bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Oncogenic Mutations in Colorectal Cancer using Cryptotanshinone
Authors: Vundavilli Haswanth , Datta Aniruddha , Sima Chao , Hua Jianping , Lopes Rosana , Bittner Michael 
Published: September 2020

AbstractColorectal cancer (CRC) is one of the most prevalent types of cancer in the world and ranks second in cancer deaths in the US. Despite the recent improvements in screening and treatment, the number of deaths associated with CRC is still very significant. The complexities involved in CRC therapy stem from multiple oncogenic mutations and crosstalk between abnormal pathways. This calls for using advanced molecular genetics to understand the underlying pathway interactions responsible for this cancer. In this paper, we construct the CRC pathway from the literature and using an existing public dataset on healthy vs tumor colon cells, we identify the genes/pathways that are mutated and are possibly responsible for the disease progression. We then introduce drugs in the CRC pathway, and using a boolean modeling technique, we deduce the drug combinations that produce maximum cell death. Our theoretical simulations demonstrate the effectiveness of Cryptotanshinone, a traditional Chinese herb derivative, achieved by targeting critical oncogenic mutations and enhancing cell death. Finally, we validate our theoretical results using wet lab experiments on HT29 and HCT116 human colorectal carcinoma cell lines.
Increased Excitability and Heightened Magnitude of Long-term Potentiation at Hippocampal CA3-CA1 Synapses in a Mouse Model of Neonatal Hyperoxia Exposure
Authors: Ramani Manimaran , Miller Kiara , Ambalavanan Namasivayam , McMahon Lori L 
Published: September 2020

AbstractPreterm infants exposed to supraphysiological oxygen (hyperoxia) during the neonatal period have hippocampal atrophy and cognitive dysfunction later in childhood and as adolescents. Previously, we reported that 14-week-old adult mice exposed to hyperoxia as newborns had spatial memory deficits and hippocampal shrinkage, findings that mirror those of adolescents who were born preterm. Area CA1 region of the hippocampus that is crucial for spatial learning and memory is highly vulnerable to oxidative stress. In this study, we investigated the long-term impact of neonatal hyperoxia exposure on hippocampal CA3-CA1 synaptic function. Male and female C57BL/6J mouse pups were continuously exposed to either 85% normobaric oxygen or air between postnatal days 2-14. Hippocampal slice electrophysiology at CA3-CA1 synapses was then performed at 14 weeks of age. We observed that hyperoxia exposed mice have heightened strength of basal synaptic transmission measured in input-output curves, increased fiber volley amplitude indicating increased axonal excitability, and heightened LTP magnitude at CA3-CA1 synapses, likely a consequence of increased postsynaptic depolarization during the tetanus. These data demonstrate that supraphysiological oxygen exposure during the critical neonatal developmental period leads to pathologically heightened CA3-CA1 synaptic function during early adulthood which may contribute to hippocampal shrinkage and learning and memory deficits we previously reported. Furthermore, these changes may account for cognitive disorders in children born preterm who were exposed to prolonged oxygen supplementation.
Targeting ischemia-induced KCC2 hypofunction rescues refractory neonatal seizures and mitigates epileptogenesis in a mouse model
Authors: Sullivan Brennan J. , Kipnis Pavel A. , Carter Brandon M. , Kadam Shilpa D. 
Published: September 2020

