bluuebunny/crossref_metadata_2025_split huggingface dataset:
22R‐ but not 22S‐hydroxycholesterol is recruited for diosgenin biosynthesis
Authors: Zhou Chen , Yang Yuhui , Tian Jingyi , Wu Yihan , An Faliang , Li Changfu , Zhang Yansheng 
Published: November 2021

SUMMARYDiosgenin is an important compound in the pharmaceutical industry and it is biosynthesized in several eudicot and monocot species, herein represented by fenugreek (a eudicot), and Dioscorea zingiberensis (a monocot). Formation of diosgenin can be achieved by the early C22,16‐oxidations of cholesterol followed by a late C26‐oxidation. This study reveals that, in both fenugreek and D. zingiberensis, the early C22,16‐oxygenase(s) shows strict 22R‐stereospecificity for hydroxylation of the substrates. Evidence against the recently proposed intermediacy of 16S,22S‐dihydroxycholesterol in diosgenin biosynthesis was also found. Moreover, in contrast to the eudicot fenugreek, which utilizes a single multifunctional cytochrome P450 (TfCYP90B50) to perform the early C22,16‐oxidations, the monocot D. zingiberensis has evolved two separate cytochrome P450 enzymes, with DzCYP90B71 being specific for the 22R‐oxidation and DzCYP90G6 for the C16‐oxidation. We suggest that the DzCYP90B71/DzCYP90G6 pair represent more broadly conserved catalysts for diosgenin biosynthesis in monocots.
Targeting plant cysteine oxidase activity for improved submergence tolerance
Authors: Taylor‐Kearney Leah J. , Flashman Emily 
Published: November 2021

SUMMARYPlant cysteine oxidases (PCOs) are plant O2‐sensing enzymes. They catalyse the O2‐dependent step which initiates the proteasomal degradation of Group VII ethylene response transcription factors (ERF‐VIIs) via the N‐degron pathway. When submerged, plants experience a reduction in O2 availability; PCO activity therefore decreases and the consequent ERF‐VII stabilisation leads to upregulation of hypoxia‐responsive genes which enable adaptation to low O2 conditions. Resulting adaptations include entering an anaerobic quiescent state to maintain energy reserves and rapid growth to escape floodwater and allow O2 transport to submerged tissues. Stabilisation of ERF‐VIIs has been linked to improved survival post‐submergence in Arabidopsis, rice (Oryza sativa) and barley (Hordeum vulgare). Due to climate change and increasing flooding events, there is an interest in manipulating the PCO/ERF‐VII interaction as a method of improving yields in flood‐intolerant crops. An effective way of achieving this may be through PCO inhibition; however, complete ablation of PCO activity is detrimental to growth and phenotype, likely due to other PCO‐mediated roles. Targeting PCOs will therefore require either temporary chemical inhibition or careful engineering of the enzyme structure to manipulate their O2 sensitivity and/or substrate specificity. Sufficient PCO structural and functional information should make this possible, given the potential to engineer site‐directed mutagenesis in vivo using CRISPR‐mediated base editing. Here, we discuss the knowledge still required for rational manipulation of PCOs to achieve ERF‐VII stabilisation without a yield penalty. We also take inspiration from the biocatalysis field to consider how enzyme engineering could be accelerated as a wider strategy to improve plant stress tolerance and productivity.
Financial structure and earnings manipulation activities in China
Authors: Khan Muhammad Kaleem , Qin Yixuan , Zhang Chengsi 
Published: November 2021

