bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a single 10mg dose of empagliflozin on postprandial insulin kinetics in patients with postbariatric hypoglycaemia
Authors: Schiavon Michele , Herzig David , Matthias Hepprich , Donath Marc Y. , Man Chiarra Dall , Bally Lia
Published: November 2021

Introduction

Postbariatric hypoglycaemia (PBH) is an increasingly recognized late metabolic complication of Roux-en-Y gastric bypass (GB) surgery. PBH typically manifests with a fact occurring post-meal hyperglycaemic peak, followed by a disproportionately exaggerated insulin response leading to low glucose levels. On this basis, we evaluated the effect of a single dose of empagliflozin 10mg vs. placebo on parameters of insulin kinetics.

Materials and methods

Insulin secretion, hepatic insulin extraction and total insulin clearance were evaluated after a single of empagliflozin 10mg vs. placebo followed by a standardized liquid mixed meal were evaluated in 11 subjects with confirmed PBH after GB over 3h. Parameters of interest were calculated using established mathematical models. Indices were compared between the groups using the Wilcoxon signed-rank test.

Results

Total beta-cell responsiveness tends to be lower with empagliflozin vs. placebo (24.83±11.00 vs. 27.15±9.68 [10−9 min-1], p=0.150). Total first-pass hepatic insulin extraction increased after empagliflozin compared to placebo (49.6±14.2 vs. 39.7±12.1 %, p=0.006), while no significant effect of empaglizflozin on basal first-pass hepatic insulin extraction was observed (79.7±7.1 vs. 81.1±6.6 %, p=0.521). Total insulin clearance resulted to be significantly lower after empagliflozin compared to placebo (3.91±1.58 vs. 3.00±1.27 l/min, p=0.002).

Conclusion

The present analysis suggests that the hypoglycaemia-attenuating effect of SGLT2-inhibition in patients with PBH is mainly mediated by an increment in insulin clearance, with also a tendency to a reduction in insulin secretion.
Using Machine Learning to Elucidate the Spatial and Genetic Complexity of the Ascending Aorta
Authors: Nekoui Mahan , Pirruccello James P. , Di Achille Paolo , Choi Seung Hoan , Friedman Samuel N. , Nauffal Victor , Ng Kenney , Batra Puneet , Ho Jennifer E. , Philippakis Anthony A. , Lubitz Steven A. , Lindsay Mark E. , Ellinor Patrick T.
Published: November 2021

Background

The left ventricular outflow tract (LVOT) and ascending aorta are spatially complex, with distinct pathologies and embryologic origins. Prior work examined genetics of thoracic aortic diameter in a single plane. We sought to elucidate the genetic basis for the diameter of the LVOT, the aortic root, and the ascending aorta.

Methods

We used deep learning to analyze 2.3 million cardiac magnetic resonance images from 43,317 UK Biobank participants. We computed the diameters of the LVOT, the aortic root, and at six locations in the ascending aorta. For each diameter, we conducted a genome-wide association study and generated a polygenic score. Finally, we investigated associations between these polygenic scores and disease incidence.

Results

79 loci were significantly associated with at least one diameter. Of these, 35 were novel, and a majority were associated with one or two diameters. A polygenic score of aortic diameter approximately 13mm from the sinotubular junction most strongly predicted thoracic aortic aneurysm in UK Biobank participants (n=427,016; HR=1.42 per standard deviation; CI=1.34-1.50, P=6.67×10−21). A polygenic score predicting a smaller aortic root was predictive of aortic stenosis (n=426,502; HR=1.08 per standard deviation; CI=1.03-1.12, P=5×10−6).

Conclusions

We detected distinct common genetic loci underpinning the diameters of the LVOT, the aortic root, and at several segments in the ascending aorta. We spatially defined a region of aorta whose genetics may be most relevant to predicting thoracic aortic aneurysm. We further described a genetic signature that may predispose to aortic stenosis. Understanding the genetic contributions to the diameter of the proximal aorta may enable identification of individuals at risk for life-threatening aortic disease and facilitate prioritization of therapeutic targets.
A Framework for Falsifiable Explanations of Machine Learning Models with an Application in Computational Pathology
Authors: Schuhmacher David , Schörner Stephanie , Küpper Claus , Großerueschkamp Frederik , Sternemann Carlo , Lugnier Celine , Kraeft Anna-Lena , Jütte Hendrik , Tannapfel Andrea , Reinacher-Schick Anke , Gerwert Klaus , Mosig Axel
Published: November 2021

