bluuebunny/crossref_metadata_2025_split huggingface dataset:
Creation of novel pediatric academic curriculum and its evaluation using mixed methods
Authors: Balicki Martha , Barr Darja , Renaud Robert , Sharma Atul , Rodd Celia 
Published: August 2022

AbstractIntroductionThe Royal College of Physicians and Surgeons of Canada and the American Accreditation Council for Graduate Medical Education require resident skills in Evidence-Based Medicine and participation in research activities. Our first-year pediatric residents (PGY1s) were required to attend a novel, call-protected, 4-week Academic Skills and Knowledge (ASK) rotation to improve their skills as consumers of medical literature. Objectives of the study were to describe this curriculum and summarize its mixed-methods evaluation.MethodsAfter 14 months of curriculum development, three annual cohorts of PGY1s wrote identical pre- and post-ASK quizzes (2017-19). In 2018 and 2019, we assessed knowledge retention with PGY1s re-writing the quiz after 6 months. Mean test scores were compared using paired t-tests. In 2017, pre- and post-ASK focus groups assessed resident feelings about the rotation.ResultsAll eligible PGY1s (n=32) participated. Mean exam scores demonstrated increased knowledge (time0 mean±SD 52.6±11.0%; vs. time1 80.2±9.0%, p <0.001). Knowledge retention at 6 months was intermediate (time2 70.2±12.0%; time0 vs time2 p<0.001). In the pre-rotation focus group, residents looked forward to ASK; goals centered around growing from learner to expert. Post-ASK, residents were very satisfied. Resident participation in our annual Research Institute poster competition increased linearly from 0% in 2014 to 8% in 2020 (r=0.74, p=0.01).DiscussionThe ASK curriculum was successfully implemented, and increased knowledge persisted over time. Residents were satisfied with ASK and appreciated the structured curriculum building on core knowledge that they could immediately apply to their clinical work.Statements and DeclarationsAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Martha Balicki, Darja Barr, Atul Sharma and Celia Rodd. The first draft of the manuscript was written by Martha Balicki and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.Financial interestsNone of the authors have any relevant financial or non-financial interests to disclose. The authors did not receive support from any organization for the submitted work.Data availabilityThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
ADAMTS2 regulates radial neuronal migration by activating TGF-β signaling at the subplate layer of the developing neocortex
Authors: Kaneko Noe , Hirai Kumiko , Oshima Minori , Yura Kei , Hattori Mitsuharu , Maeda Nobuaki , Ohtaka-Maruyama Chiaki 
Published: August 2022

ABSTRACTDuring the development of the mammalian brain, neocortical structures are formed by the sequential radial migration of newborn excitatory neurons. The early migrating neurons exhibit a multipolar shape, but they undergo a multipolar-to-bipolar transition at the subplate (SP) layer, where extracellular matrix (ECM) components are abundantly expressed. In this study, we revealed that the TGF-β signaling-related ECM proteins, such as latent TGF-β-binding protein 1 (LTBP1) and fibrillin 2, and TGF-β receptor II (TGF-βRII) and its downstream effector, p-smad2/3, are selectively expressed at the SP layer, suggesting that TGF-β is sequestered in a latent form by forming complexes with these ECM components and then its signaling is activated by ECM remodeling. We found that the migrating multipolar neurons transiently express a disintegrin and metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. Knockdown and knockout of Adamts2 suppressed the multipolar-to-bipolar transition of migrating neurons, and therefore, disturbed radial migration. Similar phenotypes were observed by the perturbation of TGF-β signaling in the migrating neurons. Time-lapse luminescence imaging of TGF-β signaling indicated that ADAMTS2 activates this signaling pathway in the migrating neurons during the multipolar-to-bipolar transition at the SP layer. These results suggest that the ADAMTS2 secreted by the migrating multipolar neurons activates TGF-β signaling by ECM remodeling of the SP layer, leading to the multipolar-to-bipolar transition. We propose that the SP layer plays an essential role in the radial neuronal migration as a signaling center of the developing neocortex.SIGNIFICANCEThe neocortex is formed by the sequential radial migration of newborn neurons, which undergo a multipolar-to-bipolar transition at the subplate (SP) layer. The extracellular matrix (ECM) is abundantly expressed in the SP layer. However, the roles of the ECM in the SP layer have been unclear. We found that migrating neurons transiently express a disintegrin and a metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. We show that ADAMTS2 secreted by multipolar migrating neurons activates TGF-β signaling through remodeling of the ECM in the SP layer, leading to the multipolar-to-bipolar transition. Thus, the SP layer plays an essential role in radial migration as a signaling center of the developing neocortex
Optogenetic activation of dorsal raphe serotonin neurons induces brain-wide activation
Authors: Hamada Hiro Taiyo , Abe Yoshifumi , Takata Norio , Taira Masakazu , Tanaka Kenji F. , Doya Kenji 
Published: August 2022

AbstractSerotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects via brain-wide projections and various receptors remains unclear. Here we measured brain-wide responses to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) of the male mouse brain using functional MRI with an 11.7T scanner and a cryoprobe. Transient activation of DRN serotonin neurons caused brain-wide activation, including the medial prefrontal cortex, the striatum, and the ventral tegmental area. The same stimulation under anesthesia with isoflurane decreased brain-wide activation, including the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 receptors. Together, these results provide insight into the DR serotonergic system, which is consistent with recent discoveries of its functions in adaptive behaviors.
Hepatitis C virus non-structural proteins modulate cellular kinases for increased cytoplasmic abundance of host factor HuR and facilitate viral replication
Authors: Raheja Harsha , George Biju , Tripathi Sachin Kumar , Saha Sandhini , Maiti Tushar Kanti , Das Saumitra 
Published: August 2022

AbstractHost protein HuR translocation from nucleus to cytoplasm following infection is crucial for the life cycle of several RNA viruses including hepatitis C virus (HCV), a major causative agent of hepatocellular carcinoma. HuR assists the assembly of replication-complex on the viral-3′UTR, and its depletion hampers viral replication. Although cytoplasmic HuR is crucial for HCV replication, little is known about how the virus orchestrates the mobilization of HuR into the cytoplasm from the nucleus. We show that two viral proteins, NS3 and NS5A, act co-ordinately to alter the equilibrium of the nucleo-cytoplasmic movement of HuR. NS3 activates protein kinase C (PKC)-δ, which in-turn phosphorylates HuR on S318 residue, triggering its export to the cytoplasm. NS5A inactivates AMP-activated kinase (AMPK) resulting in diminished nuclear import of HuR through blockade of AMPK-mediated phosphorylation and acetylation of importin-α1. Cytoplasmic retention or entry of HuR can be reversed by an AMPK activator or a PKC-δ inhibitor. Our findings suggest that efforts should be made to develop inhibitors of PKC-δ and AMPK, either separately or in combination, to inhibit HCV infection.Author summaryHepatitis C virus is a major human pathogen, which exploits cellular machinery for its propagation in liver cells. The cytoplasmic availability of cellular components is crucial for their direct influence on processes involving the viral RNA, which lacks any nuclear history. Our results establish the involvement of viral proteins, NS3 and NS5A in achieving increased cytoplasmic abundance of a host factor HuR, an RNA binding protein (RBP) critical for HCV replication. This is achieved via direct post-translational modification of HuR and indirect regulation of its nuclear carrier by coercing two host kinases, PKC-δ and AMPK-α. RBPs are emerging as novel targetable candidates for gene regulation. Similar studies with other RBPs and targeting protein modifications, in place of whole protein knockdown, could usher in a revolutionary strategy to neutralize emerging RNA virus-based diseases, while preserving their cellular functions.
Pathway and mechanism of tubulin folding mediated by TRiC/CCT conjugated with its ATPase cycle revealed by cryo-EM
Authors: Liu Caixuan , Jin Mingliang , Wang Shutian , Han Wenyu , Zhao Qiaoyu , Wang Yifan , Xu Cong , Diao Lei , Yin Yue , Peng Chao , Bao Lan , Wang Yanxing , Cong Yao 
Published: August 2022

AbstractThe eukaryotic chaperonin TRiC/CCT assists the folding of about 10% of cytosolic proteins through an ATP-driven conformational cycle, and the essential cytoskeleton protein tubulin is the obligate substrate of TRiC. Here, we present an ensemble of cryo-EM structures of human TRiC throughout its ATPase cycle, with three of them revealing endogenously engaged tubulin in different folding stages. Our structural and XL-MS analyses suggested a gradual upward translocation and stabilization of tubulin within the TRiC chamber accompanying TRiC ring closure. Remarkably, in the closed TRiC-tubulin-S3 map resolved to 3.1-Å-resolution, we captured a near-natively folded tubulin. We found the near-natively folded tubulin engaging through its N and C domains mainly with the A and I domains of the CCT3/6/8 subunits through electrostatic and hydrophilic interactions, while the tubulin I domain was found to remain dynamic. Moreover, we also showed the potential role of TRiC C-terminal tails in substrate stabilization and folding. Our study delineates the pathway and molecular mechanism of TRiC-mediated tubulin folding conjugated with TRiC ATPase cycle, and may also inform the design of therapeutic agents targeting TRiC-tubulin interactions.
Recovery of structural integrity of epithelial monolayer in response to massive apoptosis-induced defects
Authors: Yuan Yuan , Han Yu Long , Xia Jing , Li Hui , Tang Chao , Ye Fangfu , Weitz David A. , Guo Ming 
Published: August 2022

