bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review about skin lesions in children affected by Coronavirus Disease 2019 (excluding multisystem inflammatory syndrome in children): study protocol
Authors: Dondi Arianna , Sperti Giacomo , Gori Davide , Montalti Marco , Parini Lorenza , Guaraldi Federica , Lanari Marcello , Neri Iria 
Published: March 2022

AbstractCOVID-19 disease can give a range of skin manifestations, some of which specific to children and young patients. Given the different nature of the lesions in specific stages of the disease and the fact that they may be the only or predominant symptom of the disease, it is of great importance for the pediatrician and dermatologist to be familiar with COVID-19 skin lesions. The aim of this systematic review, conducted according to the PRISMA statement, is to investigate COVID-19-associated cutaneous involvement in children in terms of type of skin lesions, frequency, and time of onset, with the exclusion of those associated with multisystem inflammatory syndrome in children. A comprehensive literature search will be performed through PubMed between December 2019 and December 2021. The quality of each study will be assessed according to the STROBE tool for observational studies. This systematic review will provide evidence about the dermatological manifestations of COVID-19 disease in children published up to the end of year 2021. Recognizing skin symptoms as potential manifestations of COVID-19 in children is important for a non-delayed diagnosis, with prompt activation of the adequate tracing, isolation, and hygienic measures, and for timely treatment of unlikely but possible serious complications.
Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase
Authors: Kaur Supreet , Nieto Nicholas , McDonald Peter , Beck Josh R. , Honzatko Richard B. , Roy Anuradha , Nelson Scott W 
Published: March 2022

AbstractMalaria is caused by infection with protozoan parasites of the Plasmodium genus, which is part of the phylum Apicomplexa. Most organisms in this phylum contain a relic plastid called the apicoplast. The apicoplast genome is replicated by a single DNA polymerase (apPOL), which is an attractive target for anti-malarial drugs. We screened small-molecule libraries (206,504 compounds) using a fluorescence-based high-throughput DNA polymerase assay. Dose/response analysis and counter-screening identified 186 specific apPOL inhibitors. Toxicity screening against human HepaRG human cells removed 84 compounds and the remaining were subjected to parasite killing assays using chloroquine resistant P. falciparum parasites. Nine compounds were potent inhibitors of parasite growth and may serve as lead compounds in efforts to discover novel malaria drugs.
Hepatic Deletion of X-box Binding Protein 1 in Farnesoid X Receptor Null Mice Leads to Enhanced Liver Injury
Authors: Liu Xiaoying , Khalafalla Mahmoud , Chung Chuhan , Gindin Yevgeniy , Hubchak Susan , LeCuyer Brian , Kriegermeier Alyssa , Zhang Danny , Qiu Wei , Ding Xianzhong , Fang Deyu , Green Richard 
Published: March 2022

AbstractBackground & AimsFarnesoid X receptor (FXR) regulates bile acid metabolism and FXR null (Fxr-/-) mice have elevated bile acid levels and progressive liver injury. The inositol-requiring enzyme 1α (IRE1α)/X-box binding protein 1 (XBP1) pathway is a protective pathway of the unfolded protein response (UPR) that is activated in response to ER stress. In this study we sought to determine the role of the UPR in Fxr-/- mice.Approach & ResultsWe examined hepatic UPR gene and protein expression in 10- and 24-week-old wild type (WT) and Fxr-/- mice. Hepatic XBP1 and other UPR pathways were activated in 24-week-old Fxr-/- mice, but not WT mice. To further determine the role of the liver UPR activation in Fxr-/- mice, we generated mice with FXR and liver-specific XBP1 double knockout (DKO, Fxr-/-Xbp1LKO) and Fxr-/-Xbp1fl/fl single knockout (SKO) mice and characterized their phenotypes at different ages. DKO mice demonstrated enhanced liver injury, apoptosis and fibrosis compared with SKO mice. RNA-seq revealed increased gene expression in apoptosis, inflammation and cell proliferation pathways in DKO mice. The proapoptotic C/EBP-homologous protein (CHOP) pathway was activated in DKO mice. At age 60 weeks, all DKO mice and no SKO mice spontaneously developed liver tumors.ConclusionsThe hepatic XBP1 pathway is activated in older Fxr-/- mice and has a protective role. The potential interaction between XBP1 and FXR signaling may be important in modulating the hepatocellular cholestatic stress responses.
Type III interferons induce pyroptosis in gut epithelial cells and delay tissue restitution upon acute intestinal injury
Authors: Sposito Benedetta , Mambu Julien , Gwilt Katlynn Bugda , Spinelli Lionel , Andreeva Natalia , Galland Franck , Naquet Philippe , Mitsialis Vanessa , Thiagarajah Jay R , Snapper Scott B , Broggi Achille , Zanoni Ivan 
Published: March 2022

