bluuebunny/crossref_metadata_2025 huggingface dataset:
Prior vaccination with the rVSV-ZEBOV vaccine does not interfere with but improves the efficacy of postexposure antibody treatment in nonhuman primates exposed to Ebola virus
Authors: Cross Robert W. , Bornholdt Zachary A. , Prasad Abhishek N. , Geisbert Joan B. , Borisevich Viktoriya , Agans Krystle N. , Deer Daniel J. , Melody Kevin , Fenton Karla A. , Feldmann Heinz , Sprecher Armand , Zeitlin Larry , Geisbert Thomas W.
Published: April 2020

A replication-competent, vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic1. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP showed promise in animals and EBOV patients when administered therapeutically2-6. Given the large number of at-risk humans being prophylactically vaccinated with rVSV-ZEBOV, there is uncertainty regarding whether vaccination would preclude use of antibody treatments in the event of a known exposure of a recent vaccinee. To model a worst-case scenario, we performed a study using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. One day after vaccination, animals were challenged with a uniformly lethal dose of EBOV. Five vaccinated animals and five unvaccinated animals were then treated with the anti-EBOV GP mAb-based therapeutic MIL77 starting 3 days postexposure. Additionally, five vaccinated macaques received no therapeutic intervention. All five macaques that were vaccinated and subsequently treated with MIL77 showed no evidence of clinical illness and survived challenge. In contrast, all five animals that only received the rVSV-ZEBOV vaccine became ill and 2/5 survived; all five macaques that only received MIL77 only also became ill and 4/5 survived. Enhanced efficacy of vaccinated animals that were treated with MIL77 was associated with delayed EBOV viremia attributed to the vaccine. These results suggest that rVSV-ZEBOV augments immunotherapy.
SnoRNA signatures in cartilage ageing and osteoarthritis
Authors: Peffers Mandy J , Chabronova Alzbeta , Balaskas Panagiotis , Fang Yongxiang , Dyer Philip , Cremers Andy , Emans Pieter , Feczko Peter , Caron Marjolein , Welting Tim JM
Published: April 2020

Objectives

Osteoarthritis (OA) presents as a change in the chondrocyte phenotype and an imbalance between anabolic and catabolic processes. Age affects its onset and progression. Small nucleolar RNAs (SnoRNAs) direct chemical modification of RNA substrates to fine-tune spliceosomal and rRNA function, accommodating changing requirements for splicing and protein synthesis during health and disease. This study was undertaken to examine how changes in snoRNAs expression may have a role in OA.

Methods

Articular cartilage from young, old and OA knees was used in a microarray study to identify alterations in snoRNA expression. Changes in expression of snoRNAs in OA-like conditions were studied in chondrocytes using interleukin-1 and OA synovial fluid. SNORD26 and SNORD96A knockdown and overexpression were undertaken using antisense oligonucleotides and overexpression plasmids.

Results

We identified panels of snoRNAs differentially expressed due to ageing (including SNORD96A, SNORD44) and OA (including SNORD26 and SNORD116) and findings were validated in an independent cohort.In vitroexperiments using OA-like conditions affected snoRNA expression. Knockdown or overexpression of SNORD26 or SNORD96A resulted in changes in chondrogenic, hypertrophic, rRNA and osteoarthritis related gene expression.

Conclusion

We demonstrate that snoRNA expression changes in cartilage ageing, and OA and in OA-like conditions, and when the expression of these snoRNAs is altered this affects chondrogenic and hypertrophic gene expression. Thus, we propose an additional dimension in the molecular mechanisms underlying cartilage ageing and OA through the dysregulation of snoRNAs.
Visualising G-quadruplex DNA dynamics in live cells by fluorescence lifetime imaging microscopy
Authors: Summers Peter A. , Lewis Benjamin W. , Gonzalez-Garcia Jorge , Porreca Rosa M. , Lim Aaron H.M. , Cadinu Paolo , Martin-Pintado Nerea , Mann David , Edel Joshua B. , Vannier Jean Baptiste , Kuimova Marina K. , Vilar Ramon
Published: April 2020

Guanine rich regions of oligonucleotides fold into quadruple-stranded structures called G-quadruplexes (G4). Increasing evidence suggests that these G4 structures formin vivoand play a crucial role in cellular processes. However, their direct observation in live cells remains a challenge. Here we demonstrate that a fluorescent probe (DAOTA-M2) in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) can identify G4 within nuclei of live and fixed cells. We present a new FLIM-based cellular assay to study the interaction of non-fluorescent small molecules with G4 and apply it to a wide range of drug candidates. We also demonstrate thatDAOTA-M2can be used to study G4 stability in live cells. Reduction ofFancJandRTEL1expression in mammalian cells increases theDAOTA-M2lifetime and therefore suggests an increased number of G4 in these cells, implying thatFancJandRTEL1play a role in resolving G4 structuresin cellulo.
NOGEA: Network-Oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning
Authors: Guo Zihu , Fu Yingxue , Huang Chao , Zheng Chunli , Wu Ziyin , Chen Xuetong , Gao Shuo , Ma Yaohua , Shahen Mohamed , Li Yan , Tu Pengfei , Zhu Jingbo , Wang Zhenzhong , Xiao Wei , Wang Yonghua
Published: April 2020

