bluuebunny/crossref_metadata_2025 huggingface dataset:
Segmental duplications and their variation in a complete human genome
Authors: Vollger Mitchell R. , Guitart Xavi , Dishuck Philip C. , Mercuri Ludovica , Harvey William T. , Gershman Ariel , Diekhans Mark , Sulovari Arvis , Munson Katherine M. , Lewis Alexandra M. , Hoekzema Kendra , Porubsky David , Li Ruiyang , Nurk Sergey , Koren Sergey , Miga Karen H. , Phillippy Adam M. , Timp Winston , Ventura Mario , Eichler Evan E.
Published: May 2021

Despite their importance in disease and evolution, highly identical segmental duplications (SDs) have been among the last regions of the human reference genome (GRCh38) to be finished. Based on a complete telomere-to-telomere human genome (T2T-CHM13), we present the first comprehensive view of human SD organization. SDs account for nearly one-third of the additional sequence increasing the genome-wide estimate from 5.4% to 7.0% (218 Mbp). An analysis of 266 human genomes shows that 91% of the new T2T-CHM13 SD sequence (68.3 Mbp) better represents human copy number. We find that SDs show increased single-nucleotide variation diversity when compared to unique regions; we characterize methylation signatures that correlate with duplicate gene transcription and predict 182 novel protein-coding gene candidates. We find that 63% (35.11/55.7 Mbp) of acrocentric chromosomes consist of SDs distinct from rDNA and satellite sequences. Acrocentric SDs are 1.75-fold longer (p=0.00034) than other SDs, are frequently shared with autosomal pericentromeric regions, and are heteromorphic among human chromosomes. Comparing long-read assemblies from other human (n=12) and nonhuman primate (n=5) genomes, we use the T2T-CHM13 genome to systematically reconstruct the evolution and structural haplotype diversity of biomedically relevant (LPA, SMN) and duplicated genes (TBC1D3, SRGAP2C, ARHGAP11B) important in the expansion of the human frontal cortex. The analysis reveals unprecedented patterns of structural heterozygosity and massive evolutionary differences in SD organization between humans and their closest living relatives.
baredSC: Bayesian Approach to Retrieve Expression Distribution of Single-Cell
Authors: Lopez-Delisle Lucille , Delisle Jean-Baptiste
Published: May 2021

The number of studies using single-cell RNA sequencing (scRNA-seq) is constantly growing. This powerful technique provides a sampling of the whole transcriptome of a cell. However, the commonly used droplet-based method often produces very sparse samples. Sparsity can be a major hurdle when studying the distribution of the expression of a specific gene or the correlation between the expressions of two genes. We show that the main technical noise associated with these scRNA-seq experiments is due to the sampling (i.e. Poisson noise). We developed a new tool named baredSC, for Bayesian Approach to Retrieve Expression Distribution of Single-Cell, which infers the intrinsic expression distribution in single-cell data using a Gaussian mixture model (GMM). baredSC can be used to obtain the distribution in one dimension for individual genes and in two dimensions for pairs of genes, in particular to estimate the correlation in the two genes’ expressions. We apply baredSC to simulated scRNA-seq data and show that the algorithm is able to uncover the expression distribution used to simulate the data, even in multi-modal cases with very sparse data. We also apply baredSC to two real biological data sets. First, we use it to measure the anti-correlation between Hoxd13 and Hoxa11, two genes with known genetic interaction in embryonic limb. Then, we study the expression of Pitx1 in embryonic hindlimb, for which a trimodal distribution has been identified through flow cytometry. While other methods to analyze scRNA-seq are too sensitive to sampling noise, baredSC reveals this trimodal distribution.
Additive and epistatic effects influence spectral tuning in molluscan retinochrome opsin
Authors: Smedley G. Dalton , McElroy Kyle E. , Serb Jeanne M.
Published: May 2021

The relationship between genotype and phenotype is nontrivial due to often complex molecular pathways that make it difficult to unambiguously relate phenotypes to specific genotypes. Photopigments, an opsin apoprotein bound to a light-absorbing chromophore, present an opportunity to directly relate the amino acid sequence to an absorbance peak phenotype (λmax). We examined this relationship by conducting a series of site-directed mutagenesis experiments of retinochrome, a non-visual opsin, from two closely related species: the common bay scallop, Argopecten irradians, and the king scallop, Pecten maximus. Using protein folding models, we identified three amino acid sites of likely functional importance and expressed mutated retinochrome proteins in vitro. Our results show that the mutation of amino acids lining the opsin binding pocket are responsible for fine spectral tuning, or small changes in the λmax of these light sensitive proteins Most mutations caused a blue shift regardless of the retinochrome background, with shifts ranging from a 12 nm blue shift to a 5 nm red shift from the wild-type λmax. These mutations do not show an additive effect, but rather suggests the presence of epistatic interactions. This work highlights the importance of binding pocket shape in the evolution of spectral tuning and builds on our ability to relate genotypic changes to phenotypes in an emerging model for opsin functional analysis.

