bluuebunny/crossref_metadata_2025 huggingface dataset:
Being healthcare provider and retailer: perceiving and managing tensions in community pharmacy
Authors: Scahill S.L. , Tracey M.S. , Sayers J.G. , Warren L.
Published: June 2018

Background

Internationally, pharmaceutical policy has heightened expectations for community pharmacies to act as healthcare professionals, increasing the need to understand the health professional–retailer nexus. Literature suggests that pharmacy involves a dichotomy of roles including both retailing and healthcare provision, yet it is unknown whether pharmacists themselves perceive a tension between these roles and how such a tension might be managed.

Aim

To explore whether there is tension between being retailers and healthcare providers in community pharmacy and to understand how any such tension is perceived and managed.

Methods

Ten in‐depth semi‐structured interviews were conducted with pharmacist owners and managers of community pharmacies in New Zealand. General inductive thematic analysis was undertaken to gain insight from the data.

Results

Pharmacists experienced tension between being healthcare providers and being retailers. In total, eight themes were derived from this study. Four themes emerged to describe the tension: (i) balancing roles; (ii) tension – what tension?; (iii) we give a lot for free; and (iv) too much bureaucracy and paperwork. Four themes for managing tension were identified: (i) imparting of owner beliefs; (ii) use of incentives; (iii) effective business management skills; and (iv) being entrepreneurial.

Conclusion

This paper is expected to assist in helping policy‐makers and practitioners be aware of the role of tensions when policies are implemented to move pharmacists from a retailer role to healthcare provider. This paper aids in policy development and should inform professional practice and forthcoming business management training programs for community pharmacy.
Hospitality and tourism experts' perspectives on Chinese independent tourists' U.S. service expectations through a mobilities lens
Authors: Mejia Cynthia , Wei Wei , Fu Xiaoxiao , Hua Nan , Wang Youcheng
Published: June 2018

In response to the rapid growth of tourism in the world's emerging regions led by Asia, this study represents a seminal attempt to dissect Chinese outbound tourists' service expectations in the United States from the perspective of hospitality and tourism experts. Rapid focus group discussions were conducted with 64 academic scholars and industry professionals whose work was in close relation to U.S.‐China tourism. Utilizing qualitative data analysis through the mobility paradigm, themes were revealed in association with their hidden meanings of movement (e.g., logistics and connectivity), practices (e.g., service provision and amenities), as well as the effects of those practices on their respective representations (e.g., cultural distance and frictions). Theoretical contributions of the study include the use of the mobility framework as a tool for uncovering nuanced cross‐cultural interpretations in tourism. Recommendations for implementing best practices in welcoming Chinese tourists to the United States were offered as part of the managerial implications.
Small cell lung cancer with solitary brain metastasis treated with complete resection
Authors: Drpa Gordana , Popovic Filip , Nikolic Igor , Kukulj Suzana
Published: June 2018

The common treatment modality for extensive‐stage small cell lung cancer is chemotherapy, which significantly improves survival in these patients. However, the median survival is still poor and usually does not reach 12 months. For a long time, surgery has not played any role in the treatment of small cell lung cancer. In recent years, the operative approach has been accepted as a form of treatment for patients with limited‐stage disease. However, in patients with resectable primary carcinoma and solitary metastasis, surgery is not recommended, although it is the standard method of treatment in patients with non‐small cell lung cancer and other malignancies. We report the long‐term survival of a patient with metastatic small cell lung cancer treated with complete resection of both the primary tumor and the solitary brain metastasis.
Sample size allocation in multiregional equivalence studies
Authors: Liao Jason J.Z. , Yu Ziji , Li Yulan
Published: June 2018

With the increasing globalization of drug development, the multiregional clinical trial (MRCT) has gained extensive use. The data from MRCTs could be accepted by regulatory authorities across regions and countries as the primary sources of evidence to support global marketing drug approval simultaneously. The MRCT can speed up patient enrollment and drug approval, and it makes the effective therapies available to patients all over the world simultaneously. However, there are many challenges both operationally and scientifically in conducting a drug development globally. One of many important questions to answer for the design of a multiregional study is how to partition sample size into each individual region. In this paper, two systematic approaches are proposed for the sample size allocation in a multiregional equivalence trial. A numerical evaluation and a biosimilar trial are used to illustrate the characteristics of the proposed approaches.
Repair of a Proximal Hamstring Rupture in a 14-Year-Old Patient: A Case Report
Authors: Buckley Patrick S. , Dodson Christopher C.
Published: June 2018