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes on the interactome network, which provides a new way for predicting new drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated byin vitroexperiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and repositioning. NOGEA codes are publicly available athttps://github.com/guozihuaa/NOGEA.
Noise propagation in gene expression in the presence of decoys
Authors: Dey Supravat , Singh Abhyudai
Published: April 2020

Genetically-identical cells can show remarkable intercellular variability in the level of a given protein which is commonly known as the gene expression noise. Besides intrinsic fluctuations that arise from the inherent stochasticity of the biochemical processes, a significant source of expression noise is extrinsic. Such extrinsic noise in gene expression arises from cell-to-cell differences in expression machinery, transcription factors, cell size, and cell cycle stage. Here, we consider the synthesis of a transcription factor (TF) whose production is impacted by a dynamic extrinsic disturbance, and systematically investigate the regulation of expression noise by decoy sites that can sequester the protein. Our analysis shows that increasing decoy numbers reduce noise in the level of the free (unbound) TF with noise levels approaching the Poisson limit for large number of decoys. Interestingly, the suppression of expression noise compared to no-decoy levels is maximized at intermediate disturbance timescales. Finally, we quantify the noise propagation from the TF to a downstream target protein and find counterintuitive behaviors. More specifically, for nonlinear dose responses of target-protein activation, the noise in the target protein can increase with the inclusion of decoys, and this phenomenon is explained by smaller but more prolonged fluctuations in the TF level. In summary, our results illustrates the nontrivial effects of high-affinity decoys in shaping the stochastic dynamics of gene expression to alter cell fate and phenotype at the single-cell level.
Soft-wired long-term memory in a natural recurrent neuronal network
Authors: Casal Miguel A. , Galella Santiago , Vilarroya Oscar , Garcia-Ojalvo Jordi
Published: April 2020

Neuronal networks provide living organisms with the ability to process information. They are also characterized by abundant recurrent connections, which give rise to strong feed-back that dictates their dynamics and endows them with fading (short-term) memory. The role of recurrence inlong-termmemory, on the other hand, is still unclear. Here we use the neuronal network of the roundwormC. elegansto show that recurrent architectures in living organisms can exhibit long-term memory without relying on specific hard-wired modules. A genetic algorithm reveals that the experimentally observed dynamics of the worm’s neuronal network exhibits maximal complexity (as measured by permutation entropy). In that complex regime, the response of the system to repeated presentations of a time-varying stimulus reveals a consistent behavior that can be interpreted as soft-wired long-term memory.

A common manifestation of our ability to remember the past is the consistence of our responses to repeated presentations of stimuli across time. Complex chaotic dynamics is known to produce such reliable responses in spite of its characteristic sensitive dependence on initial conditions. In neuronal networks, complex behavior is known to result from a combination of (i) recurrent connections and (ii) a balance between excitation and inhibition. Here we show that those features concur in the neuronal network of a living organism, namelyC. elegans. This enables long-term memory to arise in an on-line manner, without having to be hard-wired in the brain.
Molecular free energy optimization on a computational graph
Authors: Cao Xiaoyong , Tian Pu
Published: April 2020

Free energy is arguably the most important property of molecular systems. Despite great progress in both its efficient estimation by scoring functions/potentials and more rigorous computation based on extensive sampling, we remain far from accurately predicting and manipulating biomolecular structures and their interactions. There are fundamental limitations, including accuracy of interaction description and difficulty of sampling in high dimensional space, to be tackled. Computational graph underlies major artificial intelligence platforms and is proven to facilitate training, optimization and learning. Combining autodifferentiation, coordinates transformation and generalized solvation free energy theory, we construct a computational graph infrastructure to realize seamless integration of fully trainable local free energy landscape with end to end differentiable iterative free energy optimization. This new framework greatly improves efficiency by replacing local sampling with differentiation. Its specific implementation in protein structure refinement achieves superb efficiency and competitive accuracy when compared with state of the art all-atom mainstream methods.
3D Hyaluronic Acid Hydrogels for Modeling Oligodendrocyte Progenitor Cell Behavior as a Function of Matrix Stiffness
Authors: Unal Deniz B. , Caliari Steven R. , Lampe Kyle J.
Published: April 2020

