bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenofovir Disoproxil Fumarate and severity of COVID-19 in people with HIV infection
Authors: Del Amo J , Polo R , Moreno S , Martínez E , Cabello A , Iribarren JA , Curran A , Macías J , Montero M , Dueñas C , Mariño AI , Pérez de la Cámara S , Díaz A , Arribas JR , Jarrín I , Hernán MA
Published: November 2021

Background

Effective, safe, and affordable antivirals are needed for COVID-19. Tenofovir has not been studied in randomized trials despite evidence consistent with its effectiveness against COVID-19.

Methods

We studied HIV-positive individuals on antiretroviral therapy (ART) in 2020 at 69 HIV clinics in Spain. We collected data on sociodemographics, ART, CD4-cell count, HIV-RNA viral load, comorbidities and the following outcomes: laboratory-confirmed SARS-CoV-2 infection, COVID-19 hospitalization, intensive care unit (ICU) admission and death. We compared the 48-week risks for individuals receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/ FTC, abacavir (ABC)/lamivudine (3TC), and other regimes. All estimates were adjusted for clinical and sociodemographic characteristics via inverse probability weighting.

Results

Of 51,558 eligible individuals, 39.6% were on TAF/FTC, 11.9% on TDF/FTC, 26.6% on ABC/3TC, 21.8% on other regimes. There were 2,402 documented SARS-CoV-2 infections (425 hospitalizations, 45 ICU admissions, 37 deaths). Compared with TAF/FTC, the estimated risk ratios (RR) (95% CI) of hospitalization were 0.66 (0.43, 0.91) for TDF/FTC and 1.29 (1.02, 1.58) for ABC/3TC, the RRs of ICU admission were 0.28 (0.11, 0.90) for TDF/FTC and 1.39 (0.70, 2.80) for ABC/3TC, and the RRs of death were 0.37 (0.23, 1.90) for TDF/FTC and 2.02 (0.88-6.12) for ABC/3TC. The corresponding RRs of hospitalization for TDF/FTC were 0.49 (0.24, 0.81) in individuals ≥50 years and 1.15 (0.59, 1.93) in younger individuals.

Conclusion

Our findings suggest that, compared with other antiretrovirals, TDF/FTC lowers COVID-19 severity among HIV-positive individuals with virological control. This protective effect may be restricted to individuals aged 50 years and older.
Impact of Starmerella bacillaris and Zygosaccharomyces bailii on ethanol reduction and Saccharomyces cerevisiae metabolism during mixed wine fermentations
Authors: Capece Angela , Pietrafesa Angela , Siesto Gabriella , Pietrafesa Rocchina , Garrigós Víctor , Romano Patrizia , Matallana Emilia , Aranda Agustín
Published: November 2021

The bulk of grape juice fermentation is carried out by the yeast Saccharomyces cerevisiae, but non-Saccharomyces yeasts can modulate many sensorial aspects of the final products in ways not well understood. In this study, some of such non-conventional yeasts were screened as mixed starter cultures in a fermentation defined medium in both simultaneous and sequential inoculations. One strain of Starmerella bacillaris and another of Zygosaccharomyces bailii were chosen by their distinct phenotypic footprint and their ability to reduce ethanol levels at the end of fermentation, particularly during simultaneous vinification. S. bacillaris losses viability strongly at the end of mixed fermentation, while Z. bailii remains viable until the end of vinification. Interestingly, for most non-Saccharomyces yeasts, simultaneous inoculation helps for survival at the end of fermentation compared to sequential inoculation. S. cerevisiae viability was unchanged by the presence of the either yeast. Characterization of both strains indicates that S. bacillaris behavior is overall more different from S. cerevisiae than Z. bailii. S. bacillaris has a less strict glucose repression mechanism and molecular markers like catabolite repression kinase Snf1 is quite different in size. Besides, S. cerevisiae transcriptome changes to a bigger degree in the presence of S. bacillaris than when inoculated with Z. bailii. S. bacillaris induces the translation machinery and repress vesicular transport. Both non-Saccharomyces yeast induce S. cerevisiae glycolytic genes, and that may be related to ethanol lowering, but there are specific aspects of carbon-related mechanisms between strains: Z. bailii presence increases the stress-related polysaccharides trehalose and glycogen while S. bacillaris induces gluconeogenesis genes.
H3K4me3 enrichment defines neuronal age, while a youthful H3K27ac signature is recapitulated in aged neurons
Authors: Giles Katherine A. , Phipps Andrew J. , Cashion Jake M. , Huskins Shannon N. , Mercer Timothy R. , Robinson Mark D. , Woodhouse Adele , Taberlay Phillippa C.
Published: November 2021

Neurons live for the lifespan of the individual and underlie our ability for lifelong learning and memory. However, aging alters neuron morphology and function resulting in age-related cognitive decline. It is well established that epigenetic alterations are essential for learning and memory, yet few neuron-specific genome-wide epigenetic maps exist into old age. Comprehensive mapping of H3K4me3 and H3K27ac in mouse neurons across lifespan revealed plastic H3K4me3 marking that differentiates neuronal age linked to known characteristics of cellular and neuronal aging. We determined that neurons in old age recapitulate the H3K27ac enrichment at promoters, enhancers and super enhancers from young adult neurons, likely representing a re-activation of pathways to maintain neuronal output. Finally, this study identified new characteristics of neuronal aging, including altered rDNA regulation and epigenetic regulatory mechanisms. Collectively, these findings indicate a key role for epigenetic regulation in neurons, that is inextricably linked with aging.
Steroid-resistant nephrotic syndrome associated MYO1E mutations have differential effects on myosin 1e localization, dynamics, and activity
Authors: Liu Pei-Ju , Gunther Laura K. , Perez Diana , Bi-Karchin Jing , Pellenz Christopher D. , Chase Sharon E. , Presti Maria F. , Plante Eric L. , Martin Claire E. , Lovric Svjetlana , Yengo Christopher M. , Hildebrandt Friedhelm , Krendel Mira
Published: November 2021

