bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with IFB-088 improves neuropathy in CMT1A and CMT1B mice
Authors: Bai Yunhong , Treins Caroline , Volpi Vera G. , Scapin Cristina , Ferri Cinzia , Mastrangelo Rosa , Touvier Thierry , Florio Francesca , Bianchi Francesca , Del Carro Ubaldo , Baas Frank F. , Wang David , Miniou Pierre , Guedat Philippe , Shy Michael E. , D’Antonio Maurizio 
Published: October 2021

AbstractCharcot Marie Tooth diseases type 1A (CMT1A), caused by duplication of Peripheral Myelin Protein 22 (PMP22) gene, and CMT1B, caused by mutations in myelin protein zero (MPZ) gene are the two most common forms of demyelinating CMT (CMT1) and no treatments are available for either. Prior studies of the MpzSer63del mouse model of CMT1B have demonstrated that protein misfolding, endoplasmic reticulum (ER) retention and activation of the unfolded protein response (UPR) contributed to the neuropathy. Heterozygous patients with an arginine to cysteine mutation in MPZ (MPZR98C) develop a severe infantile form of CMT1B which is modeled by MpzR98C/+ mice that also show ER-stress and an activated UPR. C3-PMP22 mice are considered to effectively model CMT1A. Altered proteostasis, ER-stress and activation of the UPR have been demonstrated in mice carrying Pmp22 mutations. To determine whether enabling the ER-stress/UPR and readjusting protein homeostasis would effectively treat these models of CMT1B and CMT1A we administered Sephin1/IFB-088/icerguestat, a UPR modulator which showed efficacy in the MpzS63del model of CMT1B, to heterozygous MpzR98C and C3-PMP22 mice. Mice were analyzed by behavioral, neurophysiological, morphological and biochemical measures. Both MpzR98C/+ and C3-PMP22 mice improved in motor function and neurophysiology. Myelination, as demonstrated by g-ratios and myelin thickness, improved in CMT1B and CMT1A mice and markers of UPR activation returned towards wild type values. Taken together our results demonstrate the capability of IFB-088 to treat a second mouse model of CMT1B and a mouse model of CMT1A, the most common form of CMT. Given the recent benefits of IFB-088 treatment in Amyotrophic Lateral Sclerosis and Multiple Sclerosis animal models, these data demonstrate its potential in managing UPR and ER-stress for multiple mutations in CMT1 as well as in other neurodegenerative diseases.
Therapeutic KRASG12C inhibition drives effective interferon-mediated anti-tumour immunity in immunogenic lung cancers
Authors: Mugarza Edurne , van Maldegem Febe , Boumelha Jesse , Moore Christopher , Rana Sareena , Sopena Miriam Llorian , East Philip , Ambler Rachel , Anastasiou Panayiotis , Clavijo Pablo Romero , Valand Karishma , Cole Megan , Molina-Arcas Miriam , Downward Julian 
Published: October 2021

AbstractRecently developed KRASG12C inhibitory drugs are beneficial to lung cancer patients harbouring KRASG12C mutations, but drug resistance frequently develops. Due to the immunosuppressive nature of the signaling network controlled by oncogenic KRAS, these drugs can indirectly affect anti-tumour immunity, providing a rationale for their combination with immune checkpoint blockade. In this study, we have characterised how KRASG12C inhibition reverses immune suppression driven by oncogenic KRAS in a number of pre-clinical lung cancer models with varying levels of immunogenicity. Mechanistically, KRASG12C inhibition upregulates interferon signaling via Myc inhibition, leading to reduced tumour infiltration by immunosuppressive cells, enhanced infiltration and activation of cytotoxic T cells, and increased antigen presentation. However, the combination of KRASG12C inhibitors with immune checkpoint blockade only provides synergistic benefit in the most immunogenic tumour model. KRASG12C inhibition fails to sensitize cold tumours to immunotherapy, with implications for the design of clinical trials combining KRASG12C inhibitors with anti-PD1 drugs.One sentence summaryKRAS inhibition mobilizes anti-tumour immunity in immunogenic lung cancer models through derepressing interferon signaling via repression of Myc.
Transcriptional variability accelerates pre-leukemia by cell diversification and perturbation of protein synthesis
Authors: Gupta Shikha , Dovey Oliver M. , Domingues Ana Filipa , Cyran Oliwia W. , Cash Caitlin M. , Giotopoulos George , Rak Justyna , Cooper Jonathan , Gozdecka Malgorzata , Asby Ryan J. , Al-Jabery Noor , Hernandez-Hernandez Victor , Prabakaran Sudhakaran , Huntly Brian J. , Vassiliou George S. , Pina Cristina 
Published: October 2021