AbstractTissue damage and repair are hallmarks of the inflammatory process. Despite a wealth of information focused on the mechanisms that govern tissue damage, mechanistic insight on how inflammatory immune mediators affect the restitution phase is lacking. Here, we investigated how interferons influence tissue restitution after damage of the intestinal mucosa driven by inflammatory or physical injury. We found that type III, but not type I, interferons serve a central role in the restitution process. Type III interferons induce the upregulation of ZBP1, caspase activation, and cleavage of gasdermin C, and drive epithelial cell death by pyroptosis, thus delaying tissue restitution. We also found that this pathway is transcriptionally regulated in IBD patients. Our findings highlight a new molecular signaling cascade initiated by the immune system that affects the outcome of the immune response by delaying tissue repair and that may have important implications for human inflammatory disorders.
SUMO conjugation regulates the activity of the Integrator complex
Authors: Bragado Laureano , Magalnik Melina , Mammi Pablo , Romero Agustín , Gaioli Nicolás , Pozzi Berta , Srebrow Anabella 
Published: March 2022

ABSTRACTRNA pol II transcribes snRNA genes in close proximity to Cajal bodies, subnuclear compartments that depend on the SUMO isopeptidase USPL1 for their assembly. We show here that overexpression of USPL1 alters snRNA 3’-end cleavage, a process carried out by the Integrator complex. Beyond its role in snRNA biogenesis, this complex is responsible for regulating the expression of different non-coding and coding transcripts. We validated several subunits of the complex as SUMO conjugation substrates, and found that the SUMOylation of INTS11 subunit is regulated by USPL1. We defined Lys 381, Lys 462 and Lys 475 as bona fide SUMO attachment sites within INTS11 and observed that SUMOylation of this protein is required for efficient Integrator activity. Moreover, while an INTS11 SUMOylation deficient mutant is still capable of interacting with INTS4 and INTS9, its interaction with other subunits of the complex is affected. This mutant also shows a more cytoplasmatic localization than the wild type protein. These findings point to a regulatory role of SUMO conjugation on Integrator activity and suggest the involvement of INTS11 SUMOylation in the assembly of the complex. Furthermore, this work adds the Integrator-dependent RNA processing to the growing list of cellular processes regulated by SUMO conjugation.
Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers
Authors: Wu Meiyun , Wang Yuyang , Zhao Xue , Xin Tianyu , Wu Kun , Liu Haotian , Wu Shinan , Liu Min , Chai Xiaoke , Li Jinhong , Wei Chaogang , Zhu Chaozhe , Liu Yuhe , Zhang Yu-Xuan 
Published: March 2022

SUMMARYHuman brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children with prelingual deafness provide a unique opportunity to study this developmental stage. Using functional near-infrared spectroscopy, we revealed that the brain of CI children was nearly irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. In addition, speech responses increased linearly in left sylvian parieto-temporal area and right inferior frontal gyrus, and noise responses changed in U shape in right supramarginal gyrus. Such cortical development predicted behavioral improvement. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition in the human brain.Graphic abstractHighlightsThe brain of cochlear implanted toddlers is functionally inferior to neonatesHearing experiences drive functional development in auditory related cortical areasSpeech and noise processing develop in anti-phasic oscillatory trajectoriesAuditory cortical development predicts post-implantation behavioral improvement
Medial septum activation improves strategy switching once strategies are well learned via bidirectional regulation of dopamine neuron population activity
Authors: Bortz D.M. , Feistritzer C.M. , Power C.C. , Grace A.A. 
Published: March 2022