AbstractThis study aimed to analyse the monitoring adeptness of the financial system in China, particularly in controlling earnings management activities. First, this study identifies the reasons and motivations of managers for involvement in earnings management activities. Second, this study determines whether China's financial system has developed sufficiently to be capable of establishing a strong monitoring mechanism over firms. The study compares how an equity‐based financial structure develops an efficient monitoring system with that of a bank‐based one. A panel dataset of 2997 listed Chinese firms spanning the years 1998–2015 shows that the agency issue is the main reason that firms engage in earnings management activities. Management of financially constrained firms is found to be more prudent than management of other firms because they avoid masking firm performance. The study concludes that Chinese firms are restrained from indulging in managing earnings practices owing to the overwhelming development of the financial system. Moreover, firms in capital market‐based financial structures are more inclined to avoid earnings management compared with those in bank‐based structures.
Altered plasma cytokines in dogs with atopic dermatitis
Authors: Mazrier Hamutal , Vogelnest Linda J. , Taylor Rosanne M. , Williamson Peter 
Published: November 2021

BackgroundCanine (Canis lupus familiaris) atopic dermatitis (AD) shares similar clinical signs to human AD. The abnormal immune response of AD is orchestrated by T lymphocytes, and may include variable involvement of cytokines, regulatory T (Treg) cells, eosinophils, mast cells and other immune components. Helper T (Th)2 cytokines often predominate initially, followed by Th1 cytokines in more chronic phases.Hypothesis/ObjectivesPro‐inflammatory and Treg cytokines have been shown to play a role in human AD, yet their importance is not clear in canine AD. Hence, this study aimed to measure the concentrations of cytokines/chemokines not traditionally associated with Th1/Th2 response.AnimalsCanine AD patients (n = 27), compared to control dogs (n = 11).Methods and materialsA total of 19 plasma cytokines were assayed using canine specific multiplex immuno‐assays.ResultsThe plasma concentrations of CXC Motif Chemokine Ligand 8 (CXCL8), interleukin (IL)‐7 and IL‐15 cytokines were elevated in canine AD patients, compared to control dogs. In addition, stem‐cell factor (SCF) concentrations were reduced in the plasma of canine AD patients compared to control dogs. Distinct cytokine profiles were found in dogs belonging to the Staffordshire breeds, a group with increased risk of AD. In particular, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) had significantly elevated concentrations.Conclusions and clinical relevanceSome of the plasma cytokine alterations in canine AD described here, particularly of IL‐7, have not been reported previously. Monitoring these distinctive cytokine alterations could be useful for diagnosis and monitoring of canine AD in dogs.
Balance Recoverability and Control of Bipedal Walkers With Foot Slip
Authors: Mihalec Marko , Trkov Mitja , Yi Jingang 
Published: November 2021

Abstract
Low-friction foot/ground contacts present a particular challenge for stable bipedal walkers. The slippage of the stance foot introduces complexity in robot dynamics and the general locomotion stability results cannot be applied directly. We relax the commonly used assumption of nonslip contact between the walker foot and the ground and examine bipedal dynamics under foot slip. Using a two-mass linear inverted pendulum model, we introduce the concept of balance recoverability and use it to quantify the balanced or fall-prone walking gaits. Balance recoverability also serves as the basis for the design of the balance recovery controller. We design the within- or multi-step recovery controller to assist the walker to avoid fall. The controller performance is validated through simulation results and robustness is demonstrated in the presence of measurement noises as well as variations of foot/ground friction conditions. In addition, the proposed methods and models are used to analyze the data from human walking experiments. The multiple subject experiments validate and illustrate the balance recoverability concept and analyses.
In Vitro Simulation of Shoulder Motion Driven by Three-Dimensional Scapular and Humeral Kinematics
Authors: Sulkar Hema J. , Knighton Tyler W. , Amoafo Linda , Aliaj Klevis , Kolz Christopher W. , Zhang Yue , Hermans Tucker , Henninger Heath B. 
Published: November 2021