Proximal hamstring tendon ruptures are rare in children and adolescents. The typical pediatric hamstring injury pattern involves an apophyseal avulsion fracture. We present the case of a 14-year-old male with a widely displaced ischial avulsion fracture and a bony fragment that was too small to allow for bony fixation. The patient presented with left-buttock pain and ecchymosis, as well as tenderness at the ischial tuberosity, following an injury sustained while running 2 weeks prior. Imaging demonstrated an avulsion of the proximal hamstrings with a 4-mm bony fragment, too small to allow for repair. The patient underwent primary repair using two 3-mm suture anchors. The bony fragment was not excised but incorporated into the repair. Although most proximal hamstring injuries in children and adolescents are treated non-operatively, operative treatment may confer a small but clinically important difference in rates of healing and return to play in adolescent athletes. This case demonstrates successful treatment of a proximal hamstring rupture with suture anchor fixation, which may be considered for pediatric and adolescent displaced avulsion fractures when the bony fragment is too small to allow for bony fixation.
Sedimentary proxies for Pacific water inflow through the Herald Canyon, western Arctic Ocean
Authors: Swärd Henrik , O’Regan Matt , Pearce Christof , Semiletov Igor , Stranne Christian , Tarras Henrik , Jakobsson Martin
Published: June 2018

Pacific water inflow to the Arctic Ocean occurs through the shallow Bering Strait. With a present sill depth of only 53 m, this gateway has been frequently closed during glacial sea-level low stands of the Pleistocene. Here, we investigate the sedimentological and mineralogical response to sea-level rise and the opening of the Bering Strait during the last deglaciation in a 6.1 m-long marine sediment core (SWERUS-L2-4-PC1) from the Herald Canyon. Grain size data indicate an abrupt erosional contact at 412 cm down core that likely formed when Pacific waters first started to flow into the Arctic Ocean around 11 cal ka BP, and was topographically steered into the Herald Canyon. A transitional unit between 412 and 390 cm appears to be a condensed interval with minimal local sedimentation. The underlying sediments, deposited in a shallow, river-proximal setting, exhibit a rather uniform bulk and clay mineral composition similar to mineral assemblages from surface sediment samples of the Chukchi Sea. Enhanced contributions from Pacific waters above 390 cm (< 8.5 cal ka BP) are reflected by elevated chlorite/illite and (chlorite + kaolinite)/illite ratios, and are anti-correlated with intervals of higher illite/smectite ratios, interpreted as periods of enhanced advection of shelf transformed waters originating from the East Siberian Sea. Clay mineral changes in the Holocene drift sediments are best explained by the interplay between two origins for bottom waters in the Herald Canyon and are consistent with modern oceanographic observations.
Central Asia and regional security
Authors: Somzhurek B.Zh , Yessengaliyeva A.M. , Medeubayeva Zh.M. , Makangali B.K.
Published: June 2018

This paper aims to analyze the politico-military cooperation among the Central Asian countries viewed as a key factor in ensuring the regional security. Today, the geopolitical tension in the surrounding regions, the worsening situation in Afghanistan, as well as intraregional socio-economic problems directly affect the security situation in Central Asia. In this regard, the question arises as to how well the Central Asian states are able to meet these challenges. The analysis of the situation in the region in the 1990s and at the beginning of the new century shows that attempts have been made to establish a regional security system based on military cooperation among Kazakhstan, Uzbekistan, Kyrgyzstan and Tajikistan. However, unregulated interstate relations in Central Asia, the lack of political will to cooperate with leaders of neighboring countries and the combination of external and internal threats have contributed to the creation of a regional security system based on the multilateral structures with the involvement of external actors.
Bookworms as information literacy? How Henri Lefebvre's spatial triad encouraged OCAD University to re-place the art library through site-interventions
Authors: Payne Daniel
Published: June 2018

Does the art library need re-placing? Using the commentary of an OCAD University faculty member concerning “a perception issue with the library and its use,” librarian Daniel Payne uses theorist Henri Lefebvre's spatial triad to decode, in general terms, undergraduate students’ understanding of libraries as articulated in the OCLC Perceptions of libraries surveys. In an attempt to re-align concepts of the library as place at OCAD University, an exhibition review interpretation of student site-interventions demonstrates how visual communication can offer more insightful “spatial practices” for both students and library staff. In the process, librarians were challenged to accommodate student creative voices that pushed both policy boundaries and comfort zones. Although a small-scale information literacy initiative in which no formal quantitative data was collected, the ability of having conceptual models of librarians interact and even clash with those of students helped realign both stakeholders’ understandings of libraries as complex spatial entities.
Design strategies to improve healthcare worker safety in biocontainment units: learning from ebola preparedness
Authors: DuBose Jennifer R. , Matić Zorana , Sala Maria Fernanda Wong , Mumma Joel M. , Kraft Colleen S. , Casanova Lisa M. , Erukunuakpor Kimberly , Durso Francis T. , Walsh Victoria L. , Shah Puja , Zimring Craig M. , Jacob Jesse T. ,   for the CDC Prevention Epicenters Program
Published: June 2018

Objective

To identify ways that the built environment may support or disrupt safe doffing of personal protective equipment (PPE) in biocontainment units (BCU).

Design

We observed interactions between healthcare workers (HCWs) and the built environment during 41 simulated PPE donning and doffing exercises.

Setting

The BCUs of 4 Ebola treatment facilities and 1 high-fidelity BCU mockup.

Participants

A total of 64 HCWs (41 doffing HCWs and 15 trained observers) participated in this study.

