bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nonlinearity of regulation in biological networks
Authors: Manicka Santosh , Johnson Kathleen , Levin Michael , Murrugarra David 
Published: December 2021

ABSTRACTThe extent to which the components of a biological system are (non)linearly regulated determines how amenable they are to therapy and control. To better understand this property termed ‘regulatory nonlinearity’, we analyzed a suite of 137 published Boolean network models, containing a variety of complex nonlinear regulatory interactions, using a probabilistic generalization of Boolean logic that George Boole himself had proposed. Leveraging the continuous-nature of this formulation, we used Taylor decomposition to approximate the models with various levels of regulatory nonlinearity. A comparison of the resulting series of approximations of the biological models with appropriate random ensembles revealed that biological regulation tends to be less nonlinear than expected, meaning that higher-order interactions among the regulatory inputs tend to be less pronounced. A further categorical analysis of the biological models revealed that the regulatory nonlinearity of cancer and disease networks could not only be sometimes higher than expected but also relatively more variable. We show that this variation is caused by differences in the apportioning of information among the various orders of regulatory nonlinearity. Our results suggest that there may have been a weak but discernible selection pressure for biological systems to evolve linear regulation on average, but for certain systems such as cancer, on the other hand, to also evolve more nonlinear rules.
Intramolecular interactions enhance the potency of gallinamide A analogs againstTrypanosoma cruzi
Authors: Da Silva Elany Barbosa , Sharma Vandna , Hernandez-Alvarez Lilian , Tang Arthur H. , Stoye Alexander , O’Donoghue Anthony J. , Gerwick William H. , Payne Richard J. , McKerrow James H. , Podust Larissa M. 
Published: December 2021

ABSTRACTGallinamide A, a metabolite of the marine cyanobacteriumSchizothrixsp., selectively inhibits cathepsin L-like cysteine proteases. We evaluated potency of gallinamide A and 23 synthetic analogs against intracellularTrypanosoma cruziamastigotes and the cysteine protease, cruzain. We determined the co-crystal structures of cruzain with gallinamide A and two synthetic analogs at ∼2Å. SAR data revealed that the N-terminal end of gallinamide A is loosely bound and weakly contributes in drug-target interactions. At the C-terminus, the intramolecular π−π stacking interactions between the aromatic substituents at P1’ and P1 restrict the bioactive conformation of the inhibitors, thus minimizing the entropic loss associated with target binding. Molecular dynamics simulations showed that in the absence of an aromatic group at P1, the substituent at P1’ interacts with tryptophan-184. The P1-P1’ interactions had no effect on anti-cruzain activity whereas anti-T. cruzipotency increased by ∼5-fold, likely due to an increase in solubility/permeability of the analogs.
Lack of pulmonary fibrogenicity and carcinogenicity of titanium dioxide nanoparticles in 26-week inhalation study in rasH2 mouse model
Authors: Yamano Shotaro , Takeda Tomoki , Goto Yuko , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Kasai Tatsuya , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Umeda Yumi 
Published: December 2021

