is encoded by loci involved in lipid metabolism and/or encoded by microglia. We discuss these finding and suggest that amyloid induced membrane damage may be a key factor in disease and also review the evidence that genome wide genetic analysis can substantially help in the prediction of those individuals at high risk of disease in the general population.
A fresh look at the biodiversity lexicon for fiddler crabs (Decapoda: Brachyura: Ocypodidae). Part 1: Taxonomy
Authors: Rosenberg Michael S
Published: July 2019

Fiddler crabs (Ocypodidae) have gone through a gradual series of taxonomic revisions and refinements over the last 40 years, culminating most recently with an expansion from a single genus into eleven different genera. I examine the opportunities presented by these revisions with respect to establishing formal names for previously established clades at a variety of taxonomic levels that were otherwise previously impossible to name due to historical compression of these crabs into a single genus, including the establishment or reestablishment of three tribes (Ucini, Gelasimini, and Minucini) and ten subgenera: Uca (Uca), Uca (Acanthoplax), Gelasimus (Gelasimus), Gelasimus (Mesuca), Austruca (Austruca), Austruca (Cuneatuca), Austruca (Sinduca), Tubuca (Tubuca), Tubuca (Australuca), and Tubuca (Angustuca). A previously overlooked synonymy between Gelasimus excisa (Nobili, 1906) and G. neocultrimana (Bott, 1973) is discussed, and the former name is adopted as valid.
Microanatomy of the American Malaria Vector Anopheles aquasalis (Diptera: Culicidae: Anophelinae) Midgut: Ultrastructural and Histochemical Observations
Authors: Baia-da-Silva Djane C , Orfanó Alessandra S , Nacif-Pimenta Rafael , de Melo Fabricio F , Guerra Maria G V B , Lacerda Marcus V G , Monteiro Wuelton M , Pimenta Paulo F P
Published: July 2019

The mosquito gut is divided into foregut, midgut, and hindgut. The midgut functions in storage and digestion of the bloodmeal. This study used light, scanning (SEM), and transmission (TEM) electron microscopy to analyze in detail the microanatomy and morphology of the midgut of nonblood-fed Anopheles aquasalis females. The midgut epithelium is a monolayer of columnar epithelial cells that is composed of two populations: microvillar epithelial cells and basal cells. The microvillar epithelial cells can be further subdivided into light and dark cells, based on their affinities to toluidine blue and their electron density. FITC-labeling of the anterior midgut and posterior midgut with lectins resulted in different fluorescence intensities, indicating differences in carbohydrate residues. SEM revealed a complex muscle network composed of circular and longitudinal fibers that surround the entire midgut. In summary, the use of a diverse set of morphological methods revealed the general microanatomy of the midgut and associated tissues of An. aquasalis, which is a major vector of Plasmodium spp. (Haemosporida: Plasmodiidae) in America.
Influence of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) Infection on Mortality of the Sylvatic Triatomine Vector, Mepraia spinolai (Heteroptera: Reuviidae), Under Fasting
Authors: Garcia Vanessa , Graterol Johsmar , López Angélica , Ortiz Sylvia , Solari Aldo
Published: July 2019

