bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fingolimod for treatment and or prevention of chemotherapy-induced peripheral neuropathy in humans?
Authors: Loprinzi Charles L. , Harlos Beth , Staff Nathan , Zahrieh David 
Published: September 2022

AbstractPurposeSubstantial preclinical data support that fingolimod, a drug that dysregulates sphingolipid metabolism, could both prevent chemotherapy-induced neuropathy (CIPN) and treat established chemotherapy-induced neuropathy.MethodsTwo pilot-phase clinical trials were developed to evaluate whether fingolimod could 1) inhibit the development of paclitaxel-induced peripheral neuropathy and 2) diminish established CIPN in humans.ResultsUnfortunately, both clinical trials were not able to fulfill planned accrual goals. One of the major accrual problems was the requirement for patients to be in the clinic for 8 hours following their first oral dose of fingolimod. The prevention of paclitaxel CIPN trial accrued 2 patients, one of whom did very well without any significant CIPN while the other patient developed CIPN that led to early paclitaxel dose cessation. The treatment of established CIPN trial accrued 7 of 10 planned patients. The results from the 6 patients who started daily treatment with fingolimod did not suggest that it substantially decreased CIPN over what might have been expected from a placebo effect.ConclusionFingolimod is a clinically difficult treatment for patients to start and the limited clinical data from these protocols did not support that it was able to prevent CIPN or treat established CIPN.
Cryo-EM analyses of wild-type and oncogenic KIT mutants reveal structural oncogenic plasticity and a novel “Achilles heel” for therapeutic intervention
Authors: Krimmer Stefan G. , Bertoletti Nicole , Suzuki Yoshihisa , Katic Luka , Mohanty Jyotidarsini , Shu Sheng , Lee Sangwon , Lax Irit , Mi Wei , Schlessinger Joseph 
Published: September 2022

AbstractThe receptor tyrosine kinase KIT and its ligand SCF are required for the development of hematopoietic stem cells, germ cells, and other cells. A variety of human cancers, such as acute myeloid leukemia and mast cell leukemia, are driven by somatic gain-of-function KIT mutations. Here, we report cryo-EM structural analyses of full-length wild-type and two oncogenic KIT mutants, which show that the symmetric arrangement of ligand-occupied KIT dimers is converted into asymmetric D5 homotypic contacts juxtaposing the plasma membrane. Mutational analysis of KIT reveals in D5 region an “Achilles heel” for therapeutic intervention. A ligand-sensitized oncogenic KIT mutant exhibits a more comprehensive and stable D5 asymmetric conformation. A constitutively active ligand-independent oncogenic KIT mutant adopts a V-shaped conformation solely held by D5-mediated contacts. SCF binding to this mutant fully restores the conformation of wild-type KIT dimers, revealing an unexpected structural plasticity of oncogenic mutants that may offer new therapeutic modality.
Camellia sinensis solvent extract confers trophocidal and cysticidal effects against Acanthamoeba castellanii
Authors: Fakae Lenu B. , Harun Mohammad S. R. , Ting Darren Shu Jeng , Dua Harminder S. , Cave Gareth W.V. , Zhu Xing-Quan , Stevenson Carl W. , Elsheikha Hany M. 
Published: September 2022