Myo1e is a non-muscle motor protein enriched in the podocyte foot processes. Mutations in MYO1E are associated with steroid-resistant nephrotic syndrome (SRNS). Here, we set out to differentiate between the pathogenic and neutral MYO1E variants identified in SRNS patients by exome sequencing. Based on protein sequence conservation and structural predictions, two mutations in the motor domain, T119I and D388H, were selected for this study. EGFP-tagged Myo1e constructs were delivered into the Myo1e-KO podocytes via adenoviral infection to analyze Myo1e protein stability, Myo1e localization, and clathrin-dependent endocytosis, which is known to involve Myo1e activity. Furthermore, truncated Myo1e constructs were expressed using the baculoviral expression system and used to measure Myo1e ATPase and motor activity in vitro. Both mutants were expressed as full-length proteins in the Myo1e-KO podocytes. However, unlike wild-type (WT) Myo1e, the T119I variant was not enriched at the cell junctions or clathrin-coated vesicles (CCVs) in podocytes. In contrast, the D388H variant localization was similar to the WT. Surprisingly, the dissociation of the D388H variant from cell-cell junctions and CCVs was decreased, suggesting that this mutation also affects Myo1e activity. The ATPase activity and the ability to translocate actin filaments were drastically reduced for the D388H mutant, supporting the findings from cell-based experiments. The experimental pipeline developed in this study allowed us to determine that the T119I and D388H mutations appear to be pathogenic and gain additional knowledge in the Myo1e role in podocytes. This workflow can be applied to the future characterization of novel MYO1E variants associated with SRNS.
Identification and Characterization of Stem Cells in Mammalian Esophageal Stratified Squamous Epithelia
Authors: Yang Yanan , Deng Guodong , Qiao Lili , Yuan Hui , Yu Xiaohong , Xu Lei , Lu Shih-Hsin , Jiang Wei , Yu Xiying
Published: November 2021

Somatic stem cells are essential for maintenance of cell proliferation-differentiation homeostasis in organs. Despite the importance, how the esophageal epithelium that executes its self-renewal and maintenance remains elusive. In this study, using 5-bromo-2’-deoxyuridine (BrdU) label-chase in rat and rat esophageal keratinocyte cell line-derived organoids together with genome-wide DNA methylation profiling and single-cell RNA sequencing (scRNA-seq), we identify slow cycling/quiescent stem cell population that contain high levels of hemidesmosome (HD)’s and low levels of Wnt signaling localized spatially and randomly at the basal layer of the esophageal epithelium. Pseudo-time cell trajectory from scRNA-seq indicates that cell fates begin from quiescent basal cells (the stem cells) of the basal layer that produce proliferating and/or differentiating cells in the basal layer, which, in turn, progress into differentiating cells in the suprabasal layer, ultimately transforming into differentiated keratinocytes in the differentiated layer. Perturbations of HD component expressions and/or Wnt signaling reduce stem cell in the basal layer of esophageal keratinocyte organoids, resulting in alterations of organoid formation rate, size, morphogenesis and proliferation-differentiation homeostasis. Furthermore, we show that not only high levels of HDs and low levels of Wnt signaling but also an interplay between HD and Wnt signaling defined stem cells of the basal layer in the esophageal squamous epithelium. Hence, HDs and Wnt signaling are the critical determinants for defining stem cells of the basal layer required for proliferation-differentiation homeostasis and maintenance in the mammalian esophageal squamous epithelium.
TBC1D18, a novel Rab5-GAP, coordinates endosome maturation together with Mon1
Authors: Hiragi Shu , Matsui Takahide , Sakamaki Yuriko , Fukuda Mitsunori
Published: November 2021

Endosome maturation is essential for efficient degradation of internalized extracellular molecules and plasma membrane proteins. Two Rab GTPases, Rab5 and Rab7, are known to regulate endosome maturation, and a Rab5-to-Rab7 conversion mediated by a Rab7 activator, Mon1–Ccz1, is essential for progression of the maturation process. However, the importance and mechanism of Rab5 inactivation during endosome maturation is poorly understood. Here we report a novel Rab5 inactivator (Rab5-GTPase activating protein [Rab5-GAP]), TBC1D18, which is associated with Mon1 and mediates endosome maturation. We found that Rab5 hyperactivation in addition to Rab7 inactivation occurs in the absence of Mon1. We present evidence showing that the severe defects in endosome maturation observed in Mon1-KO cells are attributable to Rab5 hyperactivation rather than to Rab7 inactivation. We then identified TBC1D18 as a Rab5-GAP by comprehensive screening of TBC-domain-containing Rab-GAPs. Expression of TBC1D18 in Mon1-KO cells rescued the defects in endosome maturation, whereas its depletion attenuated endosome formation and degradation of endocytosed cargos. Moreover, TBC1D18 was found to be able to interact with Mon1, and it localized in close proximity to lysosomes in a Mon1-dependent manner. Thus, TBC1D18 is a crucial regulator of endosome maturation that functions together with Mon1.
α-hemolysin ofStaphylococcus aureusimpairs thrombus formation
Authors: Jahn Kristin , Handtke Stefan , Palankar Raghavendra , Kohler Thomas P. , Wesche Jan , Wolff Martina , Bayer Janina , Wolz Christiane , Greinacher Andreas , Hammerschmidt Sven
Published: November 2021