The etiologic agent of Chagas disease, Trypanosoma cruzi, is transmitted by hematophagous insect vectors that subsist on repeated blood meals over their lives separated by periods of fasting. Using naturally infected Mepraia spinolai, we measured the influence of parasite infection on this host vector’s mortality during regular feeding and after fasting. After their capture, the insects were fed twice with uninfected mice to evaluate parasitic infection in their fecal samples by microscopic observation and PCR. Then the insects were subjected to a fasting period, followed by a third (final) feeding. After each feeding, a fecal sample was obtained to evaluate T. cruzi infection. To determine its progress through ontogeny, mortality and ecdysis of the infected and uninfected nymphs and adults were recorded on three occasions, over 140 d, and analyzed. Detections of infection by T. cruzi between the two first feedings increased, but this detection level was generally reduced after final feeding unless reinfected. For nymphs (stages III–V), their mortality was highest when infected after the fasting period, whereas adults were equally resistant to death after fasting when infected with T. cruzi. Metacyclic trypomastigotes were principally excreted in the fecal samples. Our results confirm that T. cruzi is pathogenic to its invertebrate hosts under nutritional stress conditions, when nymphs’ mortality is higher while infected than uninfected when they were hungry. These results are epidemiologically important because T. cruzi harms the fasting vector M. spinolai, reducing its lifespan and competence as a disease vector, and thereby its rates of parasite transmission.
Neuropathological Changes in Dementia With Lewy Bodies and the Cingulate Island Sign
Authors: Patterson Lina , Firbank Michael J , Colloby Sean J , Attems Johannes , Thomas Alan J , Morris Christopher M
Published: July 2019

The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis of the CIS is unknown; therefore, our aim was to investigate which neurodegenerative changes underpin the formation of CIS. Using quantitative neuropathology, α-synuclein, phosphorylated Tau, and amyloid-β pathology was assessed in 12 DLB, 9 AD and 6 age-matched control patients in the anterior cingulate (ACC), midcingulate, PCC, precuneus/cuneus and parahippocampal gyrus. All participants had undergone 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography imaging during life to define the presence or absence of CIS. In the DLB group, no significant correlations were observed between CIS ratios and neurodegenerative pathology in PCC. In DLB, however, the ACC showed lower HMPAO uptake, as well as significantly higher α-synuclein and amyloid-β burden compared with PCC, possibly underlying the relative preservation of perfusion in PCC when compared with ACC. Our findings suggest that neurodegenerative pathology does not directly correlate with the CIS in DLB, and other metabolic or pathological changes are therefore more likely to be relevant for the development of the CIS.
Papillary Solitary Fibrous Tumor/Hemangiopericytoma: An Uncommon Morphological Form With NAB2-STAT6 Gene Fusion
Authors: Yao Zhi-Gang , Wu Hai-Bo , Hao Ying-Hua , Wang Xing-Fu , Ma Guang-Zhen , Li Jia , Li Ji-Feng , Lin Chun-Hu , Zhong Xiu-Ming , Wang Zhou , Wang Dai-Zhong
Published: July 2019

Solitary fibrous tumor/hemangiopericytomas (SFT/HPCs) are mesenchymal tumors characterized by “staghorn” blood vessels and collagen deposition. Little is known about SFT/HPCs with papillary architecture. We summarized the clinicopathologic features of 12 patients with papillary SFT/HPCs (8 males and 4 females; median age: 59 years), including 8 previously reported cases. Tumors were present in the meninges (75%, 9/12), adrenal gland (8%, 1/12), orbit (8%, 1/12), or spinal canal (8%, 1/12). Six tumors (50%) had a true papillary architecture with fibrovascular cores and 6 tumors (50%) had a pseudopapillary architecture with vascular cores. Nuclear staining for STAT6 was present in all tested tumors (10/10). RT-PCR indicated NAB2 ex6-STAT6 ex17 fusion in 4 tumors (80%, 4/5) and NAB2 ex4-STAT6 ex2 fusion in 1 tumor (20%, 1/5). Five patients (42%, 5/12), all with tumors in the meninges, developed local recurrence at a median of 61 months after surgery (range: 56–165 months; mean: 88.6 months). These results indicated that the papillary architecture is a morphological form of SFT/HPCs. The recognition of this pattern, with appropriate immunohistochemical analysis and assessment of NAB2-STAT6 fusion, should facilitate the distinction of these rare neoplasms from morphologically similar tumors in the meninges, lung, pleura, and soft tissue.
The day after: correlates of patient-reported outcomes with actigraphy-assessed sleep in cancer patients at home (inCASA project)
Authors: Komarzynski Sandra , Huang Qi , Lévi Francis A , Palesh Oxana G , Ulusakarya Ayhan , Bouchahda Mohamed , Haydar Mazen , Wreglesworth Nicholas I , Morère Jean-François , Adam René , Innominato Pasquale F
Published: July 2019