Author summary

Site-directed mutagenesis determined that spectral tuning in retinochrome is not solely additive, but is influenced by intra-molecular epistasis.
An investigation of the credibility of and confidence in audit value: evidence from a developing country
Authors: Akther Taslima , Xu Fengju
Published: May 2021

Purpose

This study aims to investigate the factors that enhance the credibility of and confidence in audit value.

Design/methodology/approach

Data were collected from 254 institutional investors through a questionnaire survey and were analyzed using partial least squares structural equation modelling (PLS-SEM).

Findings

The findings reveal that the two influential predictors of enhanced credibility and confidence are perceived auditor independence and improved auditor communication. Factors related to auditor–client affiliation, such as restrictions on providing non-audit services, mandatory auditor rotation and the presence of effective audit committees, are identified as creating the perceived independence. Improved auditor communication is linked with improving the audit report and ensuring audit education, thus creating more sophisticated users who better understand the scope and purpose of an audit. Furthermore, independent audit oversight acts as a moderator in the relationship between perceived auditor independence, improved auditor communication and enhanced credibility. Enhanced credibility can lead to greater confidence in audit value.

Originality/value

In the wake of the global financial crisis and loss of confidence in the role of auditors, this study investigates the factors that can enhance the credibility of and confidence in audit value, especially in a non-Anglo-American setting. This study is unique in terms of methodological development, as it uses a higher-order Type II reflective–formative model using PLS-SEM.
Near-field scattering from PEC wedge excited by electric dipole in lossy medium
Authors: Öztürk Hülya , Yegin Korkut
Published: May 2021

Purpose

The purpose of this paper is to derive the dyadic representations of Green’s function in lossy medium because of the electric current dipole source radiating in close proximity of a PEC wedge and to reveal the effect of conductivity on the scattered electric field.

Design/methodology/approach

By using the scalarization procedure, the paraxial fields are obtained first and then scalar Green’s functions are used to derive asymptotic forms of the dyadic Green’s functions. The problem is also analyzed by the image theory and analytical derivations are compared. However, analytically calculated results are validated with FEKO, a commercially available numerical electromagnetic field solver.

Findings

The results indicate that excellent agreement is observed between analytical and numerical results. Moreover, it is found that the presence of conductivity introduces a reduction in scattered electric fields.

Originality/value

Asymptotically derived forms presented in this study can be used to calculate field distributions in the paraxial region of a wedge in a lossy medium.
Individual and situational predictors of intention to hire gay male and ultra-orthodox male job applicants
Authors: Brender-Ilan Yael , Kay Avi
Published: May 2021

Purpose

This paper examines personal and situational factors that may contribute to biases in hiring decisions at the workplace, focusing on willingness to hire male gay or male Jewish ultra-Orthodox Jewish job candidates.

Design/methodology/approach

942 Jewish participants in Israel responded to an anonymous online questionnaire regarding a scenario addressing the possible employments of two male applicants: a homosexual and an ultra-Orthodox Jew. A variety of statistical tools, including regression analysis were performed to test hypotheses.

Findings

Findings show that social dominance orientation, conservatism, gender and religiosity as well as frequency of contact with the “unlike other” impacted on hiring intention of the participants. These relationships varied in strength and direction with regard to the two applicant types in question.

Practical implications

The explication of the phenomenon in question has both important theoretical and practical importance in a world where – concurrently – there exists increasing contact among individuals from different backgrounds and (perhaps not coincidently) increased signs of wariness of and discrimination toward those unlike ourselves. In light of economic costs related to discrimination – not to mention the personal costs to those discriminated against – organizations must better understand the dynamics of the phenomenon in question.

Originality/value

This is one of the first empirical examinations of the relative impact of personal and situational factors on hiring bias. In addition, it is the first study of its kind in Israel focusing on the mechanisms behind hiring bias toward gay males and ultra-orthodox males.
Does quality of governance contribute to the heterogeneity in happiness levels across MENA countries?
Authors: Youssef Jamile , Diab Sara
Published: May 2021

Purpose

Happiness levels differ among the Middle East and North African (MENA) countries and follow a downtrend, making such heterogeneity a popular topic to investigate. The paper aims to study the contribution of governance quality on the heterogeneity in happiness levels across MENA countries while controlling for demographic and socioeconomic variables.

Design/methodology/approach

The paper applies panel random-effects regression analysis on three samples: full sample, rich and poor subsamples, using data from 20 MENA countries over the 2007–2017 period.