AbstractBackgroundWith the rapid development of alternative methods based on the spirit of animal welfare, the publications of animal studies evaluating endpoints such as cancer have been extremely reduced. There have been no systemic inhalation exposure studies of titanium dioxide nanoparticles (TiO2 NPs) using CByB6F1-Tg(HRAS)2Jic (rasH2) 26-week study mice model for detecting carcinogenicity.MethodsMale and female rasH2 mice were exposed to 2, 8 or 32 mg/m3 of TiO2 NPs for 6 hours/day, 5 days/week for 26 weeks using a whole-body inhalation exposure system, with reference to the Organization for Economic Co-operation and Development principles of Good Laboratory Practice. All tissues including lungs, and blood were collected and subjected to biological and histopathological analyses. Additionally, Ki67 positive index were evaluated in mice lung alveolar epithelial type 2 cell (AEC2).ResultsThis study established a stable method for generating and exposing TiO2 NPs aerosol, and clarified the dose-response relationship by TiO2 NPs inhalation to rasH2 mice. TiO2 NPs exposure induced deposition of particles in lungs and mediastinal lymph nodes in a dose-dependent manner in each exposure group. Additionally, alveolar inflammation was only observed in 32 mg/m3 exposure group in both the sexes. Exposure to TiO2 NPs, as well as other organs, did not increase the incidence of lung tumors in any group, and pulmonary fibrosis and pre-neoplastic lesions were not observed in all groups. Finally, the cell proliferative activity of AEC2 was examined, and it was not increased by exposure to TiO2 NPs.ConclusionsThis is the first report showing the lack of pulmonary fibrogenicity and carcinogenicity (no evidence of carcinogenic activity) of TiO2 NPs in 26-week inhalation study in rasH2 mice exposed up to 32 mg/m3, which is considered to be a high concentration. Macrophages undergoing phagocytosis due to TiO2 NPs exposure formed inflammatory foci in the alveolar regions of exposed mice but did not develop fibrosis or hyperplasia or tumors. Moreover, the cell proliferative ability of AEC2 in lesions was not increased. In addition, no carcinogenicity was observed for any organs other than the lungs in this study.
bulkAnalyseR: An accessible, interactive pipeline for analysing and sharing bulk multi-modal sequencing data
Authors: Moutsopoulos Ilias , Williams Eleanor C , Mohorianu Irina I 
Published: December 2021

AbstractBulk sequencing experiments (single- and multi-omics) are essential for exploring wide-ranging biological questions. To facilitate interactive, exploratory tasks, coupled with the sharing of easily accessible information, we present bulkAnalyseR, a package integrating state-of-the-art approaches using an expression matrix as the starting point (pre-processing functions are available as part of the package). Static summary images are replaced with interactive panels illustrating quality-checking, differential expression analysis (with noise detection) and biological interpretation (enrichment analyses, identification expression patterns, followed by inference and comparison of regulatory interactions). bulkAnalyseR can handle different modalities, facilitating robust integration and comparison of cis-, trans- and customised regulatory networks.bulkAnalyseR is available on CRAN and GitHub, with extensive documentation and usage examples (https://github.com/Core-Bioinformatics/bulkAnalyseR, https://cran.r-project.org/web/packages/bulkAnalyseR/)ContactIrina Mohorianu iim22@cam.ac.uk
Subject-specific features of excitation/inhibition profiles in neurodegenerative diseases
Authors: Monteverdi Anita , Palesi Fulvia , Costa Alfredo , Vitali Paolo , Pichiecchio Anna , Ramusino Matteo Cotta , Bernini Sara , Jirsa Viktor , Gandini Wheeler-Kingshott Claudia A.M. , D’Angelo Egidio 
Published: December 2021

AbstractBrain pathologies are based on microscopic changes in neurons and synapses that reverberate into large scale networks altering brain dynamics and functional states. An important yet unresolved issue concerns the impact of patients excitation/inhibition profiles on neurodegenerative diseases including Alzheimer’s disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. In this work we used a simulation platform, The Virtual Brain, to simulate brain dynamics in healthy controls and in Alzheimer’s disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis patients. The brain connectome and functional connectivity were extracted from 3T-MRI scans and The Virtual Brain nodes were represented by a Wong-Wang neural mass model endowing an explicit representation of the excitatory/inhibitory balance. The integration of cerebro-cerebellar loops improved the correlation between experimental and simulated functional connectivity, and hence The Virtual Brain predictive power, in all pathological conditions. The Virtual Brain biophysical parameters differed between clinical phenotypes, predicting higher global coupling and inhibition in Alzheimer’s disease and stronger NMDA (N-methyl-D-aspartate) receptor-dependent excitation in Amyotrophic Lateral Sclerosis. These physio-pathological parameters allowed an advanced analysis of patients’ state. In backward regressions, The Virtual Brain parameters significantly contributed to explain the variation of neuropsychological scores and, in discriminant analysis, the combination of The Virtual Brain parameters and neuropsychological scores significantly improved discriminative power between clinical conditions. Eventually, cluster analysis provided a unique description of the excitatory/inhibitory balance in individual patients. In aggregate, The Virtual Brain simulations reveal differences in the excitatory/inhibitory balance of individual patients that, combined with cognitive assessment, can promote the personalized diagnosis and therapy of neurodegenerative diseases.
Debate as a learning activity for teaching programming: a case in the subject of machine learning
Authors: Gunasilan Uma 
Published: December 2021