AbstractApoptosis exists ubiquitously in organisms and plays an essential role in maintaining the homeostasis of functional tissues. While the signaling pathway of cell apoptosis has been widely studied, the mechanism of how apoptotic cells regulate the structural homeostasis of a living tissue still remains largely elusive. Using a functional epithelial monolayer as a model system, we find that the integrity of the epithelium is interrupted by apoptosis-induced defects, with an increasing permeability to small molecules across the epithelium. The defects promote a structural reorganization through enhanced cell spreading and migratory dynamics, resulting in a quick recovery of epithelium integrity. Moreover, we show the epithelial monolayer remodeling is driven by local enhanced traction force after apoptosis, which triggers the process of fluidization and mesenchymal-like migration. Our results show the quick recovery of epithelial homeostasis when being interrupted by cell apoptosis, and indicate the importance of apoptosis-induced mechanical force in mediating cell behaviors to maintain the structural integrity of epithelium.
Revealing the drivers of antibiotic resistance trends inStreptococcus pneumoniaeamidst the 2020 COVID-19 pandemic: Insights from mathematical modeling
Authors: Kovacevic Aleksandra , Smith David R M , Rahbé Eve , Novelli Sophie , Henriot Paul , Varon Emmanuelle , Cohen Robert , Levy Corinne , Temime Laura , Opatowski Lulla 
Published: August 2022

AbstractNon-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasiveStreptococcus pneumoniaeisolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains ofS. pneumoniae. To test hypotheses underlying these trends five mechanisms were built in into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus- bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
Enhancing customer satisfaction, personnel satisfaction and company reputation with total quality management: combining traditional and new views
Authors: Lepistö Kari , Saunila Minna , Ukko Juhani 
Published: August 2022

PurposeThis study investigates the effect of total quality management (TQM) on customer satisfaction, personnel satisfaction and company reputation.Design/methodology/approachThe study results rely on a structured survey conducted among an extensive sample of Finnish SMEs. In addition to the examination of the relationship between TQM and company performance in terms of customer satisfaction, personnel satisfaction and company reputation, the study takes a view on the possible effects of the industry, the company size and the certified quality system.FindingsThe results reveal that two TQM dimensions, namely Customer Focus and Product Management, were related to companies' customer satisfaction, whereas four TQM dimensions, namely Management/leadership, Customer Focus, Personnel Management and Risk Management, were related to personnel satisfaction. None of the TQM dimensions were related to company reputation. The control variables – the industry, the company size and the certified quality system – were not found to affect customer satisfaction, personnel satisfaction or company reputation.Originality/valueMost previous studies have been based on traditional TQM classification and have not shown the effects of the latest TQM-related dimensions. Compared to previous studies, this work integrates risk management, digitization, system deployment efficiency and stakeholder management into TQM, which has not been implemented in any previous study. The roles of hard and soft TQM factors have been carefully considered in this study; thus, the study does not place too much emphasis on either direction but provides a balanced picture of the performance of the management systems studied. Although there are studies on the effects of TQM on personnel satisfaction, customer satisfaction and reputation, they are based on a much narrower definition of TQM than that in this study. The business environment is constantly changing, but only a few studies have been conducted to extend the TQM approach. This has led to duplication of studies, and the effects of performance-relevant procedures have not been extensively studied in the past as part of TQM. Therefore, the concept of this study brings significant added value to TQM research and returns the TQM concept to the overall level while considering the requirements of the ISO 9001: 2015 and EFQM 2019 quality standards. The study also considers the effects of ISO 9001 certification and EFQM requirements.
A new scheme for extracting fault features of rolling element bearings
Authors: Liu Xiangnan , He Kuanfang 
Published: August 2022

PurposeThe purpose of this paper is to propose a new fault feature extraction scheme for the rolling element bearing.Design/methodology/approachThe generalized Stockwell transform (GST) and the singular value ratio spectrum (SVRS) methods are combined. A time-frequency distribution measurement criterion named the energy concentration measurement (ECM) is initially used to determine the parameter of the optimal GST method. Then, the optimal GST is applied to conduct a time-frequency transformation for a raw signal. Subsequently, the two-dimensional time-frequency matrix is obtained. Finally, the improved singular value decomposition (SVD) analysis is used to conduct a noise reduction of the time-frequency matrix. The SVRS is proposed to select the effective singular values. Furthermore, the time-domain feature of the impact signal is obtained by taking the inverse GST transform.FindingsThe simulated and experimental signals are used to verify the superiority of the proposed method over conventional methods. The obtained results show that the proposed method can effectively extract fault features of the rolling element bearing.Research limitations/implicationsThis paper mainly discusses the application of GST and SVRS methods to analyze the weak fault feature extraction problem. The next research direction is to explore the application of the Hilbert Huang transform (HHT) and variational modal decomposition (VMD) in the impact feature extraction of rolling bearing.Originality/valueIn the present study, a new SVRS method is proposed to select the number of effective singular values. This paper proposed an effective way to obtain the fault feature in monitoring of rotating machinery.
Interactions among antecedents of project outsourcing strategies: evidence from Chinese construction firms
Authors: Lai Jingyi , Fu Yongcheng , Chen Yongqiang , Du Bo 
Published: August 2022