In recent years, deep learning has been the key driver of breakthrough developments in computational pathology and other image based approaches that support medical diagnosis and treatment. The underlying neural networks as inherent black boxes lack transparency, and are often accompanied by approaches to explain their output. However, formally defining explainability has been a notorious unsolved riddle. Here, we introduce a hypothesis-based framework for falsifiable explanations of machine learning models. A falsifiable explanation is a hypothesis that connects an intermediate space induced by the model with the sample from which the data originate. We instantiate this framework in a computational pathology setting using label-free infrared microscopy. The intermediate space is an activation map, which is trained with an inductive bias to localize tumor. An explanation is constituted by hypothesizing that activation corresponds to tumor and associated structures, which we validate by histological staining as an independent secondary experiment.
Distilling a High Precision Drug Adverse Effect Benchmark Using Wikipedia’s Wisdom of the Crowd
Authors: Bilu Yonatan , Yanover Chen
Published: November 2021

Background

Large datasets of relational medical data, such as the adverse effects of drugs or vaccines, typically attain their large size, by relying on automatic, or semi-automatic, methods for generation. This often comes with a compromise on the precision of the generated data, which can be at least partially alleviated by having experts curate the data.

Aim

Since having experts review a large dataset can be costly and time consuming, here we suggest using Wikipedia for this task – that is, augment the automatic generation step by an automatic curation step based on the expert knowledge accumulated in Wikipedia.

Methods

To curate a dataset of adverse drug effects (ADEs), we suggest retrieving the Wikipedia page associated with the drug, and checking whether the ADE appears in the sections describing adverse effects. Drug indications, typically described in the opening paragraph of the page, are similarly filtered out.

Results

We use the method to curate two large adverse drug effect datasets and show that the obtained datasets have a much higher precision relative to their originating ones.

Conclusions

Algorithms which aim to infer drug-ADE relations, should at the very least be able to identify the “clear cut” cases. The high-precision benchmark constructed herein may therefore be a valuable resource for the evaluation of such algorithms.
Equipment-free detection of SARS-CoV-2 and Variants of Concern using Cas13
Authors: Arizti-Sanz Jon , Bradley A’Doriann , Zhang Yibin B. , Boehm Chloe K. , Freije Catherine A. , Grunberg Michelle E. , Kosoko-Thoroddsen Tinna-Solveig F. , Welch Nicole L. , Pillai Priya P. , Mantena Sreekar , Kim Gaeun , Uwanibe Jessica N. , John Oluwagboadurami G. , Eromon Philomena E. , Kocher Gregory , Gross Robin , Lee Justin S. , Hensley Lisa E. , Happi Christian T. , Johnson Jeremy , Sabeti Pardis C. , Myhrvold Cameron
Published: November 2021

The COVID-19 pandemic, and the recent rise and widespread transmission of SARS-CoV-2 Variants of Concern (VOCs), have demonstrated the need for ubiquitous nucleic acid testing outside of centralized clinical laboratories. Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes. SHINEv2 represents an important advance towards rapid nucleic acid tests that can be performed in any location.
Assessment of Plasmodium falciparum infection and fitness of genetically modified Anopheles gambiae aimed at mosquito population replacement
Authors: Tapanelli Sofia , Inghilterra Maria Grazia , Cai Julia , Philpott James , Capriotti Paolo , Windbichler Nikolai , Christophides George K.
Published: November 2021

Genetically modified (GM) mosquitoes expressing anti-plasmodial effectors propagating through wild mosquito populations by means of gene drive is a promising tool to support current malaria control strategies. The process of generating GM mosquitoes involves genetic transformation of mosquitoes from a laboratory colony and, often, interbreeding with other GM lines to cross in auxiliary traits. These mosquito colonies and GM lines thus often have different genetic backgrounds and GM lines are invariably highly inbred, which in conjunction with their independent rearing in the laboratory may translate to differences in their susceptibility to malaria parasite infection and life history traits. Here, we show that laboratory Anopheles gambiae colonies and GM lines expressing Cas9 and Cre recombinase vary greatly in their susceptibility to Plasmodium falciparum NF54 infection. Therefore, the choice of mosquitoes to be used as a reference when conducting infection or life history trait assays requires careful consideration. To address these issues, we established an experimental pipeline involving genetic crosses and genotyping of mosquitoes reared in shared containers throughout their lifecycle. We used this protocol to examine whether GM lines expressing the antimicrobial peptide (AMP) Scorpine in the mosquito midgut interfere with parasite infection and mosquito survival. We demonstrate that Scorpine expression in the Peritrophin 1 (Aper1) genomic locus reduces both P. falciparum sporozoite prevalence and mosquito lifespan; both these phenotypes are likely to be associated with the disturbance of the midgut microbiota homeostasis. These data lead us to conclude that the Aper1-Sco GM line could be used in proof-of-concept experiments aimed at mosquito population replacement, although the impact of its reduced fitness on the spread of the transgene through wild populations requires further investigation.
Immunoglobulin-producing AT2-like cells secrete IgA into the extracellular matrix in pulmonary fibrosis
Authors: Chen Mengling , Wang Jing , Yuan Mengqin , Long Min , Wang Sha , Luo Wei , Huang Jie , Cheng Yusi , Zhang Wei , Jiang Wei , Chao Jie
Published: November 2021