AbstractTranscriptional variability facilitates stochastic cell diversification and can in turn underpin adaptation to stress or injury. We hypothesize that it may analogously facilitate progression of pre-malignancy to cancer. To investigate this, we initiated pre-leukemia in mouse cells with enhanced transcriptional variability due to conditional disruption of the histone lysine acetyltransferase gene Kat2a. By combining single-cell RNA-sequencing of pre-leukemia with functional analysis of transformation, we show that Kat2a loss results in global variegation of cell identity and accumulation of pre-leukemic cells. Leukemia progression is subsequently facilitated by destabilization of ribosome biogenesis and protein synthesis, which confer a transient transformation advantage. The contribution of transcriptional variability to early cancer evolution reflects a generic role in promoting cell fate transitions, which, in the case of well-adapted malignancies, contrastingly differentiates and depletes cancer stem cells. In other words, transcriptional variability confers forward momentum to cell fate systems, with differential multi-stage impact throughout cancer evolution.One-sentence summaryLoss of Kat2a enhances transcriptional variability of ribosome biosynthetic programs and transiently accelerates pre-leukemia
Liposomal encapsulation of polysaccharides (LEPS) as an effective vaccine strategy to protect aged hosts against S. pneumoniae infection
Authors: Bhalla Manmeet , Nayerhoda Roozbeh , Tchalla Essi Y. I. , Abamonte Alexsandra , Park Dongwon , Simmons Shaunna R. , Pfeifer Blaine A. , Bou Ghanem Elsa N. 
Published: October 2021

AbstractDespite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts elderly individuals ≥65 years old. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2-3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (20-22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.
Experimental evolution of extremophile levels of radiation resistance in Escherichia coli
Authors: Bruckbauer Steven T. , Minkoff Benjamin B. , Shinohara Takeshi , Lipzen Anna , Guo Jie , Wood Elizabeth A. , Sussman Michael R. , Pennacchio Christa , Cox Michael M. 
Published: October 2021

AbstractRecent human development of high-level sources of ionizing radiation (IR) prompts a corresponding need to understand the effects of IR on living systems. One approach has focused on the capacity of some organisms to survive astonishing levels of IR exposure. Using experimental evolution, we have generated populations of Escherichia coli with IR resistance comparable to the extremophile Deinococcus radiodurans. Every aspect of cell physiology is affected. Cellular isolates exhibit approximately 1,000 base pair changes plus major genomic and proteomic alterations. The IR resistance phenotype is stable without selection for at least 100 generations. Defined and probable contributions include alterations in cellular systems involved in DNA repair, amelioration of reactive oxygen species, Fe metabolism and repair of iron-sulfur centers, DNA packaging, and intermediary metabolism. A path to new mechanistic discoveries, exemplified by an exploration of rssB function, is evident. Most important, there is no single molecular mechanism underlying extreme IR resistance.
Plant growth and phytoactive alkaloid synthesis in Mitragyna speciosa (kratom) in response to varying radiance
Authors: Zhang Mengzi , Sharma Abhisheak , León Francisco , Avery Bonnie , Kjelgren Roger , McCurdy Christopher R. , Pearson Brian J. 
Published: October 2021

AbstractThe dose-dependent consumptive effect of kratom and its potential application as an alternative source of medicine to mitigate opioid withdrawal symptoms has brought considerable attention to this plant. Increased interest in the application and use of kratom has emerged globally, including North America. Although the chemistry and pharmacology of major kratom alkaloids, mitragynine and 7-hydroxymitragynine, are well documented, foundational information on the impact of plant production environment on growth and kratom alkaloids synthesis is unavailable. To directly address this need, kratom plant growth, leaf chlorophyll content, and alkaloid concentration were evaluated under three lighting conditions: outdoor full sun, greenhouse unshaded, and greenhouse shaded. Nine kratom alkaloids were quantified using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Contents of six alkaloids to include: mitragynine, speciogynine, speciociliatine, mitraphylline, coynantheidine, and isocorynantheidine were not significantly impacted by lighting conditions, whereas 7-hydroxymitragynine was below the lower limit of quantification across all treatments. However, paynantheine concentration per leaf dry mass was increased by 40% and corynoxine was increased by 111% when grown under shade conditions in a greenhouse compared to outdoor full sun. Additionally, total alkaloid yield per plant was maximized when plants were under such conditions. Greenhouse cultivation generally promoted height and width extension, leaf number, leaf area, average leaf size, and total leaf dry mass, compared to outdoor full sun condition. Rapid, non-destructive chlorophyll evaluation correlated well (r2 = 0.68) with extracted chlorophyll concentrations. Given these findings, production efforts where low-light conditions can be implemented are likely to maximize plant biomass and total leaf alkaloid production.
Collaborative spaces: at the intersection of design and management
Authors: Bachnik Katarzyna , Moll Isa , Montaña Jordi 
Published: October 2021

