bluuebunny/crossref_metadata_2025 huggingface dataset:
A clinician’s perspective on co-developing and co-implementing a digital tumor board solution
Authors: Hammer Richard D , Prime Matthew S
Published: January 2020

Healthcare has entered the information age. This will deliver huge opportunities for healthcare providers to deliver more individualized treatments for patients, and as such improve outcomes. Nowhere is the prospect greater than in cancer care. Healthcare providers now need to manage the challenge of how to best capture, interpret and exploit insights from real-world clinical data. A significant aspect of cancer care is the challenge of preparing and conducting tumor boards. Currently, data are distributed across multiple systems and cannot be easily aggregated or integrated. In recognition that no suitable solution existed, the University of Missouri School of Medicine, in partnership with Roche, have co-developed and co-implemented a digital tumor board solution. This article describes the development process and the enablers and barriers for adoption from a clinician’s perspective. In addition, it reflects on some of the key factors for success and some of the future opportunities.
Prediction of esterification rate constants for secondary alkan-2-ols based on one- and two-parameter Taft equations
Authors: Vojtko Ján , Durdiak Jaroslav , Lukáčová-Chomisteková Zuzana , Tomčík Peter
Published: January 2020

Equilibrium constants and reaction rate constants for the esterification of secondary alkan-2-ols with acetic acid were measured at 60°C in 1,4-dioxane. Taft coefficients, as single parameter (without inductive effects), and two-parameter correlation (including inductive and steric effects), of the measurements were used for the prediction of esterification rate constants for secondary alkan-2-ols with monocarboxylic acids. For this prediction, previously observed results of linear correlation of rate constants for the esterification of propan-1-ol with monocarboxylic acids measured under identical experimental conditions were applied. Two parameter Taft equations for the correlation of secondary alkan-2-ols and for monocarboxylic acids were combined, resulting in an overall correlation equation usable for the prediction of reaction rates for secondary alkan-2-ols with any monocarboxylic acid. This equation was experimentally verified for the esterification of three randomly chosen alkan-2-ols with three randomly chosen monocarboxylic acids.
Banana fibre-based structures for acoustic insulation and absorption
Authors: Singh Vikas Kumar , Mukhopadhyay Samrat
Published: January 2020

In this article, acoustic properties of fibrous structures made of banana fibres have been studied. Impedance tube method was used for the testing of acoustic barrier properties. An attempt to counter low-frequency noise as well as enhancing transmission loss characteristics of fibrous structures was carried out. The effect of different parameters and arrangement of structures with respect to sound source on sound absorption as well as sound insulation of these structures has been reported. A unique structure has been developed with varying compactness throughout its thickness, and it was observed that the areal density of samples, compactness of structure and arrangement of structures can be utilised to customise its sound barrier and absorption behaviour. Maximum noise reduction coefficient of 0.78 and transmission loss up to 23 dB was observed for samples with gradient in compactness. Acoustic performance of the structure developed as a part of this research is at par or better than acoustic materials reported in literature and other commercial products.
Urban Renewal through the Lens of Unsuccessful Projects: The Pralltown Neighborhood of Lexington, Kentucky
Authors: Appler Douglas R. , Riesenweber Julie
Published: January 2020

This article examines the Pralltown neighborhood of Lexington, Kentucky, and the concept of the “unsuccessful” urban renewal project. Pralltown was created for and by freed slaves following the Civil War, and for virtually its entire existence, it has endured public policy efforts to change the neighborhood in order to address its real or perceived failings. By framing the two urban renewal projects proposed for Pralltown as points in a long line of reform efforts, this article draws attention to the persistent need for residents of postbellum African American neighborhoods to devote time and energy countering policies of marginalization.
Beyond competencies and silos: Embedding graduate capabilities for a multicultural globalizing world across the mainstream curriculum
Authors: Killick David
Published: January 2020

This article presents a critical analysis of key elements within the conference question as the basis for proposals for an inclusive and systematic approach to the development of mainstream disciplinary higher education curricula designed to meet the needs of students and societies in a multicultural globalizing world. The critical analysis considers key objectives, understandings and limitations of GII ‘competencies’, how we conceptualize ‘students’ within a globalizing higher education, how ‘effective’ strategies might be framed, and how internationalization abroad and at home might be re-envisioned in the era of the post-national university. The article illustrates how this critical analysis points to the need to embed internationalization efforts, and their success indicators, within the mainstream curriculum across the disciplines.
Lost in Translation: The Construct Representation of Character Virtues
Authors: Ng Vincent , Tay Louis
Published: January 2020