Toxins are key virulence determinants of pathogens and can impair the function of host immune cells including platelets. Insights into pathogen toxin interference with platelets will be pivotal to improve treatment of patients with bacterial bloodstream infections. In this study, we deciphered the effects ofStaphylococcus aureustoxins α-hemolysin, LukAB, LukDE and LukSF on human platelets and compared the effects with the pore forming toxin pneumolysin ofStreptococcus pneumoniae. In contrast to pneumolysin, α-hemolysin initially activates platelets as indicated by CD62P and αIIbβ3 integrin expression, but the resulting pores also induce alterations in the phenotype of platelets and induce apoptosis of platelets. The presence of small amounts of α-hemolysin (0.2 µg/mL) in whole blood abrogates thrombus formation indicating that in systemic infections withS. aureusthe stability of formed thrombi is impaired. This might be of high clinical relevance forS. aureusinduced endocarditis of the aortic valves. Stabilizing the thrombi by inhibiting α-hemolysin induced impairment of platelets likely reduces the risk for septic (micro-)embolization. However, in contrast to pneumolysin, α-hemolysin induced platelets damage could not be neutralized by intravenous immune globulins. In contrast to α-hemolysin,S. aureusbi-component pore forming leukocidins LukAB, LukED and LukSF do not bind to platelets and had no significant effect on platelet activation and viability.

Main point 1: α-hemolysin forms pores in platelets, which first activate but then result in apoptosis and impairs thrombus formation and stability

Main point 2: Polyvalent immunoglobulins do not neutralize the mode of action of the toxin
A single-cell massively parallel reporter assay detects cell type specific cis-regulatory activity
Authors: Zhao Siqi , Hong Clarice KY , Myers Connie A , Granas David M , White Michael A , Corbo Joseph C , Cohen Barak A
Published: November 2021

Massively parallel reporter gene assays are key tools in regulatory genomics, but cannot be used to identify cell-type specific regulatory elements without performing assays serially across different cell types. To address this problem, we developed a single-cell massively parallel reporter assay (scMPRA) to measure the activity of libraries of cis-regulatory sequences (CRSs) across multiple cell-types simultaneously. We assayed a library of core promoters in a mixture of HEK293 and K562 cells and showed that scMPRA is a reproducible, highly parallel, single-cell reporter gene assay that detects cell-type specific cis-regulatory activity. We then measured a library of promoter variants across multiple cell types in ex vivo mouse retinas and showed that subtle genetic variants can produce cell-type specific effects on cis-regulatory activity. We anticipate that scMPRA will be widely applicable for studying the role of CRSs across diverse cell types.
Cross-stress gene expression atlas of Marchantia polymorpha reveals the hierarchy and regulatory principles of abiotic stress responses
Authors: Tan Qiao Wen , Lim Peng Ken , Chen Zhong , Pasha Asher , Provart Nicholas , Arend Marius , Nikoloski Zoran , Mutwil Marek
Published: November 2021

Abiotic stresses negatively impact ecosystems and the yield of crops, and climate change will increase their frequency and intensity. Despite progress in understanding how plants respond to individual stresses, our knowledge of plant acclimatization to combined stresses–typically occurring in nature is still lacking. Here, we used a plant with minimal regulatory network redundancy, Marchantia polymorpha, to study how seven abiotic stresses, alone and in 19 pairwise combinations, affect the phenotype, gene expression, and activity of cellular pathways. We found a high divergence of transcriptomic stress responses between Arabidopsis and Marchantia, suggesting that the stress-specific gene regulatory networks (GRNs) between bryophytes and angiosperms are not strongly conserved. The reconstructed high-confidence GRNs demonstrated that the response to specific stresses dominates those of others by relying on a large ensemble of transcription factors. We also showed that a regression model could accurately predict the gene expression under combined stresses, indicating that Marchantia performs arithmetic addition to respond to multiple stresses. Finally, we provide two online resources (https://conekt.plant.tools and http://bar.utoronto.ca/efp_marchantia/cgi-bin/efpWeb.cgi) to facilitate the study of gene expression in Marchantia exposed to abiotic stresses.
Frizzled-4 regulates β-catenin in endothelial cells exposed to disturbed flow via an atypical Wnt pathway leading to proinflammatory activation and increased permeability
Authors: Rickman Matthew , Ghim Mean , Pang Kuin Tian , von Huelsen Rocha Ana Cristina , Drudi Elena M. , Sureda-Vives  , Ayoub Nicolas , Tajadura-Ortega Virginia , George Sarah J. , Weinberg Peter D. , Warboys Christina M.
Published: November 2021

Objective

Endothelial cells are regulated by hemodynamic wall shear stress and multidirectional shear stress is known to promote endothelial dysfunction, although the molecular mechanisms are poorly defined. Wnt pathways play an important role in non-vascular mechanoresponsive cells. Here we investigated their role in endothelial mechanosignalling and endothelial dysfunction.