Pulmonary fibrosis is an interstitial lung disease that can be caused by various factors. Here, we first observed extensive IgA deposition in the extracellular matrix (ECM) of the lungs of mice with pulmonary fibrosis induced by silica inhalation. Consistent with this phenomenon, spatial transcriptomic sequencing of fresh mouse lung tissues from control mice and model mice showed that Igha transcripts were highly expressed in the lesion area. Single-cell RNA sequencing (scRNA-seq) and reconstruction of B cell receptor (BCR) sequences revealed a new cluster of cells with a shared BCR and high expression of genes related to immunoglobulin IgA production. Surprisingly, these clonal cells had more characteristics of AT2 (alveolar epithelial cell type 2) cells than B cells; thus, these cells were named AT2-like cells. Therefore, we propose that secretion of IgA into the ECM by AT2-like cells is an important process that occurs during lung fibrosis.
Mouse Organ Specific Proteins and Functions
Authors: Sun B. , Lorang C. , Qin S. , Zhang Y. , Liu K. , Li G. , Sun Z. , Francke A. , Utleg A. G. , Flores P. , Hu Z. , Wang K. , Moritz R. , Hood L.
Published: November 2021

Organ specific proteins (OSPs) possess great medical potentials both in clinics and in biomedical research. Applications of them — such as alanine transaminase, aspartate transaminase, and troponins — in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human population are well known, yet their effects on OSPs are less addressed. Here we use mouse as a model and implemented a scheme of breadth study to examine the pan-organ proteome for potential variations of organ specificity in different genetic backgrounds. Using reasonable resources, we generated pan-organ proteomes of four in-bred mouse strains. The results revealed a large diversity that is more profound among OSPs than the overall proteomes. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ specific that are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.
Universal Calcium fluctuations inHydramorphogenesis
Authors: Agam Oded , Braun Erez
Published: November 2021

Understanding how the collective physical processes drive robust morphological transitions in animal development requires the characterization of the relevant fields underlying morphogenesis. Calcium (Ca2+) is known to be such a field. Here we show that the Ca2+spatial fluctuations, in whole-bodyHydraregeneration, exhibit universal properties captured by a field-theoretic model describing fluctuations in a tilted double-well potential. We utilize an external electric field andHeptanol, a drugblocking gap junctions, as two separate controls affecting the Ca2+activity and pausing the regeneration process in a reversible way. Subjecting theHydratissue to an electric field increases the calcium activity and its spatial correlations, while applyingHeptanolinhibits the activity and weakens the spatial correlations. The statistical characteristics of the Ca2+spatial fluctuations – i.e., the coefficient of variation and the skewness - exhibit universal shape distributions across tissue samples and conditions, demonstrating the existence of global constraints over this field. Our analysis shows that theHydra’s tissue resides near the onset of bistability; the local Ca2+activity in different regions fluctuates between low and high excited states. The controls modulate the dynamics near that onset, preserving the universal characteristics of the Ca2+fluctuations and, by that, maintaining the tissue’s ability to regenerate.
SARS-CoV-2 infection induces cross-reactive autoantibodies against angiotensin II
Authors: Briquez Priscilla S. , Rouhani Sherin J. , Yu Jovian , Pyzer Athalia R. , Trujillo Jonathan , Dugan Haley L. , Stamper Christopher T. , Changrob Siriruk , Sperling Anne I. , Wilson Patrick C. , Gajewski Thomas F. , Hubbell Jeffrey A. , Swartz Melody A.
Published: November 2021

Patients infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can experience life-threatening respiratory distress, blood pressure dysregulation and thrombosis. This is thought to be associated with an impaired activity of angiotensin-converting enzyme-2 (ACE-2), which is the main entry receptor of SARS-CoV-2 and which also tightly regulates blood pressure by converting the vasoconstrictive peptide angiotensin II (AngII) to a vasopressor peptide. Here, we show that a significant proportion of hospitalized COVID-19 patients developed autoantibodies against AngII, whose presence correlates with lower blood oxygenation, blood pressure dysregulation, and overall higher disease severity. Anti-AngII antibodies can develop upon specific immune reaction to the SARS-CoV-2 proteins Spike or RBD, to which they can cross-bind, suggesting some epitope mimicry between AngII and Spike/RBD. These results provide important insights on how an immune reaction against SARS-CoV-2 can impair blood pressure regulation.
Combining X-ray excited optical luminescence and X-ray absorption spectroscopy for correlative imaging on the nanoscale
Authors: Hageraats Selwin , Keune Katrien , Stanescu Stefan , Laurent Jean-Michel , Fresquet William , Thoury Mathieu
Published: November 2021