AbstractNeonatal seizures pose a clinical challenge for their early detection, acute management, and mitigation of long-term comorbidities. A major cause of neonatal seizures is hypoxic-ischemic encephalopathy that results in seizures that are frequently refractory to the first-line anti-seizure medication phenobarbital (PB). One proposed mechanism for PB-inefficacy during neonatal seizures is the reduced expression and function of the neuron-specific K+/Cl−cotransporter 2 (KCC2), the main neuronal Cl−extruder that maintains chloride homeostasis and influences the efficacy of GABAergic inhibition. To determine if PB-refractoriness after ischemic neonatal seizures is dependent upon KCC2 hypofunction and can be rescued by KCC2 functional enhancement, we investigated the recently developed KCC2 functional enhancer CLP290 in a CD-1 mouse model of refractory ischemic neonatal seizures quantified with vEEG. We report that acute CLP290 intervention can rescue PB-resistance, KCC2 expression, and the development of epileptogenesis after ischemic neonatal seizures. KCC2 phosphorylation sites have a strong influence over KCC2 activity and seizure susceptibility in adult experimental epilepsy models. Therefore, we investigated seizure susceptibility in two different knock-in mice in which either phosphorylation of S940 or T906/T1007 was prevented. We report that KCC2 phosphorylation regulates both neonatal seizure susceptibility and CLP290-mediated KCC2 functional enhancement. Our results validate KCC2 as a clinically relevant target for refractory neonatal seizures and provide insights for future KCC2 drug development.
The potential of parrotfish faeces in replenishing reefs with coral-associated microbiome
Authors: Velásquez-Rodríguez Trigal M. , Zuluaga-Arias Catalina , Montaño-Salazar Sandra M. , González John M. , Sánchez Juan Armando 
Published: September 2020

AbstractSparisoma virideis the most abundant parrotfish in the Caribbean and is considered as the most important excavator due to corallivore behaviour. Parrotfishes are a keystone group that favour the growth and resilience of coral reefs removing macroalgae and structuring the benthic communities. The microbial symbiotic communities are involved in multiple functions related to nutrition and immunity maintaining corals health. BecauseS. viridescrape coral tissues, the skeleton and the algae on coral, it could be important reservoirs or vectors of microorganism for the corals through the faeces dispersion, however, the role of parrotfishes as reservoirs are poorly studied. Establishing microbial communities present in parrotfish faeces will contribute to understand the ecological impact of parrotfishes in coral resilience. We investigated the composition of disseminated bacteria and the extent to which the cell integrity of dinoflagellate photosymbionts (Symbiodiniaceae) is maintained in the faeces and compare with sediments and water column controls. Then, we analysed diversity and structure of bacterial communities at family level and search similarities between faeces of the study and coral associated microbiome reported in the literature. Similar levels of structural integrity and photosynthetic health of Symbidiodinaceae cells were found in both faeces and reef sediments. Besides, the sediments microbiome echoes the parrotfish faecal microbiome by sharing high diversity and a similar bacterial community composition. Several bacterial families were present in parrotfish faeces and in coral microbiome reported in the literature highlighting the dispersal potential of parrotfishes replenishing coral reefs. Despite the sampling limitations, these findings uncover the potential role of the excavator parrotfish in enriching environmental reservoirs, especially reef sediments, with coral-associated bacteria and photosynthetic microalgae. Parrotfishes could reinforce the coral microbiome and facilitate coral symbiont acquisition, key features critical to maintaining the fitness of one of the most threatened ecosystems on Earth. This finding could be considered as a first step in uncovering a mechanism for reef-microbiome maintenance.
Antifungal benzimidazoles disrupt vasculature by targeting one of nine β-tubulins
Authors: Garge Riddhiman K. , Cha Hye Ji , Lee Chanjae , Gollihar Jimmy D. , Kachroo Aashiq H. , Wallingford John B. , Marcotte Edward M. 
Published: September 2020

ABSTRACTThiabendazole (TBZ) is an FDA-approved benzimidazole widely used for its antifungal and antihelminthic properties. We showed previously that TBZ is also a potent vascular disrupting agent and inhibits angiogenesis at the tissue level by dissociating vascular endothelial cells in newly formed blood vessels. Here, we uncover TBZ’s molecular target and mechanism of action. Using human cell culture, molecular modeling, and humanized yeast, we find that TBZ selectively targets only 1 of 9 human β-tubulin isotypes (TUBB8) to specifically disrupt endothelial cell microtubules. By leveraging epidemiological pesticide resistance data and mining chemical features of commercially used benzimidazoles, we discover that a broader class of benzimidazole compounds, in extensive use for 50 years, also potently disrupt immature blood vessels and inhibit angiogenesis. Thus, besides identifying the molecular mechanism of benzimidazole-mediated vascular disruption, this study presents evidence relevant to the widespread use of these compounds while offering potential new clinical applications.
Evaluation of the electrochemical corrosion behavior of anodic aluminum oxide produced by the two-step anodization process
Authors: Yılmaz Bengisu , Hapçı Ağaoğlu Gökçe , Yüksel Behiye , Orhan Gökhan 
Published: September 2020

Purpose
This study aims to investigate the effect of different pore diameter and pore length on corrosion properties of anodic aluminum oxide (AAO) film.