A seemingly universal lesson is that anything taken to its extreme is detrimental. Indeed, there has been growing interest in testing this idea within psychology. These studies have often been framed in terms of Aristotle’s doctrine of the golden mean or the idea that virtue lies between the vices of deficiency and excess. Recent explicit reviews of this hypothesis in the psychological literature have led to the paradoxical conclusion that one can have too much virtue (i.e., the too-much-of-a-good-thing effect) despite virtue being identified by the golden mean. We argue in this article that this conclusion is due to a reductionist account of virtues in psychology and the resultant measurement of virtues as general dispositional tendencies in behavior. We review philosophical theory on the golden mean to show that the relationship between virtue and relevant behavior is fundamentally about situation-specific optimality. Using schematic models, we contrast the former measurement approach against the latter to explain the too-much-of-a-good-thing effect and further demonstrate why virtues cannot be properly measured as general tendencies in behavior. We conclude with methodological implications of our theory-informed approach to virtue measurement for research design, evaluation, and conceptualization.
Influences of Experience and Visual Cues of Virtual Arm on Distance Perception
Authors: Yang Zhen , Shi Jinlei , Xiao Yi , Yuan Xiaojian , Wang Duming , Li Hongting , Xu Weidan
Published: January 2020

Egocentric distance perception refers to the perception of distance from a target to a perceiver, which is an important component of visual space perception. It is important to activities in virtual environments and influenced by several factors, such as action capacities and visual cues. However, few studies have investigated such aspects. Hence, Experiments 1 and 2 investigated the effect of using experience and visual cues, respectively, of virtual arms on egocentric distance perception in near and far spaces at equal, prolonged, and shortened lengths of a virtual arm. Results revealed that using experience and visual cues of the virtual arm had a significant effect on egocentric distance perception when the length of virtual arm was equal to the real arm and prolonged but not when shortened. The egocentric distance perception on the conditions of having using experience and virtual arm was most precise. The findings provide implications for the design and implementation of virtual body self-representation in virtual environments.
Understanding learner participation at scale: How and why
Authors: Haniya Samaa , Paquette Luc
Published: January 2020

Understanding learner participation is essential to any learning environment to enhance teaching and learning, especially in large scale digital spaces, such as massive open online courses. However, there is a lack of research to fully capture the dynamic nature of massive open online courses and the different ways learners participate in these emerging massive e-learning ecologies. To fill in the research gap, this paper attempted to investigate the relationship between how learners choose to participate in a massive open online course, their initial motivation for learning, and the barriers they faced throughout the course. This was achieved through a combination of data-driven clustering approaches—to identify patterns of learner participation—and qualitative analysis of survey data—to better understand the learners’ motivation and the barriers they faced during the course. Through this study we show how, within the context of a Coursera massive open online course offered by the University of Illinois, learners with varied patterns of participation (Advanced, Balanced, Early, Limited, and Delayed Participation) reported similar motivations and barriers, but described differences in how their participation was impacted by those factors. These findings are significant to gain insights about learners’ needs which in turn serve as the basis to innovate more adaptive and personalized learning experiences and thus advance learning in these large scale environments.
Leader of the free world or pioneer in democracy’s decline? Examining the democratic deconsolidation hypothesis on the mass level in East and West Germany
Authors: Wuttke Alexander , Gavras Konstantin , Schoen Harald
Published: January 2020

A stable democratic society is unthinkable if its citizens oppose the principles of self-governance. Yet, recent studies suggest that citizens of consolidated democracies increasingly turn their backs on this system of government. Nonetheless, the evidence is mixed and mainly focuses on attitudes toward democracy as a generic concept, while less is known about mass support for the liberal variant of democracy. This study contributes to this debate by 1) analyzing citizen attitudes toward core elements of liberal democracy in addition to direct measures of democratic support and 2) separating age, period, and cohort effects. We investigated the development of democracy-related attitudes in probability-based samples collected in Germany from 1982 through 2018. Although Germany’s Eastern region can be considered a likely case of democratic deconsolidation, the analysis did not provide evidence for a decline in support of democracy as a generic concept or its fundamental principles in West or East Germany.
Inheritance and Dissemination of Cultural Collective Memory: An Analysis of a Traditional Festival
Authors: Liao Zhenjie , Dai Guangquan
Published: January 2020

The traditional festivals in urban societies constitute public memory and are essential for constructing a sense of locality. Therefore, it is of great significance to study the collective memory of traditional urban festivals to promote the sense of locality. In this research, the Guangzhou Winter Jasmine Flower Market was selected as a case study. By examining the historical literature, and conducting field research and interviews, the collective memory of the Guangzhou Winter Jasmine Flower Market was classified and sorted from the perspective of the categories of collective memory. A collective memory graph of the Guangzhou Winter Jasmine Flower Market was constructed using Gephi complex network analysis software. By examining the rich memory content and hierarchical structure of the Guangzhou Winter Jasmine Flower Market, we can better understand and foster the function of traditional urban festivals as collective memory and achieve the sustainability of collective memory.
A configurational approach to the impact of trade fairs and trade missions on firm export activity
Authors: Monreal-Pérez Joaquín , Geldres-Weiss Valeska V.
Published: January 2020

Export promotion programmes (EPPs) are argued to support firms’ export activity. However, the empirical evidence for the link between EPPs and exporting is inconclusive. We argue and demonstrate by using fuzzy set methods one can uncover configurations that combine the firm’s participation in specific EPPs, namely trade missions and fairs, together with certain firm-specific characteristics. We base our analysis on a sample of 641 Chilean exporters (2010-2015), and show regression results are mostly insignificant and with a much lower model fit level compared with our fuzzy set analysis. Our main findings illustrate that small, young and non-export-experienced firms gain the most from trade fairs and trade missions, which supports the notion that EPPs provide the information required in export markets.