Subjective sleep assessment in cancer patients poorly correlates with actigraphy parameters that usually encompass multiple nights. We aimed to determine the objective actigraphy measures that best correlated with subjective sleep ratings on a night-by-night basis in cancer patients. Thirty-one cancer patients daily self-rated sleep disturbances using the single dedicated item of the MD Anderson Symptom Inventory (0–10 scale) with 18 other items, and continuously wore a wrist actigraph for 30 days. Objective sleep parameters were computed from the actigraphy nighttime series, and correlated with subjective sleep disturbances reported on the following day, using repeated measures correlations. Multilevel Poisson regression analysis was performed to identify the objective and subjective parameters that affected subjective sleep rating. Poor subjective sleep score was correlated with poor sleep efficiency (rrm = −0.13, p = 0.002) and large number of wake episodes (rrm = 0.12, p = 0.005) on the rated night. Multilevel analysis demonstrated that the expected sleep disturbance score was affected by the joint contribution of the wake episodes (exp(β) = 1.01, 95% confidence interval = 1.00 to 1.02, p = 0.016), fatigue (exp(β) = 1.35, 95% confidence interval = 1.15 to 1.55, p < 0.001) and drowsiness (exp(β) = 1.70, 95% confidence interval = 1.19 to 2.62, p = 0.018), self-rated the following evening, and sleep disturbance experienced one night before (exp(β) = 1.77, 95% confidence interval = 1.41 to 2.22, p < 0.001). The night-by-night approach within a multidimensional home tele-monitoring framework mainly identified the objective number of wake episodes computed from actigraphy records as the main determinant of the severity of sleep complaint in cancer patients on chemotherapy. This quantitative information remotely obtained in real time from cancer patients provides a novel framework for streamlining and evaluating interventions toward sleep improvement in cancer patients.
The Current Epidemic of the Barley Pathogen Ramularia collo-cygni Derives from a Population Expansion and Shows Global Admixture
Authors: Stam Remco , Sghyer Hind , Tellier Aurélien , Hess Michael , Hückelhoven Ralph
Published: July 2019

Ramularia leaf spot is becoming an ever-increasing problem in main barley-growing regions since the 1980s, causing up to 70% yield loss in extreme cases. Yet, the causal agent Ramularia collo-cygni remains poorly studied. The diversity of the pathogen in the field thus far remains unknown. Furthermore, it is unknown to what extent the pathogen has a sexual reproductive cycle. The teleomorph of R. collo-cygni has not been observed. To study the genetic diversity of R. collo-cygni and get more insights in its biology, we sequenced the genomes of 19 R. collo-cygni isolates from multiple geographic locations and diverse hosts. Nucleotide polymorphism analyses of all isolates shows that R. collo-cygni is genetically diverse worldwide, with little geographic or host specific differentiation. Next, we used two different methods to detect signals of recombination in our sample set. Both methods find putative recombination events, which indicate that sexual reproduction happens or has happened in the global R. collo-cygni population. Lastly, we used these data on recombination to perform historic population size analyses. These suggest that the effective population size of R. collo-cygni decreased during the domestication of barley and subsequently grew with the rise of agriculture. Our findings deepen our understanding of R. collo-cygni biology and can help us to understand the current epidemic. We discuss how our findings support possible global spread through seed transfer, and we highlight how recombination, clonal spreading, and lack of host specificity could amplify global epidemics of this increasingly important disease and suggest specific approaches to combat the pathogen.
Specific diagnostic method for St. Louis Encephalitis Virus using a non-structural protein as antigen
Authors: Simari M.B. , Goñi S.E. , Luppo V.C , Fabbri C.M. , Argüelles M.H. , Lozano M.E. , Morales M.A. , Iglesias N.G.
Published: July 2019