Design/methodology/approach
AAO layer was produced by two-step anodization aluminum in oxalic acid. The surface morphology was investigated using field emission scanning electron microscopy. The pore diameters were ranging from 25 ± 5 to 65 ± 5 nm and the pore length ranging from 5 to 17 µm. The corrosion properties of the AAO films was analyzed by potentiodynamic polarization and electrochemical impedance spectroscopy tests. Corrosion properties and morphology of the anodic films depending on anodization times and pore expansion times were evaluated.

Findings
All highlights of this work can be summarized with the following specified below: more treatment with the protective barrier layer of the solution as the pore diameter increases depends on the morphology of the nanotube structured AAO layer. The excellent corrosion resistance renders AAO films without pore expansion very promising. The oxide layer thickness does not affect the corrosion resistance. The better corrosion resistance of AAO films at low pore length can be ascribed to the barrier layer thickness and the more homogeneous structure. The presence of defects for the higher pore length decreases its corrosion resistance.

Originality/value
The AAO films were fabricated by a two-step anodization method in oxalic acid. The anodization times and pore expansion times affect the corrosion performance. The AAO film without pore expansion has good corrosion resistance. The corrosion resistance decreases as the pore length increases.
Teratogenic potential of traditional Malaysian vegetables (ulam) in the zebrafish model
Authors: Omar Alya Hanisah , Kue Chin Siang , Dianita Roza , Yu Ke-Xin 
Published: September 2020

PurposeTraditional Malaysian vegetables, also known as ulam, are believed to have healing properties among the local community. Ulam is commonly reported to have high antioxidant content which makes it a popular food. The purpose of this paper is to determine the teratogenic potential of eight ulam, using zebrafish model. The tested ulam were Cosmos caudatus, Gynura procumbens, Labisia pumila var. alata, Phaleria macrocarpa, Polygonum minus, Piper sarmentosum, Premna foetida and Sauropus androgynous.Design/methodology/approachMethanol extract of ulam was prepared using the maceration method. Various concentrations of extracts were tested against fish embryo short-term toxicity test. The lethal concentration (LC50) and teratogenic effect of the ulam were determined.FindingsAmong all tested species, L. pumila, P. foetida and S. androgynous showed 100% lethal effect towards zebrafish embryos at concentrations of 10 µg/mL, 1,000 µg/mL and 100 µg/mL, respectively. The three ulam have exhibited teratogenic effect on zebrafish embryos after 72 h post-fertilization. L. pumila had induced yolk sac edema at 1.0 µg/mL for normalized measurement of 108.3 ± 2.0% (which is higher than negative control, p < 0.05, median = 110.7%), while P. foetida had induced pericardial edema at 100 µg/mL for normalized measurement of 124.0 ± 4.6% (which is higher than negative control, p < 0.05, median = 124.3%). On the other hand, S. androgynus induced curve trunk at 30 µg/mL for the presence of 70.9 ± 4.2%.Originality/valueThe teratogenic effect of L. pumila, P. foetida and S. androgynous suggests the possible disruption in the embryogenesis in zebrafish, namely Notch, vascular endothelial growth factor (VEGF) and retinoic acid pathways. The results of ulam gave possible implications and insights on the cancer pathways involved, which could be a useful target for cancer research. This is the first report on teratogenicity evaluation of Malaysian ulam showing relationship to cancer pathways by using zebrafish embryo model.
A bibliometric analysis on packaging research: towards sustainable and healthy packages
Authors: Vila-Lopez Natalia , Küster-Boluda Inés 
Published: September 2020