The lack of regenerative solutions for demyelination within the central nervous system (CNS) motivates the need for better understanding of the oligodendrocytes that give rise to myelination. In this work, we introduce a 3D hyaluronic acid (HA) hydrogel system to study the effects of mechanical properties on the behavior of oligodendrocyte progenitor cells (OPCs), the cells that differentiate into myelin-producing oligodendrocytes in the CNS. We tuned the stiffness of the hydrogels to match brain tissue (storage modulus 200 – 2000 Pa) and studied the effects of stiffness on metabolic activity, proliferation, and cell morphology of OPCs over a 7 day period. Although hydrogel mesh size decreased with increasing stiffness, all hydrogel groups facilitated OPC proliferation and mitochondrial metabolic activity to similar degrees. However, OPCs in the two lower stiffness hydrogel groups (169.8 ± 42.1 Pa and 793.9 ± 203.3 Pa) supported greater adenosine triphosphate (ATP) levels per cell than the highest stiffness hydrogels (2178.7 ± 127.2 Pa). Lower stiffness hydrogels also supported higher levels of cell viability and larger cell spheroid formation compared to the highest stiffness hydrogels. Together, these data suggest that 3D HA hydrogels are a useful platform for studying OPC behavior and that OPC growth/metabolic health may be favored in lower stiffness microenvironments mimicking brain tissue mechanics.
Caenorhabditis elegansdauers vary recovery in response to bacteria from natural habitat
Authors: Bubrig Louis T. , Sutton John M. , Fierst Janna L.
Published: April 2020

Many species use dormant stages for habitat selection by tying recovery from the stage to informative external cues. Other species have an undiscerning strategy in which they recover randomly despite having advanced sensory systems. We investigated whether elements of a species’ habitat structure and life history can bar it from developing a discerning recovery strategy. The nematodeCaenorhabditis eleganshas a dormant stage called the dauer larva that disperses between habitat patches. On one hand,C. eleganscolonization success is profoundly influenced by the bacteria found in its habitat patches, so we might expect this to select for a discerning strategy. On the other hand,C. elegans’ habitat structure and life history suggest that there is no fitness benefit to varying recovery, which might select for an undiscerning strategy. We exposed dauers of three genotypes to a range of bacteria acquired from the worms’ natural habitat. We found thatC. elegansdauers recover in all conditions but increase recovery on certain bacteria depending on the worm’s genotype, suggesting a combination of undiscerning and discerning strategies. Additionally, the worms’ responses did not match the bacteria’s objective quality, suggesting that their decision is based on other characteristics.
Understanding the use of YouTube as a learning resource: a social cognitive perspective
Authors: Zhou Quan , Lee Chei Sian , Sin Sei-Ching Joanna , Lin Sijie , Hu Huijie , Fahmi Firdaus Bin Ismail Muhammad
Published: April 2020

Purpose

Drawing from social cognitive theory, the purpose of this study is to examine how personal, environmental and behavioral factors can interplay to influence people's use of YouTube as a learning resource.

Design/methodology/approach

This study proposed a conceptual model, which was then tested with data collected from a survey with 150 participants who had the experience of using YouTube for learning. The bootstrap method was employed to test the direct and mediation hypotheses in the model.

Findings

The results revealed that personal factors, i.e. learning outcome expectations and attitude, had direct effects on using YouTube as a learning resource (person → behavior). The environmental factor, i.e. the sociability of YouTube, influenced the attitude (environment → person), while the behavioral factor, i.e. prior experience of learning on YouTube, affected learning outcome expectations (behavior → person). Moreover, the two personal factors fully mediated the influences of sociability and prior experience on YouTube usage for learning.

Practical implications

The factors and their relationships identified in this study provide important implications for individual learners, platform designers, educators and other stakeholders who encourage the use of YouTube as a learning resource.

Originality/value

This study draws on a comprehensive theoretical perspective (i.e. social cognitive theory) to investigate the interplay of critical components (i.e. individual, environment and behavior) in YouTube's learning ecosystem. Personal factors not only directly influenced the extent to which people use YouTube as a learning resource but also mediated the effects of environmental and behavioral factors on the usage behavior.
Scattering by cracks in a conducting surface
Authors: Jacobs Ralf T. , Kost Arnulf
Published: April 2020

Purpose

The purpose of this study is the formulation of an efficient method to compute and analyse the scattering characteristics of cracks or grooves in a conducting object, where the size of the crack is significantly larger than the wavelength of an incident plane wave.

Design/methodology/approach

A hybrid finite element-boundary element procedure is formulated for the computation of the scattering properties of the object, where the fast multipole method is used in the boundary integral formulation. The basic fast multipole procedure is enhanced by utilising a fast Fourier transform-based convolution algorithm for the computation of the interactions between groups of source and field elements.

Findings

The algorithm accelerates the evaluation of the group interactions and enables the reduction of the memory requirements without introducing an additional approximation into the procedure.

Originality/value

The fast multipole method with convolution algorithm shows to be more efficient for the computation of scattering problems with a large number of unknowns than the conventional procedure.
Factors influencing the intention to buy over-the-counter medicines: empirical study
Authors: Habash Raeda , Al-Dmour Hani
Published: April 2020

Purpose

This study aims to examine the antecedent factors (internal and external) that influence intentions to buy over-the-counter (OTC) medicines in Jordan.

Design/methodology/approach

A conceptual framework was developed based on consumer buying behavior theoretical background and a review of the relevant literature. A quantitative approach and a convenience sampling method were used to obtain data from self-administered questionnaires, which were completed by 351 academic staff from selected Jordanian universities.