St. Louis encephalitis virus (SLEV) is a mosquito-borne reemerging flavivirus in Argentina. It is currently necessary to develop specific serological tests that can efficiently discriminate the flaviviruses that circulate in our country. The immunoassays to diagnose SLEV lack specificity because they are based on the detection of structural viral proteins and the human immunoglobulins produced during infection against these proteins cross-react with other flaviviruses. Here, we describe an enzyme-immunoassay designed to detect human IgG antibodies specific to the viral nonstructural protein NS5. The results indicate that NS5 is a promising antigen useful to discriminate SLEV from other circulating flaviviruses.
Is therapeutic inertia present in primary diabetes care in Malaysia? A prospective study
Authors: Chew Boon-How , Hussain Husni , Supian Ziti Akthar
Published: July 2019

Aims

This prospective study aimed to determine the proportions of therapeutic inertia when treatment targets not achieved in adults T2D at three public health clinics in Malaysia.

Methods

The index prescriptions were those when the annual blood tests were reviewed. Prescriptions were verified and classified as 1) no change, 2) stepping up and 3) stepping down. Multivariable logistic regression and sensitive analyses were conducted.

Results

At follow-up, 552 participants were available for the assessment of therapeutic inertia (78.9% response rate). The mean (SD) age and diabetes duration were 60.0 (9.9) years and 5.0 (6.0) years, respectively. High therapeutic inertia were observed in oral anti-diabetic (61-72%), anti-hypertensive (34-65%) and lipid-lowering therapies (56-77%), and lesser in insulin (34- 52%). Insulin therapeutic inertia was more likely among those with shorter diabetes duration (adjusted OR 0.9, 95% CI 0.87, 0.98). Those who did not achieve treatment targets were less likely to experience therapeutic inertia: HbA1c ≥ 7.0%: adjusted OR 0.10 (0.04, 0.24); BP ≥ 140/90 mmHg: 0.28 (0.16, 0.50); LDL-cholesterol ≥ 2.6 mmol/L: 0.37 (0.22, 0.64).

Conclusions

Although therapeutic intensifications were more likely in the present of non- achieved treatment targets but the proportions of therapeutic inertia were high.

Trial registration

NCT02730754 https://clinicaltrials.gov/ct2/show/NCT02730754

Highlights

Probably the first study in Malaysia or Asian countries

Assessing three main therapeutic inertia among T2D at primary diabetes care

Proportions of therapeutic inertia were high

Therapeutic inertia was unlikely in non-achieved treatment targets

Possible causes of therapeutic inertia require identification and rectification
Rfx6 promotes the differentiation of peptide-secreting enteroendocrine cells while repressing genetic programs controlling serotonin production
Authors: Piccand Julie , Vagne Constance , Blot Florence , Meunier Aline , Beucher Anthony , Strasser Perrine , Lund Mari L. , Ghimire Sabitri , Nivlet Laure , Lapp Céline , Petersen Natalia , Engelstoft Maja S. , Thibault-Carpentier Christelle , Keime Céline , Correa Sara Jimenez , Schreiber Valérie , Molina Nacho , Schwartz Thue W. , De Arcangelis Adèle , Gradwohl Gérard
Published: July 2019

Objective

Enteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake and storage. Our goal is to decipher the gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context, we studied the role of the transcription factor Rfx6 which had been identified as the cause of Mitchell-Riley syndrome characterized by neonatal diabetes and congenital malabsorptive diarrhea. We previously reported that Rfx6 was essential for pancreatic beta cell development and function, however, the role of Rfx6 in EECs differentiation remained to be elucidated.

Methods

We examined the molecular, cellular and metabolic consequences of constitutive and conditional deletion of Rfx6 in the embryonic and adult mouse intestine. We performed single cell and bulk RNA-Seq to characterize EECs diversity and identify Rfx6-regulated genes.