Results

In each facility, we observed how the physical environment influences risky behaviors by the HCW. The environmental design impeded communication between trained observers (TOs) and HCWs because of limited window size or visual obstructions with louvers, which allowed unobserved errors. The size and configuration of the doffing area impacted HCW adherence to protocol, and lack of clear demarcation of zones resulted in HCWs inadvertently leaving the doffing area and stepping back into the contaminated areas. Lack of standard location for items resulted in equipment and supplies frequently shifting positions. Finally, different solutions for maintaining balance while removing shoe covers (ie, chair, hand grips, and step stool) had variable success. We identified the 5 key requirements that doffing areas must achieve to support safe doffing of PPE, and we developed a matrix of proposed design strategies that can be implemented to meet those requirements.

Conclusions

Simple, low-cost environmental design interventions can provide structure to support and improve HCW safety in BCUs. These interventions should be implemented in both current and future BCUs.
Early post-embryonic development inEllipsostrenua(Trilobita, Cambrian, Sweden) and the developmental patterns in Ellipsocephaloidea
Authors: Laibl Lukáš , Cederström Peter , Ahlberg Per
Published: June 2018

This study documents the early post-embryonic developmental stages (protaspides and early meraspides) of the Cambrian trilobiteEllipsostrenua granulosa(Ahlberg, 1984) from the Gärdsjön Formation of Jämtland, Sweden. The early protaspid stage is characterized by a circular outline of the exoskeleton, two pairs of fixigenal spines, a short preglabellar field, a genal swelling, and prominent bacullae. The late protaspid stage differs only in having the trunk portion discernible. Early meraspid cranidia are sub-rectangular with prominent palpebral lobes, a wide anterior margin, a proportionally long anterior branch of the facial suture, and intergenal spines. Meraspid pygidia tentatively assigned to this species possess comparatively long macrospines. Small hypostomes associated withE.granulosabear at least four pairs of marginal spines. A comparison of the early developmental stages ofE.granulosawith some other species of Ellipsocephalidae and with species of the closely related Estaingiidae reveals several similarities. The conservative morphology of the early protaspid stage with only two pairs of fixigenal spines, the timing of the development of the trunk portion, and the presence of genal swellings and prominent bacullae could be phylogenetically informative. The range of size variation of the early protaspid stages in two families may be related either to taxonomical differences between Ellipsocephalidae and Estaingiidae, or to environmental differences in various paleogeographic settings.
Rational arc length
Authors: Gordon Russell A.
Published: June 2018

Finding an expression for the length of a curve is one of the simpler geometric applications of the integral. If f is a function with a continuous derivative, then the expression gives the length of the curve y = f (x) on an interval [a, b]. However, after writing out the integrand for familiar functions such as y = x2 and y = sin x, it quickly becomes apparent that, in general, finding an antiderivative is a challenge. Of course, a computer can give accurate approximations for the value of the integral for the length of a curve, but it would be nice to find the exact length rather than a decimal approximation. In his work on geometry (from 1637), Descartes stated that he believed it was not possible to determine the exact lengths of curves. However, just twenty years later, William Neile was able to find the length of arcs of semicubical parabolas (see Katz [1]). These curves have the form y = kx3/2 and are usually the first examples or exercises given to students since the resulting integral is very easy to compute. In this paper, we are going to examine this curve and other related curves and consider problems such as the following: find rational numbers a and b so that the length of the curve over the interval is an [a, b] integer. As we shall see, problems such as this provide a variety of opportunities for undergraduate students to explore some interesting mathematics arising from a few simple and accessible questions.
Can our coinage system be improved?
Authors: Shiu Peter
Published: June 2018

Some forty years ago my wife Christine and I considered the problems in this article, which involves a fair amount of computation. Computing facilities were not good then, so we considered instead the problems in [1] in which we showed, without using computers, that there were 64703 ways to make up £1 using coins; this was before the introduction of the 20p and £1 coins, and the ½p coin was in circulation. If Christine were still with us, this would have been another piece of joint work. I therefore dedicate this article to her memory.

The design of a coinage system depends on considerations we give to various criteria: for example, the number of denominations for the coins, the maximum number of coins required to deliver any given amount in a range, or the required number of coins averaged over the range; see also §3.
Determinants of parasite distribution in Arctic charr populations: catchment structure versus dispersal potential
Authors: Paterson R.A. , Knudsen R. , Blasco-Costa I. , Dunn A.M. , Hytterød S. , Hansen H.
Published: June 2018

Parasite distribution patterns in lotic catchments are driven by the combined influences of unidirectional water flow and the mobility of the most mobile host. However, the importance of such drivers in catchments dominated by lentic habitats are poorly understood. We examined parasite populations of Arctic charr Salvelinus alpinus from a series of linear-connected lakes in northern Norway to assess the generality of lotic-derived catchment-scale parasite assemblage patterns. Our results demonstrated that the abundance of most parasite taxa increased from the upper to lower catchment. Allogenic taxa (piscivorous birds as final host) were present throughout the entire catchment, whereas their autogenic counterparts (charr as final hosts) demonstrated restricted distributions, thus supporting the theory that the mobility of the most mobile host determines taxa-specific parasite distribution patterns. Overall, catchment-wide parasite abundance and distribution patterns in this lentic-dominated system were in accordance with those reported for lotic systems. Additionally, our study highlighted that upper catchment regions may be inadequate reservoirs to facilitate recolonization of parasite communities in the event of downstream environmental perturbations.
Adjective production by Russian-speaking children with developmental language disorder and Dutch–Russian simultaneous bilinguals: Disentangling the profiles
Authors: TRIBUSHININA ELENA , MAK MARLOES , DUBINKINA ELENA , MAK WILLEM M.
Published: June 2018