ABSTRACTAimWe examined the anti-acanthamoebic efficacy of solvent extract of C. sinensis) and its chemical constituents against trophozoites and cysts of A. castellanii.Materials and methodsThe effects of C. sinensis solvent extract on A. castellanii was investigated by using anti-trophozoite, anti-encystation, and anti-excystation assays. The solvent extract was also fractionated using Gas Chromatography and the chemical constituents of C. sinensis were tested, individually or combined, against the trophozoites.ResultsTrophozoite replication was inhibited within 24-72 h with exposure to 625-5000 µg/mL of C. sinensis solvent extract. C. sinensis also exhibited a dose-dependent inhibition of encystation, with a marked cysticidal activity at 2500-5000 µg/mL concentrations. Two constituents of C. sinensis, namely epigallocatechin-3-gallate and caffeine, significantly inhibited trophozoite replication and encystation at 100 μM and 200 μM, respectively. Cytotoxicity analysis showed that 156.25-2500 µg/mL of solvent extract was not toxic to human corneal epithelial cells, while up to 625 µg/mL was not toxic to Madin-Darby Canine Kidney cells.ConclusionsThis study shows the anti-acanthamoebic potential of C. sinensis solvent extract against trophozoites and cysts. Further pre-clinical studies are required to elucidate the in vivo efficacy and safety of C. sinensis solvent extract.Graphical abstract
Dysregulation of The Chromatin Environment Leads to Differential Alternative Splicing as A Mechanism Of Disease In a Human Model of Autism Spectrum Disorders
Authors: Leung Calvin S. , Rosenzweig Shoshanna , Yoon Brian , Marinelli Nicholas A. , Hollingsworth Ethan W. , Maguire Abbie M. , Cowen Mara M. , Schmidt Michael , Imitola Jaime , Gamsiz Uzun Ece D. , Lizarraga Sofia B. 
Published: September 2022

ABSTRACTAutism spectrum disorder (ASD) affects 1 in 44 children. Chromatin regulatory proteins are overrepresented among genes that contain high risk variants in ASD. Disruption of the chromatin environment leads to widespread dysregulation of gene expression, which is traditionally thought as a mechanism of disease pathogenesis associated with ASD. Alternatively, alterations in chromatin dynamics could also lead to dysregulation of alternative splicing, which is understudied as a mechanism of ASD pathogenesis. The anticonvulsant valproic acid (VPA) is a well-known environmental risk factor for ASD that acts as a class I histone deacetylase (HDAC) inhibitor. However, the precise molecular mechanisms underlying defects in human neuronal development associated with exposure to VPA are understudied. To dissect how VPA exposure and subsequent chromatin hyperacetylation influence molecular signatures involved in ASD pathogenesis, we conducted RNA sequencing (RNA-seq) in human cortical neurons that were treated with VPA. We observed that differentially expressed genes (DEGs) were enriched for mRNA splicing, mRNA processing, histone modification, and metabolism related gene sets. Furthermore, we observed widespread increase in the number and the type of alternative splicing events. Analysis of differential transcript usage (DTU) showed that exposure to VPA induces extensive alterations in transcript isoform usage across neurodevelopmentally important genes. Finally, we find that DEGs and genes that display DTU overlap with known ASD-risk genes. Together, these findings suggest that, in addition to differential gene expression, changes in alternative splicing correlated with alterations in the chromatin environment could act as an additional mechanism of disease in ASD.
Genetic Risk Factors for ME/CFS Identified using Combinatorial Analysis
Authors: Das Sayoni , Taylor Krystyna , Kozubek James , Sardell Jason , Gardner Steve 
Published: September 2022

AbstractBackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help to alleviate some of these issues for patients.MethodsWe applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case-control design with 1,000 cycles of fully random permutation. Results from this study were supported by a series of replication and cohort comparison experiments, including use of disjoint Verbal Interview CFS, post-viral fatigue syndrome and fibromyalgia cohorts also derived from UK Biobank, and results compared for overlap and reproducibility.ResultsCombinatorial analysis revealed 199 SNPs mapping to 14 genes, that were significantly associated with 91% of the cases in the ME/CFS population. These SNPs were found to stratify by shared cases into 15 clusters (communities) made up of 84 high-order combinations of between 3-5 SNPs. p-values for these communities range from 2.3 × 10−10 to 1.6 × 10−72. Many of the genes identified are linked to the key cellular mechanisms hypothesized to underpin ME/CFS, including vulnerabilities to stress and/or infection, mitochondrial dysfunction, sleep disturbance and autoimmune development. We identified 3 of the critical SNPs replicated in the post-viral fatigue syndrome cohort and 2 SNPs replicated in the fibromyalgia cohort. We also noted similarities with genes associated with multiple sclerosis and long COVID, which share some symptoms and potentially a viral infection trigger with ME/CFS.ConclusionsThis study provides the first detailed genetic insights into the pathophysiological mechanisms underpinning ME/CFS and offers new approaches for better diagnosis and treatment of patients.
Awareness and practice of the principles of circular economy among built environment professionals
Authors: Amudjie Judith , Agyekum Kofi , Adinyira Emmanuel , Amos-Abanyie Samuel , Kumah Victoria Maame Afriyie 
Published: September 2022