Approach & Results

Human aortic endothelial cells were exposed to shear stress using an orbital shaker. The expression of Frizzled-4 receptors was significantly increased in endothelial cells exposed to low magnitude multidirectional flow (LMMF) relative to high magnitude uniaxial flow (HMUF). Increased expression was also detected in regions of the murine aortic arch exposed to LMMF. The increased Frizzled-4 expression in cultured cells was abrogated following knockdown of R-spondin-3 (RSPO-3) using RNA interference. LMMF also increased the stabilisation and nuclear localisation of β-catenin, an effect that was dependent on Frizzled-4 and RSPO-3. Inhibition of β-catenin using a small molecule inhibitor (iCRT5), or knockdown of Frizzled-4 or R-spondin-3 resulted in a significant reduction of pro-inflammatory gene expression in endothelial cells exposed to LMMF. Stabilisation of the β-catenin destruction complex using IWR-1 under LMMF also reduced pro-inflammatory gene expression, as did inhibition of Wnt5a signalling. Interestingly, inhibition of the canonical Wnt pathway had no effect. Inhibition of β-catenin signalling also reduced endothelial permeability; this was associated with altered junctional and focal adhesion organisation and cytoskeletal remodelling.

Conclusions

These data suggest the presence of an atypical Wnt-β-catenin pathway in endothelial cells that promotes inflammatory activation and barrier disruption in response to LMMF.
Ibuprofen and sila-ibuprofen: polarization effects in the crystal and enzyme environments
Authors: Kleemiss Florian , Puylaert Pim , Duvinage Daniel , Fugel Malte , Sugimoto Kunihisa , Beckmann Jens , Grabowsky Simon
Published: November 2021

Sila-ibuprofen is a new potential nonsteroidal anti-inflammatory drug which deviates from its parent ibuprofen in terms of the electrostatic potential around the carbon/silicon-switched C/Si—H group. Therefore, sila-ibuprofen is more water soluble and has a lower melting enthalpy. However, its binding and inhibition properties of cyclooxygenases appear to be very similar to regular ibuprofen. Therefore, in this study, intermolecular interactions and interaction densities of both ibuprofen and sila-ibuprofen in their biologically active forms, i.e. deprotonated and as the pure S-enantiomers are investigated. Quantum-crystallographically refined salts with argininium and 1-phenylethan-1-amoninium (PEA) counter-cations as crystalline models of the interactions with the guanidine functional group of arginine inside cyclooxygenases are presented. The similarities and differences between the polarization of ibuprofen and sila-ibuprofen in the crystal, enzyme, solvent and isolated environments are discussed based on quantum-chemical calculations. For the explicit crystal and enzyme environments, specifically, molecular dynamics simulations starting from the crystal models were combined with QM/MM calculations.
Playing the cards right: exploring the way leadership influences organizational citizenship behavior for the environment in megaprojects
Authors: Wang Ge , Locatelli Giorgio , Zhang Huijin , Wan Jingyuan , Chen Yufan
Published: November 2021

Purpose

Organizational citizenship behaviors for the environment (OCBEs) represent a crucial element of environmental sustainability for a wide range of organizations. However, the leadership mechanisms underlying OCBEs are as yet unexplored, particularly regarding the delivering megaprojects. The paper aims to investigate how transformational leadership (TFL) and transactional leadership (TSL) styles shape the environmental commitment (EC) of subordinates, motivating OCBEs in megaprojects.

Design/methodology/approach

Partial least squares modeling and hierarchical regression were performed on data obtained from 140 experts who have been involved in megaprojects.

Findings

Both TFL and TSL styles are effective in motivating OCBEs, although the EC of subordinates partially mediates these relationships. The power distance (PD) orientation significantly moderates the relationship between TFL and OCBEs, with the relationship being more positive when the PD of subordinates is lower. Unexpectedly, a collectivist orientation (CO) was found to elevate the effect of TSL but weaken the effect of TFL.

Originality/value

The mixed and contradictory findings regarding TFL and TSL styles are reconciled in the current study by integrating the contextual factors of PD and CO. The findings of the study shed new light on “playing the cards right” when using the leadership practices, i.e. how leadership can be better leveraged to cultivate subordinates' OCBEs. They also provide targeted guidance for shaping contextual factors to increase the environmental sustainability of megaprojects.
How can we promote co-creation in communities? The perspective of health promoting professionals in four European countries
Authors: Darlington Emily Joan , Pearce Gemma , Vilaça Teresa , Masson Julien , Bernard Sandie , Anastácio Zélia , Magee Paul , Christensen Frants , Hansen Henriette , Carvalho Graça S.
Published: November 2021

Purpose

The aim was to identify the competencies professionals need to promote co-creation engagement within communities.

Design/methodology/approach

Co-creation could contribute to building community capacity to promote health. Professional development is key to support co-creative practices. Participants were professionals in a position to promote co-creation processes in health-promoting welfare settings across Denmark, Portugal, France and United Kingdom. An overarching unstructured topic guide was used within interviews, focus groups, questionnaires and creative activities.

Findings

The need to develop competencies to promote co-creation was high across all countries. Creating a common understanding of co-creation and the processes involved to increase inclusivity, engagement and shared understanding was also necessary. Competencies included: How to run co-creation from the beginning of the process right through to evaluation, using feedback and communication throughout using an open action-oriented approach; initiating a perspective change and committing to the transformation of co-creation into a real-life process.