Findings

The results indicate that all antecedent factors (internal, external and combined) have significant positive influences on the intentions to buy OTC medicines. Internal factors are more influential than external factors; however, the combination of internal and external factors resulted in the greatest influence on buying OTC medicines compared to each category separately.

Originality/value

This paper has integrated and examined empirically the antecedent factors that influence intentions to buy OTC medicines (internal, external and combined) in Jordan’s business environment context as a developing country for the first time.
Factors affecting spectators’ adoption of digital ticketing: the case of interscholastic sports
Authors: Marquez Armin , Cianfrone Beth A. , Kellison Timothy
Published: April 2020

Purpose

The paper investigates the factors influencing spectators’ adoption of digital (mobile) ticketing by expanding the Technology Acceptance Model (TAM; Davis, 1989) to include two variables overlooked in previous ticketing research: (1) trust of digital ticketing and (2) willingness to pay convenience fees. The study provides information on consumer behavior that may aid sports managers’ decision-making.

Design/methodology/approach

Through a paper-and-pencil survey of high school American football spectators (N = 523) over 12 games, the study examined perceived ease of use, perceived usefulness, the trust of digital ticketing, willingness to pay convenience fees and their effects on spectators’ intention to use digital ticketing.

Findings

Trust of digital ticketing, willingness to pay a convenience fee and the perceived ease of use were found to influence the perceived usefulness of the technology, which, in turn, had a significant effect on the intention to use. Willingness to pay fees also had a direct effect on intention.

Research limitations/implications

Although every intention was made to ascertain a diverse sampling of schools (urban vs. suburban, large vs. small), it is worth noting that the sample location may be a limitation for the overall applicability.

Practical implications

The manuscript includes practical applications for marketers and ticket sales staff. Digital (mobile) ticketing is on the rise. As segments like high school athletics adopt the technology, spectators’ evaluation of digital ticketing must be considered, given its impact on intentions to use.

Originality/value

The findings support the use of willingness to pay convenience fees and trust of digital ticketing as considerations in the TAM for understanding digital ticketing.
Managing international distributors’ complaints: an exploratory study
Authors: Kuster-Boluda Amparo , Vila Natalia Vila , Kuster Ines
Published: April 2020

Purpose

Complaint management is at the heart of customer relationship management. While many studies have analyzed a client’s complaint behavior in business-to-business (B2B) relationships, there is a lack of research in the study of complaints by distributors from different countries. The purpose of this paper is to explain the following two main objectives: to analyze if the complaint management strategy of a manufacturer varies depending on the type of international distributor used (indirect exporters, direct exporters and commercial subsidiaries); and to analyze the potential effects of complaint management on the satisfaction and fidelity of distributors and the quantity of complaints that they put.

Design/methodology/approach

A stratified probabilistic sampling method was used, dividing the entire population of distributors of a leading Spanish manufacturer into three different groups. In total, 79 valid responses were obtained as follows: 24 per cent from indirect exporters (organizational commitment Grade 1), 68 per cent from direct exporters (organizational commitment Grade 2) and 8 per cent from commercial subsidiaries (organizational commitment Grade 3). Partial least squares were used to analyze the proposed relationships.

Findings

The results have confirmed that the procedure for resolving the complaint and its length (resolution time) depends on the seriousness of the complaint (the type of complaint). In turn, the resolution of the complaint influences the satisfaction of the vendor and the latter will influence its fidelity. Regarding the number of complaints, those distributors with the highest number of complaints satisfactorily resolved are those who remain loyal to the company. On the contrary, it is not possible to affirm that the type of distribution channel affects the types of complaints that are presented. Different kinds of distributors of the same manufacturer (indirect exporters, direct exporters and commercial subsidiaries) complain equally. In addition, those whose complaints take longer to resolve are not significantly less satisfied. Even more, low-satisfied distributors will present more complaints than the most satisfied ones.

Originality/value

First, this study investigates if different kinds of distributors with different international commitments (indirect exporting, direct exporting and commercial subsidiary) behave differently in terms of claims and complaints. Second, this paper analyzes the role of complaint management in international B2B relations to improve distributors' satisfaction and loyalty; but considering the join impact of three dimensions of a successful complaint management strategy that literature usually has examined separately as follows: what (the type of complaint), how it is resolved (management procedure) and when it is closed (duration).
Exploring market-oriented relations in the digital era
Authors: Tong Suk Chong , Chan Fanny Fong Yee
Published: April 2020

Purpose

Market-oriented relations has been regarded as a kind of public relations practices widely performed by the practitioners of public relations and marketing. This study attempts to discuss market-oriented relations in the digital era in which public relations and marketing practitioners' involvement in managing market-oriented relations was simultaneously related to their perceptions of interactivity effects, value of public relations and benefits of digital media usage in public relations practices.

Design/methodology/approach

A self-administrated online survey targeting 241 practitioners engaged in coordinating public relations activities in Hong Kong was conducted in 2017.