JEL CLASSIFICATION M160; M380; C120
A contingency view of alliance management capabilities for innovation in the biotech industry
Authors: Cabello-Medina Carmen , Carmona-Lavado Antonio , Cuevas-Rodriguez Gloria
Published: January 2020

In this research, we analyze the influence of two alliance management capabilities, coordination and interorganizational learning, on the performance of alliances for innovation. By adopting a contingency view, we explore whether the effectiveness of these capabilities depends on certain features of the alliance portfolio configuration (partner and geographic diversity). Based on a sample of Spanish companies belonging to the five leading biotech clusters, our results demonstrate that alliance management capabilities are not equally effective across different contexts. Alliance coordination capabilities become more effective when partner diversity is low and geographic diversity is high. By contrast, interorganizational learning capabilities have a positive effect on alliance portfolio performance when partner diversity is high and geographic diversity is low. These results also have useful implications for managers involved in alliances for innovation, who can direct the organizational efforts towards the most effective alliance capabilities, depending on the features of their alliance portfolio.

JEL CLASSIFICATION M19
The domestic geopolitics of racial capitalism
Authors: Vasudevan Pavithra , Smith Sara
Published: January 2020

In this paper, we analyze the racialized burden of toxicity in the US as a case study of what we call “domestic geopolitics.” Drawing on the case studies of Badin, North Carolina, and Flint, Michigan, we argue that maintaining life in conditions of racialized toxicity is not only a matter of survival, but also a geopolitical praxis. We propose the term domestic geopolitics to describe a reconceived feminist geopolitics integrating an analysis of Black geographies as a domestic form of colonialism, with an expanded understanding of domesticity as political work. We develop the domestic geopolitics framework based on the dual meaning of domestic: the inward facing geopolitics of racialization and the resistance embodied in domestic labors of maintaining life, home, and community. Drawing on Black feminist scholars, we describe three categories of social reproductive labor in conditions of racialized toxicity: the labor of keeping wake, the labor of tactical expertise, and the labor of revolutionary mothering. We argue that Black survival struggles exemplify a domestic geopolitics of everyday warfare against racial capitalism’s onslaught.
The detection of canine anti-sperm antibody following parenteral immunization of bitches against homogenized whole sperm
Authors: Esmailnejad Atefeh , Nikahval Behrooz , Mogheiseh Asghar , Karampour Romina , Karami Sanaz
Published: January 2020

Backgrounds

The development of a canine-specific method of immunocontraception is one of the non-invasive controlling strategies for humanely decreasing the dog population. This study was aimed to investigate the potential of whole sperm in stimulating the immune system and producing specific anti-sperm antibodies (ASAs) in female dogs. Mature, mixed-breed bitches were subcutaneously immunized with high (200 × 106cells/mL) and low (100 × 106cells/mL) doses of sperm vaccine, emulsified with Freund’s adjuvants. Booster immunizations were given at weeks 1, 2, 4, and 6, and serum samples were collected at days 0, 14, 28, 42, 63, and 84 prior to each immunization. Reproductive tract samples, including vaginal and uterine lavages, were also collected by flushing each section with sterile PBS at the end of the experiment. Canine anti-sperm antibody titer and specificity in sera and genital secretions were measured using an enzyme-linked immunosorbent assay technique.

Results

Specific anti-sperm antibodies were detected in the serum of both high and low dose groups and were significantly higher than those observed in the controls. A high dose of sperm induced elevated immune responses over the low dose antigen. Immunization with a high dose of sperm increased the level of ASAs in the uterine secretions and vaginal secretions significantly. Higher ASAs were observed to have transduced to the uterine lumen compared to the vagina.

Conclusions

Based on the results obtained in this study, parenteral immunization with whole sperm can induce a high level of specific antibodies in the serum and genital secretions of female dogs and the response would be dose-dependent.
A methodological quality assessment of systematic reviews and meta-analyses of antidepressants effect on low back pain using updated AMSTAR
Authors: Panahi Mohammad Hossein , Mohseni Mostafa , Bidhendi Yarandi Razieh , Ramezani Tehrani Fahimeh
Published: January 2020

Background

Antidepressants are prescribed widely to manage low back pain. There are a number of systematic reviews and meta-analyses which have investigated the efficacy of the treatments, while the methodological quality of them has not been assessed yet. This study aims to evaluate the methodological quality of the systematic reviews and meta-analyses investigating the effect of antidepressants on low back pain.

Methods

A systematic search was conducted in PubMed, EMBASE, Medline, and Cochrane Library databases up to November 2018. The 16-item Assessment of Multiple Systematic Reviews (AMSTAR2) scale was used to assess the methodological quality of the studies. Systematic reviews and meta-analyses of the Antidepressants treatment effects on low back pain published in English language were included. There was no limitation on the type of Antidepressants drugs, clinical setting, and study population, while non-systematical reviews and qualitative and narrative reviews were excluded.