Practical implications

Overall, learning about underlying principles, process initiation, implementation and facilitation of co-creation were areas identified to be included within a co-creation training programme. This can be applied through the framework of enabling change, advocating for co-creative processes, mediating through partnership, communication, leadership, assessment, planning, implementation, evaluation and research, ethical values and knowledge of co-creative processes.

Originality/value

This study provides novel findings on the competencies needed for health promoting professionals to embed co-creative processes within their practice, and the key concerns that professionals with a position to mediate co-creation have in transferring the abstract term of co-creation into a real-world practice.
Mobilisation of survivability capital – family firm response to the coronavirus crisis
Authors: Żukowska Beata Agnieszka , Martyniuk Olga Anna , Zajkowski Robert
Published: November 2021

Purpose

Survivability capital is a unique resource resulting from the “familiness” constituting an inherent feature of family firms. Familiness represents the ability of family members to reinforce the financial and non-financial resources of businesses facing threats to their economic existence. This work proposes and examines various dimensions of the survivability capital construct, verifying whether family firms expecting deterioration of their economic situation or problems with survival due to the COVID-19 crisis can mobilise sufficient capital to survive.

Design/methodology/approach

This article provides empirical evidence based on a cross-sectional online survey of 167 Polish family firms, conducted at the beginning of the COVID-19 pandemic. The method (scale) of survivability capital measurement was elaborated and validated using principal component analysis (PCA) and confirmatory factor analyses (CFA). Next, the mobilisation of the different dimensions of survivability capital was examined using PLS-SEM modelling.

Findings

The survivability capital of family firms is composed of two dimensions: internal (based on directly involved family members) and external (based on not directly involved family members). Family firms facing crisis-induced deterioration of the economic situation engage its internal component. Subsequently, family firms forecasting decreasing probability of survival during a crisis try to engage both the internal and the external components of survivability capital. Such behaviour is in line with the resource-based view as well as with the sustainable family business theory.

Originality/value

To the best of the authors' knowledge, this is one of the first studies to examine analytically the survivability capital construct. While previous studies mentioned the existence of survivability capital, this study attempts to introduce its various dimensions and test the mobilisation of survivability capital during the COVID-19 crisis.
Tax enforcement and private firms' audited financial statements: the moderating role of secrecy culture
Authors: Prabowo Ronny , Sucahyo Usil Sis , Damayanti Theresia Woro , Supramono Supramono
Published: November 2021

Purpose

The research aims to investigate the moderating role of secrecy culture on the effect of tax enforcement on the likelihood that private firms hire external auditors.

Design/methodology/approach

The study generates more than 70,000 observations from 83 country-years from the World Bank Enterprise Survey 2018 dataset. Because the study focuses on private firms in emerging countries, data on publicly listed firms and firms from OECD (Organisation for Economic Co-operation and Development) countries are deleted. The secrecy culture data are generated from Hofstede's website. The data are then analyzed with logit analyses because the dependent variable is binary.

Findings

The results demonstrate that tax enforcement increases the likelihood that private firms hire external auditors. Further, secrecy culture weakens the relationship between tax enforcement and audit demand.

Practical implications

Governments in emerging countries need to encourage private firms to hire external auditors by intensifying tax enforcement because private firms often do not appreciate the importance of high-quality financial statements. However, secretive national culture may reduce tax enforcement's effectiveness in motivating private firms to hire external auditors. Hence, governments of highly secretive countries need to address this issue and find alternative ways to promote audited financial statements.

Originality/value

Audit demand of private firms in emerging countries is relatively understudied, especially concerning tax enforcement. Furthermore, the research also focuses on the moderating role of national culture (secrecy) in explaining the relationship between tax enforcement and audit demand.
Mean–variance relationship and uncertainty
Authors: Kim Jun Sik
Published: November 2021

This study investigates the impact of uncertainty on the mean-variance relationship. We find that the stock market's expected excess return is positively related to the market's conditional variances and implied variance during low uncertainty periods but unrelated or negatively related to conditional variances and implied variance during high uncertainty periods. Our empirical evidence is consistent with investors' attitudes toward uncertainty and risk, firms' fundamentals and leverage effects varying with uncertainty. Additionally, we discover that the negative relationship between returns and contemporaneous innovations of conditional variance and the positive relationship between returns and contemporaneous innovations of implied variance are significant during low uncertainty periods. Furthermore, our results are robust to changing the base assets to mimic the uncertainty factor and removing the effect of investor sentiment.
Intelligent automation in hospitality: exploring the relative automatability of frontline food service tasks
Authors: Tuomi Aarni , Ascenção Mário Passos
Published: November 2021

Purpose

Automation poses to change how service work is organized. However, there is a lack of understanding of how automation influences specific sectors, including specific hospitality jobs. Addressing this gap, this paper looks at the relative automatability of jobs and tasks which fall within one specific hospitality context: frontline food service.

Design/methodology/approach

Study 1 analyzes the UK Office for National Statistics' Standard Occupational Classification (2020) data to determine the degree to which frontline food service jobs consist of tasks requiring mechanical, analytical, intuitive or empathetic intelligence. Study 2 contrasts these findings to current state of intelligent automation technology development through interviews and a focus group with food service technology experts (n = 13).

Findings

Of all the tasks listed under food service in the ONS SOC 2020, 58.8% are found to require mechanical, 26.8% analytical, 11.3% intuitive and 3.1% empathetic intelligence. Further, the automatability of these tasks is found to be driven by three streams of technology development in particular: (1) autonomous navigation, (2) object manipulation and (3) natural language processing.