Abstract
In vitro simulation of three-dimensional (3D) shoulder motion using in vivo kinematics obtained from human subjects allows investigation of clinical conditions in the context of physiologically relevant biomechanics. Herein, we present a framework for laboratory simulation of subject-specific kinematics that combines individual 3D scapular and humeral control in cadavers. The objectives were to: (1) robotically simulate seven healthy subject-specific 3D scapulothoracic and glenohumeral kinematic trajectories in six cadavers, (2) characterize system performance using kinematic orientation accuracy and repeatability, and muscle force repeatability metrics, and (3) analyze effects of input kinematics and cadaver specimen variability. Using an industrial robot to orient the scapula range of motion (ROM), errors with repeatability of ±0.1 mm and &lt;0.5 deg were achieved. Using a custom robot and a trajectory prediction algorithm to orient the humerus relative to the scapula, orientation accuracy for glenohumeral elevation, plane of elevation, and axial rotation of &lt;3 deg mean absolute error (MAE) was achieved. Kinematic accuracy was not affected by varying input kinematics or cadaver specimens. Muscle forces over five repeated setups showed variability typically &lt;33% relative to the overall simulations. Varying cadaver specimens and subject-specific human motions showed effects on muscle forces, illustrating that the system was capable of differentiating changes in forces due to input conditions. The anterior and middle deltoid, specifically, showed notable variations in patterns across the ROM that were affected by subject-specific motion. This machine provides a platform for future laboratory studies to investigate shoulder biomechanics and consider the impacts of variable input kinematics from populations of interest, as they can significantly impact study outputs and resultant conclusions.
Thermal Analyses of Nanowarming-Assisted Recovery of the Heart From Cryopreservation by Vitrification
Authors: Joshi Purva , Ehrlich Lili E. , Gao Zhe , Bischof John C. , Rabin Yoed 
Published: November 2021

Abstract
This study explores thermal design aspects of nanowarming-assisted recovery of the heart from indefinite cryogenic storage, where nanowarming is the volumetric heating effect of ferromagnetic nanoparticles excited by a radio frequency electromagnet field. This study uses computational means while focusing on the human heart and the rat heart models. The underlying nanoparticle loading characteristics are adapted from a recent, proof-of-concept experimental study. While uniformly distributed nanoparticles can lead to uniform rewarming, and thereby minimize adverse effects associated with ice crystallization and thermomechanical stress, the combined effects of heart anatomy and nanoparticle loading limitations present practical challenges which this study comes to address. Results of this study demonstrate that under such combined effects, nonuniform nanoparticles warming may lead to a subcritical rewarming rate in some parts of the domain, excessive heating in others, and increased exposure potential to cryoprotective agents (CPAs) toxicity. Nonetheless, the results of this study also demonstrate that computerized planning of the cryopreservation protocol and container design can help mitigate the associated adverse effects, with examples relating to adjusting the CPA and/or nanoparticle concentration, and selecting heart container geometry, and size. In conclusion, nanowarming may provide superior conditions for organ recovery from cryogenic storage under carefully selected conditions, which comes with an elevated complexity of protocol planning and optimization.
Periodic Unsteady Kinematics of Hub Flows in a Shrouded Multistage Compressor
Authors: Lee Jaehyoung , Lim Sungkyung , Shin Hyoun-Woo , Lee Sungryong , Song Seung Jin 
Published: November 2021

Abstract
Periodic unsteady flow kinematics in a shrouded multistage low-speed axial compressor has been measured for the first time. Data have been acquired at the inlet and exit of a shrouded third-stage stator with a particular focus on the hub flows. The newly found features of the hub flow in a shrouded multistage compressor are different from those at the midspan or in unshrouded (i.e., cantilevered) compressors. First, the merging of the second-stage stator and third-stage rotor wakes causes positive radial migration near the rotor wake pressure surface at the hub of the third-stage stator inlet. Second, the low-momentum labyrinth seal leakage flow of the third-stage stator merges with the third-stage rotor wake to create streamwise vorticity at the third-stage stator inlet hub. Third, contrary to unshrouded stators, suction side hub corner separation in the shrouded third-stage stator reduces rotor wake stretching. Thus, velocity disturbances are attenuated less, and amplitudes of periodic fluctuations in flow angles are larger at the third-stage stator exit hub than at midspan. The positive radial migration of the rotor wake hub flow and wake stretching reduction are expected to decrease efficiency, whereas streamwise vorticity generation is expected to increase efficiency.
A Nonparametric Method for Estimating Rates of Intracellular Ice Formation Due to Independent Competing Mechanisms
Authors: Karlsson Jens O. M. 
Published: November 2021