PurposeThis study examines the level of awareness and practice of the principles of circular economy (CE) among built environment (BE) professionals in Ghana.Design/methodology/approachA structured questionnaire survey was used to solicit the views of 162 BE professionals working in construction, consulting and developer firms on the issue under investigation. Data were analysed through descriptive and inferential analysis.FindingsThe findings revealed that the BE professionals possessed moderate awareness of the six CE principles (i.e. repair, recycle, reuse, renewable energy usage, reduce and redesign) examined. The findings further revealed that only two out of the six principles (i.e. repair and reuse) received some moderate level of practice among the professionals.Practical implicationsPractically, the findings would be relevant to government, policymakers, researchers and other construction professionals. For the government and policymakers, these findings would inform them on the laws and policies to enact to increase awareness and practice of CE principles. For researchers, these findings will assist in exploring gaps for further studies. For the construction professionals, the findings would inform them of the need to step up measures to practice the various principles of CE in their firms adequately.Originality/valueThis study provides insights into an under-investigated topic in the construction industry worldwide. It offers new and additional insights into the current state-of-the-art practice of CE principles among BE professionals.
Chinese multinationals post-merger integration evolutions in developed markets from autonomy to actual-form integration: a lens of ambidexterity
Authors: Yang Yanan 
Published: September 2022

Purpose
This paper aims to examine how Chinese multinational enterprises’ (CMNEs) autonomy-style post-merger integration (PMI) modes of managing developed-market targets evolve into actual-form integration through the lens of ambidexterity.

Design/methodology/approach
This study adopts multi-case comparisons with content analysis. A data set was collected from 37 conversations by in-depth interviewing 29 respondents regarding four cases of Chinese acquisitions in the German market.

Findings
This study develops a three-stage framework that theorised CMNEs’ autonomy PMIs’ evolution to actual-form integration over time and the effect on acquisition value based on structural, temporal and contextual ambidexterity manifestations. The findings divide the evolutionary trajectory into two sub-trajectories, from great autonomy to autonomy-integration balanced or full integration, to illuminate the effect of different degrees of actual-form integration on value creation or value destruction.

Originality/value
The existing literature on CMNEs’ PMI discovered that CMNEs frequently grant ample autonomy when managing targets acquired from developed markets. However, long-term acquisition benefit is dependent on combining autonomy and actual-form integration; insights into how this can be accomplished are limited. The research is unique in that it reveals the evolutions of CMNEs’ PMIs on developed-market targets, from autonomy to actual-form integration through the lens of ambidexterity.
Industry 4.0 in industrial district SMEs: understanding collective knowledge transfer by research and transfer institutes
Authors: Hervas-Oliver Jose-Luis 
Published: September 2022

Purpose
This paper aims to understand the contribution of research and transfer institutes (RTIs) to digitising in traditional Marshallian industrial districts (IDs). This study answers how to digitise small and medium-size enterprises (SMEs) in IDs capitalising on RTIs? As collective actors, RTIs introduce change in local/regional innovation systems where they are embedded.

Design/methodology/approach
This paper uses qualitative evidence based on interviews and secondary data analysis on digitising the Vinalopo Footwear district in Spain.

Findings
This paper provides empirical insights about how RTIs perform research and development (R&D) and non-R&D activities to digitise, facilitated by leading firms that frequently engage with RTIs. Subsequently, leading firms interact and diffuse Industry 4.0 within their networks of SMEs. RTIs activate digitising in districts avoiding the manifested reluctance of SMEs to engage with them, capitalising on leading firms’ networks orchestration.

Research limitations/implications
Because of the chosen research approach, the findings are limited to the chosen setting and method.

Practical implications
This paper includes implications for policymakers, responding to the paradox of how to activate knowledge transfer from RTIs to SMEs, when the latter are reluctant to use RTIs.