Findings

The empirical results for the full sample conclude that better technical quality of governance increases happiness in the region. Furthermore, findings suggest that political stability and absence of violence matters for people's happiness only in rich countries. Whereas, control of corruption is positively associated with happiness level in the full sample and poor subsample. Across all three samples, voice and accountability has no impact on happiness.

Research limitations/implications

A possible limitation of the paper is using an index for happiness based on a subjective weight distribution. Therefore, researchers are encouraged to implement a novel method using data envelopment analysis.

Practical implications

This paper includes implications for policymakers in the MENA region. Governments should strengthen existing laws and create a comprehensive database of laws, fight corruption and prioritize raising income.

Originality/value

This paper is the first to categorize MENA countries into rich and poor to analyze how governance quality contributes to the heterogeneity in happiness levels.
An explanatory model of authentic leadership, flourishing and work–family balance of nurses in French hospitals
Authors: Chevalier Séverine , Coillot Hélène , Colombat Philippe , Bosselut Grégoire , Guilbert Laure , Fouquereau Evelyne
Published: May 2021

Purpose

This study aims to investigate the relationship between a positive leadership style [i.e. authentic leadership (AL)] and nurses’ psychological health (i.e. nurses’ flourishing and satisfaction with work–family balance), including psychological capital (PsyCap) as a mediational variable.

Design/methodology/approach

A cross-sectional study was conducted with a self-report questionnaire including 1,076 nurses from public and private hospitals in France.

Findings

Structural equation modeling results revealed that AL is related to nurses’ flourishing and satisfaction with work–family balance and that PsyCap acted as a partial mediator between this leadership style and positive outcomes.

Practical implications

This research indicated that hospitals can enhance nurses’ psychological health not only in their work but also in their lives in general by improving leaders’ authentic management style and developing PsyCap (e.g. staffing, training and development).

Originality/value

An original feature of this paper concerns its focus on the mediating role of PsyCap in the relationship between AL and these positive outcomes. Moreover, this study underlined the influence of leadership style on nurses’ psychological health beyond occupational health. The research makes a valuable contribution to the existing AL literature by establishing a new explanatory model of AL and nurses’ psychological health in the French context. It also highlights the interest in developing this leadership style in health-care settings.
The day the clock stopped. Primitive states of unintegration, multidimensional working through and the birth of the analytical subject
Authors: de Rienzo Antonio
Published: May 2021

This paper is based on one idea and built around one clinical experience that helped me to broaden my comprehension of it. The idea, underlying the work of several authors, is that when the analytic field is saturated with primitive and unintegrated mental contents, the analyst’s somatic countertransference is a precious indicator of a deep, dissociated form of communication. The clinical experience concerns the difficult elaboration of a complex, multifaceted countertransference that took place during the early stages of the analysis of a sensitive patient who used to communicate in a very dissociated way and that I found hard to contain. This experience, closely described in the article, led me to formulate the clinical idea that the transference field may be made of distinct layers (psychoid, affective, verbal), and that each one of them may potentially convey dissociated, even contrasting bits of information. The corollary of this is that the analyst should be ready to accept contrasting sensations, feelings and thoughts at the same time, as they might be the basic ingredients of a complex reverie. The analyst could find himself/herself in front of his/her own internal unelaborated multiplicity before a symbolic image may emerge to link the scattered pieces of the experience. Nevertheless, the heart of this paper is not about suggesting an idea, but in the sharing of a complex working through, which fostered the birth of a new, more human relational perspective: the capacity of being together in time, in a transitional space where there is neither total separation nor fusion.
Trichomoniasis and adverse birth outcomes: a systematic review and meta‐analysis
Authors: Van Gerwen OT , Craig‐Kuhn MC , Jones AT , Schroeder JA , Deaver J , Buekens P , Kissinger PJ , Muzny CA
Published: May 2021

Background

Trichomoniasis commonly affects women of childbearing age and has been linked to several adverse birth outcomes.

Objective

To elucidate the association between trichomoniasis in pregnant women and adverse birth outcomes, including preterm delivery, prelabour rupture of membranes and low birthweight.

Search strategy

MEDLINE, EMBASE andClinicalTrials.govwere systematically searched in December 2020 without time or language restrictions.

Selection criteria

Original research studies were included if they assessed at least one of the specified adverse birth outcomes in pregnant women with laboratory‐diagnosed trichomoniasis.

Data collection and analysis

Estimates from included articles were either extracted or calculated and then pooled to produce a combined estimate of the association of trichomoniasis with each adverse birth outcome using the random effects model. Heterogeneity was assessed using theI2statistic and Cochran'sQtest.

Main results

Literature search produced 1658 publications after removal of duplicates (n = 770), with five additional publications identified by hand search. After screening titles and abstracts for relevance, full text of 84 studies was reviewed and 19 met inclusion criteria for meta‐analysis. Significant associations were found between trichomoniasis and preterm delivery (OR 1.27; 95% CI 1.08–1.50), prelabour rupture of membranes (OR 1.87; 95% CI 1.53–2.29) and low birthweight (OR 2.12; 95% CI 1.15–3.91).