Abstract
The probability of intracellular ice formation (IIF) has conventionally been analyzed by counting the cumulative number of IIF events observed in a cell population, and normalizing to the total cell count to estimate the cumulative IIF probability. However, this method is invalid when attempting to distinguish among multiple, independent IIF mechanisms, because of confounding effects due to competition for a finite pool of unfrozen cells. Therefore, an alternative approach for analyzing IIF data is proposed, based on treating IIF as a marked point process, in which the points represent IIF events and the marks represent different mechanisms of IIF. Using the new method, it is possible to quantify the kinetics associated with any IIF mechanism for which corresponding events can be marked (i.e., experimentally distinguished from competing IIF mechanisms). The proposed approach is nonparametric, making possible characterization of IIF mechanisms that have not yet been fully elucidated. The new analytical approach was compared to the conventional method of IIF analysis using data from a simulated experiment, demonstrating that the new method yielded superior estimates of the cumulative distribution function of IIF times when two competing mechanisms of IIF were active. The proposed algorithm was also applied to cryomicroscopic IIF observations in adherent endothelial cells, yielding rate estimates for two concurrent IIF processes. Furthermore, a proof is presented to demonstrate that when the proposed data analysis algorithm is applied to IIF data from a single mechanism of IIF, the results are equivalent to those obtained by the conventional method of analysis.
Interaction Assessment of Diagonally Spaced Identical Corrosion Defects and Fully Aligned Unequal-Sized Corrosion Defects Under Combined Loads
Authors: Zhang Shulong , Zhou Wenxing 
Published: November 2021

Abstract
In this study, the interaction effects of closely spaced corrosion defects on the burst capacity of oil and gas pipelines under combined internal pressure and longitudinal compression are investigated by using parametric three-dimensional elasto-plastic finite element analyses. Full-scale burst tests reported in the literature are used to validate the finite element model. It is observed that the interaction effects of diagonally spaced defects on the burst capacity are strongly related to the overlapping portion of the defect width or circumferential spacing between the two defects. The analysis results indicate that the strongest interaction between diagonally spaced defects under combined loads occurs if the defects have zero circumferential separation. The interaction weakens as the defects are more and more overlapped or separated circumferentially. It is also observed that the interaction effect associated with longitudinally or circumferentially aligned, unequal-sized corrosion defects is negligible under the internal pressure only or combined loads.
Trust and responsibility in food systems transformation. Engaging with Big Food: marriage or mirage?
Authors: Yates Joe , Gillespie Stuart , Savona Natalie , Deeney Megan , Kadiyala Suneetha 
Published: November 2021

Concentration of power among transnational ‘Big Food’ companies has contributed to food systems that are unsustainable, unhealthy and inequitable for people and planet. Given these commercial determinants of health, if ‘food systems transformation’ is to be authentic—more than a passing narrative—then leveraging Big Food is paramount. To this end, researchers, practitioners and policy-makers are increasingly encouraged to engage with these powerful entities. However, given the conflicts of interest at stake, engagement relies on trust and transparency, that all stakeholders take responsibility for their actions and demonstrate commitment to do no harm. Given Big Food’s track record in influencing policy, shifting costs and responsibility for their harms—and while profit primarily drives business decision making—we question whether it is logical to expect trust.This analysis explores concepts of responsibility and trust in relation to food systems transformation involving public-private partnerships. Through short cautionary case studies—looking at the United Nations Food Systems Summit, and Big Food’s plastic burden—it argues that unless such companies take responsibility for their cross-cutting effects and earn authentic trust through demonstrably doing no harm, their participation in evidence generation and policy processes should be limited to responding to information requests and adhering to regulation. Any involvement in research agenda-setting or formulating policy solutions introduces conflicts of interest, legitimises corporate irresponsibility and jeopardises scientific integrity. Big Food has dynamism and power to address food system problems, but while it contributes to so many of these problems it should follow—not formulate—transformational evidence, policies and regulations.
Children and Young People’s Health Partnership Evelina London Model of Care: economic evaluation protocol of a complex system change
Authors: Soley-Bori Marina , Lingam Raghu , Satherley Rose-Marie , Forman Julia , Cecil Lizzie , Fox-Rushby Julia , Wolfe Ingrid 
Published: November 2021