Purpose
Because of the differing perceptions held by each position or professional subculture, forming a collaborative and productive workplace with design and management teams can be challenging. In light of these anticipated obstacles to success in the workplace, this paper aims to ascertain the prospects for common undertakings within a business.

Design/methodology/approach
This paper reports on an analysis of a survey conducted among design and business students who had the opportunity to work together on a joint project and present their recommendations for an actual market-based organization.

Findings
Despite differences between the groups, there is a common understanding of organizational goals and willingness to undertake a joint effort to achieve them. This is accomplished through leveraging one another’s professional expertise, building trust through finishing the business projects and discovering tangible end results. Any evident differences between the groups seem to complement one another, thus creating common ground for effective collaboration.

Research limitations/implications
This is a study of a limited number of students enrolled in two universities in Spain. To ensure generalizability, research extended to more higher education institutions is needed.

Practical implications
The authors strongly believe that students are the future of business. As a result, understanding how they perceive any tension, integration or responsibilities of design and management helps with curriculum development two-fold: first, student perceptions help address any issues that can increase or hinder chances for efficient collaboration; second, student perceptions address the larger issue of design–management integration in business.

Originality/value
The authors studied a unique environment for collaboration beyond traditional organizational divisions and allowed study behaviors of students representing two professional backgrounds.
Hybrid organizational forms in public sector’s digital transformation: a technology enactment approach
Authors: Faro Benjamin , Abedin Babak , Cetindamar Dilek 
Published: October 2021

PurposeThe purpose of this paper is to examine how public sector organizations become nimbler while retaining their resilience during digital transformation.Design/methodology/approachThe study adopts a hermeneutic approach in conducting deep expert interviews with 22 senior executives and managers of multiple organizations. The method blends theory and expert views to study digital transformation in the context of enterprise information management.FindingsDrawing on technology enactment framework (TEF), this research poses that organizational form is critical in the enactment of technologies in digital transformation. By extending the TEF, the authors claim that organizations are not in pure bureaucratic or network organizational form during digital transformation; instead, they need a hybrid combination in order to support competing strategic needs for nimbleness and resilience simultaneously. The four hybrid organizational forms presented in this model (4R) allow for networks and bureaucracy to coexist, though at different levels depending on the level of resiliency and nimbleness required at each point in the continuous digital transformation journey.Research limitations/implicationsThe main theoretical contribution of this research is to extend the TEF to illustrate that the need for coexistence of nimbleness with stability in a digital transformation results in a hybrid of networks and bureaucratic organization forms. This research aims to guide public sector organizations' digital transformation with extended the TEF as a tool for building the required organizational forms to influence the technology enactment to best meet their strategic needs in the digital era.Practical implicationsThe results from expert interviews point to the fact that the hybrid organizational forms create a multi-modal organization, extending the understanding of enterprise information management. Depending on the department or business needs, a hybrid organizational form mode would be dominant. This dominance creates a paradox in organizations to handle both resilience and nimbleness. Therefore, the 4R model is provided as a guide to public sector managers and consultants to guide strutting their organization for digital transformation.Originality/valueThe model (4R), the extended TEF, shows that organizations still work towards networks and bureaucracy; however, they are not two distinct concepts anymore; they coexist at different levels in hybrid forms depending on the needs of the organization.
A systematic bibliometric review of the strategic entrepreneurship domain
Authors: Thomas Gareth H. , Douglas Evan J. , Yamada Jin-Ichiro , Senyard Julienne 
Published: October 2021

Purpose
The strategic entrepreneurship (SE) literature exists at the intersection of the strategy and entrepreneurship literatures and has grown rapidly over the past two decades. This study aims to document the proliferation of research papers and identifies the major thematic clusters of topics and other summary information for the SE research domain.