Originality/value
This paper fulfils an identified need to study how to digitise IDs and clusters.
Serial robotic plasma additive manufacturing on complex NURBS surface
Authors: Wang Zhaoqin , Shi Yu , Wang Xiaorong 
Published: September 2022

Purpose
This paper aims to investigate the additive manufacturing (AM) approach of a spatial complex curve feature (SCCF, mapped from two-dimensional nonuniform rational B-splines [2D-NURBS] curve) on a complex surface based on a serial robot using plasma built-up welding, and lays a foundation for plasma AM SCCFs on complex surfaces by combining the NURBS theory with the serial robotic kinematics.

Design/methodology/approach
Combining serial robotic kinematics and NURBS theory, a SCCF mapped from a square-like 2D-NURBS curve is prepared on a predefined complex NURBS surface using serial robotic plasma AM. The interpolation points C (ui) on the square-like 2D-NURBS curve are obtained using the equi-chord length interpolation method, and mapped on a predefined NURBS surface to get mapped points S (ui, vj). The homogeneous transformation matrix T = [n o a S (ui, vj)] of the plasma torch is calculated using the mapped points S (ui, vj) and the designated posture [n o a]. Using the inverse kinematics of the serial robot, the joint vector θ of the serial robot can be computed. After that, the AM programs are generated and transferred into the serial robotic controller and carried out by the serial robot of Motoman-UP6. The 2D-NURBS curve (square-like) is considered as AM trajectory planning curve, while its corresponding SCCF mapped from the 2D-NURBS curve as AM trajectory.

Findings
Simulation and experiments show that the preparation of SCCF (mapped from 2D-NURBS curve) on complex NURBS surface using robotic plasma AM is feasible and effective.

Originality/value
A SCCF mapped from a 2D-NURBS curve is prepared on a complex NURBS surface using the serial robotic plasma AM for the first time. It provides a theoretical and technical basis for plasma AM to produce SCCFs on complex surfaces. With the increasing demand for surface remanufacturing of complex parts, the serial robotic plasma AM of SCCFs on complex NURBS surfaces has a broad application prospect in aero-engine components, high-speed rail power components, nuclear industry components and complex molds.
The organizational culture of scale-ups and performance
Authors: Strengers Julia , Mutsaers Leonie , van Rossum Lisa , Graamans Ernst 
Published: September 2022

PurposeScale-ups have a crucial role in our society and economy, are known for their fast growth and high performance and undergo significant organizational change. Research on the organizational elements that ensure scale-ups sustaining high performance is limited. This empirical study aims to investigate the organizational culture in scale-ups using the Competing Values Framework, including the clan, adhocracy, the market, hierarchy cultures and its relation to performance.Design/methodology/approachQuantitative and qualitative data were collected in five scale-ups. Surveys provided data of 116 employees on organizational culture, assessed using the Organizational Culture Assessment Instrument (OCAI) and perceived performance. The aggregate outcomes and performance measures were analyzed using correlation analysis. Interviews were held with ten top managers and mirrored against the quantitative data.FindingsThe results show that top managers and employees have different perspectives on the culture scale-ups are supposed to have. Top managers perceive market culture as more and hierarchy culture as less present in their organizations than employees. The clan and adhocracy culture are positively correlated to performance and are preferred by employees. Market and hierarchy culture types are negatively correlated to performance and are least preferred by employees.Research limitations/implicationsIt enables scale-up leaders to specifically intervene when cultural elements are experienced by employees that will not drive performance and fit the high performance and fast-growing scale-up environment.Originality/valueThis study is the first that showed that organizational-wide surveys, combined with in-depth interviews, are suitable for top managers of scale-ups to diagnose the organizational culture and the effect on the organization's performance.
Bringing a background variable into focus: a multimethod investigation of IT security climate’s influence on elicited IT security beliefs
Authors: Warner Janis , Wipawayangkool Kamphol 
Published: September 2022

Purpose
IT security breaches plague organizations worldwide, yet there continues to be a paucity of comprehensive research models for protective technologies. This study aims to develop an IT security user behavior model focusing on the protective technology anti-spyware which includes organizational climate, a theory of planned behavior (TPB) background variable and elicited salient user beliefs.