AbstractStrategy switching is a form of cognitive flexibility that requires inhibiting a previously successful strategy and then switching to a new strategy of a different categorical modality. It is dependent on dopamine (DA) receptor activation and release in ventral striatum and prefrontal cortex, two primary targets of ventral tegmental area (VTA) DA projections. Although the circuitry that underlies strategy switching early in learning has been studied, few studies have examined it after extended discrimination training. This may be important as DA activity and release patterns change across learning, with several studies demonstrating a critical role for substantia nigra pars compacta (SNc) DA activity and release once behaviors are well learned.Our previous studies demonstrated that medial septum (MS) activation simultaneously increased VTA and decreased SNc DA population activity, as well as improved reversal learning via these actions on DA population activity. We hypothesized that MS activation would improve strategy switching both early in learning and after extended training through its ability to increase VTA DA population activity and decrease SNc DA population activity, respectively. To test this, we activated the MS of male and female rats with designer receptors exclusively activated by designer drugs and measured their performance on an operant-based strategy switching task, following 1, 10, or 15 days of discrimination training. Contrary to our hypothesis, MS activation did not affect strategy switching after 1 day of discrimination training. MS activation improved strategy switching after 10 days of discrimination training, but only in females. MS activation improved strategy switching in both sexes after 15 days of discrimination training. This improvement in strategy switching was attenuated by intra-ventral subiculum bicuculline infusion, which selectively inhibited the MS-mediated decrease in SNc DA population activity, and prevented by infusion of both bicuculline and scopolamine, which inhibited both the MS-mediated decrease in SNc and increase in VTA DA population activity. These data indicate that MS activation improves strategy switching, but only once the original strategy has been sufficiently well learned. They also suggest that the mechanism by which this occurs is likely via the MS’s regulation of DA neuron responsivity, primarily via its ability to down-regulate DA population activity in the SNc.
Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase
Authors: Yang Xiaoli , Ding Zhanyu , Peng Lisi , Song Qiuyue , Cui Fang , Zhang Deyu , Xia Chuanchao , Li Keliang , Yin Hua , Li Shiyu , Li Zhaoshen , Huang Haojie 
Published: March 2022

AbstractThe enteropeptidase (EP) initiates the intestinal digestion by proteolytic processing of trypsinogen, generating catalytic active trypsin. The dysfunction of EP will cause a series of pancreatic diseases, the most severe of which is acute necrotizing pancreatitis. However, the molecular mechanism of EP activation and substrate recognition remain elusive due to the lack of structural information, hampering the structure-based research of EP and even further EP-targeted drug design. Here we report cryo-EM structures of human EP in multiple states, covering the functional cycle spanning from inactive to active state and eventually to the substrate binding state, with the inactive core region reached an atomic 2.7-Å-resolution. The heavy chain of EP exhibits a clamping configuration with the CUB2 domain serving for substrate recognition. The N-terminus of light chain induces the surface loop remodeling from inactive to active conformation, resulting in a highly dynamic and active EP. Then the heavy chain performs like a hinge to ensure the flexibility of light chain for substrate recruitment and subsequent cleavage. Our study provides structural insights of EP remodeling and heavy chain dynamics while performing enzymatic function, facilitating our understanding of the pathogenies of EP-related pancreatitis and the EP-targeted treatment of pancreatitis.
Hybridity in a hotel chain: designing a package of controls to sustain a hybrid mission
Authors: Bouten Lies , Hoozée Sophie 
Published: March 2022