Originality/value

Hospitality management literature has started to conceptualize a move from mechanical and analytical service tasks to tasks centered around intuition and empathy. While previous studies have adopted a general view to what this might mean for hospitality jobs, this paper develops a novel, task-centric framework for Actioning Intelligent Automation in Frontline Food Service.
Hsp90 regulates the tumorigenic function of tyrosine protein kinase in osteosarcoma
Authors: Yao Zhao‐Peng , Zhu Hui , Shen Feng , Gong Dan
Published: November 2021

Despite recent advances in diagnosis and treatment, osteosarcoma remains as the most common bone cancer in children and is associated with poor prognosis. Growing evidence has supported dysregulation of threonine and tyrosine protein kinase (TTK) expression as a hallmark of multiple cancers, however, its function in osteosarcoma remains to be elucidated. In the present study, we found that TTK was frequently overexpressed in osteosarcoma and associated with increased tumour growth and progression. Moreover, using both in vitro and in vivo assays, we provided evidence that TTK level was regulated by a molecular chaperone, heat shock protein 90 (Hsp90). Hsp90 directly interacted with TTK and prevents proteasome‐dependent TTK degradation, leading to the accumulation of TTK in osteosarcoma cells. Elevated TTK promoted cancer cell proliferation and survival by activating cell‐cycle progression and inhibiting apoptosis. Consistently, depletion of TTK by Hsp90 inhibition induced cell‐cycle arrest, generated aneuploidy and eventually resulted in apoptotic cancer cell death. Together, our study revealed an important Hsp90‐TTK regulatory axis in osteosarcoma cells to promote cancer cell growth and survival. These findings expand our knowledge on osteosarcoma pathogenesis and offer novel therapeutic options for clinical practice.
Score manipulation, density continuity and intent‐to‐treat effect for regression discontinuity
Authors: Choi Jin‐young , Lee Myoung‐jae
Published: November 2021

Regression discontinuity (RD) is widely used in many disciplines of science to find treatment effect when the treatment is determined by an underlying running variable (‘score') crossing a cutoff or not. The main attraction of RD is local randomization around , which is, however, often ruined by manipulation on . To detect manipulation, the continuity of score density function at is routinely tested in practice. In this paper, we examine how informative is for RD, and show the following. First, for incumbency effect in election to which RD has been heavily applied, may have no information content. Second, for RD in general, the continuity is neither necessary nor sufficient for RD validity. Third, if the treatment cannot be implemented without manipulation of , then the manipulation had better be considered as part of the treatment effect, much as in ‘intent‐to‐treat effect’ for clinical trials. These findings call for relying less on continuity tests and, instead, thinking more about how subjects react to the treatment to modify their , how to design the treatment to lessen manipulation, and what to take as the desired treatment effect.
Evaluating the effect of conjugation on the bioactivities of whey protein hydrolysates
Authors: Minj Shayanti , Anand Sanjeev , Martinez‐Monteagudo Sergio
Published: November 2021

In this study, the ability of a whey protein hydrolysate to exhibit the antimicrobial, antioxidant, and antihypertensive behavior after combining with a reducing carbohydrate was studied. Whey protein hydrolysates with varying degrees of hydrolysis (WPH10, WPH15, and WPH20) were determined for their antimicrobial, antioxidant, and antihypertensive activities. Of these, hydrolysate (WPH10) exhibited the highest antimicrobial activity (with 10–11.2 mm zone of inhibition) against tested microorganisms: Listeria innocua, Staphylococcus aureus, and Bacillus coagulans. Also, the WPH10 exhibited the highest antioxidant (866.56 TEAC µmol/L) and antihypertensive (67.52%) attributes. Hence, based on the highest bioactivity, hydrolysate WPH10 was selected for conjugation with maltodextrin, and the effect of conjugation on the bioactivities was evaluated. The conjugated WPH10 solution demonstrated higher antimicrobial (17.16 mm) and antioxidant activity (1044.37 TEAC µmol/L), whereas a slight decrease in the antihypertensive activity (65.4%) was observed, as compared to WPH10 alone. The conjugated solution was further spray dried and alternatively, freeze‐dried. The dried WPH10 conjugate exhibited even higher antimicrobial (18.5 mm) and antioxidant activity (1268.89 TEAC µmol/L) while retaining the antihypertensive activity (65.6%). Overall, the results indicate the ability of the WPH10‐maltodextrin to retain the bioactive behavior after combining with a reduced carbohydrate.

Practical Application

Whey protein hydrolysates upon conjugation with carbohydrates retain the bioactive properties of whey protein, which provides opportunities for application as an ingredient to develop novel health formulations.
Use of betel leaf (Piper betle L.) ethanolic extract in combination with modified atmospheric packaging and nonthermal plasma for shelf‐life extension of Nile tilapia (Oreochromis niloticus) fillets
Authors: Tagrida Mohamed , Benjakul Soottawat , Zhang Bin
Published: November 2021