Design/methodology/approach
A multimethod approach, including interviews and a survey, is used to elicit salient user beliefs and test hypotheses of the influences of perceived IT security climate on those user beliefs and ultimately user behavioral intentions. Primary data were collected through interviews following the prescribed TPB methodology and an offline survey method with 254 valid responses recorded. Partial least squares was used to investigate the hypotheses.

Findings
The authors found that attitudinal beliefs – protecting organizational interests for data/privacy, preventing disruptions to work and control beliefs – monetary resources and time constraints mediate significant relationships between IT security climate and attitude and perceived behavioral control, respectively. Implications are discussed.

Originality/value
This study is the first, to the best of the authors’ knowledge, that uses both interviews and a survey to examine the relationships among IT security climate, elicited user beliefs and behavioral intentions in a TPB-based model for a protective technology.
Positive affective tone as an underlying mechanism between leader's motivating language and career outcomes
Authors: Syed Fauzia , Naseer Saima , Bashir Fatima , Fatima Tasneem 
Published: September 2022

PurposeRecent evidence suggests that leaders' communication is central to an organization's success. The purpose of the current research is to examine how the leader's motivating language (direction giving, empathetic and meaning-making) translates into positive career outcomes through the mechanism of positive affective tone.Design/methodology/approachA three-wave time-lagged research design was applied to collect data (N = 320) from employees of the telecom sector of Pakistan.FindingsEmploying structural equation modeling (SEM) analysis, the study results indicate that high levels of leader's motivating language (direction giving and meaning-making) result in positive affective tone in employees, which further creates career motivation (career insight, career resilience and career identity) and career satisfaction. In contrast, positive affective tone does not mediate between empathetic language and career motivation (career insight, career resilience and career identity) and career satisfaction relationship.Research limitations/implicationsThe present study's findings explicate the unique effects and mechanism through which leaders motivating language becomes influential in reaping its benefits for followers' career outcomes. More research is warranted to examine other attitudinal and behavioral outcomes of leaders motivating language. This study research prepares future researchers to investigate other mediators and moderators in the leaders motivating language–career outcomes relationship. The authors recommend further implications of the study's findings for research and practice in the domain of leadership, affect and careers.Originality/valueThe current study opens up a new perspective in leaders motivating language literature by examining the underlying mechanism of positive affective tone.
Exploring third-party’s brand rankings from consumers’ persuasion knowledge
Authors: Huang Li-Shia , Huang Wan-Ju , Lin Hsiao-Yun 
Published: September 2022

PurposeGiven the importance of third-party endorsements as external cues during purchase evaluations, the manipulation of endorsements may raise consumers’ suspicion and thereby reduce the effectiveness of marketing messages. Consumers find it increasingly difficult to distinguish between authentic and biased brand reviews. This research conducts two experiments regarding brand rankings of third-parties in four industries. Study 1 aims to probes the interaction effect of persuasion knowledge and fairness of rating method (fair vs. unfair) on brand rankings’ credibility and brand image enhancement. Study 2 examines the interplay of dispositional persuasion knowledge and reputation of third parties (high vs. low).Design/methodology/approachThis research builds on an analysis of data (Study 1, N = 122; Study 2, N = 123) from Taiwan, where brand rankings held by third-party organizations are regular. The hypotheses were tested using SPSS’s PROCESS macro.FindingsDrawing on previous research of persuasion knowledge, the authors find that a fair rating method and a high reputation of third-party organization can mitigate the negative effect of persuasion knowledge.Practical implicationsThe results of this research suggest that marketers need to manage third-party endorsements carefully. Consumer skepticism toward these endorsements (e.g. third-party’s brand rankings) can be weakened when persuasion attempt is considered appropriate.Originality/valueThis is one of the first efforts to empirically explore the influences of persuasion knowledge on third-party endorsements. The importance of this work is underscored by the fact that a growing number of third-party endorsements are sponsored or even manipulated by brand owners.