Conclusions

Trichomoniasis in pregnant women is associated with preterm delivery, prelabour rupture of membranes and low birthweight. Rigorous studies are needed to determine the impact of universal trichomoniasis screening and treatment during pregnancy on reducing perinatal morbidity.

Tweetable abstract

This systematic review and meta‐analysis found that in the setting of pregnancy, trichomoniasis is significantly associated with multiple adverse birth outcomes, including preterm delivery, low birthweight, and prelabour rupture of membranes.
Elucidating the relationship between nutrition indices and coronary artery calcification in patients undergoing maintenance hemodialysis
Authors: Huang Yingzi , Ge Yongchun , Li Furong , Zhang Chuanzhen , Zhang Zhaoyong , Xu Na , Wang Rui , Wu Shun , Geng Xin , Quan Yongqiang , Ren Hongqi
Published: May 2021

Cardiovascular diseases (CVD) are common in maintenance hemodialysis (MHD) patients, and vascular calcification is associated with the incidence of CVD. Malnourished MHD patients are particularly prone to CVD events. Thus far, there is no clear explanation for the relationship of nutrition status with vascular calcification; therefore, we investigated the relationship between malnutrition and vascular calcification. One hundred thirty‐one patients underwent laboratory testing, assessment of vascular calcification, modified quantitative subjective global assessment (MQSGA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The patients were divided into two groups based on the presence or absence of coronary artery calcification (CAC), and nutritional statuses were compared between the two groups. The MQSGA score was higher in the CAC group (mean 10.9 ± 1.81) than in the no‐CAC group (mean 10.2 ± 1.51); in addition, the mean phase angle (PA) value was significantly lower in the CAC group than in the no‐CAC group. Stratification according to CAC score showed that age, Kt/V, incidence of valve calcification, incidence of abdominal aortic calcification, MQSGA score, and blood cell mass were related to the severity of CAC. In addition, quartile analysis revealed that MQSGA score and PA value were related to the incidence and severity of vascular calcification. Binary regression analysis showed that MQSGA score, age, hemoglobin level, and high‐density lipoprotein level were independent risk factors for dialysis‐related CAC. Patients on MHD who exhibited malnutrition were more likely to have vascular calcification, especially CAC. Namely, the higher the MQSGA score, the lower the PA, and the more likely the occurrence of CAC.
Evaluating Instream Restoration Effectiveness in Reducing Nitrogen Export from an Urban Catchment with a Data‐Model Approach
Authors: Lin Laurence , Reisinger Alexander J. , Rosi Emma J. , Groffman Peter M. , Band Lawrence E.
Published: May 2021

Urbanization increases stormwater runoff into streams, resulting in channel erosion, and increases in sediment and nutrient delivery to receiving water bodies. Stream restoration is widely used as a Best Management Practice to stabilize banks and reduce sediment and nutrient loads. While most instream nutrient retention measurements are often limited to low flow conditions, most of the nutrient load is mobilized at high stream flows in urban settings. We, therefore, use a process‐based stream ecosystem model in conjunction with measurements at low flows and focus on estimation of stream nitrogen retention over the full streamflow distribution. The model provides a theoretical framework to evaluate the geomorphic, hydrologic, and ecological factors that are manipulated by stream restoration, and drive nitrogen retention. We set a model for a pool‐riffle sequence restored stream (190 m) in Baltimore County, Maryland and calibrated the model to the in situ measured primary production (Nash–Sutcliffe model efficiency coefficient [NSE] NSE = 0.89), respiration (NSE = 0.74), and nitrate uptake lengths (R2 = 0.88). At the daily scale, simulations showed low nitrogen retention during high flows due to high transport rates, mobilization of stored hyporheic nitrogen, and scouring of periphyton biomass. This result underscores the need to reduce contributing watershed runoff flashiness to promote aquatic nutrient cycling and retention. At monthly and yearly time scale, model predicted a higher percent reduction in summer than in winter and estimated 5.7%–9.5% of annual nitrate reductions. While the model was tested in a pool‐riffle sequence restoration design, the approach can be adapted to evaluate a range of channel restoration design characteristics, and the effects of upland watershed restoration to mitigate stormwater loading through both restored and unrestored streams.
Genetic associations for two biological age measures point to distinct aging phenotypes
Authors: Kuo Chia‐Ling , Pilling Luke C. , Liu Zuyun , Atkins Janice L. , Levine Morgan E.
Published: May 2021

Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome‐wide association scans of two age‐adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers (Levine et al., 2018; Levine, 2013) in European‐descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein‐coding SNPs, PhenoAgeAccel—rs429358 (APOE e4 determinant) (p = 1.50 × 10−72); BioAgeAccel—rs7412 (APOE e2 determinant) (p = 3.16 × 10−60). Interestingly, we observed inverse APOE e2 and e4 associations and unique pathway enrichments when comparing the two biological age measures. Genes associated with BioAgeAccel were enriched in lipid related pathways, while genes associated with PhenoAgeAccel showed enrichment for immune system, cell function, and carbohydrate homeostasis pathways, suggesting the two measures capture different aging domains. Our study reaffirms that aging patterns are heterogeneous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition.
The important role of non‐covalent drug‐protein interactions in drug hypersensitivity reactions
Authors: Pichler Werner J.
Published: May 2021

Drug hypersensitivity reactions (DHR) are heterogeneous and unusual immune reactions with rather unique clinical presentations. Accumulating evidence indicates that certain non‐covalent drug‐protein interactions are able to elicit exclusively effector functions of antibody reactions or complete T‐cell reactions which contribute substantially to DHR. Here, we discuss three key interactions; (a) mimicry: whereby soluble, non‐covalent drug‐protein complexes (“fake antigens”) mimic covalent drug‐protein adducts; (b) increased antibody affinity: for example, in quinine‐type immune thrombocytopenia where the drug gets trapped between antibody and membrane‐bound glycoprotein; and (c) p‐i‐stimulation: where naïve and memory T cells are activated by direct binding of drugs to the human leukocyte antigen and/or T‐cell receptors. This transient drug‐immune receptor interaction initiates a polyclonal T‐cell response with mild‐to‐severe DHR symptoms. Notable complications arising from p‐i DHR can include viral reactivations, autoimmunity, and multiple drug hypersensitivity. In conclusion, DHR is characterized by abnormal immune stimulation driven by non‐covalent drug‐protein interactions. This contrasts DHR from “normal” immunity, which relies on antigen‐formation by covalent hapten‐protein adducts and predominantly results in asymptomatic immunity.
The hypertrophic cartilage induction influences the building‐block capacity of human adipose stem/stromal cell spheroids for biofabrication
Authors: Kronemberger Gabriela S. , Beatrici Anderson , Dalmônico Gisele M. L. , Rossi André L. , Miranda Guilherme A. S. C. , Boldrini Leonardo C. , Mauro Granjeiro José , Baptista Leandra Santos
Published: May 2021

As an alternative to the classical tissue engineering approach, bottom‐up tissue engineering emerges using building blocks in bioassembly technologies. Spheroids can be used as building blocks to reach a highly complex ordered tissue by their fusion (bioassembly), representing the foundation of biofabrication. In this study, we analyzed the biomechanical properties and the fusion capacity of human adipose stem/stromal cell (ASC) we spheroids during an in vitro model of hypertrophic cartilage established by our research group. Hypertrophic induced‐ASC spheroids showed a statistically significant higher Young's modulus at weeks 2 (P < .001) and 3 (P < .0005) compared with non‐induced. After fusion, non‐induced and induced‐ASC spheroids increased the contact area and decreased their pairs' total length. At weeks 3 and 5, induced‐ASC spheroids did not fuse completely, and the cells migrate preferentially in the fusion contact region. Alizarin red O staining showed the highest intensity of staining in the fused induced‐ASC spheroids at week 5, together with intense staining for collagen type I and osteocalcin. Transmission electron microscopy and element content analysis (X‐ray Energy Dispersive Spectroscopy) revealed in the fused quartet at week 3 a crystal‐like structure. Hypertrophic induction interferes with the intrinsic capacity of spheroids to fuse. The measurements of contact between spheroids during the fusion process, together with the change in viscoelastic profile to the plastic, will impact the establishment of bioassembly protocols using hypertrophic induced‐ASC spheroids as building blocks in biofabrication.
Oxidative stress, inflammation, and peritoneal dialysis: A molecular biology approach
Authors: Innico Georgie , Gobbi Laura , Bertoldi Giovanni , Rigato Matteo , Basso Anna , Bonfante Luciana , Calò Lorenzo A.
Published: May 2021