Fish is perishable and has the short shelf‐life. To maintain its quality, it is necessary to implement the appropriate technology, particularly nonthermal processing along with safe additive, especially from plant origin under the concept of "hurdle technology". The use of potential vesicle including liposome for loading the plant extract could be a means to enhance the stability and activities of the extract. The current study aimed to evaluate the effect of liposomes loaded with betel leaf ethanolic extract (L/BLEEs) or unencapsulated BLEE (U/BLEE) in conjunction with modified atmospheric packaging (MAP) and nonthermal plasma (NTP) on the quality changes and shelf‐life of Nile tilapia fillets (TFs) stored under refrigerated condition (4°C). TFs treated with L/BLEE or U/BLEE at 400 ppm, packed under modified atmosphere (CO2:Ar:O2 = 60:30:10) and subjected to NTP for 300 s (L/BLEE‐400/MAP‐NTP and U/BLEE‐400/MAP‐NTP, respectively) had the lowest microbial and chemical changes during storage, while the control showed the highest changes (p < 0.05). Lipid oxidation was lower in these samples, ascertained by more retained polyunsaturated fatty acids and lower lipid oxidation based on Fourier transform infrared (FT‐IR) spectra. Overall likeness scores were similar (p > 0.05) between all the samples at day 0 of storage. Only L/BLEE‐400/MAP‐NTP and U/BLEE‐400/MAP‐NTP were still sensorially acceptable after 12 days at 4°C. Therefore, L/BLEE or U/BLEE combined with MAP/NTP treatment could be adopted as a potent hurdle for shelf‐life extension of TFs.

Practical Application

Natural additives and nonthermal processing technologies have gained increasing interest for preservation of fish. Liposomes loaded with betel leaf ethanolic extract (L/BLEE) rich in polyphenolics could be used together with modified atmospheric packaging (MAP) and nonthermal plasma (NTP) to retard bacterial growth and chemical deterioration in Nile tilapia fillets. These hurdles were proven to be able to maintain the qualities of tilapia fillets stored at 4°C up to 12 days, especially when L/BLEE was used at 400 ppm. Therefore, shelf‐life extension of Nile tilapia fillets or other fish can be achieved by using the natural additive and nonthermal processing technologies.
MetaComNet: A random forest‐based framework for making spatial predictions of plant–pollinator interactions
Authors: Sydenham Markus A. K. , Venter Zander S. , Reitan Trond , Rasmussen Claus , Skrindo Astrid B. , Skoog Daniel I. J. , Hanevik Kaj‐Andreas , Hegland Stein Joar , Dupont Yoko L. , Nielsen Anders , Chipperfield Joseph , Rusch Graciela M.
Published: November 2021

Predicting plant–pollinator interaction networks over space and time will improve our understanding of how environmental change is likely to impact the functioning of ecosystems. Here we propose a framework for producing spatially explicit predictions of the occurrence and number of pairwise plant–pollinator interactions and of the species richness, diversity and abundance of pollinators visiting flowers. We call the framework ‘MetaComNet’ because it aims to link metacommunity dynamics to the assembly of ecological networks.

To illustrate the MetaComNet functionality, we used a dataset on bee–flower networks sampled at 16 sites in southeast Norway along with random forest models to predict bee–flower interactions. We included variables associated with climatic conditions (elevation) and habitat availability within a 250 m radius of each site. Regional commonness, site‐specific distance to conspecifics, social guild and floral preference were included as bee traits. Each plant species was assigned a score reflecting its site‐specific abundance, and four scores reflecting the bee species that the plant family is known to attract. We used leave‐one‐out cross‐validations to assess the models' ability to predict pairwise plant–bee interactions across the landscape.

The relationship between observed occurrence or absence of interactions and the predicted probability of interactions was nearly proportional (GLMlogistic regression slope = 1.09), matching the data well (AUC = 0.88), and explained 30% of the variation. Predicted probability of interactions was also correlated with the number of observed pairwise interactions (r = 0.32). The sum of predicted probabilities of bee–flower interactions were positively correlated with observed species richness (r = 0.50), diversity (r = 0.48) and abundance (r = 0.42) of wild bees interacting with plant species within sites.

Our findings show that the MetaComNet framework can be a useful approach for making spatially explicit predictions and mapping plant–pollinator interactions. Such predictions have the potential to identify areas where the pollination potential for wild plants is particularly high, and where conservation action should be directed to preserve this ecosystem function.
Clinical factors associated with significant coronary lesions following out‐of‐hospital cardiac arrest
Authors: Helfer David R. , Helber Andrew R. , Ferko Aarika R. , Klein Daniel D. , Elchediak Daniel S. , Deaner Traci S. , Slagle Dustin , White William B. , Buckler David G. , Mitchell Oscar J. L. , Fiorilli Paul N. , Isenberg Derek , Nomura Jason , Murphy Kathleen A. , Sigal Adam , Saif Hassam , Reihart Michael J. , Vernon Tawnya M. , Abella Benjamin S.
Published: November 2021

Objectives

Out‐of‐hospital cardiac arrest (OHCA) afflicts >350,000 people annually in the United States. While postarrest coronary angiography (CAG) with percutaneous coronary intervention (PCI) has been associated with improved survival in observational cohorts, substantial uncertainty exists regarding patient selection for postarrest CAG. We tested the hypothesis that symptoms consistent with acute coronary syndrome (ACS), including chest discomfort, prior to OHCAs are associated with significant coronary lesions identified on postarrest CAG.

Methods

We conducted a multicenter retrospective cohort study among eight regional hospitals. Adult patients who experienced atraumatic OHCA with successful initial resuscitation and subsequent CAG between January 2015 and December 2019 were included. We collected data on prehospital documentation of potential ACS symptoms prior to OHCA as well as clinical factors readily available during postarrest care. The primary outcome in multivariable regression modeling was the presence of significant coronary lesions (defined as >50% stenosis of left main or >75% stenosis of other coronary arteries).