Bilingual children with reduced exposure to one or both languages may have language profiles that are apparently similar to those of children with developmental language disorder (DLD). Children with DLD receive enough input, but have difficulty using this input for acquisition due to processing deficits. The present investigation aims to determine aspects of adjective production that are differentially affected by reduced input (in bilingualism) and reduced intake (in DLD). Adjectives were elicited from Dutch–Russian simultaneous bilinguals with limited exposure to Russian and Russian-speaking monolinguals with and without DLD. An antonym elicitation task was used to assess the size of adjective vocabularies, and a degree task was employed to compare the preferences of the three groups in the use of morphological, lexical, and syntactic degree markers. The results revealed that adjective–noun agreement is affected to the same extent by both reduced input and reduced intake. The size of adjective lexicons is also negatively affected by both, but more so by reduced exposure. However, production of morphological degree markers and learning of semantic paradigms are areas of relative strength in which bilinguals outperform monolingual children with DLD. We suggest that reduced input might be counterbalanced by linguistic and cognitive advantages of bilingualism.
The Moving Location of Empire: Indirect Rule, International Law, and theBantu Educational Kinema Experiment
Authors: ESLAVA LUIS
Published: June 2018

Between 1935 and 1937, the International Missionary Council conducted theBantu Educational Kinema Experiment. The objective was to produce silent educational films and screen them to ‘native’ people via mobile cinemas in the British territories in East and Central Africa. Embracing the principle of ‘indirect rule’, and its role in training colonial subjects in economic self-sufficiency and political self-rule, as then advocated by leading colonial figures and the League of Nations, the films strived to capture ‘the native point of view’ through an ‘ethnographic sensitivity’ towards local cultures, concerns and needs. Hoping to educate the natives from ‘within’, they used local actors, familiar locations and pedagogical instructions that were believed to meet the target audience's cognitive capacity. Though in many respects unsuccessful, the experiment cemented the use of cinema in the late colonial project and, more importantly, embodied the clear move at the time towards a more dynamic and disaggregated, yet perhaps never fully post-imperial, international order. I argue in this article that theBantu Experimentis thus a telling instance through which to examine both the mobility and multiplicity of late imperial locations and the system of modern international administration that emerged during the interwar period. I suggest that this mobility and multiplicity continue to characterize the workings of today's international order, indicating the key role that ‘indirect rule’, as a silent principle of international law, still plays in its functioning today.
Successful retrieval of a migrated neonatal ductal stent and strategies to reposition the expanded stent in the duct
Authors: Pavithran Sreeja , Sivakumar Kothandam
Published: June 2018

A neonatal ductal stent deployed in a straight short conical duct on second postnatal day migrated owing to inadequate ductal constriction. It was successfully retrieved using a larger balloon and redeployed in the duct again. Intravenous indomethacin prevented further stent migration. This is the first report of successful transcatheter retrieval and repositioning of a migrated expanded neonatal ductal stent.
Sex consideration in diet–biomarker-related indices: a systematic review
Authors: Song Sihan , Kim Sejin , Lee Jung Eun
Published: June 2018

Objective

An index of biomarkers derived from dietary factors (diet–biomarker-related index) identifies foods and nutrients that encompass physiological potentials and provides scientific evidence for dietary patterns that increase the risk of disease associated with specific biomarkers. Although men and women have different dietary patterns and physiological characteristics, sex is not often considered when investigators develop a diet–biomarker-related index. We aimed to review whether epidemiological studies developed diet–biomarker-related indices in a sex-specific way.

Design

We systematically searched for epidemiological studies that developed diet–biomarker-related indices, including (i) biomarker prediction indices that include dietary factors as explanatory variables and (ii) dietary patterns to explain biomarker variations, in the PubMed and EMBASE databases. We qualitatively reviewed the sex consideration in index development.

Results

We identified seventy-nine studies that developed a diet–biomarker-related index. We found that fifty-four studies included both men and women. Of these fifty-four studies, twenty-nine (53·7 %) did not consider sex, eleven (20·3 %) included sex in the development model, seven (13·0 %) considered sex but did not include sex in the development model, and seven (13·0 %) derived a diet–biomarker-related index for men and women separately. A list of selected dietary factors that explained levels of biomarkers generally differed by sex in the studies that developed a diet–biomarker-related index in a sex-specific way.

Conclusions

Most studies that included both men and women did not develop the diet–biomarker-related index in a sex-specific way. Further research is needed to identify whether a sex-specific diet–biomarker-related index is more predictive of the disease of interest than an index without sex consideration.
An exploration of the attitudes and views of general practitioners on the use of video consultations in a primary healthcare setting: a qualitative pilot study
Authors: Randhawa Ratan S. , Chandan Joht S. , Thomas Tom , Singh Surinder
Published: June 2018

Background

In 2014, in the United Kingdom, the government made a commitment to spend £3.6 million on the introduction of Skype video calling consultations in general practice, however the efficacy of such technology has not yet been explored fully.