PurposeDebates are well known to encompass a variety of skills we would like higher education candidates to embody when they graduate.Design/methodology/approachDebates in a classroom with computer science as the main subject has been popular in high schools particularly with emerging issues around the area, however it does not have as an extensive similar documented outreach in tertiary education, particularly in the area of hard computer sciences and more recent concentrations of computer science, such as machine learning, artificial intelligence and cloud computing.FindingsTo explore further, the debate dataset had more methodologies applied and was split into training and testing sets, whose results were then compared by a standardized measure: Root Mean Square Error (RMSE) which is currently standard in the industry. The rationale of the approach is to quantify that debate activities have an immensely positive impact towards both the teaching and learning in technical subjects and needs to be more often and robustly used within higher education.Originality/valueThe rationale of the approach is that classroom debate activities equip students with verbal and social learning styles and an opportunity to engage with content in a way that is more comfortable than working with traditional lecture-and-laboratory style learning.
Getting students out there; using community partnerships to engage students
Authors: Cain Liz , Goldring John E. , Scott Jones Julie 
Published: December 2021

PurposeThe purpose of the paper is to discuss the “Q-Step in the Community” programme, part of the Q-Step Centre based in the Sociology Department at Manchester Metropolitan University, designed to help address the skills gap in quantitative methods (QM) that is evident across parts of the UK higher-education sector. “Q-Step in the Community” is a data-driven work-based learning programme that works in partnership with local organisations to provide placement opportunities for final year undergraduates and postgraduates. Students conduct a quantitative research project, which is typically identified by the placement provider.Design/methodology/approachThe authors use quantitative and qualitative feedback from students and placement providers, along with our own reflections on the process to evaluate the placement programme. Data were collected through a focus group and email interviews with placement providers, along with a questionnaire, which was distributed to “Q-Step in the Community” alumni.FindingsData-driven work-based learning opportunities allow students to develop and demonstrate their quantitative skills and support networking opportunities whilst also developing valuable soft-skills experience of the workplace that develops their career-readiness. In addition, those opportunities provide valuable research for placement providers, which support their sustainability and enhance their service delivery.Research limitations/implicationsThe research focusses solely on one programme at one university offering quantitative data driven work-based learning opportunities at undergraduate and post-graduate level. It is not possible to make valid comparisons between those who do a placement with those who do not.Originality/valueViews of key stakeholders in the process have been sought for this research, which can be useful to consider for others considering developing similar programmes for their students.
A review and content analysis of U.S. Department of Corrections end-of-life decision making policies
Authors: Helmly Victoria , Garica Marisol , Williams Brie , Howell Benjamin A. 
Published: December 2021

Purpose
With a rapidly growing population of older adults with chronic illness in US prisons, the number of people who die while incarcerated is increasing. Support for patients’ medical decision-making is a cornerstone of quality care for people at the end of life (EOL). This study aims to identify, describe, and analyze existing policies regarding EOL decision-making in U.S. Departments of Corrections.

Design/methodology/approach
This study performed an iterative content analysis on all available EOL decision-making policies in US state departments of corrections and the Federal Bureau of Prisons.