Findings

Structural equation modeling (SEM) analysis showed that practitioners' involvement in market-oriented relations practices had significant positive effects on their perceptions of interactivity effects, value of public relations and benefits of digital media usage. Practitioners' perceptions of interactivity effects and benefits of digital media usage were positively affected by their perceptions of public relations value, particularly public relations effectiveness. Clients' profitability and business intelligence, as well as interactivity effects in terms of involvement and perceived customization were practitioners' key concerns in managing market-oriented relations.

Originality/value

This study explores how practitioners of public relations and marketing perceived and practiced public relations in the digital era. Specifically, the conception of market-oriented relations in regard to the use of digital media was discussed in the proposed structural model.
The impact of the prison environment on behavioral changes of inmates: a study of inmates in Kosovo and Finland
Authors: Azemi Ferid
Published: April 2020

Purpose

This study aims to focus on understanding the prison environment, inmates’ behavior and perceptions of the prison environment, analyzing the degree of awareness, rehabilitation and the programs that apply to prisons in both countries. It is assumed that the data that emerge from this research will contribute to a better understanding of the prisoner’s world of their perception about the prison environment in Kosovo and Finland. The study focused on inmates’ perception about the prison environment and their attitudes toward their sentences.

Design/methodology/approach

Qualitative study through in-depth interviews.

Findings

The results of this study indicated that inmates in Kosovo perceived the prison environment in a very negative light. The main reasons for this were the dissatisfaction with their status of being inmates and also lack of an appropriate classification of inmates. However, even though inmates in Finland perceived prison environment in a positive light, they still think that more educative programs are needed.

Practical implications

The results of this study indicated that Kosovo Correctional Service should implement more rehabilitative programs and improve its classification system. Criminal Sanction Agency in Finland as per results should increase efforts for implementation of new programs and aftercare action plans.

Originality/value

To the best of the author’s knowledge, it is the first research on inmates in two countries Kosovo and Finland, and this added new knowledge to the existing information about the prison environment in Kosovo and Finland. The results of this research gave an idea to respective institutions to add new rehabilitative and aftercare programs.
Halal Malaysia brand equity mishap
Authors: Wan Ismail Wan Rusni , Othman Mohhidin , Md Nor Norfezah , Badiuzaman Ahmad Fauzan , Nik Mohd Nor Nik Mohd Shahril
Published: April 2020

Purpose

Brand mere recognition is the fundamental step in brand awareness and the first hurdle that any brand needs to achieve before brand equity can come into the picture. Thus, consumers’ ability to recognize a brand through its symbol or logo is very crucial and despite its significance, it is considered the lowest order in brand equity assessment but it reveals the initial clue on how well the brand is performing in the market. Therefore, the purpose of this study is to test how well consumers are able to identify the right Halal Malaysia brand (HMB) using Halal semiotic cues.

Design/methodology/approach

This study is an exploratory, based on a mixed method approach using qualitative and quasi-experimental design using the implicit association test (IAT) as the instrument. A total of 23 Malay Muslim consumers were involved in the first stage of the study carried out using a semi-structured interview. The second stage of this study was carried out using quasi-experimental design where IAT was used as an instrument. A total of 66 respondents participated in both states of the experiment and the response time was recorded and analysed using D-measure and descriptive.

Findings

Findings from qualitative investigation indicate that most of the respondents failed in the mere recognition test. The findings are further supported using IAT where a hesitation in response when facing the current HMB logo has provided a clear indication of lack of mere recognition for this brand. Unfortunately, the proliferation of other Halal logos that have flooded the market, comprising both recognized and unrecognized logos by Jabatan Kemajuan Islam Malaysia (JAKIM), which often adopted a similar logo design strategy, only add to the confusion. Clearly, the findings on HMB logo mere recognition also revealed that there are some problems during the transition from the old JAKIM Halal logo to the current logo, where the information related to the new logo has failed to reached targeted audiences.

Originality/value

Despite there are a lot of studies focussing on the positive impact of Halal Malaysia logo on Muslim consumers purchase decision, however there are few publications that suggest otherwise. Thus, this study will investigate the extend of this problem.
Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers
Authors: Mazzilli Sara , Lanna Caterina , Chiaramonte Carlo , Cesaroni Gaia Maria , Zangrilli Arianna , Palumbo Vincenzo , Cosio Terenzio , Dattola Annunziata , Gaziano Roberta , Galluzzo Marco , Chimenti Maria Sole , Gisondi Paolo , Bianchi Luca , Campione Elena
Published: April 2020