PurposeWhile prior control studies typically focus on organizations with an instrumental approach to corporate sustainability, this study concentrates on organizations with an integrative approach, as the latter is needed to address the grand challenge of sustainable development. As such organizations do not single out the financial objective as the dominant one, they pursue a hybrid mission. This study investigates how a control package can be designed that ensures the persistence of such a hybrid mission.Design/methodology/approachA case study is undertaken at a luxury hotel chain in which a financial and an environmental objective are continuously balanced. Self-determination theory is used to substantiate insights into how psychological need-supportive controls can be designed at all organizational levels.FindingsThis study highlights how controls are not only needed to direct staff behaviour towards the environmental objective but also to ensure that staff at all organizational levels prioritize the objectives in such way that the hybrid mission can be sustained. Besides structural differentiation and centralization of decision-making, the case organization designed need-supportive controls to foster staff's internalization of the environmental objective and value as well as of the integrative approach.Social implicationsAs the need-supportive socialization process fostered staff's integration of the environmental value, this study highlights the transformational potential of controls.Originality/valueThis study provides a unique account of a control package directing staff behaviour towards the balancing of multiple objectives.
Knowledge management capability, entrepreneurial creativity, entrepreneurial intensity and firm performance: the mediating role of ambidexterity
Authors: Garousi Mokhtarzadedeh Nima , Jafarpanah Ismail , Zamani Babgohari Ali 
Published: March 2022

PurposeLiterature survey shows that it is not clear how knowledge management capability (KMC) and ambidexterity capability affect entrepreneurial creativity (EC) and entrepreneurial intensity (EI) promotion. While empirical studies have emphasized the importance of these factors in improving business performance, the cumulative effect and self-reinforcing loops of these factors in improving firm performance have not been identified. In this regard, the study seeks to investigate how to increase the entrepreneurial capabilities of KMC, EI, EC and ambidexterity of food firms to improve their performance.Design/methodology/approachThe method of the present study is applied in terms of purpose and is quantitative in terms of data collection. In order to collect the data, a questionnaire was designed that contained the variables of the conceptual model of the research. This questionnaire was distributed among industrial and academic experts in the Iranian food industry. The method of data collection is an online cross-sectional survey, and the method of data analysis is structural equation modeling using Smart PLS software to analyze the conceptual model.FindingsThe present study is cross-sectional survey research that examines the impact of KMC, EC and EI on firm performance by considering the mediating role of organizational ambidexterity. The research study shows a positive impact of entrepreneurial capabilities as KMC, EI, EC and ambidexterity on performance. Accordingly, if a firm builds KMC and fosters EC, it can achieve ambidextrous innovation and thus enhance its EI and performance in the food industry.Research limitations/implicationsThis study highlights the knowledge-based view (KBV) in explaining the role of KMC on innovative capabilities and its influence on performance. Research findings shed light on the importance of KMC as a prerequisite for innovation strategy. The study has also established the mediating role of ambidexterity in entrepreneurial value creation. According to the results, small and medium-sized enterprises (SMEs)' performance is positively influenced by entrepreneurial capabilities as KMC, EI, EC and ambidexterity.Originality/valueThis paper gives insights into how SMEs can improve their performance to gain a competitive advantage by developing knowledge and creative ideas in line with entrepreneurial goals. In this regard, the food industry can adopt new strategies to reduce the impact of these challenges to achieve superior performance and competitive advantage.
Benchmarking Industry 4.0 readiness evaluation using fuzzy approaches
Authors: Wankhede Vishal Ashok , Vinodh S. 
Published: March 2022