Results

Four‐hundred patients were included. Median (interquartile range) age was 59 (51–69) years; 31% were female. At least one significant stenosis was found in 62%, of whom 71% received PCI. Clinical factors independently associated with a significant lesion included a history of myocardial infarction (adjusted odds ratio [aOR] = 6.5, [95% confidence interval {CI} = 1.3 to 32.4], p = 0.02), prearrest chest discomfort (aOR = 4.8 [95% CI = 2.1 to 11.8], p ≤ 0.001), ST‐segment elevations (aOR = 3.2 [95% CI = 1.7 to 6.3], p < 0.001), and an initial shockable rhythm (aOR = 1.9 [95% CI = 1.0 to 3.4], p = 0.05).

Conclusions

Among survivors of OHCA receiving CAG, history of prearrest chest discomfort was significantly and independently associated with significant coronary artery lesions on postarrest CAG. This suggests that we may be able to use prearrest symptoms to better risk stratify patients following OHCA to decide who will benefit from invasive angiography.
Effectiveness comparison between endometrial receptivity array, immune profiling and the combination in treating patients with multiple implantation failure
Authors: Jia Yan , Dong Ya‐Jun , Sha Yu‐Lin , Cai Song‐Chen , Diao Liang‐Hui , Qiu Zhu , Guo Yan‐Hua , Huang Yan , Ye Hong‐Xia , Liu Su
Published: November 2021

Problem

The clinical value of endometrial receptivity array (ERA), endometrial immune profiling, or a combination of both for multiple implantation failure patients is unclear.

Method of study

One hundred and seventy‐two women with a history of at least two or more consecutive implantation failures in IVF/ICSI treatment were included. According to patients’ willingness, they were divided into four groups, ‘no treatment’, ‘Immune Profiling’, ‘ERA’ and ‘ERA + Immune Profiling’. Endometrial biopsy was examined by ERA, immune profiling alone, or combination, and intention was adopted accordingly. Pregnancy outcomes were compared, and the association between ERA phases and endometrial immune profiling was also assessed.

Results

The overall incidence rate of the displaced window of implantation (WOI) and endometrial immune dysregulations were 84.9% and 75.3%, respectively. Implantation rate was significantly higher in the ‘ERA + Immune Profiling’ group than the ‘no treatment’ group (P = .007). Clinical pregnancy rate was somewhat improved in the three treatment groups but with a borderline significance (P = .071). After controlling for other confounders, ‘ERA + Immune Profiling’ treatment was associated with a higher pregnancy rate [aOR (95%CI)  =  3.412 (1.387–8.395), P = .008]. There was no association between endometrial immune profiling and ERA phases.

Conclusions

Our findings highlight the high incidence of displaced WOI and endometrial immune dysregulation in multiple implantation failure patients. The combination of ERA and endometrial immune profiling is more likely to have clinical value than ERA or immune profiling alone. These data suggested the unsubstitutability of ERA and endometrial immune profiling on the treatment outcome for multiple implantation failure patients.
Ureteric injuries during hysterectomy—A Norwegian retrospective study of occurrence and claims for compensation over an 11‐year period
Authors: Ravlo Merethe , Moen Mette Haase , Bukholm Ida Rashida Khan , Lieng Marit , Vanky Eszter
Published: November 2021

Introduction

Ureteric injury is a rare but serious, iatrogenic complication of hysterectomy. The risk depends on indication for surgery, predisposing risk factors, and peroperative conditions. Our aims were to evaluate and learn from compensation claims to The Norwegian System of Patient Injury Compensation (NPE) for ureteric injury occurring during hysterectomies to predict risk factors, time of identification, symptoms, and consequences, and to relate these cases to injuries registered in The Norwegian Patient Registry.

Material and methods

A retrospective study of ureteric injuries occurring during hysterectomies, reported to NPE and the Norwegian Patient Registry from 2009 through 2019.

Results

During the study period, 53 096 hysterectomies were registered in The Norwegian Patient Registry, of which ureteric injury was documented in 643 (1.2%). More ureteric injuries were registered in large hospital trusts than in small trusts (1.3% vs. 0.7%, p < 0.05). NPE received 69 claims due to ureteric injury occurring during hysterectomy, comprising 11% of all injuries in the study period. Compensation was approved for 15%. Women who claimed compensation were younger (48.1 ± 8.9 years vs. 55.1 ± 13.6 years, p < 0.01), more likely to have had a benign diagnosis (89.9% vs. 52.1%, p < 0.01), and more likely to have had the ureteric injury recognized after discharge (58.0% vs. 33.0%, p < 0.001) compared with non‐complainants. Identification of the ureters during the hysterectomy was documented in 30% of the NPE patient files. Additional information for the NPE cases included the following. The most common symptoms of unidentified injury were pain (77%), fever (12%), urinary leakage (13%), and anuria (8%). Re‐operation was necessary in 77% of the cases, and 10% of the women lost one kidney. Long‐term consequences after repair, such as loss of a kidney or persistent pain, were seen in 17%. No women died because of the injury.

Conclusions

The incidence of ureteric injury occurring during hysterectomy in Norway was 1.2%; 11% involved a claim for compensation, and 15% of these had their case approved. Most ureteric injuries were not recognized during the hysterectomy. Documentation of peroperative identification of the ureters during hysterectomy was often missing. Vigilance to pain as a postoperative symptom of peroperative unrecognized ureteric injury may result in earlier diagnosis and treatment.