Psoriasis is a common inflammatory skin condition, affecting 2–4% of the worldwide population. Psoriasis remains an important public health challenge because there are many clinical forms of psoriasis in particular sites, probably related to the dysregulation of different cytokines. Therefore, there is a continuous need to improve treatment options with mechanisms of action different from those of the currently known therapies. Advances in knowledge of the molecular bases of pathogenesis lead to a better understanding of the disease, thus influencing the development and management of effective treatments. Moreover, data from recent published work indicate that psoriasis coexists with cardiovascular diseases, metabolic syndrome, diabetes mellitus and psychiatric disorders. We present results from our 52‐week open‐label trial in a cohort of psoriatic and psoriatic arthritis patients treated with daily p.o. doses of apremilast 60 mg. We confirmed the efficacy and safety of the drug in favoring the improvement of skin and joint disease as well as the modulation of metabolic biomarkers in diabetic and non‐diabetic psoriatic patients. Apremilast could be used successfully in psoriatic patients affected by cardiometabolic comorbidities, ensuring an improvement in both diseases.
Our extended genotype—An argument for the study of domesticated microbes
Authors: Bruessow Friederike , Brüssow Harald
Published: April 2020

We interpret the domesticated organisms—plants, animals, and the domesticated microbes used for food fermentation—as an extended genotype of humans due to their close relationship with our species. We propose to analyse the role of microbes in traditionally fermented food with the approaches used in the human microbiome project, and we expect to find associations with ethnic groups, explaining part of human (culinary) culture.
Colorectal tumour characteristics and oncological outcome in patients with inflammatory bowel disease
Authors: Askari Alan , Guillén Luis Sánchez , Millan Monica , Nachiappan Subramanian , Bottle Alex , Athanasiou Thanos , Faiz Omar
Published: April 2020

Introduction

Patients with inflammatory bowel disease (IBD) may be at higher risk of colorectal cancer (CRC), but it is unclear whether they have worse surgical and oncological outcomes compared with patients with sporadic colorectal cancer (SCRC). The aim of this paper is to determine whether there are differences in surgical and oncological outcomes following treatment for IBD‐CRC and SCRC.

Methods

A tertiary referral hospital′s cancer database from 2004 to 2014 was retrospectively reviewed. Patient records as well as electronic radiological, pathological and administrative sources were used to collect data on patient demographics, tumour characteristics, surgical treatment, cancer recurrence and survival. Survival analyses (Kaplan Meier and Cox regression) were carried out to compare disease free and overall survival between IBD‐CRC and SCRC patient groups.

Results

A total of 1911 patients underwent surgery for CRC over the study period. Of these, 81 patients (4.2%) had a diagnosis of IBD. There was a significant difference in terms of patient demographics and surgical outcomes between the two groups. Colorectal cancer patients with IBD were younger at time of diagnosis (median age IBD‐CRC 57 years, median age SCRC 69 years, P < .001), were more likely to have an open procedure (P < .001), had a higher rate of stoma formation (P < .001) and had a longer length of hospital stay (P = <.001). Patients with IBD‐CRC more frequently exhibited poorly differentiated tumours (30.9% compared with 10.0%, P < .001). South Asian patients had a higher rate of IBD‐CRC than SCRC (33.3% compared with 17.4%, P = .015). At the end of follow up 69.2% (n = 1266/1830) of sporadic and 81.5% (n = 66/81) patients were alive. In this institutional case series, IBD was not demonstrated to be an independent predictor of disease free survival (HR 0.67, CI 0.33–1.36, P = .267) or overall survival (HR 0.78, 95% CI 0.46–1.30, P = .335).

Conclusion

Patient and tumour characteristic differences exist between patients presenting with IBD‐CRC and SCRC. IBD‐CRC patients are more likely to be diagnosed with CRC at a younger age, are more likely to have poorly differentiated tumours and have worse surgical outcomes. There were no differences in overall survival between IBD‐CRC and SCRC although due to small sample size in the IBD‐CRC group, results of the survival analysis should be interpreted with caution.
Feasibility Study of a Quasi‐experimental Regional Opioid Safety Prescribing Program in Veterans Health Administration Emergency Departments
Authors: Dieujuste Nathalie , Johnson‐Koenke Rachel , Christopher Melissa , Gunzburger Elise C. , Emmendorfer Thomas , Kessler Chad , Haukoos Jason , Smith Jason , Sasson Comilla
Published: April 2020

Background

The Veterans Health Administration (VHA) Opioid Safety Initiative (OSI) was implemented in 2013 and was associated with a 25% relative decrease in the dispensing of opioids. Although emergency department (ED) providers play a role in the initiation and continuation of opioids, the incumbent OSI did not target EDs.

Objective

The goal of this feasibility study was to leverage the existing VHA OSI and test a novel ED‐based quality improvement (QI) program to decrease opioid prescribing in multiple ED settings.

Methods

This was a quasi‐experimental study of phased‐in implementation of a QI ED‐based OSI. The general setting for this pilot were four VHA EDs across the Veterans Integrated Services Network (VISN) region 19: Denver, Oklahoma City, Muskogee, and Salt Lake City. We developed and disseminated a dashboard to assess ED‐specific prescribing rates and an ED‐tailored toolkit to implement the program. Academic detailing pharmacists provided focused audits and feedback with the highest prescribing providers. We measured change in ED‐provider prescribing rate of opioids for patients discharged from the ED, by provider and aggregated up to facility level, pre‐ and postimplementation.