PurposeThe basis of this paper is to carry on a bibliometric analysis to investigate how “marketing” decisions have affected “packaging” success in different disciplines. This analysis covers from the first paper published on this topic (in 1956) to the last papers published in 2019.Design/methodology/approachA total of 1,170 scientific papers (including 14,177 citations within those papers) were retrieved from the Web of Science (WOS) and Scopus, dated from 1956 to 2019. Scimat software was used to analyse the data.FindingsThe results of this paper show that two main sectors constitute the focus of packaging studies from a marketing approach: food and tobacco. Recently, the main topics of research have evolved towards sustainable and health packaging, concerning different agents involved in packaging decisions: retailers, marketers, consumers and producers. So, both lines of research represent promising lines of research.Originality/valueThree different investigating profiles (i.e. engineers, marketers-psychologists and doctors-scientists) have examined how packaging should be prepared to succeed. However, a holistic bibliometric analysis about “packaging” and “marketing” is missing from those three branches of knowledge. This study is important to guide future lines of research to fill the identified gaps.
Organic and conventional apple fermented bySaccharomyces boulardii– The effect of the antioxidant quercetin on cellular oxidative stress
Authors: Silva Farinazzo Fernanda , Bervelieri Madeira Tiago , Carlos Fernandes Maria Thereza , Ishii Mauro Carolina Saori , Bosso Tomal Adriana Aparecida , Nixdorf Suzana Lucy , Garcia Sandra 
Published: September 2020

PurposeThe objective of this study was to evaluate the influence ofSaccharomyces boulardiion the kinetics of fermentation for organic and conventional apple pulp and to verify the effect of the antioxidant quercetin on the response to cellular oxidative stress.Design/methodology/approachThe kinetic parameters, the content of phenolic compounds, the quantity of quercetin and the antioxidant activity were determined during the fermentation process. The effect of quercetin on cellular oxidative stress was also investigated.FindingsThe content of phenolic compounds, the antioxidant activity and the quercetin concentration were higher in the organic fermented apple pulp (ORG) than in the conventional fermented apple pulp (CON). However, both apple pulps were considered ideal substrates for the growth ofS. boulardii, suggesting that they are potentially probiotic. After fermentation, the quercetin concentration in the ORG treatment and YPDQ treatment (YPD broth with 0.1 mg quercetin rhamnoside/mL) increased viability by 9%, while in the CON treatment generated there was an increase of 6% in viability, compared to the YPD control treatment (YPD broth).Originality/valueThe high concentration of quercetin in the organic apple pulp supports the proposal that quercetin reduces the oxidative stress mediated by reactive oxygen species through its antioxidant action onS. boulardiithat have similarities to mammalian eukaryotic cells. These findings suggest that fermented organic apple pulp could be consumed as a potential non-dairy probiotic product.
Stakeholder management in open innovation projects: a multiple case study analysis
Authors: Urbinati Andrea , Landoni Paolo , Cococcioni Francesca , De Giudici Ludovico 
Published: September 2020

PurposeIn recent years, companies have started to open up their Research and Development (R&D) and their innovation activities to external partners. They aim to access new resources and capabilities and to gain shorter time-to-markets. However, as several studies have shown, it can be difficult to manage collaborative (open) innovation projects to achieve desired outcomes. Starting from this premise, the paper investigates how project stakeholder management is different in open innovation projects from traditional R&D projects.Design/methodology/approachThe study has a qualitative nature and is based on the interpretative paradigm with an inductive orientation. The paper leverages interviews with experts involved in open innovation projects conducted in two Science and Technology Parks between Sweden and Italy.FindingsThe analysis shows how companies manage multiple stakeholders in open innovation projects and the peculiarities project stakeholder management faces in these projects when compared with traditional R&D projects. The paper shows how the relationships with external partners in open innovation projects are regulated by informal identification and analysis frameworks, which reduce the tensions deriving from these multiple collaborations. In addition, it underlines a set of good practices, and project management aspects for developing effective absorptive capacity of know-how, resources, and capabilities from external stakeholders in open innovation projects.Originality/valueThe paper analyzes for the first time how companies manage multiple stakeholders in open innovation projects in a different way from traditional R&D projects. Furthermore, the paper introduces a shift in the focus of the analysis: it focuses on the level of the project conducted through multiple collaborations instead of on the level of the firms involved in the project. Finally, the paper integrates open innovation research with project management research.
The mediating effect of meaningful work between human resource practices and innovative work behavior: a study of emerging market
Authors: Singh Nishant , Bamel Umesh , Vohra Veena 
Published: September 2020