Aim

The study aimed to explore the views and attitudes of General Practitioners (GPs) towards video consultation in primary care; specifically, in three broad areas

∙

The benefits of video consultations to patients and healthcare professionals.

∙

Potential problems with video consultation and its implementation.

∙

The cost-effectiveness of video consultation in this setting.

Method

A convenience sample of the views of 12 general practitioners across two primary care centres in North London were identified using topic guide based semi-structured interviews. A thematic framework approach was used to analyse the data collected to isolate main and sub-themes.

Findings

Three main themes were identified

1.

Technology – GPs expressed concerns about the ability of patients to use technology, the availability of technology and the quality of technology available.

2.

Utility – encompassing GP’s ideas about the usefulness of video consultations to patients, practitioners and the doctor–patient relationship. GPs presented mixed views on the extent to which video consultation would be useful.

3.

Practicality – covering the views of GPs on implementation and effects on workload. GPs unanimously felt that it was not a practical substitute for face-to-face consultation. There were mixed feelings about it being used as an alternative to telephone consultation.

Conclusion

GPs did see potential benefits to using video consultations but also expressed concerns that need to be addressed if they are to have full confidence in the system. The views of those who are going to use video consultation as a means of increasing patient access are paramount if such tools are to be a core part of primary care.
The effect of maternal intake of sucrose or high-fructose corn syrup (HFCS)-55 during gestation and lactation on lipogenic gene expression in rat offspring at 3 and 12 weeks of age
Authors: Kaur H. , Toop C. R. , Muhlhausler B. S. , Gentili S.
Published: June 2018

Perinatal exposure to sucrose or high-fructose corn syrup-55 (HFCS-55) in rats has previously been associated with altered hepatic fat content and composition post-weaning, although the effects on hepatic metabolism are unknown. The current study aimed to determine the sex-specific effects of maternal consumption of sucrose or HFCS-55 on the expression of hepatic lipogenic genes in the offspring. Liver samples were collected from offspring of albino Wistar rats provided withad libitumaccess to either water (control), 10% sucrose or 10% HFCS-55 solution during pregnancy and lactation at 3 weeks (controln=16, sucrosen=22, HFCS-55n=16) and 12 weeks (controln=16, sucrosen=10, HFCS-55n=16) of age. Hepatic expression of the transcription factors such as carbohydrate response element-binding protein, sterol regulatory element-binding protein-1c and downstream genes was determined by quantitative real-time PCR. Sucrose-exposed offspring had higher hepatic SREBP-1c messenger RNA expression compared with control and HFCS-55 groups at both 3 weeks (P=0.01) and 12 weeks (P=0.03) of age. There were no differences in the expression of other hepatic lipogenic genes between groups at either 3 or 12 weeks. Thus, perinatal exposure to sucrose may be more detrimental to offspring hepatic metabolism compared with HFCS-55, independent of sex, and it will be important to evaluate the longer-term effects of perinatal sucrose exposure in future studies.
Challenges to the use of BECCS as a keystone technology in pursuit of 1.5⁰C
Authors: Gough Clair , Garcia-Freites Samira , Jones Christopher , Mander Sarah , Moore Brendan , Pereira Cristina , Röder Mirjam , Vaughan Naomi , Welfle Andrew
Published: June 2018

Non-technical summary

Biomass energy with carbon capture and storage (BECCS) is represented in many integrated assessment models as a keystone technology in delivering the Paris Agreement on climate change. This paper explores six key challenges in relation to large scale BECCS deployment and considers ways to address these challenges. Research needs to consider how BECCS fits in the context of other mitigation approaches, how it can be accommodated within existing policy drivers and goals, identify where it fits within the wider socioeconomic landscape, and ensure that genuine net negative emissions can be delivered on a global scale.
Behandlungsbereitschaft bei schizophrenen Störungen aufbauen: Was hilft?
Authors: Vauth Roland
Published: June 2018

Zusammenfassung. Mangelnde Behandlungsbereitschaft ist der gewichtigste Einzelfaktor für Rückfälle bei schizophrenen Störungen. Rückfälle ihrerseits wirken als kumulativ fortschreitende Recovery vernichtende neurotoxische Prozesse. In dieser Übersicht wird die Abkehr von klassischer einsichtsfördernder edukativer Intervention gefordert. Auf der Basis neuer Forschungsergebnisse wird ein heuristisches Vier-Ebenen-Modell zur individuell zugeschnittenen Verbesserung von Behandlungsbereitschaft vorgestellt: Ausgehend von (a) einer Motivationsdiagnostik (Bedingungs- und Problemanalyse von Adhärenz, Exploration behandlungsrelevanter Erwartungen) werden (b) Einstellungs- (individuelle Krankheits- und Behandlungserfahrungen sowie Folgeerwartungen), (c) Beziehungs- und (d) Verhaltensaspekte von Behandlungsbereitschaft als intentionales Verhalten durch differenzielle Strategien fokussiert (Anreize und Befähigungsaspekte).
CXCR1/Akt signaling activation induced by mesenchymal stem cell-derived IL-8 promotes osteosarcoma cell anoikis resistance and pulmonary metastasis
Authors: Du Lin , Han Xiu-guo , Tu Bing , Wang Min-qi , Qiao Han , Zhang Shu-hong , Fan Qi-ming , Tang Ting-ting
Published: June 2018