Results

A total of 25 systematic reviews and meta-analyses were evaluated; the studies were reported between 1992 and 2017. Obtained results from AMSTAR2 showed that 11 (44%), 9 (36%) and 5 (20%) of the included studies had high, moderate and low qualities, respectively. 13(52%) of studies assessed risk of bias and 2(20%) of meta analyses considered publication bias. Also, 16 (64%) of the included reviews provided a satisfactory explanation for any heterogeneity observed in the results.

Conclusions

Although the trend of publishing high quality papers in ADs effect on LBP increased recently, performing more high-quality SRs and MAs in this field with precise subgroups of the type of pains, the class of drugs and their dosages may give clear and more reliable evidence to help clinicians and policymakers.
A 2-year point-prevalence surveillance of healthcare-associated infections and antimicrobial use in Ferrara University Hospital, Italy
Authors: Antonioli Paola , Bolognesi Niccolò , Valpiani Giorgia , Morotti Chiara , Bernardini Daniele , Bravi Francesca , Di Ruscio Eugenio , Stefanati Armando , Gabutti Giovanni
Published: January 2020

Background

Healthcare-Associated Infections (HAIs) represent one of the leading issues to patient safety as well as a significant economic burden. Similarly, Antimicrobial Use (AMU) and Resistance (AMR) represent a growing threat to global public health and the sustainability of healthcare services.

Methods

A Point Prevalence Survey (PPS) following the 2016 ECDC protocol for HAI prevalence and AMU was conducted at Ferrara University Hospital (FUH). Data were collected by a team of trained independent surveyors in 2016 and 2018. Risk factors independently associated with HAI were assessed by a multivariate logistic regression model.

Results

Of the 1102 patients surveyed, 115 (10.4%) had an active HAI and 487 (44.2%) were on at least 1 systemic antimicrobial agent. Factors independently associated with increased HAI risk were a “Rapidly Fatal” McCabe score (expected fatal outcome within 1 year), presence of medical devices (PVC, CVC, indwelling urinary catheter or mechanically assisted ventilation) and a length of hospital stay of at least 1 week. The most frequent types of HAI were pneumonia, bloodstream infections, and urinary tract infections. Antimicrobial resistance to third-generation cephalosporins was observed in about 60% of Enterobacteriaceae.

Conclusions

The survey reports a high prevalence of HAI and AMU in FUH. Repeated PPSs are useful to control HAIs and AMU in large acute-care hospitals, highlighting the main problematic factors and allowing planning for improvement actions.
Breastfeeding practices 2008–2009 among Chinese mothers living in Ireland: a mixed methods study
Authors: Zhou Qianling , Younger Katherine M. , Cassidy Tanya M. , Wang Wenyi , Kearney John M.
Published: January 2020

Background

Migration to another country has a potential influence on breastfeeding practices. A significant difference in breastfeeding rates between Irish nationals and non-nationals has been reported. This study was conducted to explore breastfeeding practices of the Chinese in Ireland, one of the largest Irish ethnic groups, and to explore the influence of living in Ireland on breastfeeding practices. This is the first and the only migration study so far on breastfeeding practices among the Chinese in Ireland.

Methods

A sequential explanatory mixed methods approach was adopted. The first phase was a cross-sectional self-administered retrospective mailed survey, to explore breastfeeding practices and determinants of breastfeeding among a convenience sample of Chinese mothers living in Ireland (n = 322). Recruitment was conducted in the Dublin metropolitan area, with the application of the snowball technique to increase sample size. The second phase consisted of seven semi-structured focus groups (n = 33) conducted in Dublin, to explore the influence of living in Ireland on breastfeeding among Chinese mothers who had given birth in Ireland. Quantitative data were analyzed by univariate and multivariate logistic regression analyses, and informed the qualitative data collection. Qualitative data were analyzed by thematic content analyses, to explain and enrich the qualitative results.

Results

The breastfeeding initiation rate among Chinese immigrants to Ireland who gave birth in Ireland (CMI) (75.6%) was high and close to that of Chinese immigrant mothers who gave birth in China (CMC) (87.2%). However, giving birth in Ireland was independently associated with a shorter duration of breastfeeding (< 4 months) among Chinese immigrants. Qualitative results explained that a shorter breastfeeding duration among CMI than that of CMC was mainly due to cultural conflicts, a lack of family support, language barriers, immigrants’ low socioeconomic status, and mothers’ preference for infant formula on the Irish market. Both quantitative and qualitative data revealed a strong cultural belief in the efficacy of the traditional Chinese postpartum diet for breast milk production for both CMC and CMI. Antenatal feeding intention was a strong determinant for breastfeeding initiation and duration among CMI.

Conclusion

Migration to Ireland was found to be associated with a shorter duration of breastfeeding of the Chinese. Culturally sensitive and language-specific education and support of breastfeeding is needed for the Chinese mothers living in Ireland. The mixed methods design presented here might serve as a template for future migration research on breastfeeding.
The impact of mal-angulated femoral rotational osteotomies on mechanical leg axis: a computer simulation model
Authors: Jud Lukas , Vlachopoulos Lazaros , Häller Thomas V. , Fucentese Sandro F. , Rahm Stefan , Zingg Patrick O.
Published: January 2020

Background

Subtrochanteric or supracondylar femoral rotational osteotomies are established surgical treatments for femoral rotational deformities. Unintended change of the mechanical leg axis is an identified problem. Different attempts exist to plan a correct osteotomy plane, but implementation of the preoperative planning into the surgical situation can be challenging. Goal of this study was to identify the critical threshold of mal-angulation of the osteotomy plane and of femoral rotation that leads to a relevant deviation of the postoperative mechanical leg axis using a computer simulation approach.