IntroductionThe Children and Young People’s Health Partnership (CYPHP) Evelina London Model of Care is a new approach to integrated care delivery for children and young people (CYP) with common health complaints and chronic conditions. CYPHP includes population health management (services shaped by data-driven understanding of population and individual needs, applied in this case to enable proactive case finding and tailored biopsychosocial care), specialist clinics with multidisciplinary health teams and training resources for professionals working with CYP. This complex health system strengthening programme has been implemented in South London since April 2018 and will be evaluated using a cluster randomised controlled trial with an embedded process evaluation. This protocol describes the within-trial and beyond-trial economic evaluation of CYPHP.Methods and analysisThe economic evaluation will identify, measure and value resources and health outcome impacts of CYPHP compared with enhanced usual care from a National Health Service/Personal Social Service and a broader societal perspective. The study population includes 90 000 CYP under 16 years of age in 23 clusters (groups of general practitioner (GP) practices) to assess health service use and costs, with more detailed cost-effectiveness analysis of a targeted sample of 2138 CYP with asthma, eczema or constipation (tracer conditions). For the cost-effectiveness analysis, health outcomes will be measured using the Paediatric Quality of Life Inventory and quality-adjusted life years (QALYs) using the Child Health Utility 9 Dimensions (CHU-9D) measure. To account for changes in parental well-being, the Warwick-Edinburg Mental Well-being Scale will be integrated with QALYs in a cost–benefit analysis. The within-trial economic evaluation will be complemented by a novel long-term model that expands the analytical horizon to 10 years. Analyses will adhere to good practice guidelines and National Institute for Health and Care Excellence public health reference case.Ethics and disseminationThe study has received ethical approval from South West-Cornwall and Plymouth Research Ethics Committee (REC Reference: 17/SW/0275). Results will be submitted for publication in peer-reviewed journals, made available in briefing papers for local decision-makers, and provided to the local community through website and public events. Findings will be generalisable to community-based models of care, especially in urban settings.Trial registration numberNCT03461848.
Doctors’ engagement with a formal system of continuing professional development in Ireland: a qualitative study in perceived benefits, barriers and potential improvements
Authors: Hanlon Holly Rose , Prihodova Lucia , Russell Thelma , Donegan Deirdre , O'Shaughnessy Ann , Hoey Hilary 
Published: November 2021

ObjectivesTo examine experiences of participation in a mandatory system of continuing professional development (CPD) among doctors in Ireland, in order to identify areas for improvement.DesignA qualitative cross-sectional design was used.Participants1408 participants (701 male, 707 female) were recruited via email from a population of 4350 doctors enrolled on a Royal College of Physicians of Ireland Professional Competence Scheme (PCS) for the 2017/2018 year, and completed an online survey as part of a larger study examining experiences and attitudes towards participation in PCS. A subset of the sample (434 participants) responded to an optional open-ended question about PCS participation. Responses to the open-ended question were analysed using thematic analysis.ResultsThematic analysis resulted in five main themes relating to perceived barriers to PCS participation across a wide range of areas: ‘Evidence of participation’, ‘The structure of PCS’, ‘Questioning the benefits of formal CPD’, ‘Workplace challenges’ and ‘Access issues’.ConclusionsTaken together, the five themes outlined in this study give a wide-ranging, in-depth picture of the challenges faced by Irish doctors, which expand on well-documented factors such as time constraints, to illustrate a series of complex, interacting factors. Some barriers, such as difficulty obtaining evidence of participation, may be relatively easily addressed. Others, such as issues with the way the PCS is structured, are more intractable, and require further research to understand more fully and develop appropriate solutions.