X-ray absorption and optical luminescence can both provide valuable but very different information on the chemical and physical properties of materials. Although it is known that the spectral characteristics of many materials are highly heterogeneous on the micro- and/or nanoscale, no methodology has so far been shown to be capable of spatially resolving both full X-ray absorption and X-ray excited optical luminescence (XEOL) spectra on the nanoscale in a correlative manner. For this purpose, the scanning transmission X-ray microscope at the HERMES beamline of the SOLEIL synchrotron was equipped with an optical detection system capable of recording high-resolution XEOL spectra using a 40 nm soft X-ray probe. The functionality of the system was demonstrated by analyzing ZnO powder dispersions — showing simultaneously the X-ray linear dichroism and XEOL behavior of individual submicrometric ZnO crystallites.
Salts of 4-[(benzylamino)carbonyl]-1-methylpyridinium and iodide anions with different cation:iodine stoichiometric ratios
Authors: Rudiuk Vitalii V. , Shaposhnyk Anna M. , Baumer Vyacheslav M. , Levandovskiy Igor A. , Shishkina Svitlana V.
Published: November 2021

The two iodide salts, 4-[(benzylamino)carbonyl]-1-methylpyridinium iodide–iodine (2/1), C14H15N2O+·I−·0.5I2, I, and 4-[(benzylamino)carbonyl]-1-methylpyridinium triiodide, C14H15N2O+·I3
−, II, with different cation:iodine atoms ratios were studied. Salt I contains one cation, one iodide anion and half of the neutral I2 molecule in the asymmetric unit (cation:iodine atoms ratio is 1:2). Salt II contains two cations, one triiodide anion (I
3
−) and two half triiodide anions (cation:iodine atoms ratio is 1:3). The NH group forms N—H...I hydrogen bonds with the I− anion in the crystal of I or N—H...O hydrogen bonds in II where only triiodide anions are present.
N-tert-Butyl-2-{2-[2-(4-chlorophenyl)-4-hydroxy-1-(5-methylisoxazol-3-yl)-5-oxo-2,5-dihydro-1H-pyrrol-3-yl]-N-(4-methoxyphenyl)acetamido}-2-(4-methoxyphenyl)acetamide methanol monosolvate: single-crystal X-ray diffraction study and Hirshfeld surface analysis
Authors: Shyshkina Mariia O. , Sakhno Yana I. , Radchenko Oleksandr V. , Shishkina Svitlana V. , Desenko Sergey M. , Chebanov Valentyn A.
Published: November 2021

The title compound, C36H37ClN4O7·CH3OH, which crystallizes as a methanol solvate, may possess biological activity, which is inherent for a natural peptide or protein. In the crystal, molecules of the title compound form hydrogen-bonded tetramers with the solvate molecules acting as bridges as a result of the O—H...O and N—H...O intermolecular hydrogen bonds. Hirshfeld surface analysis was used to study the different types of intermolecular interactions whose contributions are: H...H = 53.8%, O...H/H...O = 19.0%, C...H/H...C = 14.8%, Cl...H/H...Cl = 5.3%, N...H/H...N = 3.2%.
Crystal structures and Hirshfeld analysis of 4,6-dibromoindolenine and its quaternized salt
Authors: Konovalova Irina S. , Shishkina Svitlana V. , Kobzev Dmytro , Semenova Olha , Tatarets Anatoliy
Published: November 2021

4,6-Dibromo-2,3,3-trimethyl-3H-indole, C11H11Br2N, exists as a neutral molecule in the asymmetric unit. The asymmetric unit of 4,6-dibromo-2,3,3-trimethyl-3H-indol-1-ium iodide, C12H14Br2N+·I−, contains one organic cation and one iodine anion. The positive charge is localized on the quaternized nitrogen atom. In the crystal, molecules of 4,6-dibromoindolenine are linked by C—Br...π halogen bonds, forming zigzag chains propagating in the [001] direction. The molecules of the salt form layers parallel to the (010) plane where they are linked by C—H...Br hydrogen bonds, C—Br...Br and C—Br...I halogen bonds. The Hirshfeld surface analysis and two dimensional fingerprint plots were used to analyse the intermolecular contacts present in both crystals.
Effect of wall covering materials on the perception of cafe environments
Authors: Coşgun Büşra , Yıldırım Kemal , Hidayetoglu Mehmet Lutfi
Published: November 2021

Purpose

This study aims to determine the effects of wall covering materials (wood, concrete and metal) used indoors on participants’ perceptual evaluations. The differences among participants’ perceptual evaluations regarding indoor physical environmental factors by occupation and gender were examined.

Design/methodology/approach

Cafes were selected as research environments. Virtual experimental spaces using three different wall covering materials were modelled and participants’ assessment of the physical environmental factors of these virtual spaces was measured through a detailed questionnaire.

Findings

Cafes using light-coloured wall covering materials were perceived more favourably than cafes using dark-coloured wall covering materials, and cafes with light-coloured wooden wall coverings were considered as a warmer material than cafes using concrete and metal. Participants who received design education (architect, interior architect) perceived physical environmental factors of cafes more negatively than those who did not receive design education (lawyer, economist, accountant, etc.). Male participants evaluated the physical environmental factors of cafes more positively than female participants for all adjective pairs. Except for two adjective pairs, no significant difference was found among the evaluations according to genders for the other adjective pairs.