PurposeOutsourcing is a common practice that is often adopted to reduce costs and enhance capabilities. The underlying logic of a firm's outsourcing strategy is not always evident due to multiple antecedents with interacting effects. This study identifies critical factors that influence outsourcing strategies and reveals their interactions with empirical evidence from Chinese construction firms.Design/methodology/approachThe quantitative decision-making trial and evaluation laboratory (DEMATEL) method was applied to analyze the interrelationships among the antecedents of project outsourcing strategies. First, 24 experts from 13 Chinese construction firms were invited to evaluate and score the influence of each factor on the other. Second, the graph theory and matrix tools of DEMATEL were used to quantitatively obtain the causality among factors and the prominence of each factor within the system.FindingsAmong the antecedents, a firm's pursuit of cost efficiency, identity, technological capability and contracting capability are the most prominent factors influencing project outsourcing strategies. For the interactions among these factors, this study reveals that the focal firm's technological capability significantly influences its contracting capability, and they jointly influence the firm's outsourcing practices, the selection of outsourcing vendors and, eventually, its pursuit of cost efficiency. Moreover, legal restrictions in the institutional environment strongly shape this capability–cost efficiency relationship.Originality/valueTwelve critical factors following different theoretical perspectives at varying levels of analysis were identified from the literature review. By revealing the interrelationships among these factors, this study develops a holistic framework that integrates the transaction cost and capability perspectives for understanding project outsourcing strategies embedded in different institutional environments.
Assessing burnout in diversity and inclusion professionals
Authors: Pemberton Andrea , Kisamore Jennifer 
Published: August 2022

PurposeBurnout has been linked to a myriad of negative organizational and individual health outcomes which threaten employee and organizational well-being. This study examines how unique features of diversity and inclusion (D&I) work are related to burnout.Design/methodology/approachParticipants were recruited using network and convenience sampling strategies. A total of 64 full-time employees whose primary responsibility is to implement the D&I strategy for their organization provided useable data for analysis. Participants completed measures of burnout, role ambiguity, role conflict, subjective experiences of tokenism, and top management support. Measures were administered online via Qualtrics.FindingsResults suggest lack of clear job duties, conflicting job demands, lack of top management support, and experiences of tokenism are associated with D&I professionals' experiences of burnout. The current study, however, indicates that while D&I professional experience higher levels of exhaustion than other professionals, they also experience greater professional efficacy, which suggests D&I roles are both challenging and rewarding.Practical implicationsResults suggest organizational leaders may mitigate employee burnout by providing clear support to and role definitions for D&I professionals.Originality/valueThis study is the first to explore burnout experiences among D&I professionals. Additionally, this study examines how burnout experiences are associated with role dysfunctions, top management support, and subjective experiences of tokenism.
Are temporary jobs stepping stones or dead ends? A systematic review of the literature
Authors: Filomena Mattia , Picchio Matteo 
Published: August 2022

PurposeThis study aims to investigate the heterogeneous results about the impact of temporary jobs on subsequent labour market performances and to provide policymakers with further information on the effects of temporary contracts under particular circumstances.Design/methodology/approachThe authors present a quantitative systematic review on the debate about the “stepping stone vs dead end” hypothesis related to the causal effect of temporary jobs on future labour market performances.FindingsAmong 78 observations from 64 articles, 32% support the hypothesis according to which temporary contracts are a port of entry into stable employment positions, 23% report ambiguous or mixed findings and the remaining 45% provide evidence in favour of the dead end hypothesis. The results from meta-regressions suggest that the stepping stone effect is more likely to emerge when self-selectivity issues are dealt with. The studies focussing on temporary work agency jobs and casual/seasonal jobs support more easily the dead end hypothesis. Finally, in more recent years and when the unemployment rate is larger, the dead end hypothesis is more likely to prevail.Originality/valueAlthough many studies have been published on this issue, to the best of the authors’ knowledge, there are no recent analytic economic surveys on the “stepping stone vs dead end” debate. The main contribution of this article is to fill this gap.