Findings
This study collected and reviewed available policies from 37 of 51 prison systems (73%). Some areas of commonality included the importance of establishing health-care proxies and how to transfer EOL decision documents, although policies differed in terms of which patients can complete advance care planning documents, and who can serve as their surrogate decision-makers.

Practical implications
Many prison systems have an opportunity to enhance their patient medical decision-making policies to bring them in line with community standard quality of care. In addition, this study was unable to locate policies regarding patient decision-making at the EOL in one quarter of US prison systems, suggesting there may be quality-of-care challenges around formalized approaches to documenting patient medical wishes in some of those prison systems.

Originality/value
To the best of the authors’ knowledge, this is the first content analysis of EOL decision-making policies in US prison systems.
Low-carbon VRP for cold chain logistics considering real-time traffic conditions in the road network
Authors: Bai Qinyang , Yin Xaioqin , Lim Ming K. , Dong Chenchen 
Published: December 2021

PurposeThis paper studies low-carbon vehicle routing problem (VRP) for cold chain logistics with the consideration of the complexity of the road network and the time-varying traffic conditions, and then a low-carbon cold chain logistics routing optimization model was proposed. The purpose of this paper is to minimize the carbon emission and distribution cost, which includes vehicle operation cost, product freshness cost, quality loss cost, penalty cost and transportation cost.Design/methodology/approachThis study proposed a mathematical optimization model, considering the distribution cost and carbon emission. The improved Nondominated Sorting Genetic Algorithm II algorithm was used to solve the model to obtain the Pareto frontal solution set.FindingsThe result of this study showed that this model can more accurately assess distribution costs and carbon emissions than those do not take real-time traffic conditions in the actual road network into account and provided guidance for cold chain logistics companies to choose a distribution strategy and for the government to develop a carbon tax.Research limitations/implicationsThere are some limitations in the proposed model. This study assumes that there are only one distribution and a single type of vehicle.Originality/valueExisting research on low-carbon VRP for cold chain logistics ignores the complexity of the road network and the time-varying traffic conditions, resulting in nonmeaningful planned distribution routes and furthermore low carbon cannot be discussed. This study takes the complexity of the road network and the time-varying traffic conditions into account, describing the distribution costs and carbon emissions accurately and providing the necessary prerequisites for achieving low carbon.
Information technology investment and innovation performance: does investment paradox exist?
Authors: Ji Peinan , Yan Xiangbin , Shi Yan 
Published: December 2021

Purpose
The purpose of this study is to deepen the understanding of the effects of information technology (IT) investment on firm innovation performance and examining the investment paradox effect in China.

Design/methodology/approach
Using a sample of China’ public firms IT investment data between 2010 and 2016, the authors establish a test model of IT investment and innovation performance.

Findings
The result indicates that IT investment in firms have no effect on innovation performance in the investment period. However, in the full sample and manufacturing sample, the IT investment has a significant positive effect on innovation performance in the post-investment years. In addition, this study finds that large companies and low-age companies may contribute more to innovation when firm investment in IT.

Research limitations/implications
There are several limitations in this research. First, the authors are failed to obtain a larger sample about the IT investment information data set in China, so this study was compelled to use limited sample data from China, hence, this could lead to errors of too early generalization. Second, the authors use the number of invention patent applications to represent the performance of enterprise innovation, which may not show enterprise innovation effectively. Third, the firms in the sample are all in China Listed Companies, so this may not accurately reflect the entire environment of firm innovation performance, and could possibly.

Practical implications
The research confirms that there is a paradox and time lag effect in IT investment, which enterprises should pay attention to.