Methods

Three-dimensional (3D) surface models of the lower extremity of two patients (Model 1: 42° femoral antetorsion; Model 2: 6° femoral retrotorsion) were generated from computed tomography data. First, baseline subtrochanteric and supracondylar rotational osteotomies, perpendicular to the femoral mechanical axis were simulated. Afterwards, mal-angulated osteotomies in sagittal and frontal plane followed by different degrees of rotation were simulated and frontal mechanical axis was analyzed.

Results

400 mal-angulated osteotomies have been simulated. Mal-angulation of ±30° with 30° rotation showed maximum deviation from preoperative mechanical axis in subtrochanteric osteotomies (4.0° ± 0.4°) and in supracondylar osteotomies (12.4° ± 0.8°). Minimal mal-angulation of 15° in sagittal plane in subtrochanteric osteotomies and mal-angulation of 10° in sagittal plane in supracondylar osteotomies altered the mechanical axis by > 2°. Mal-angulation in sagittal plane showed higher deviations of the mechanical axis (up to 12.4° ± 0.8°), than in frontal plane mal-angulation (up to 4.0° ± 1.9°).

Conclusion

A femoral rotational osteotomy, perpendicular to the femoral mechanical axis, has no considerable influence on the mechanical leg axis. However, mal-angulation of femoral rotational osteotomies showed relevant changes of the mechanical leg axis. In supracondylar respectively subtrochanteric procedures, mal-angulation of only 10° in combination with already 15° of femoral rotation respectively mal-angulation of 15° in combination with 30° of femoral rotation, can lead to a relevant postoperative mechanical leg axis deviation of more than 2°, wherefore these patients probably would benefit from the use of navigation aids.
Germacrone exerts anti-cancer effects on gastric cancer through induction of cell cycle arrest and promotion of apoptosis
Authors: Wu Lei , Wang Lifen , Tian Xiangguo , Zhang Junyong , Feng Hua
Published: January 2020

Background

Germacrone is one of the natural bioactive compounds found inRhizoma curcumaessential oils. In this study, the potential anti-cancer effect of germacrone in gastric cancer cell line BGC823 was investigated.

Methods

The cell viability and proliferative activity were assessed, and cell cycle analysis was also performed. Hoechst 33258 and Annexin V/PI double staining was used for detection of cell apoptosis. Protein profiles of cell cycle-related and apoptosis-related proteins were assessed.

Results

MTT assay revealed that germacrone had marked cytotoxicity on BGC823 cells. Germacrone induced cell cycle arrest in the G2/M phase via remarkably decreased expression levels of cyclin B1, cdc 2 and cdc 25c. In addition, the treatment with germacrone induced caspase-3 activity and PARP cleavage. These findings demonstrated the effects of germacrone on inhibiting cell proliferation through induction of G2/M phase cell cycle arrest and promotion of cell apoptosis. It also indicated that germacrone functioned through modulations of cell cycle-associated protein expression and mitochondria-mediated apoptosis.

Conclusion

These findings will be valuable as the molecular basis for the germacrone-mediated anti-cancer effect against gastric cancer.
Communication skills training for physicians improves health literacy and medical outcomes among patients with hypertension: a randomized controlled trial
Authors: Tavakoly Sany Seyedeh Belin , Behzhad Fatemeh , Ferns Gordon , Peyman Nooshin
Published: January 2020

Background

Improving the training of physicians about communication skills and patient health literacy (HL) is a major priority that remains an open question. We aimed to examine the effectiveness of communication skills training for physicians on the hypertension outcomes and the health literacy skills, self-efficacy and medication adherence in patients with uncontrolled blood pressure (BP).

Methods

A randomized, controlled trial method was conducted on 240 hypertensive patients and 35 physicians presenting to healthcare clinics in the Mashhad, Iran, from 2013 to 2014. Using stratified blocking with block sizes of 4 and 6, eligible patients with uncontrolled blood pressure were randomly allocated to the intervention and control groups. Physicians in the intervention group received educational training over 3 sessions of Focus –Group Discussion and 2 workshops. The control group received the routine care. The primary outcome was a reduction in systolic and diastolic BP from baseline to 6 months. The secondary outcome was promoting HL skills in hypertensive patients. Data were analyzed using the regression model and bivariate tests.

Results

After the physician communication training, there was a significant improvement in physicians-patient communication skills, hypertension outcomes, medication adherence, and self-efficacy among the patients being managed by the physicians receiving training, compared to the control group.

Conclusion

The educational intervention leads to better BP control; it may have been sufficient training of physicians change to impact counseling, HL and self-efficacy and adherence. The quality of physician-patient communication is an important modifiable element of medical communication that may influences health outcomes in hypertensive Iranian patients.