PurposeThis study is aimed at examining the mediating effect of meaningful work (MFW) between human resource practices (HRP) i.e. staffing, training, participation, performance-based evaluation, and reward with innovative work behavior (IWB) of Indian small and medium-sized enterprise (SME) employees.Design/methodology/approachThis is a cross-sectional study with data of 199 respondents collected from the Indian SME sector. The mediation path was analyzed using multiple hierarchical regression analysis and processes.FindingsResults of the study indicate that human resource practices, i.e. staffing, training and participatory decision making, are positively related to IWB; MFW mediates the relationships between these human resource practices and IWB. Interestingly, performance-based evaluation and reward are not found to be related positively to IWB in SMEs.Originality/valueThe study adds value to SME literature on how SMEs may promote innovation amongst their employees. In addition, the findings of the present study add to human resource management (HRM) literature regarding practices in Indian SMEs.
A novel systematic product ideation model using technology trends
Authors: Tauqeer Muhammad Ahmad , Bang Knut Erik 
Published: September 2020

PurposeThis study aims to present a novel approach of using technology trends to trigger product ideas. It is primarily addressed to product ideation where limited applied approaches are available.Design/methodology/approachThe model is built by extending the theoretical framework of ideation study. It comprises morphological analysis with product breakdown as primary and technological trends as a secondary dimension to prompt product ideas from user’s intuition. The approach is multidisciplinary using insights from the areas of cognition, management strategy and project management. The model is further tested in two different test configurations with university students (n= 81).FindingsThe results indicate that this systematic model can increase the quality and number of ideas generated by the students compared to generally practised approaches. It is shown that this approach increases the chances of triggering ideas.Research limitations/implicationsThe testing of the present model is comprehensive and in no means exhaustive.Practical implicationsBecause of the shrinking product life cycle, organisations have a need for systematic product ideation models that can assist in innovating their product ranges. It is important to study idea generation for products to not only assist product innovation but also comprehensively understand the process of creativity. The proposed model is primarily addressed to product innovation projects where limited practical tools are available for product ideation. The present model is easy to apply and has the tendency to generate novel product ideas that can lead to successful product innovations.Originality/valueProduct innovation currently has limited systematic ideation tools where this study contributes.
Contract design and supplier performance: an empirical investigation using multi-criteria, decision analysis
Authors: Vlachos Ilias 
Published: September 2020

PurposeThis study aims to investigate how contract design influences supplier performance. This study synthesises three theoretical views (efficiency, relational, contingency) and provides empirical support on how effective contract design improves supplier performance.Design/methodology/approachThis study reviewed contract design literature and uncovered 18 factors that may impact supplier performance. Multi-criteria, decision-making analysis examined the impact of contract factors on three supplier groups: average-, over- and under-performers. Procurement experts working with a large multinational company dealing with hundreds of procuring contracts, yearly, provided their judgement on the impact of these factors on supplier performance. Semi-structured interviews with experts and other evidence were used for data and method triangulation.FindingsResults show that contracting with under- and over- performers presents significant differences: in the case of over-performers, contracts have a dual, yet discrete, efficiency and relational role: at transaction level, they emphasise formality, protect from opportunism and include both liquidated damages and legal action clauses. At relational level, they focus on relational learning and incentivising suppliers. However, in the case of under-performers, contracts appear to focus on contingency factors, which can be a source of ambiguity, particularly in complex environments, and trust, which has a negative impact on supplier performance.Social implicationsImproving contract design can help reduce partner opportunism, reduce inter-firm conflicts and avoid disputes that can bear a social cost. This study demonstrates that companies can use advanced analytical tools to reflect upon their own decision-making process of contact design in making transparent supplier performance assessments.Originality/valueTo the author’s knowledge, this is the first study using decision-making techniques to enhance supplier performance by improving the contract design process.