Originality/value
Existing research confirms that corporate IT investments can bring new products or services. However, the authors still do not know whether IT investment has improved the company’s ability of innovation. This study will fill this gap and the industry effect and time lag effect of the influence of IT investment on innovative performance are also examined.
Assessing international students' satisfaction of a Jordanian university using the service quality model
Authors: Abu-Rumman Ayman , Qawasmeh Rasha 
Published: December 2021

PurposeEducation plays a key role in socio-economic development and globalization has increased the numbers of students wanting to study abroad. Attracting international students is therefore an important objective for universities as international students open up opportunities to bring economic, cultural and academic benefits to both the universities themselves and to the countries in which they are located. This study therefore aimed to assess student satisfaction with a Jordanian university using the dimensions of quality contained within the established SERVQUAL model.Design/methodology/approachTo achieve these goals, quantitative data was collected from international students attending one university located in Jordan via a questionnaire survey, using a randomized sample. Structural equation modeling (SEM) was used to analyze the construct validity, and correlations between student satisfaction and the different dimensions of quality were tested.FindingsConsistent with other studies, the findings demonstrated that the five dimensions of service quality, i.e. tangibility, reliability, responsiveness, assurance and empathy, and the university of study, have a strong relationship with student satisfaction. However, there was no statistically significant correlation between country satisfaction and the tangibility and assurance sub-dimensions of quality.Practical implicationsPractical implications – The findings of this study are of interest and practical benefit to university leaders in developing their quality and student acquisition strategies.Originality/valueThis study makes a useful contribution to the growing body of evidence of service quality in higher education set within the context of a developing country.
Through the looking glass: perceiving risk and emotions toward cosmetic procedure engagement
Authors: Sood Abhinav , Quintal Vanessa Ann , Phau Ian 
Published: December 2021

Purpose
This research aims to develop a user risk segmentation typology and implement a method that traces how user emotions adapt before, after and toward a next cosmetic procedure. It introduces the user risk segments to an empirical framework to explain re-engagement with the procedure.

Design/methodology/approach
A survey was self-administered to online consumer panels in the USA. The survey targeted users who had previously undertaken one of three elective procedures, namely, Botox (N = 550), hair transplant (N = 350) or liposuction (N = 350).

Findings
The typology identified timid image seekers, daring image crafters, approval-seeking socialites and mainstream image adopters. The method tracking user emotions found significant differences before, after and toward a next cosmetic procedure in the user risk segments. The framework predicted user re-engagement with the procedure for each segment.

Research limitations/implications
The typology presents more sophisticated user risk profiles. The method maps adapting user emotions toward engagement pre- and post-procedure. However, findings are limited to the USA and three cosmetic procedures.

Practical implications
The typology offers a profile of users and their risk perceptions of a behavior. The method presents an instrument that follows how user emotions adapt. The framework advances understanding of user re-engagement with the behavior.

Originality/value
Arguably, to the best of the authors’ knowledge, this is the first research to explore how perceived risk operates on emotional states and adaptation, which manifest user well-being and impact user behavior.
Value co-creation in services for animal companions
Authors: Hendricks Jennifer , Schmitz Gertrud 
Published: December 2021

PurposeAs other actors in the service ecosystem often have a pivotal role in value creation for actors experiencing vulnerability, this paper aims to explore caregiving customer value co-creation in services for animal companions.Design/methodology/approachStudy 1 follows a two-step procedure, using two different qualitative approaches (interviews and observations) to identify caregiving customer value co-creation activities. Study 2 serves to empirically test a higher-order structure of caregiving customer participation behaviour in value co-creation and test for differences regarding customer and service characteristics (questionnaire survey;n= 680).FindingsThe results reveal the existence of various value co-creation activities towards the service provider (e.g. cooperation under consideration of the animal companion’s needs) and animal companion (e.g. emotional support). Significant differences in individual caregiving customers’ activities were found regarding gender, age, type of service and animal companion. Caregiving customer value co-creation is influenced by emotional attachment and has a positive effect on value outcomes for both the caregiving customer and the animal companion.Originality/valueThis study extends and enriches customer value co-creation literature by providing innovative findings on various such caregiving activities and value outcomes in services for (non-human) actors experiencing vulnerability. It also adds knowledge by showing differences in customer value co-creation behaviour regarding specific customer and service characteristics.