Results

Interrupted time‐series analysis of provider‐level data from the program implementation sites indicated a significant decrease in the trend for proportion of opioid prescriptions relative to the preintervention trend. The results of the analysis suggest that the intervention was associated with accelerating the rate at which ED provider prescribing rates decreased.

Conclusion

Due to the high volume of patients and the vital role the ED plays in patient treatment and hospital admissions, it is evident that the ED is an important site for QI programs as well as the implementation of opioid safety measures. Given the findings of this pilot, we believe that implementation of a national Veterans Affairs ED OSI implementation is feasible practice.
Cross‐sectional study identifying high‐alert substances in medication error reporting among Swedish paediatric inpatients
Authors: Nydert Per , Kumlien Antonia , Norman Mikael , Lindemalm Synnöve
Published: April 2020

Aim

The aims were to characterise paediatric medication errors and to identify the prevalence of known high‐alert substances in these errors.

Methods

All paediatric drug‐related incident reports and complaints nationally reported to the Health and Social Care Inspectorate in Sweden 2011‐2017 regarding inpatients were characterised by context and modal details. In addition, drug use at a university hospital was matched to local incident reports. Drug substances were classified using three high‐alert lists.

Results

On a national level, there were 160 reports (2.5 per 10 000 patients) in which the three high‐alert lists were found in different degrees (17/35/47%). Morphine (n = 12), vancomycin (n = 11) and potassium (n = 7) were most frequently involved. Eighty per cent of the reports concerned patients aged 0‐6 years. Intravenous was the most common route of administration (66%). On a university hospital level, the prevalence of all types of drug incidents reports was 1.7% among all inpatients. The prevalence of local incident reports involving high‐alert substances was almost double that of non‐alert substances.

Conclusion

Existing high‐alert drug lists are relevant for paediatric inpatients. A higher awareness and usage of such lists among hospital staff prescribing, dispensing and administering drugs to children may have the potential to reduce medication errors.
Higher educational and economic status are key factors for the timely initiation of breastfeeding in Ethiopia: A review and meta‐analysis
Authors: Habtewold Tesfa Dejenie , Mohammed Shimels Hussien , Endalamaw Aklilu , Mulugeta Henok , Dessie Getenet , Berhe Derbew Fikadu , Birhanu Mulugeta Molla , Islam Md. Atiqul , Teferra Andreas A. , Asefa Nigus Gebremedhin , Alemu Sisay Mulugeta
Published: April 2020

Aim

To investigate the association between initiation of breastfeeding within 1 hour after birth (TIBF) and maternal educational status, paternal educational status, household income, marital status, media exposure and parity in Ethiopia.

Methods

We searched PubMed, EMBASE, Web of Science, SCOPUS, CINAHL and WHO Global health library databases. All studies were conducted in Ethiopia and published from 2000 to 2019 were included. To obtain the pooled odds ratio (OR), data were fitted in random‐effects meta‐analysis model. Statistical heterogeneity was quantified using Cochran's Q test, τ2 and I2 statistics. This meta‐analytic review was reported in compliance with the PRISMA statement.

Results

Out of 553 studies retrieved, 25 fulfilled our inclusion criteria. High maternal educational status (P < .001), paternal educational status (P = .001) and household income (P = .002), being married (P = .001) and multiparity (P = .01) were significantly associated with TIBF. There was no significant publication bias.

Conclusions

Our meta‐analysis showed that TIBF was associated with high educational and economic status, being married and multiparity. This suggests that the meta‐analysis detected small associations that many previous studies in Ethiopia have not been able to show. Our findings can be useful for comparisons with other countries.
The violence of homelessness: Exile and arbitrary detention in Cambodia's war on the poor
Authors: Springer Simon
Published: April 2020

This article examines the plight of homeless peoples in Phnom Penh, Cambodia as a consequence of their enmeshment in a new logic of urban governance being rolled out by city officials and municipal planners. The widespread adoption of neoliberal economics has resulted in a globalised version of urban entrepreneurialism, to which Phnom Penh is a participant. The (re)production of enterprise zones, cultural spectacles, waterfront development, and privatised forms of local governance all reflect the powerful disciplinary effects of interurban competition as cities aggressively engage in mutually destructive place‐marketing policies. Against this neoliberal backdrop, the ongoing pattern of violence utilised by municipal authorities against homeless peoples in Phnom Penh is part of a gentrifying process that the local government has dubbed a ‘beautification’ agenda. Of particular concern is how city officials have begun actively promoting the criminalization of the urban homeless and poor through arbitrary arrests and illegal detention, holding them in so‐called re‐education or ‘rehabilitation’ centres. Yet these centres are not what they seem. Such euphemisms attempt to mask the systemic abuse of marginalised peoples who are deemed to present Phnom Penh in a negative light and are consequently unwanted on the streets of the capital city.
Individual profiles and team classes of the climate for creativity: A multilevel latent profile analysis
Authors: Lee Yunsoo , Yoo Sangok
Published: April 2020