The loss of appropriate cell adhesion normally induces apoptosis via a process termed anoikis. The aim of this study was to investigate the effects of mesenchymal stem cells (MSCs) in the cancer microenvironment on the anoikis resistance and pulmonary metastasis of osteosarcoma (OS) cells, and to evaluate the critical role of the interleukin (IL)-8/C-X-C chemokine receptor (CXCR) 1/Akt-signaling pathway in these processes. Metastatic OS subtype cells, which did or did not interact with MSC-conditioned medium (MSC-CM) in vitro, were isolated from the pulmonary site and named Saos2-lung-M. Both MSC-CM and IL-8 treatment increased the anoikis resistance of Saos2 cells in vitro. Moreover, exogenous MSC-CM promoted the survival and metastasis of Saos2 cells in nude mice. Saos2-lung-M cells were more malignant and resistant to anoikis than parental cells. MSCs secreted IL-8, thereby protecting OS cells from anoikis. Blocking the IL-8/CXCR1/Akt pathway via CXCR1 knockdown inhibited the pulmonary metastasis of Saos2-lung-MSCs and prolonged the survival of tumor-bearing mice. In conclusion, MSCs enhanced OS cell resistance to anoikis and pulmonary metastasis via regulation of the IL-8/CXCR1/Akt pathway. These findings suggest that MSCs can “select for” OS cells with high metastatic potential in vivo, and highlight CXCR1 as a key target in the regulation of pulmonary metastasis of OS cells.
MicroRNA-378 is involved in hedgehog-driven epithelial-to-mesenchymal transition in hepatocytes of regenerating liver
Authors: Kim Jieun , Hyun Jeongeun , Wang Sihyung , Lee Chanbin , Jung Youngmi
Published: June 2018

Healthy livers have a remarkable regenerative capacity for reconstructing functional hepatic parenchyma after 70% partial hepatectomy (PH). Hepatocytes, usually quiescent in normal healthy livers, proliferate to compensate for hepatic loss after PH. However, the mechanism of hepatocyte involvement in liver regeneration remains unclear. Hedgehog (Hh) pathway plays an important role in tissue reconstitution by regulating epithelial-to-mesenchymal transition (EMT) in liver disease. MicroRNA (miRNA) is involved in cell proliferation and differentiation during embryonic development and carcinogenesis. It was recently reported that miR-378 inhibits transdifferentiation of hepatic stellate cells into myofibroblasts by suppressing Gli-Krüppel family member 3 (Gli3), the Hh-target gene. We hypothesized that miR-378 influences EMT in hepatocytes by interfering with Hh signaling during liver regeneration. As hepatocytes were highly proliferative after PH in mice, miR-378 and epithelial marker, Ppar-g or E-cadherin were downregulated, whereas both Hh activators, Smoothened (Smo) and Gli3, and the EMT-inducing genes, Tgfb, Snail and Vimentin, were upregulated in the regenerating livers and in hepatocytes isolated from them. Compared to cells with or without scramble miRNA, primary hepatocytes transfected with miR-378 inhibitor contained higher levels of Gli3 with increased expression of the EMT-promoting genes, Tgfb, Snail, Col1a1, and Vimentin, suggesting that miR-378 influenced EMT in hepatocytes. Smo-depleted hepatocytes isolated from PH livers of Smo-flox mice showed downregulation of EMT-promoting genes and Gli3, with upregulation of miR-378 and E-cadherin compared to Smo-expressing hepatocytes from PH liver. In addition, delivery hepatocyte-specific AAV8 viral vector bearing Cre recombinase into Smo-flox mice impeded EMT in Smo-suppressed hepatocytes of PH liver, indicating that Smo is critical for regulating hepatocyte EMT. Furthermore, the application of miR-378 mimic into mice with PH delayed liver regeneration by interrupting hepatocyte EMT. In conclusion, our results demonstrate that miR-378 is involved in hepatocyte EMT by regulating Hh signaling during liver regeneration.
Differential antiviral immunity to Japanese encephalitis virus in developing cortical organoids
Authors: Zhang Boya , He Yangzhige , Xu Yanpeng , Mo Fan , Mi Tingwei , Shen Qing Sunny , Li Chunfeng , Li Yali , Liu Jing , Wu Yihui , Chen Guilai , Zhu Wenliang , Qin Chengfeng , Hu Baoyang , Zhou Guomin
Published: June 2018

Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) poses a serious threat to the world’s public health yet without a cure. Certain JEV-infected neural cells express a subset of previously identified intrinsic antiviral interferon stimulated genes (ISGs), indicating brain cells retain autonomous antiviral immunity. However, whether this happens in composited brain remains unclear. Human pluripotent stem cell (hPSC)-derived organoids can model disorders caused by human endemic pathogens such as Zika virus, which may potentially address this question and facilitate the discovery of a cure for JE. We thus generated telencephalon organoid and infected them with JEV. We found JEV infection caused significant decline of cell proliferation and increase of cell death in brain organoid, resulting in smaller organoid spheres. JEV tended to infect astrocytes and neural progenitors, especially the population representing outer radial glial cells (oRGCs) of developing human brain. In addition, we revealed variable antiviral immunity in brain organoids of different stages of culture. In organoids of longer culture (older than 8 weeks), but not of early ones (less than 4 weeks), JEV infection caused typical activation of interferon signaling pathway. Preferential infection of oRGCs and differential antiviral response at various stages might explain the much more severe outcomes of JEV infection in the younger, which also provide clues to develop effective therapeutics of such diseases.
Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data
Authors: Campbell Kieran R , Yau Christopher
Published: June 2018

Pseudotime algorithms can be employed to extract latent temporal information from cross-sectional data sets allowing dynamic biological processes to be studied in situations where the collection of time series data is challenging or prohibitive. Computational techniques have arisen from single-cell ‘omics and cancer modelling where pseudotime can be used to learn about cellular differentiation or tumour progression. However, methods to date typically implicitly assume homogeneous genetic, phenotypic or environmental backgrounds, which becomes limiting as data sets grow in size and complexity. We describe a novel statistical framework that learns how pseudotime trajectories can be modulated through covariates that encode such factors. We apply this model to both single-cell and bulk gene expression data sets and show that the approach can recover known and novel covariate-pseudotime interaction effects. This hybrid regression-latent variable model framework extends pseudotemporal modelling from its most prevalent area of single cell genomics to wider applications.
Single-dose testosterone administration increases men’s preference for status goods
Authors: Nave G. , Nadler A. , Dubois D. , Zava D. , Camerer C. , Plassmann H.
Published: June 2018

In modern human cultures where social hierarchies are ubiquitous, people typically signal their hierarchical position through consumption of positional goods—goods that convey one’s social position, such as luxury products. Building on animal research and early correlational human studies linking the sex steroid hormone testosterone with hierarchical social interactions, we investigate the influence of testosterone on men’s preferences for positional goods. Using a placebo-controlled experiment (N = 243) to measure individuals’ desire for status brands and products, we find that administering testosterone increases men’s preference for status brands, compared to brands of similar perceived quality but lower perceived status. Furthermore, testosterone increases positive attitudes toward positional goods when they are described as status-enhancing, but not when they are described as power-enhancing or high in quality. Our results provide novel causal evidence for the biological roots of men’s preferences for status, bridging decades of animal behavioral studies with contemporary consumer research.
Breathlessness and sexual activity in older adults: the Australian Longitudinal Study of Ageing
Authors: Ekström Magnus , Johnson Miriam J. , Taylor Bridget , Luszcz Mary , Wohland Pia , Ferreira Diana H. , Currow David C.
Published: June 2018

Sexual activity is important to older adults (65 + ). Breathlessness affects about 25% of older adults but impact on sexual activity is unknown. We evaluated the relationships between breathlessness and sexual inactivity and self-reported health among older community-dwelling adults in the Australian Longitudinal Study of Ageing. Associations between self-reported breathlessness (hurrying on level ground or walking up a slight hill) at baseline, self-reported sexual activity, overall health and health compared to people of the same age were explored using logistic regression at baseline and 2 years, adjusted for potential confounders (age, sex, marital status, smoking status and co-morbidities). Of 798 participants (mean age 76.4 years [SD, 5.8] 65 to 103; 53% men, 73% married), 688 (86.2%) had 2-year follow-up data. People with breathlessness had higher prevalence and duration of sexual inactivity (77.7% vs. 65.6%; p < 0.001; 12 [IQR, 5–17] vs. 9.5 [IQR, 5−16] years; p = 0.043). Breathlessness was associated with more sexual inactivity, (adjusted OR 1.75; [95% CI] 1.24−2.45), worse health (adjusted OR 2.02; 1.53−2.67) and worse health compared to peers (adjusted OR 1.72; 1.25−2.38). Baseline breathlessness did not predict more sexual inactivity at 2 years. In conclusion, breathlessness contributes to sexual inactivity and worse perceived health in older adults, which calls for improved assessment and management.
Population genetic signatures of a climate change driven marine range extension
Authors: Ramos Jorge E. , Pecl Gretta T. , Moltschaniwskyj Natalie A. , Semmens Jayson M. , Souza Carla A. , Strugnell Jan M.
Published: June 2018