The key role of oxidative stress (OxSt) and inflammation for the induction of cardiovascular disease, the leading cause of excess morbidity/mortality in chronic kidney disease and dialysis patients, is known and both the activations of NADPH oxidase and RhoA/Rho kinase (ROCK) pathway are pivotal for their effects. While specific hemodialysis procedures, such as hemodiafiltration with on‐line reinfusion of ultrafiltrate and/or the use of vitamin E‐coated dialyzers, are beneficial for OxSt and inflammation, studies in peritoneal dialysis (PD) are instead scarce and results seem not favorable. In nine patients under PD OxSt in terms of mononuclear cell protein level of p22phox(Western blot), subunit of NADPH oxidase, essential for the generation of OxSt, and MYPT‐1 phosphorylation state (Western blot), a marker of ROCK activity, have been measured at the beginning and after 3 and 6 months of PD. Blood levels of interleukin 6 (IL‐6), ferritin, and albumin have been considered for evaluating the inflammatory state. p22phoxprotein expression, MYPT‐1‐phosphorylation, and ferritin level were increased both at baseline vs healthy subjects (P = .02,P < .0001,P = .004, respectively) and vs baseline after 3 and 6 months of peritoneal dialysis (P = .007,P < .001,P = .004, respectively). Albumin was lower after 6 months of PD (P = .0014). IL‐6 was increased at baseline vs reference values and remained unchanged at 3 and 6 months. OxSt and inflammation increase during PD confirming via molecular biology approach a report at biochemical level. To improve OxSt state in PD, a multitarget approach is necessary. It might include the use of more physiologic pH, low glucose degradation products, low lactate and iso‐osmolar PD solutions, patients’ strict glycemic control, optimal volume management, and antioxidant administration, such as N‐acetylcysteine.
How does collaborative economy contribute to common good?
Authors: Gomez‐Alvarez Rosario , Morales‐Sánchez Rafael
Published: May 2021

Collaborative economy emerged as a response to the need of people to exchange, produce and share in a more humane and cooperative manner. However, the growth of collaborative economy organizations and the terminological confusion have led to debates about their possible effects, both positive and negative. In this study, we have created a guideline that can be used to evaluate the contribution of organizations considered within collaborative economy to common good. We used the conceptualization of common good, which, from its Aristotelian‐Thomist philosophy, was developed by the personalist‐humanist perspective of management. Our analysis leads us to conclude that the evaluation of the contribution of any organization to the common good must take into account how the participants develop their virtues, the creation of the community and its impact on the common good of society. At the end of the article, we present the aspects that society must take into account regarding collaborative economy. Firstly, society, in general, must approach collaborative economy as a tool that must complement others in the search for solutions to economic and social problems and, secondly, the governance of the platform‐network is essential to foster organizational models that favour the common good.
Heparanase confers temozolomide resistance by regulation of exosome secretion and circular RNA composition in glioma
Authors: Si Jinchao , Li Wei , Li Xin , Cao Lixing , Chen Zhiqiang , Jiang Zhi
Published: May 2021

Temozolomide (TMZ) resistance is the main challenge in the management of glioma patients. Heparanase can mediate the secretion and function of exosomes, which are considered to be a promising molecular delivery system for cancer therapy. Therefore, this study aimed to investigate whether heparanase‐mediated delivery of exosomes was related to TMZ resistance of glioma. Heparanase was upregulated in TMZ‐resistant glioma cells, and overexpression of heparanase led to increased resistance of U87 cells to TMZ. Knockdown of heparanase led to increased sensitivity of TMZ‐resistant U251 cells (U251R) cells to TMZ. Heparanase promoted the secretion of exosomes from glioma cells, and coculture with exosomes derived from heparanase knockdown U251R cells partly restored the sensitivity of U251 cells to TMZ compared with exosomes derived from si‐control transfected U251R cells. It was identified by circular RNA microarrays that hsa_circ_0042003 was upregulated in exosomes derived from U251R, which could be positively regulated by heparanase. U251R cell‐derived exosomal hsa_circ_0042003 conferred the resistance of U251 cells to TMZ. In vivo studies also showed that U251R cell‐derived exosomes induced resistance of U251 cells to TMZ, and the combination of tail‐injected exosomal si‐heparanase or exosomal si‐hsa_circ_0042003 and intraperitoneal TMZ applied to nude mice abolished TMZ resistance. Heparanase mediated the transfer of exosomal hsa_circ_0042003 from TMZ‐resistant glioma cells to drug‐sensitive cells, which contributed to the chemoresistance of glioma to TMZ.
Fucosyltransferase 8 regulation and breast cancer suppression by transcription factor activator protein 2γ
Authors: Ma Minxing , Guo Dong , Tan Zengqi , Du Jun , Guan Feng , Li Xiang
Published: May 2021