Results

Rfx6 is expressed in the gut endoderm; later it is turned on in, and restricted to, enteroendocrine progenitors and persists in hormone-positive EECs. In the embryonic intestine, the constitutive lack of Rfx6 leads to gastric heterotopia, suggesting a role in the maintenance of intestinal identity. In the absence of intestinal Rfx6, EECs differentiation is severely impaired both in the embryo and adult. However, the number of serotonin-producing enterochromaffin cells and mucosal 5-HT content are increased. Concomitantly, Neurog3-positive enteroendocrine progenitors accumulate. Combined analysis of single-cell and bulk RNA-Seq data revealed that enteroendocrine progenitors differentiate in two main cell trajectories, the enterochromaffin (EC) cells and the Peptidergic Enteroendocrine (PE) cells, whose differentiation programs are differentially regulated by Rfx6. Rfx6 operates upstream of Arx, Pax6 and Isl1 to trigger the differentiation of peptidergic EECs such as GIP-, GLP-1- or CCK-secreting cells. On the contrary, Rfx6 represses Lmx1a and Tph1, two genes essential for serotonin biosynthesis. Finally, we identified transcriptional changes uncovering adaptive responses to the prolonged lack of enteroendocrine hormones and leading to malabsorption and lower food efficiency ratio in Rfx6-deficient mouse intestine.

Conclusion

These studies identify Rfx6 as an essential transcriptional regulator of EECs specification and shed light on the molecular mechanisms of intestinal failures in human RFX6-deficiencies such as Mitchell-Riley syndrome.
TREEasy: an automated workflow to infer gene trees, species trees, and phylogenetic networks from multilocus data
Authors: Mao Yafei , Hou Siqing , Economo Evan P.
Published: July 2019

Multilocus genomic datasets can be used to infer a rich set of information about the evolutionary history of a lineage, including gene trees, species trees, and phylogenetic networks. However, user-friendly tools to run such integrated analyses are lacking, and workflows often require tedious reformatting and handling time to shepherd data through a series of individual programs. Here, we present a tool written in Python—TREEasy—that performs automated sequence alignment (with MAFFT), gene tree inference (with IQ-Tree), species inference from concatenated data (with IQ-Tree), species tree inference from gene trees (with ASTRAL, MP-EST, and STELLS2), and phylogenetic network inference (with SNaQ and PhyloNet). The tool only requires FASTA files and nine parameters as inputs. The Tool can be run as command line or through a Graphical User Interface (GUI). As examples, we reproduced a recent analysis of staghorn coral evolution, and performed a new analysis on the evolution of the WGD clade of yeast. The latter revealed novel inferences that were not identified by previous analyses. TREEasy represents a reliable and simple tool to accelerate research in systematic biology (https://github.com/MaoYafei/TREEasy).
Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice
Authors: Eid Rand S. , Lieblich Stephanie E. , Wong Sarah J. , Galea Liisa A.M.
Published: July 2019