Originality/value

This study revealed new results about customers’ choices of wall covering materials and offered designers new alternatives for materials that can be used in the design of cafes.
The G20, climate change and COVID-19: critical juncture or critical wound?
Authors: Johnstone Injy
Published: November 2021

Purpose

The Group of 20 (G20) is tasked with responding to economic shocks in the global financial system, with COVID-19 having proved to be the most significant shock since the G20's inception. COVID-19 also represents the first economic crisis accompanied by a concerted attempt to “build back better”, principally through a climate-compatible recovery. In 2021, there is little clarity as to the G20's response to this challenge, primarily due to considerable divergence in the green stimulus practices of its member states. The paper aims to investigate whether the G20, climate change and COVID-19 are critical juncture or critical wound.

Design/methodology/approach

Historical institutionalism (HI) suggests that one can explain an institution's future response by reference to its developmental pathway to date. This contribution adopts its concept of “critical junctures” to shed light on the G20's possible institutional response to COVID-19. The contribution undertakes a comparative analysis of the global financial crisis (GFC) and COVID-19 as possible critical junctures for the G20.

Findings

In doing so, the work demonstrates that the G20 “building back better” from COVID-19 requires a shift away from its institutional orthodoxy to a much larger degree than its response to the GFC. Accordingly, whilst both the GFC and COVID-19 may be considered critical junctures for the G20, only COVID-19 has the potential to be a “critical wound” that leads to institutional redundancy.

Research limitations/implications

Through interrogating this further, this exposition prospectively outlines two possible futures the G20 faces as a consequence of COVID-19: reform or redundancy. In this way, it offers an ex ante perspective on policy-reform options for the G20's ongoing response to COVID-19.

Practical implications

Whichever choice the G20 makes in its response to COVID-19 has profound consequences for global governance in an increasingly unpredictable world.

Originality/value

Herein lies the importance of an exploratory assessment of COVID-19 as a critical juncture or a critical wound for the G20.
Aerodynamic simulation of a high-pressure compressor stage using the lattice Boltzmann method
Authors: de Laborderie Jerome , Babin Cedric , Fontaneto Fabrizio
Published: November 2021

Purpose

The present paper aims at evaluating the lattice Boltzmann method (LBM) on a high-subsonic high-pressure compressor stage at nominal regime.

Design/methodology/approach

The studied configuration corresponds to the H25 compressor operated in a closed-loop test rig at the von Karman Institute. Several operating points are simulated with LBM for two grids of successive refinements. A detailed analysis is performed on the time-averaged flow predicted by LBM, using a comparison with experimental and existing RANS data.

Findings

The finest grid is found to correctly predict the mean flow across the machine, as well as the influence of the rotor tip gap size. Going beyond time-averaged data, some flow analysis is performed to show the relevance of such a high-fidelity method applied to a compressor configuration. In particular, vortical structures and their evolution with the operating points are clearly highlighted. Spectral analyses finally hint at a proper prediction of tonal and broadband contents by LBM.

Originality/value

The application of LBM to high-speed turbomachinery flows is very recent. This paper validates one of the first LBM simulations of a high-subsonic high-pressure compressor stage.
Examining the use of fsQCA in B2B marketing research: benefits, current state and agenda for future research
Authors: Gligor David Marius , Golgeci Ismail , Rego Carla , Russo Ivan , Bozkurt Sıddık , Pohlen Terrance , Hiatt Brian , Garg Vipul
Published: November 2021

Purpose

The purpose of this paper is to build on recent efforts occurring within business-to-business (B2B) marketing research to advance methodological developments. As phenomena within B2B relationships have become increasingly complex, marketing scholars have begun to point out the limitations associated with correlation-based methodological approaches and highlight the need for new developments in this area. One such development is the fuzzy set qualitative comparative analysis (fsQCA).

Design/methodology/approach

This study uses a literature review to examine the use of fsQCA in B2B marketing research.

Findings

First, the current manuscript presents the benefits that the application of fsQCA can offer to market researchers investigating B2B phenomena. Second, the paper presents the current state of fsQCA use within B2B marketing. Third, it suggests possible marketing B2B research topics that can be explored using fsQCA.

Originality/value

The study highlights the benefits of fsQCA, presents the current state of fsQCA use within B2B marketing and offers a rich future research agenda for B2B marketing scholars. This agenda can also help spur additional method developments in the discipline.
The asymmetric and threshold impact of external debt on economic growth: new evidence from Egypt
Authors: Sharaf Mesbah Fathy
Published: November 2021

Purpose

Within a multivariate framework, this study examines the asymmetric and threshold impact of external debt on economic growth in Egypt during the period 1980–2019.