Alterations of glycosyltransferase expression are often associated with tumor occurrence and progression. Among the many glycosyltransferases, increased expression of fucosyltransferase 8 (FUT8) has been frequently observed to be involved in progression and metastasis of various types of cancer. The regulatory mechanisms of FUT8 expression remain unclear. FUT8 expression was shown, in this study, to be elevated in breast cancer. Systematic analysis revealed that transcription factor activator protein 2γ (AP‐2γ) is the target gene of microRNA‐10b (miR‐10b), which we previously identified as a positive regulator of FUT8. Overexpression of AP‐2γ inhibited FUT8 expression, with associated reduction of cell invasiveness and migration ability. AP‐2γ was capable of binding to transcription factor STAT3, and phosphorylation of STAT3 induced transcription of the FUT8 gene. On the basis of our findings, we propose that binding of AP‐2γ to STAT3 results in formation of the AP‐2γ/STAT3 complex and consequent inhibition of STAT3 phosphorylation, thereby preventing entry of p‐STAT3 into the nucleus to initiate FUT8 transcription. This study clarifies the molecular mechanisms whereby transcription factor AP‐2γ regulates FUT8 expression in breast cancer.
Community structure and collapses in multichannel food webs: Role of consumer body sizes and mesohabitat productivities
Authors: Dijoux Samuel , Boukal David S.
Published: May 2021

Multichannel food webs are shaped by the ability of apex predators to link asymmetric energy flows in mesohabitats differing in productivity and community traits. While body size is a fundamental trait underlying life histories and demography, its implications for structuring multichannel food webs are unexplored. To fill this gap, we develop a model that links population responses to predation, and resource availability to community‐level patterns, using a tri‐trophic food web model with two populations of intermediate consumers and a size‐selective top predator. We show that asymmetries in mesohabitat productivities and consumer body sizes drive food web structure, merging previously separate theory on apparent competition and emergent Allee effects (i.e. abrupt population collapses) of top predators. Our results yield theoretical support for empirically observed stability of asymmetric multichannel food webs and discover three novel types of emergent Allee effects involving intermediate consumers, multiple populations or multiple alternative stable states.
Thermal performance under constant temperatures can accurately predict insect development times across naturally variable microclimates
Authors: von Schmalensee Loke , Hulda Gunnarsdóttir Katrín , Näslund Joacim , Gotthard Karl , Lehmann Philipp
Published: May 2021

External conditions can drive biological rates in ectotherms by directly influencing body temperatures. While estimating the temperature dependence of performance traits such as growth and development rate is feasible under controlled laboratory settings, predictions in nature are difficult. One major challenge lies in translating performance under constant conditions to fluctuating environments. Using the butterfly Pieris napi as model system, we show that development rate, an important fitness trait, can be accurately predicted in the field using models parameterized under constant laboratory temperatures. Additionally, using a factorial design, we show that accurate predictions can be made across microhabitats but critically hinge on adequate consideration of non‐linearity in reaction norms, spatial heterogeneity in microclimate and temporal variation in temperature. Our empirical results are also supported by a comparison of published and simulated data. Conclusively, our combined results suggest that, discounting direct effects of temperature, insect development rates are generally unaffected by thermal fluctuations.
Family firms going international: Integrating corporate identity‐building processes and socioemotional wealth dimensions
Authors: Tomo Andrea , Mangia Gianluigi , Pezzillo Iacono Mario , Canonico Paolo
Published: May 2021

This study aims to improve understanding of how identity‐building processes shape corporate identity and how dimensions of socioemotional wealth affect internationalization pathways in a family firm. The paper uses an in‐depth case study of an Italian family firm internationally recognized as excellent in its industry. We developed an integrative theoretical model, combining socioemotional wealth frameworks and elements of the corporate identity mix. This enabled us to incorporate more theoretical knowledge from the field of international management into the domain of family business research. The latent construct of socioemotional wealth provides an in‐depth understanding of the multidimensional nature of corporate identity‐building processes and shows the intertwined nature of corporate identity and the “affective endowment” in the development of internationalization strategies.
Brain transcriptomic responses of Yarrow's spiny lizard, Sceloporus jarrovii, to conspecific visual or chemical signals
Authors: Romero‐Diaz Cristina , Xu Cindy , Campos Stephanie M. , Herrmann Morgan A. , Kusumi Kenro , Hews Diana K. , Martins Emília P.
Published: May 2021

Species with multimodal communication integrate information from social cues in different modalities into behavioral responses that are mediated by changes in gene expression in the brain. Differences in patterns of gene expression between signal modalities may shed light on the neuromolecular mechanisms underlying multisensory processing. Here, we use RNA‐Seq to analyze brain transcriptome responses to either chemical or visual social signals in a territorial lizard with multimodal communication. Using an intruder challenge paradigm, we exposed 18 wild‐caught, adult, male Sceloporus jarrovii to either male conspecific scents (femoral gland secretions placed on a small pebble), the species‐specific push‐up display (a programmed robotic model), or a control (an unscented pebble). We conducted differential expression analysis with both a de novo S. jarrovii transcriptome assembly and the reference genome of a closely related species, Sceloporus undulatus. Despite some inter‐individual variation, we found significant differences in gene expression in the brain across signal modalities and the control in both analyses. The most notable differences occurred between chemical and visual stimulus treatments, closely followed by visual stimulus versus the control. Altered expression profiles could explain documented aggression differences in the immediate behavioral response to conspecific signals from different sensory modalities. Shared differentially expressed genes between visually‐ or chemically‐stimulated males are involved in neural activity and neurodevelopment and several other differentially expressed genes in stimulus‐challenged males are involved in conserved signal‐transduction pathways associated with the social stress response, aggression and the response to territory intruders across vertebrates.
Easy albumin–bilirubin score as a new prognostic predictor in hepatocellular carcinoma
Authors: Ho Shu‐Yein , Liu Po‐Hong , Hsu Chia‐Yang , Ko Chih‐Chieh , Huang Yi‐Hsiang , Su Chien‐Wei , Hsia Cheng‐Yuan , Tsai Ping‐Hsing , Chou Shih‐Jie , Lee Rheun‐Chuan , Hou Ming‐Chih , Huo Teh‐Ia
Published: May 2021