Design/methodology/approach
This is a systematic bibliometric review of 586 articles published over the period 2009–2019 in 143 journals. The inductive quantitative assessment of these articles uses meta-data driven techniques that prioritize reproducibility and rigor in the process of literature analysis.

Findings
This study identifies six main themes in the strategic literature, namely, Sustainable Competitive Advantage; Knowledge Management; Ecosystems; Strategy; Entrepreneurialism; and Organization and Management. It also reports data on a variety of issues including research techniques, country of data, co-author count and trends and differences between journals based on their journal impact factors and calls for more research in key areas.

Originality/value
An innovative original analytical tool was developed to facilitate the analysis of research papers in this growing field. This online tool allows multiple tags to be attached to each paper by multiple authors working simultaneously to identify keywords and other aspects that were subsequently used to identify six main thematic areas within the SE literature. This paper highlights emerging research trends and identifies gaps in the literature that provide opportunities for further research in this field.
Applying the trans-theoretical model to determine the mediating effect self-efficacy in breakfast consumption among children
Authors: Mohajeri Mahsa , Narimani Sajad , Shahbazzadeh Fardin , Bahrampanah Saniyeh , Ghaderi Vida 
Published: October 2021

PurposeRegular breakfast with a variety of nutrients can lead to improving educational performance, learning ability, reducing behavioral problems in elementary students. This study aims to use the Trans-Theoretical Model (TTM) to assess the mediating effect of self-efficacy in regular breakfast consumption among children of Ardabil elementary schools.Design/methodology/approachThis cross-sectional study was performed between 300 students from elementary schools of different regions of Ardabil city by cluster sampling method. The instrument used in this study was the TTM standard questionnaire. Data was analyzed with Spearman correlation and regression using SPSS v18 software to identify the mediating effects of self-efficacy.FindingsThe mean age (SD) OF children was 11.2 (1.26) and 50% of them were female. Self-efficacy was the strongest predictor in stage promotion (ß= 0.44,P= 0.001), as well as had a mediating effect on the impact of other constructs of the model such as experiential processes (ß= 0.35,P= 0.04) and pros (ß= 0.44,P= 0.03) with stages of change. Pros were a significant predictor of self-efficacy in the first equation (ß= 0.17,P= 0.001) and Pros were a significant predictor of stages of change in the second equation when mediated by self-efficacy (ß= 0.11,P= 0.03). In the third equation, both the mediator, myself-efficacy and the predictor, Pros of breakfast consumption, were significantly associated with stages of change. The mediating effects of self-efficacy on the association between experiential processes and stages of change were also confirmed. The increased standardized beta coefficients of experiential processes between equations 3(ß= 0.35) and 2(ß= 0.29).Originality/valueDue to the importance of eating a healthy breakfast regularly in children, this study aimed to use TTM to assess mediating effects of self-efficacy in regular breakfast consumption in Ardabil elementary students.
Ethics and accounting education: does teaching stand-alone religious courses affect accounting students’ ethical decisions?
Authors: Ebaid Ibrahim El-Sayed 
Published: October 2021

Purpose
Undergraduate accounting program at Umm Al-Qura University in Saudi Arabia is a unique case. The program includes 147 credit hours of which 28 credit hours are religious courses. This study aims to examine the effect of teaching these religious courses on students’ ethical perceptions and decisions.

Design/methodology/approach
A survey was conducted for a sample of accounting students at Umm Al-Qura University. The sample was divided into two groups; the first group includes students who did not study religious courses, while the second group includes students who study religious courses. The questionnaire contained three groups of questions that aimed to explore students’ perceptions of ethics in general, students’ perceptions of business ethics and explored their ethical attitudes regarding some accounting decisions that involve ethical dilemmas. Independent two-sample t-test and multiple regression analysis were used to determine whether the responses of the two groups were significantly different.

Findings
The findings of the study revealed that teaching religious courses led to an improvement in students’ perception of business ethics and an improvement in students’ ethical decision-making. However, the results of the independent sample t-test showed that this improvement was not significant. The results of the study also revealed that male students tend to make less ethical decisions than female students.

Research limitations/implications
The findings offer an indication for those responsible for managing the accounting program at Umm Al-Qura University to start developing the program so that some of the general religious courses are replaced with specialized courses in accounting ethics that focus directly on ethical dilemmas faced by the accountant when practicing the accounting profession.

Originality/value
This study contributes to the current literature related to examining the effect of teaching ethics courses on the ethical perception of accounting students by focusing on accounting students in Saudi Arabia as a context that has not been examined before.