Design/methodology/approach

The paper uses a nonlinear autoregressive distributed lag (NARDL) bounds testing approach to cointegration and a vector error-correction model to estimate the short- and long-run parameters of equilibrium dynamics. A multiple structural breaks model is estimated to test nonlinearity in the relationship between external debt and economic growth.

Findings

Results of the NARDL model show a robust statistically significant negative long-run impact on economic growth stemming from both positive and negative external-debt-induced shocks. In terms of magnitude, on the one hand, the impact of external-debt-induced negative shocks exceeds that of the positive. In the short and long run, on the other hand, the growth impact of external debt in Egypt is symmetric. There is also support for the nonlinearity hypothesis in which a negative impact on growth of external debt obtains once the threshold level of external debt-to-GDP ratio equals or exceeds 96.7%.

Practical implications

Identifying the threshold level after which external debt becomes harmful to economic growth would help inform policymakers in Egypt about maximum external debt levels that can be sustained without impairing economic growth.

Originality/value

The current study makes a substantial contribution to the extant literature on the debt-growth tradeoffs. It breaks ground by being the first tract that examines, using a NARDL model, asymmetry and nonlinearity of debt-growth tradeoffs in Egypt.
Clinical guidelines and clinical autonomy: exploring the missing link
Authors: Andri Maria
Published: November 2021

Purpose

This paper aims at understanding how clinical guidelines' use in the labour process relates to clinical autonomy, that is, the self-control medical professionals exercise over medical practice.

Design/methodology/approach

Drawing on a qualitative case study research strategy, this paper explores how medical professionals use clinical guidelines in the labour process in one public general hospital of the Greek National Health System. Supplemented by an extensive study of documents, semi-structured interviews were conducted with 33 doctors of several specialties.

Findings

The analysis shows (1) how clinical autonomy, as a self-control structure, mediates the use of clinical guidelines as a knowledge tool in the labour process, and (2) how employing clinical guidelines as a means towards coordinating medical work, but also towards regulating and standardising medical practice, is exercising pressure on the individualistic character of clinical autonomy.

Originality/value

Advancing the analytic value of workplace control structures, this paper contributes novel theoretical understanding of emerging tendencies characterising medical work organisation and clinical autonomy, and explains how medical professionals' non-adherence to clinical practice guidelines (CPGs) relates to CPGs' role as a resource to medical practice. Finally, this research proposes a more critical approach to health policy towards addressing the challenges associated with centrally introducing clinical guidelines in healthcare organisations.
Member surveys on employee ownership and the COVID-19 pandemic
Authors: Rodgers Loren
Published: November 2021

Purpose

To gather data about how employee-owned companies performed during the COVID-19 pandemic and whether employee ownership was a competitive advantage.

Design/methodology/approach

Surveys of members of the National Center for Employee Ownership.

Findings

Employee-owned companies were more likely to have positive than negative outcomes and many attribute part of their success to their employee ownership structure.

Research limitations/implications

Data was from NCEO member companies and not a representative sample of employee-owned companies.

Practical implications

Companies should consider employee ownership as a strategy; employee-owned companies should consider employee engagement efforts.

Originality/value

This includes the first data gathered specifically on employee-owned companies during the pandemic.
Reinterpreting a signature pedagogy for entrepreneurship education
Authors: Ramsgaard Michael Breum , Blenker Per
Published: November 2021

Purpose

The importance of contextualizing theory development in entrepreneurship education has recently been raised. Nevertheless, efforts often lead to rather decontextualized concepts and generic theories that are unable to bring together the complexities of applying entrepreneurship education to particular institutional logics and local pedagogical understandings. Based on a narrow and selective literature review, this study aims to identify and reconstruct how entrepreneurship education can adjust to the disciplines in which it unfolds. To contribute to transcending this dilemma, this article raises the following question: How can entrepreneurship education be understood in a differentiated manner and contextually reconstructed to the many disciplines and professions in which it unfolds?

Design/methodology/approach

The study follows the general idea of an integrative literature review, meaning that a few references, in particular Jones' work on a signature pedagogy for entrepreneurship education, led to a deeper search of the older background literature from Shulman on the idea of a signature pedagogy for professions.

Findings

The authors identify three existing notions (MK-0, MK-1 and MK-2) of signature pedagogy within entrepreneurship education and propose a fourth notion that combines the established understandings into a signature pedagogy, MK-3, in which entrepreneurship education should be adjusted to the disciplines in which it unfolds, by integrating and balancing general, disciplinary/professional and entrepreneurial purposes of education.

Originality/value

Accepting that context matters to entrepreneurship education creates a need for understanding the contextual influence on pedagogies. The paper contributes by establishing a theory-based framework that can help educators formulate and balance general, professional and entrepreneurial purposes of education, depending on the particular context of their educational activities. Furthermore, the paper is a call to action for additional scholarship that identifies avenues for future research.
Innovating resilience
Authors: Robertson James Andrew
Published: November 2021

Purpose:

This paper aims to review the latest management developments across the globe and pinpoint practical implications from cutting-edge research and case studies.