Trial registration

Iranian Registry of Clinical Trials (IRCT), IRCT20160710028863N24. Registered April 4, 2018 [retrospectively registered].
Control of glutamate release by complexes of adenosine and cannabinoid receptors
Authors: Köfalvi Attila , Moreno Estefanía , Cordomí Arnau , Cai Ning-Sheng , Fernández-Dueñas Victor , Ferreira Samira G. , Guixà-González Ramón , Sánchez-Soto Marta , Yano Hideaki , Casadó-Anguera Verònica , Cunha Rodrigo A. , Sebastião Ana Maria , Ciruela Francisco , Pardo Leonardo , Casadó Vicent , Ferré Sergi
Published: January 2020

Background

It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 receptors (CB1R) localized in glutamatergic nerve terminals mediate the integration of adenosine and endocannabinoid signaling involved in the modulation of striatal excitatory neurotransmission. Previous studies have demonstrated the existence of A2AR-CB1R heteromers in artificial cell systems. A dependence of A2AR signaling for the Gi protein-mediated CB1R signaling was described as one of its main biochemical characteristics. However, recent studies have questioned the localization of functionally significant A2AR-CB1R heteromers in striatal glutamatergic terminals.

Results

Using a peptide-interfering approach combined with biophysical and biochemical techniques in mammalian transfected cells and computational modeling, we could establish a tetrameric quaternary structure of the A2AR-CB1R heterotetramer. This quaternary structure was different to the also tetrameric structure of heteromers of A2AR with adenosine A1 receptors or dopamine D2 receptors, with different heteromeric or homomeric interfaces. The specific quaternary structure of the A2A-CB1R, which depended on intermolecular interactions involving the long C-terminus of the A2AR, determined a significant A2AR and Gs protein-mediated constitutive activation of adenylyl cyclase. Using heteromer-interfering peptides in experiments with striatal glutamatergic terminals, we could then demonstrate the presence of functionally significant A2AR-CB1R heteromers with the same biochemical characteristics of those studied in mammalian transfected cells. First, either an A2AR agonist or an A2AR antagonist allosterically counteracted Gi-mediated CB1R agonist-induced inhibition of depolarization-induced glutamate release. Second, co-application of both an A2AR agonist and an antagonist cancelled each other effects. Finally, a CB1R agonist inhibited glutamate release dependent on a constitutive activation of A2AR by a canonical Gs-Gi antagonistic interaction at the adenylyl cyclase level.

Conclusions

We demonstrate that the well-established cannabinoid-induced inhibition of striatal glutamate release can mostly be explained by a CB1R-mediated counteraction of the A2AR-mediated constitutive activation of adenylyl cyclase in the A2AR-CB1R heteromer.
SP1 induced long non-coding RNA LINC00958 overexpression facilitate cell proliferation, migration and invasion in lung adenocarcinoma via mediating miR-625-5p/CPSF7 axis
Authors: Yang Longhai , Li Lili , Zhou Zizi , Liu Yi , Sun Jinyuan , Zhang Xiaoming , Pan Huiyu , Liu Song
Published: January 2020

Background

Increasing evidences have underlined the importance of long non-coding RNAs (lncRNAs) in human malignancies. LINC00958 has been found involved in some cancers. However, the underlying mechanical performance of LINC00958 in lung adenocarcinoma (LAD) has not been explored yet.

Methods

The expression of relevant mRNA and protein were measured by qRT-PCR and western blot assays. EdU, colony formation, TUNEL and transwell assays were performed to investigate the function of LINC00958 on LAD progression. Luciferase reporter, RNA pull down and RIP assays were conducted to investigate the molecular mechanism of relevant RNAs.

Results

LINC00958 was found notably overexpressed in LAD, which was associated with the stimulation of its promoter activity induced by SP1. LINC00958 depletion dramatically inhibited LAD cell proliferation, migration and invasion capacities by acting as a miR-625-5p sponge. MiR-625-5p curbed LAD progression via targeting CPSF7 and down-regulating its expression. Mechanically, LINC00958 was identified as a competing endogenous RNA (ceRNA) and positively regulated the expression of CPSF7 via sponging miR-625-5p.

Conclusions

LINC00958 might drive LAD progression via mediating miR-625-5p/CPSF7 axis, indicating the potential of targeting LINC00958 for the treatment of LAD.
Health gains and financial risk protection afforded by public financing of selected malaria interventions in Ethiopia: an extended cost-effectiveness analysis
Authors: Assebe Lelisa Fekadu , Kwete Xiaoxiao Jiang , Wang Dan , Liu Lingrui , Norheim Ole Frithjof , Jbaily Abdulrahman , Verguet Stéphane , Johansson Kjell Arne , Tolla Mieraf Taddesse
Published: January 2020

Background

Malaria is a public health burden and a major cause for morbidity and mortality in Ethiopia. Malaria also places a substantial financial burden on families and Ethiopia’s national economy. Economic evaluations, with evidence on equity and financial risk protection (FRP), are therefore essential to support decision-making for policymakers to identify best buys amongst possible malaria interventions. The aim of this study is to estimate the expected health and FRP benefits of universal public financing of key malaria interventions in Ethiopia.