Shifts in species distribution, or ‘range shifts’, are one of the most commonly documented responses to ocean warming, with important consequences for the function and structure of ecosystems, and for socio-economic activities. Understanding the genetic signatures of range shifts can help build our knowledge of the capacity of species to establish and persist in colonised areas. Here, seven microsatellite loci were used to examine the population connectivity, genetic structure and diversity ofOctopus tetricus, which has extended its distribution several hundred kilometres polewards associated with the southwards extension of the warm East Australian Current along south-eastern Australia. The historical distribution and the range extension zones had significant genetic differences but levels of genetic diversity were comparable. The population in the range extension zone was sub-structured, contained relatively high levels of self-recruitment and was sourced by migrants from along the entire geographic distribution. Genetic bottlenecks and changes in population size were detected throughout the range extension axis. Persistent gene flow from throughout the historical zone and moderate genetic diversity may buffer the genetic bottlenecks and favour the range extension ofO. tetricus. These characteristics may aid adaptation, establishment, and long-term persistence of the population in the range extension zone.
Microstructures and mechanical properties of in situ TiC–β–Ti–Nb composites with ultrafine grains fabricated by high-pressure sintering
Authors: Liu Z. , Zhang D. C. , Gong L. J. , Lin J. G. , Wen Cuie
Published: June 2018

In this study, anin situβ–Ti–Nb composites reinforced with TiC particles with an ultrafine grain size were fabricated using a powder metallurgical (PM) method. The microstructures and mechanical properties of the composites were characterized using X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and compression tests. TiC particles were formed in the ball-milled powders after annealing at 600 °C due to a chemical reaction between stearic acid and titanium. Using high-pressure sintering (HPS) on an apparatus with six tungsten carbide anvils, a fully dense β–Ti–Nb composite reinforced with finein situTiC particles was obtained. The TiC particles exhibit particle sizes of ~500 nm, uniformly distributed in the composite matrix, which had grain sizes of ~600 nm. Thus, the TiC–β–Ti–Nb composite show very high compression yield strength and relatively high plasticity contributed by grain refinement and TiC particles strengthening. The composite with 45 vol.% TiC exhibited excellent mechanical properties, with a yield compressive strength of 1990 MPa and plastic strain of 9.12%. More over, a modified rule-of-mixture (ROM) was presented to describe the combined strengthening effect of grain refinement and TiC particles.
The effect of double counting, spin density, and Hund interaction in the different DFT+U functionals
Authors: Ryee Siheon , Han Myung Joon
Published: June 2018

A systematic comparative study has been performed to better understand DFT+U (density functional theory + U) method. We examine the effect of choosing different double counting and exchange-correlation functionals. The calculated energy distribution and the Hund-J dependence of potential profile for representative configurations clearly show the different behaviors of each DFT+U formalism. In particular, adopting spin-dependent exchange-correlation functionals likely leads to undesirable magnetic solution. Our analyses are further highlighted by real material examples ranging from insulating oxides (MnO and NiO) to metallic magnetic systems (SrRuO3 and BaFe2As2). The current work sheds new light on understanding DFT+U and provides a guideline to use the related methods.
Different novelties revealed by infants’ pupillary responses
Authors: Chen Yi-Chuan , Westermann Gert
Published: June 2018

To account for infants’ perceptual and cognitive development, the constructivist model proposes that learning a new object depends on the capability of processing simpler lower-level units, and then integrating these units into more complex higher-level units based on their relationships, such as regular co-occurrence. Here, we demonstrate that the process of associating visual and auditory attributes to build a new multisensory object representation is not only observed in the course of development, but also in the course of infants’ in-the-moment information processing. After a brief familiarization session of learning two pairs of novel audiovisual stimuli, 15-month-old infants showed two components in pupil dilations over time: A rapid dilation was observed when processing perceptually novel compared to familiar stimuli, and a slower dilation was observed when processing novel combinations of familiar stimuli. However, in 10-month-old infants, only the effect elicited by novel stimuli was observed. Our results therefore demonstrate that detecting perceptual novelty occurred earlier than detecting association novelty in infants’ information processing. These results support the view that infants perceive newly-learned objects by processing their constituent attributes and then integrating these components, as suggested by the constructivist model.
PROX1 is a transcriptional regulator of MMP14
Authors: Gramolelli Silvia , Cheng Jianpin , Martinez-Corral Ines , Vähä-Koskela Markus , Elbasani Endrit , Kaivanto Elisa , Rantanen Ville , Tuohinto Krista , Hautaniemi Sampsa , Bower Mark , Haglund Caj , Alitalo Kari , Mäkinen Taija , Petrova Tatiana V. , Lehti Kaisa , Ojala Päivi M.
Published: June 2018

The transcription factor PROX1 is essential for development and cell fate specification. Its function in cancer is context-dependent since PROX1 has been shown to play both oncogenic and tumour suppressive roles. Here, we show that PROX1 suppresses the transcription of MMP14, a metalloprotease involved in angiogenesis and cancer invasion, by binding and suppressing the activity of MMP14 promoter. Prox1 deletion in murine dermal lymphatic vessels in vivo and in human LECs increased MMP14 expression. In a hepatocellular carcinoma cell line expressing high endogenous levels of PROX1, its silencing increased both MMP14 expression and MMP14-dependent invasion in 3D. Moreover, PROX1 ectopic expression reduced the MMP14-dependent 3D invasiveness of breast cancer cells and angiogenic sprouting of blood endothelial cells in conjunction with MMP14 suppression. Our study uncovers a new transcriptional regulatory mechanism of cancer cell invasion and endothelial cell specification.