Design:

This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context.

Findings:

Organizational areas which deal with innovation are often the first to see costs cut when an economic crisis emerges. Yet this can actually have a dramatic negative effect on recovery after a crisis, compared to cutting costs elsewhere.

Originality:

The briefing saves busy executives, strategists and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.
Celebrity capitalism
Authors: Robertson James Andrew
Published: November 2021

Purpose:

This paper aims to review the latest management developments across the globe and pinpoint practical implications from cutting-edge research and case studies.

Design:

This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context.

Findings:

Celebrity CEOs are a new type of celebrity able to profoundly impact their own companies and brands just through their personal actions, in ways previous CEOs have not been able to do.

Originality:

The briefing saves busy executives, strategists and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.
Exploring the influence of lean manufacturing practices on employee social sustainability
Authors: Ciannella Stéfano , Santos Luciano Costa
Published: November 2021

Purpose

The benefits of adopting lean manufacturing for leveraging corporate sustainability have been highlighted in the literature. However, these studies have neglected the social side of sustainability compared with the attention given to the environmental aspects. Addressing this gap, this paper aims to investigate the influence of lean practices on the dimensions of employee social sustainability (ESS), which enabled the identification of the most critical practices.

Design/methodology/approach

This paper conducted an exploratory study in two phases: first, seeking evidence in the literature, and second, applying the analytic hierarchy process (AHP) to connect ESS to lean practices based on expert opinion.

Findings

From the literature review, this paper found linkages between eight lean manufacturing practices and four dimensions of ESS. Based on evidence from the literature, the authors designed and applied an AHP model to set priorities among lean practices and social dimensions. Therefore, “health and safety” was evaluated as the most critical social dimension, and 5S was considered the most influential lean practice on ESS.

Originality/value

This study contributed to introducing the perspective of lean manufacturing practices as enablers of ESS. Notably, it pointed out which specific practices should be prioritized in the lean implementation process with social sustainability purposes. In addition, it identified relationships not reported in the literature, raising questions for further investigation.
Identification of patients at high risk of secondary extramedullary multiple myeloma development
Authors: Stork Martin , Sevcikova Sabina , Minarik Jiri , Krhovska Petra , Radocha Jakub , Pospisilova Lenka , Brozova Lucie , Jarkovsky Jiri , Spicka Ivan , Straub Jan , Pavlicek Petr , Jungova Alexandra , Jelinek Tomas , Sandecka Viera , Maisnar Vladimir , Hajek Roman , Pour Ludek
Published: November 2021

Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4·38, 95% confidence interval (CI): 2·46–7·80, P < 0·0001], high lactate dehydrogenase (LDH) levels (>5 μkat/l; OR 2·07, 95% CI: 1·51–2·84, P < 0·0001), extensive osteolytic activity (OR 2·21, 95% CI: 1·54–3·15, P < 0·001), and immunoglobulin A (IgA; OR 1·53, 95% CI: 1·11–2·11, P = 0·009) or the non‐secretory type of MM (OR 2·83; 95% CI: 1·32–6·04, P = 0·007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression‐free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13·8 months (95% CI: 11·4–16·3) vs 18·8 months (95% CI: 17·7–19·9), P = 0·006; mOS: 26·7 months (95% CI: 18·1–35·4) vs 58·7 months (95% CI: 54·8–62·6), P < 0·001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops.
Parenthood in the shadow of COVID‐19: The contribution of gender, personal resources and anxiety to first time parents' perceptions of the infant
Authors: Chasson Miriam , Ben‐Yaakov Ofir , Taubman – Ben‐Ari Orit
Published: November 2021

We sought to examine new parents' perceptions of their infant during the worldwide spread of COVID‐19, exploring the contribution of gender, personal resources (attachment orientation, presence of meaning in life and intolerance of uncertainty) and COVID‐19‐related anxieties. A convenience sample of 606 Israeli first‐time parents (137 fathers and 469 mothers), whose child was 3–12 months old, was recruited through social media during April 2020. Findings indicate that being a woman, younger age, lower education, better physical health, older infant's age, lower attachment anxiety, higher presence of meaning in life and greater COVID‐19‐related anxiety over the infant's health contributed significantly to a greater perception of infant's warmth; being a father, higher education and economic status, poorer physical health, higher attachment anxiety and intolerance of uncertainty and less presence of meaning in life contributed significantly to a greater perception of infant's invasiveness. Gender moderated the associations between the personal resources and infant's perception, and both the presence of meaning in life and intolerance of uncertainty mediated the associations between COVID‐19‐related anxieties and parent's perception of the infant. The findings reveal the crucial contribution of gender, and both risk and resilience factors, to the parent's perception of the infant in the shadow of COVID‐19.
Classification of pain in children with cerebral palsy
Authors: Vinkel Michael N , Rackauskaite Gija , Finnerup Nanna B
Published: November 2021