Methods

Using extended cost-effectiveness analysis (ECEA), the potential health and FRP benefits were estimated, and their distributions across socio-economic groups, of publicly financing a 10% coverage increase in artemisinin-based combination therapy (ACT), long-lasting insecticide-treated bed nets (LLIN), indoor residual spraying (IRS), and malaria vaccine (hypothetical).

Results

ACT, LLIN, IRS, and vaccine would avert 358, 188, 107 and 38 deaths, respectively, each year at a net government cost of $5.7, 16.5, 32.6, and 5.1 million, respectively. The annual cost of implementing IRS would be two times higher than that of the LLIN interventions, and would be the main driver of the total costs. The averted deaths would be mainly concentrated in the poorest two income quintiles. The four interventions would eliminate about $4,627,800 of private health expenditures, and the poorest income quintiles would see the greatest FRP benefits. ACT and LLINs would have the largest impact on malaria-related deaths averted and FRP benefits.

Conclusions

ACT, LLIN, IRS, and vaccine interventions would bring large health and financial benefits to the poorest households in Ethiopia.
Evaluation of DawaPlus 3.0 and DawaPlus 4.0, deltamethrin–PBO combination nets against pyrethroid-resistant Anopheles culicifacies in experimental huts in India
Authors: Gunasekaran Kasinathan , Sahu Sudhansu Sekhar , Vijayakumar Tharmalingam , Subramanian Swaminathan , Rahi Manju , Jambulingam Purushothaman
Published: January 2020

Background

The development of resistance in vectors is one of the major impediments for malaria control. Adding synergists to insecticides has proven to be an alternative choice for controlling resistant mosquitoes. DawaPlus 3.0 and DawaPlus 4.0 are new long-lasting insecticidal nets (LLINs) in which deltamethrin and a synergist, piperonyl butoxide (PBO) are added into filaments and their efficacy was tested against resistant malaria vector, Anopheles culicifacies in experimental huts in India.

Methods

The performance of two trial nets in terms of deterrence induced exiting, blood-feeding inhibition and mortality of An. culicifacies was compared with DawaPlus 2.0 and untreated net.

Results

There was a significant reduction in entry, blood feeding and mortality (p < 0.05) and increase in exit rates of An. culicifacies in the treatment arms compared to untreated arm. But, both candidate LNs washed 20 times could not perform better than the washed reference net (DawaPlus 2.0). Cone bioassay results showed that all the treatment arms (both washed and unwashed) produced < 80% mortality of An. culicifacies before and after hut evaluation.

Conclusions

DawaPlus 3.0 and DawaPlus 4.0 with their current specification may not be as effective as required to control the resistant vector, An. culicifacies, in east-central India.
Core–shell polymeric nanoparticles co-loaded with photosensitizer and organic dye for photodynamic therapy guided by fluorescence imaging in near and short-wave infrared spectral regions
Authors: Chepurna O. M. , Yakovliev A. , Ziniuk R. , Nikolaeva O. A. , Levchenko S. M. , Xu H. , Losytskyy M. Y. , Bricks J. L. , Slominskii Yu. L. , Vretik L. O. , Qu J. , Ohulchanskyy T. Y.
Published: January 2020

Background

Biodistribution of photosensitizer (PS) in photodynamic therapy (PDT) can be assessed by fluorescence imaging that visualizes the accumulation of PS in malignant tissue prior to PDT. At the same time, excitation of the PS during an assessment of its biodistribution results in premature photobleaching and can cause toxicity to healthy tissues. Combination of PS with a separate fluorescent moiety, which can be excited apart from PS activation, provides a possibility for fluorescence imaging (FI) guided delivery of PS to cancer site, followed by PDT.

Results

In this work, we report nanoformulations (NFs) of core–shell polymeric nanoparticles (NPs) co-loaded with PS [2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a, HPPH] and near infrared fluorescent organic dyes (NIRFDs) that can be excited in the first or second near-infrared windows of tissue optical transparency (NIR-I, ~ 700–950 nm and NIR-II, ~ 1000–1350 nm), where HPPH does not absorb and emit. After addition to nanoparticle suspensions, PS and NIRFDs are entrapped by the nanoparticle shell of co-polymer of N-isopropylacrylamide and acrylamide [poly(NIPAM-co-AA)], while do not bind with the polystyrene (polySt) core alone. Loading of the NIRFD and PS to the NPs shell precludes aggregation of these hydrophobic molecules in water, preventing fluorescence quenching and reduction of singlet oxygen generation. Moreover, shift of the absorption of NIRFD to longer wavelengths was found to strongly reduce an efficiency of the electronic excitation energy transfer between PS and NIRFD, increasing the efficacy of PDT with PS-NIRFD combination. As a result, use of the NFs of PS and NIR-II NIRFD enables fluorescence imaging guided PDT, as it was shown by confocal microscopy and PDT of the cancer cells in vitro. In vivo studies with subcutaneously tumored mice demonstrated a possibility to image biodistribution of tumor targeted NFs both using HPPH fluorescence with conventional imaging camera sensitive in visible and NIR-I ranges (~ 400–750 nm) and imaging camera for short-wave infrared (SWIR) region (~ 1000–1700 nm), which was recently shown to be beneficial for in vivo optical imaging.