Understanding the team climate to enhance creativity is important in academia and industry given the need for organizations to respond to the changing environment. Research on team creativity is a relatively recent trend, but most studies have been conducted from a variable‐centered perspective. Despite the contributions of this type of research, there are limitations in understanding subgroups based on individuals' perceptions. To address the limitations, the purposes of this person‐centered study are firstly to identify individual‐level latent profiles and team‐level latent classes based on the climate for creativity, and secondly to examine the differences in individual‐ and team‐level outcomes between the identified profiles and classes. This study used multilevel latent profile analysis (MLPA) with 238 individuals in 26 project teams. We identified two individual profiles, high impediments and high stimulants, and two team classes, low impediments teams and mixed impediments teams. Low impediments teams included mostly high stimulants, and mixed impediments teams included half high stimulants and half low impediments. We further determined that high stimulants and low impediments teams showed higher individual‐ and team‐level outcomes than the other profile and class. This study theoretically and practically contributes to team creativity management from a person‐centered perspective.
Pathways between parental and individual determinants of dental caries and dental visit behaviours among children: Validation of a new conceptual model
Authors: Buldur Burak
Published: April 2020

Objectives

To delineate the pathways between the parental and individual determinants of dental caries and dental visit behaviours among children, using path analysis.

Methods

The study employed an observational design; the study sample consisted of 583 parent‐child dyads. Data were collected using a sociodemographic and oral health behaviour form, the Parenting Styles and Dimensions Questionnaire, the Corah Dental Anxiety Scale and the Children's Fear Survey Schedule‐Dental Subscale. A conceptual model was developed, and it consisted of four endogenous variables (dental caries, children's oral health, dental visit behaviours and children's dental anxiety) and four exogenous ones (parental socioeconomic status, parental dental anxiety, parental oral health behaviours and parenting style). Path analysis was used to test the compatibility of the conceptual model, with a statistical significance at P < .001.

Results

49.1% of participants (n = 286) were male. The mean age of participants was 8.3 (SD = 2.1). The mean DMFT score was 6.0 (SD = 3.0) and the mean Frankl behaviour score 3.0 (SD = 1.0). Parental socioeconomic status showed the strongest association with dental caries (β = .276; P < .001), and children's dental anxiety had the strongest association with dental visit behaviours (β = −.414; P < .001). Parental socioeconomic status and oral health behaviours were directly associated with dental caries (P < .001), and parental socioeconomic status had the most association. Parenting style and parental and children's dental anxiety were associated with dental visit behaviours (P < .001). Further, while all parental variables except prior exposure to training about oral and dental health were significantly correlated with dental caries, only educational level and coverage by health insurance were significantly associated with Frankl behaviour scale score.

Conclusions

This study developed and validated a conceptual model that delineates the pathways between the parental and individual determinants of children's oral health and dental visit behaviours. The model should help us to understand these pathways to lower the incidence of dental caries and improve dental visit behaviours among children.
Clinical, hemodynamic, and functional variables affecting success rate of coronary flow velocity reserve detection during vasodilator stress echocardiography
Authors: Cortigiani Lauro , Bovenzi Francesco , Picano Eugenio
Published: April 2020

Aim

Stress echocardiography (SE) with state‐of‐the‐art imaging protocol allows a comprehensive assessment of regional wall‐motion abnormalities and Doppler‐based coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD). We sought to assess the variables potentially impacting on success rate of SE with CFVR.

Methods and results

In a single‐center, prospective, observational study design, from 2007 to 2019, we enrolled 2989 consecutive patients (age 67 ± 12 years; 1723 men) referred for SE, without contrast, for chronic known (n = 1130) or suspected (n = 1859) coronary syndromes. Coronary flow velocity reserve was measured as stress/rest peak diastolic flow velocity. The same operator (LC) performed all examinations with the same machine (GE Vivid 7). Interpretable CFVR was obtained in 2808 patients (feasibility = 93.9%). Overall success rate was lowest (91.4%) in 2007–2008 and steadily rose to 97.8% in 2017–2019 (P for trend <.0001). Feasibility was excellent for men (93.7%) and women (94.3%) (P = .47) across all values of body mass index (BMI): <25 (P = .09), 25–29 (P = .84), and ≥30 (P = .23). At multivariable logistic regression analysis, women with BMI ≥ 30 (OR 1.94, 95% CI 1.14–3.29, P = .02), resting heart rate ≥77 beats/min (OR 2.25, 95% CI 1.64–3.11; P < .0001), and stress‐induced ischemia in the LAD territory (OR 3.14, 95% CI 1.67–5.90; P < .0001) predicted unfeasible CFVR.

Conclusion

Vasodilator SE with CFVR combined with wall‐motion analysis is highly feasible also without contrast although with a slight decline in presence of high resting heart rate (reducing diastolic time essential for flow imaging), women with BMI ≥ 30 (increasing tissue thickness interposed between transducer and artery), and anterior ischemia (for underlying low‐absent anterograde flow for severely stenotic or occluded LAD).