Pain in patients with cerebral palsy (CP) is a major health issue strongly associated with reduced quality of life. In this study, we provide an overview of pain conditions in children with CP using the International Classification of Diseases, 11th Revision (ICD‐11), which has been updated with a classification of chronic pain. Common causes of pain in children with CP, including hip displacement, muscle spasms, and procedures, are discussed; less studied pain types including headaches, neuropathic pain, visceral pain, and acute versus chronic pain are also highlighted. The addition of chronic pain to the ICD‐11 is an important step forward in optimizing both the registration and assessment of pain conditions. However, a tool designed specifically for the different types of pain in patients with CP is imperative. In this paper, we propose a Cerebral Palsy Pain Classification that is aligned with the underlying mechanisms of pain and the ICD‐11 pain classification.
Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast
Authors: Chen Xiaofei , Zhang Chenyang , Guo Dingjie , Wang Yashan , Hu Junjun , Hu Jiayi , Wang Song , Liu Xin
Published: November 2021

Objective

To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis.

Method

We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C‐index and calibration curves were used to measure the performance of nomogram. Kaplan‐Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log‐rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry.

Result

Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C‐index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease‐specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log‐rank test: χ2 = 18784, p < 0.001; χ2 = 47.1, p < 0.001; χ2 = 20, p < 0.001).

Conclusion

The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision‐making and reference.
Early warning signs of population irruptions in Eastern Grey Kangaroo (Macropus giganteus)
Authors: Wilson Michelle , Coulson Graeme
Published: November 2021

Left unchecked, macropods (kangaroos and wallabies) can exhibit irruptive population dynamics, rising rapidly to a peak, then crashing when overwhelmed by inadequate resources. This predictable population trajectory frequently leads to overabundance issues, particularly in peri‐urban parks and nature reserves. Management decisions are usually guided by estimates of population density, which can be difficult to obtain, sometimes inaccurate and often inadequate because long‐term data are needed to estimate population growth. Alternatively, density‐dependent vital rates could be used to predict the growth trajectory of a population before management issues become evident. We applied a framework of sequential changes in vital rates to examine potential indicators of population growth trajectory. We sampled 16 populations of Eastern Grey Kangaroo (Macropus giganteus) in south‐eastern Australia. Using a range of methods, we measured one vital rate (female reproductive rate) and one surrogate rate (adult sex ratio). As population density increased before irruptive peaks, female reproductive rate (90% breeding) was higher than during post‐peak declines (66% breeding). Similarly, sex ratios in increasing populations were at parity and then became more female‐biased (65% females) after peaks. These variables are readily measured in small parks and reserves, and therefore offer promising indicators of population growth trajectory, which can be used to forecast management issues and initiate timely management actions.
Hyaluronan: A key player or just a bystander in skin photoaging?
Authors: Šínová Romana , Pavlík Vojtěch , Ondrej Martin , Velebný Vladimír , Nešporová Kristina
Published: November 2021

Photoaged skin exhibits signs of inflammation, DNA damage and changes in morphology that are visible at the macroscopic and microscopic levels. Photoaging also affects the extracellular matrix (ECM) including hyaluronan (HA), the main polysaccharide component thereof. HA is a structurally simple but biologically complex molecule that serves as a water‐retaining component and provides both a scaffold for a number of the proteins of the ECM and the ligand for cellular receptors. The study provides an overview of the literature concerning the changes in HA amount, size and metabolism, and the potential role of HA in photoaging. We also suggest novel HA contributions to photoaging based on our knowledge of the role of HA in other pathological processes, including the senescence and inflammation‐triggered ECM reorganization. Moreover, we discuss potential direct or indirect intervention to mitigate photoaging that targets the hyaluronan metabolism, as well as supplementation.
Insight into the fracture evolution behavior of pre‐flawed hollow‐cylinder granite under multi‐stage increasing‐amplitude cyclic loads: A lab‐scale testing
Authors: Wang Yu , Yang Haonan , Han Jianqiang , Zhu Chun
Published: November 2021

The structural deterioration and associated fracture evolution behavior of pre‐flawed hollow‐cylinder granite subjected to multi‐stage increasing‐amplitude (MSIA) cyclic loads are studied herein. The influences of rock structure on volumetric deformation, damage accumulation, energy dissipation, and failure pattern were investigated. It is shown that the volumetric deformation is relatively large for rock having high flaw angle, and it is the minimum and maximum for rock having a 10° and 70° flaw angle. A damage evolution model that can describe a first fast and then steady damage propagation was proposed based on the irreversible axial strain. Much energy needs to be consumed to drive crack propagation and hole collapse for rock having high angle flaws. A series of 2D computed tomography (CT) images reveal the different crack network pattern and how it is affected by the rock structure. A more complicated crack network is found for rock having a high flaw angle.