Ovarian hormones influence the outcomes of stress exposure and are implicated in stress-related disorders including depression, yet their roles are often complex and seemingly contradictory. Importantly, depression and stress exposure are associated with immune dysregulation, and ovarian hormones have immunomodulatory properties. However, how ovarian hormones can influence the inflammatory outcomes of stress exposure is poorly understood. Here, we examined the effects of long-term ovariectomy on the behavioral and neuroinflammatory outcomes of sub-chronic stress exposure in middle-aged mice. Briefly, sham-operated and ovariectomized mice were assigned to non-stress groups or exposed to 6 days of variable stress. Mice were assessed on a battery of behavioral tests, and cytokine concentrations were quantified in the frontal cortex and hippocampus. In the frontal cortex, postsynaptic density protein-95 expression was examined as an index of excitatory synapse number and/or stability, and phosphorylated mitogen-activated protein kinases (MAPKs) were measured to explore potential cell signaling pathways elicited by stress exposure and/or ovarian hormones. Long-term ovariectomy modified the central cytokine profile by robustly reducing cytokine concentrations in the frontal cortex and modestly increasing concentrations in the hippocampus. Under non-stress conditions, long-term ovariectomy also reduced extracellular signal-regulated kinase (ERK) phosphoprotein expression in the frontal cortex and increased some measures of depressive-like behavior. The effects of sub-chronic stress exposure were however more pronounced in sham-operated mice. Notably, in sham-operated mice only, sub-chronic stress exposure increased IL-1β and IL-6:IL-10 ratio in the frontal cortex and hippocampus and reduced pERK1/2 expression in the frontal cortex. Further, although sub-chronic stress exposure increased anhedonia-like behavior regardless of ovarian status, it increased passive-coping behavior in sham-operated mice only. These data indicate that long-term ovariectomy has potent effects on the central cytokine milieu and dictates the neuroinflammatory and behavioral effects of sub-chronic stress exposure in middle-aged mice. These findings therefore suggest that the immunomodulatory properties of ovarian hormones are of relevance in the context of stress and possibly depression.
BIAFLOWS: A collaborative framework to reproducibly deploy and benchmark bioimage analysis workflows
Authors: Rubens Ulysse , Mormont Romain , Paavolainen Lassi , Bäcker Volker , Michiels Gino , Pavie Benjamin , Scholz Leandro A. , Maška Martin , Ünay Devrim , Ball Graeme , Hoyoux Renaud , Vandaele Rémy , Golani Ofra , Chessel Anatole , Stanciu Stefan G. , Sladoje Natasa , Paul-Gilloteaux Perrine , Marée Raphaël , Tosi Sébastien
Published: July 2019

Automated image analysis has become key to extract quantitative information from scientific microscopy bioimages, but the methods involved are now often so refined that they can no longer be unambiguously described using written protocols. We introduce BIAFLOWS, a software tool with web services and a user interface specifically designed to document, interface, reproducibly deploy, and benchmark image analysis workflows. BIAFLOWS allows image analysis workflows to be compared fairly and shared in a reproducible manner, safeguarding research results and promoting the highest quality standards in bioimage analysis. A curated instance of BIAFLOWS is available online; it is currently populated with 34 workflows that can be triggered to process image datasets illustrating 15 common bioimage analysis problems organized in 9 major classes. As a complete case study, the open benchmarking of 7 nuclei segmentation workflows, including classical and deep learning techniques, was performed on this online instance. All the results presented can be reproduced online.
REAVER: Improved Analysis of High-resolution Vascular Network Images Revealed Through Round-robin Rankings of Accuracy and Precision
Authors: Corliss Bruce A. , Doty Richard , Mathews Corbin , Yates Paul A. , Zhang Tingting , Peirce Shayn M.
Published: July 2019

Alterations in vascular networks, including angiogenesis and capillary regression, play key roles in disease, wound healing, and development. Imaging of microvascular networks can reveal their spatial structures, but effective study of network architecture requires methods to accurately quantify them using a variety of metrics. We present REAVER (Rapid Editable Analysis of Vessel Elements Routine), a freely available open source tool that researchers can use to analyze and quantify high resolution fluorescent images of blood vessel networks, and assess its performance compared to alternative state-of-the-art image analysis software programs. Top performing programs for each metric are identified by assigning a rank based on statistical multiple comparisons of accuracy and precision, modeled as matches in a round-robin style tournament. This comparison method yields a clearly defined and consistent standard for characterizing program performance, avoiding the use of non-standard ad hoc interpretations of multiple comparisons between programs. Using this comparison method and a dataset of manually analyzed images as a ground-truth, we show that REAVER was the top ranked program for both accuracy and precision for all metrics quantified, including vessel length density, vessel area fraction, mean vessel diameter, and branchpoint count. REAVER can be used to quantify differences in blood vessel architectures between study groups, which makes it particularly useful in experiments designed to evaluate the effects of different external perturbations (e.g. drugs or disease states).