Conclusions

A combination of PS with fluorescence in visible and NIR-I spectral ranges and, NIR-II fluorescent dye allowed us to obtain PS nanoformulation promising for see-and-treat PDT guided with visible-NIR-SWIR fluorescence imaging.
Recent sylvatic yellow fever virus transmission in Brazil: the news from an old disease
Authors: Silva Natalia Ingrid Oliveira , Sacchetto Lívia , de Rezende Izabela Maurício , Trindade Giliane de Souza , LaBeaud Angelle Desiree , de Thoisy Benoit , Drumond Betânia Paiva
Published: January 2020

Yellow fever (YF) is an acute viral disease, affecting humans and non-human primates (NHP), caused by the yellow fever virus (YFV). Despite the existence of a safe vaccine, YF continues to cause morbidity and mortality in thousands of people in Africa and South America. Since 2016, massive YF outbreaks have taken place in Brazil, reaching YF–free zones, causing thousands of deaths of humans and NHP. Here we reviewed the main epidemiological aspects, new clinical findings in humans, and issues regarding YFV infection in vectors and NHP in Brazil. The 2016–2019 YF epidemics have been considered the most significant outbreaks of the last 70 years in the country, and the number of human cases was 2.8 times higher than total cases in the previous 36 years. A new YFV lineage was associated with the recent outbreaks, with persistent circulation in Southeast Brazil until 2019. Due to the high number of infected patients, it was possible to evaluate severity and death predictors and new clinical features of YF.Haemagogus janthinomysandHaemagogus leucocelaenuswere considered the primary vectors during the outbreaks, and no human case suggested the occurrence of the urban transmission cycle. YFV was detected in a variety of NHP specimens presenting viscerotropic disease, similar to that described experimentally. Further studies regarding NHP sensitivity to YFV, YF pathogenesis, and the duration of the immune response in NHP could contribute to YF surveillance, control, and future strategies for NHP conservation.
Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis
Authors: Huang Xiu-Yan , Huang Zi-Li , Huang Jin , Xu Bin , Huang Xin-Yu , Xu Yong-Hua , Zhou Jian , Tang Zhao-You
Published: January 2020

Background

Exosomes play crucial roles in regulating the crosstalk between normal and cancer cells in the tumor microenvironment, and in regulating cancer proliferation, migration and invasion through their cargo molecules.

Methods

We analyzed the pro-invasiveness of exosomal circRNA-100,338 in HCC using the transwell invasion assay. The co-culture of human umbilical vein endothelial cells (HUVEC) and exosomes derived from HCC cell lines were used to evaluate the impact of HCC derived exosomes on HUVEC. Nude mice models were used to validate the findings in vitro. Clinically, quantitative RT-PCR was used to quantify the expression of serum exosomal circRNA-100,338 in HCC patients at both pre-surgery within one week and post-surgery within three weeks.

Results

We aim to investigate the pro-invasive role of exosomal circRNA-100,338 in HCC metastasis. We for the first time demonstrated that circRNA-100,338 was highly expressed in both highly metastatic HCC cells and their secreted exosomes. The transwell invasion assay showed that the overexpression or knockdown of exosomal circRNA-100,338 significantly enhanced or reduced the invasive abilities of HCC cells. Subsequently, in vitro and in vivo assays showed that exosomal circRNA-100,338 affected the cell proliferation, angiogenesis, permeability, and vasculogenic mimicry (VM) formation ability of human umbilical vein endothelial cells (HUVEC), and tumor metastasis. Furthermore, we also observed that the persistent high expression of exosomal circRNA-100,338 in serum of HCC patients who underwent curative hepatectomy may be a risk indicator of pulmonary metastasis and poor survival.

Conclusions

Our findings indicated that metastatic ability of HCC cells could be enhanced by transferring exosomal circRNA-100,338 to recipient HUVECs, which could affect proangiogenic activity by regulating angiogenesis.
Symptomatic pes planus in children: a synthesis of allied health professional practices
Authors: Morrison Stewart C. , Tait Madeleine , Bong Elaine , Kane Kyra J. , Nester Chris
Published: January 2020

Background

This study sought to explore professional perspectives on the assessment and management of symptomatic pes planus in children.

Methods

Data was collected from three professional groups (podiatrists, physiotherapists, and orthotists) with experience of managing foot problems in children. The survey was undertaken in the United Kingdom via a self‐administered, online survey. Data was captured over a four‐month period in 2018.

Results

Fifty‐five health professionals completed the survey and the results highlighted that assessment techniques varied between professions, with standing tip‐toe and joint range of motion being the most common. Treatment options for children were diverse and professionals were adopting different strategies as their first line intervention. All professions used orthoses.

Conclusions

There were inconsistencies in how the health professionals assessed children presenting with foot symptoms, variation in how the condition was managed and differences in outcome measurement. These findings might be explained by the lack of robust evidence and suggests that more effort is needed to harmonise assessment and treatment approaches between professions. Addressing discrepancies in practice could help prioritise professional roles in this area, and better support the management of children with foot pain.