PurposeThe purpose is to assess Industry 4.0 (I4.0) readiness index using fuzzy logic and multi-grade fuzzy approaches in an automotive component manufacturing organization.Design/methodology/approachI4.0 implies fourth industrial revolution that necessitates vital challenges to be dealt with. In this viewpoint, this article presents the evaluation of I4.0 Readiness Index. The evaluation includes two levels with appropriate criteria and factors. Fuzzy logic approach is used for assessment. Furthermore, the results obtained from fuzzy logic have been benchmarked with multi-grade fuzzy approach.FindingsThe proposed assessment model has successfully utilized fuzzy logic approach for assessment of I4.0 readiness index of automotive component manufacturing organization. Based on fuzzy logic approach, readiness index of I4.0 has been found to be (4.74, 6.26, 7.80) which is further benchmarked using multi-grade fuzzy approach. Industry 4.0 readiness index obtained from multi-grade fuzzy approach is 6.258 and thus, validated. Furthermore, 20 weaker areas have been identified and improvement suggestions are provided.Research limitations/implicationsThe assessment module include two levels (Six Criteria and 50 Factors). The assessment model could be expanded based on advancements in industrial developments. Therefore, future researchers could utilize findings of the readiness model to further develop multi-level assessment module for Industry 4.0 readiness in organization. The developed readiness model helped researchers in understanding the methodology to assess I4.0 readiness of organization.Practical implicationsThe model has been tested with reference to automotive component manufacturing organization and hence the inferences derived have practical relevance. Furthermore, the benchmarking strategy adopted in the present study is simple to understand that makes the model unique and could be applied to other organizations. The results obtained from the study reveal that fuzzy logic-based readiness model is efficient to assess I4.0 readiness of industry.Originality/valueThe development of model for I4.0 readiness assessment and further analysis is the original contribution of the authors. The developed fuzzy logic based I4.0 readiness model indicated the readiness level of an organization using I4RI. Also, the model provided weaker areas based on FPII values which is essential to improve the readiness of organization that already began with the adoption of I4.0 concepts. Further modification in the readiness model would help in enhancing I4.0 readiness of organization. Moreover, the benchmarking strategy adopted in the study i.e. MGF would help to validate the computed I4.0 readiness.
Do corporate social responsibility reduce crash risk of stock price: evidence from China
Authors: Su Kun , Zhou Ziting 
Published: March 2022

PurposeThe 2008 global financial crisis stimulated the research interest in stock price crash risk. However, the determinants of stock price crash risk remain unclear, especially in transitional economies. The purpose of this paper is to investigate the association between corporate social responsibility (CSR) and stock price crash risk, as well as the moderating effects under different contexts.Design/methodology/approachUsing firm-level data of listed firms in China from 2010 to 2019, this paper estimates with correlation analysis and multiple regression analysis.FindingsThis paper’s empirical results show that the constraint of CSR on bad news hoarding behavior can reduce stock price crash risk. Further research shows that internal CSR has a significant effect on crash risks, while external CSR has not. Additionally, CSR has a relatively weak impact on crash risk in state-owned enterprises, enterprises with higher internal control quality and enterprises with better regional financial development.Originality/valueThis paper contributes to the stock price crash risks literature by examining the CSR-stock price crash risk linkage in a Chinese context, revealing collective explanations under different contexts with important implications for the application of CSR in business practice.
Evaluating megaprojects from a sustainability perspective: a case of China-Pakistan economic corridor (CPEC)
Authors: Hassan Masoodul , Mahmood Zeeshan , Janjua Saleem , Asif Numra 
Published: March 2022

PurposeThis paper aims to examine the impact of various economic, social and environmental issues on the sustainable development of Pakistan, both directly and indirectly through the sustainability dimensions of China–Pakistan Economic Corridor (CPEC), a multi-billion-dollar megaproject.Design/methodology/approachUsing a quantitative (deductive) methodological approach, data were collected using a strategy of an online questionnaire survey from diverse stakeholders of CPEC in Pakistan. Partial least squares-based structural equation modeling technique was used to test the relationship between observed and latent variables.FindingsThe results confirmed the positive impact of various economic, social and environmental issues on the sustainable development of Pakistan directly and indirectly through the partial mediation of sustainability dimensions of CPEC.Practical implicationsSustainability perceptions of stakeholders about CPEC and its relationship with sustainable development are critical issues for governments and policymakers. This paper suggest how economic, social and environmental dimensions of CPEC can enhance the positive perception which is necessary for stakeholder involvement and support for megaprojects such as CPEC.Originality/valueThis study evaluated the megaprojects of CPEC from a sustainability perspective through stakeholders’ perceptions by proposing and testing a parsimonious research model that has never been examined in the existing literature.