Background

Liver functional reserve is a major prognostic determinant in patients with hepatocellular carcinoma (HCC). The albumin–bilirubin (ALBI) score is an objective method to assess the severity of cirrhosis in this setting. However, calculation of the ALBI score is complex and difficult to access in clinical practice. Recently, the EZ (easy)‐ALBI score was proposed as an alternative biomarker of liver injury. We aimed to evaluate the prognostic role of the EZ‐ALBI score in HCC from early to advanced stages.

Methods

A total of 3794 newly diagnosed HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were determined by using the multivariate Cox proportional hazards model.

Results

The EZ‐ALBI score showed good correlation with the ALBI score (correlation coefficient, 0.965; p < 0.001). The correlation of the EZ‐ALBI score was highly preserved in different Child–Turcotte–Pugh (CTP) classifications, treatment methods, and Barcelona Clinic Liver Cancer (BCLC) stages (correlation coefficients, 0.90–0.97). In the Cox multivariate analysis, age >65 years, male sex, serum α‐fetoprotein >20 ng/ml, large or multiple tumors, total tumor volume >100 cm3, vascular invasion or distant metastasis, ascites, poor performance status, EZ‐ALBI grade 2 and 3, and noncurative treatments were independently associated with increased mortality (all p < 0.05). Moreover, EZ‐ALBI grade can stratify long‐term survival in patients with different CTP class, treatment strategy, and BCLC stage.

Conclusions

The EZ‐ALBI score is an easy and feasible method to evaluate liver functional reserve. As a new prognostic biomarker in HCC, the predictive power of the EZ‐ALBI grade is independent across different cancer stages and treatments.
Enhancing employability opportunities for Pharmacy students; a case study of processes to implement competency‐based education in Pharmacy in Kenya
Authors: Ruparelia Jalpa , McMullen Jessica , Anderson Claire , Munene Daniella , Arakawa Naoko
Published: May 2021

This paper challenges the western concept of graduate employability as a measure of student success through a case study of a collaboration between pharmacy colleagues in universities in Nairobi, Kenya and Nottingham, UK. As Pharmacy programmes globally adapt their courses to a competency‐based education (CBE) approach, we outline the implications of this for graduate success in Kenya. The Ministry of Education in Kenya recently announced a move to CBE across all educational sectors. This has led to a reconfiguring of how pharmacy is not only taught, but also assessed, and what success means for pharmacy graduates in Kenya. The collaboration has highlighted the need for key stakeholders to work together and influence policy change, and redefine employability in terms of behaviours that meet country‐wide needs. We outline some of the processes and collaborations we formed to redevelop pharmacy programmes in Kenya, and suggest recommendations for continuing partnerships and sustainability.
Aberrant expression of SATB2, CDX2, CDH17 and CK20 in hepatocellular carcinoma: a pathological, clinical and outcome study
Authors: Kmeid Michel , Lukose Georgi , Hodge Kyle , Cho Daniel , Kim Kelly‐Ann , Lee Hwajeong
Published: May 2021

Aims

Data regarding expression of intestinal markers in hepatocellular carcinoma (HCC) are limited. We determined the clinicopathological associations of cytokeratin (CK)19, a progenitor liver epithelial cell marker as well as biliary epithelial marker, and intestinal immunohistochemical markers expression in HCC and assessed their prognostic value.

Methods and results

Tissue sections and/or tissue microarrays (TMAs) from 202 known HCCs were immunostained using CK19, CK20, CDH17, CDX2 and SATB2 antibodies. Haematoxylin and eosin (H&E)‐stained slides were reviewed for tumour grading. Clinical and oncological outcomes were retrieved. Associations of staining with clinicopathological features and survival outcomes were evaluated. CK19, CK20, CDH17, CDX2 and SATB2 were positive in 12.8, 5.4, 10.3, 8.6 and 59.9%, respectively. All but SATB2 were strongly associated with higher tumour grade and AFP levels > 400 ng/ml (P < 0.05). CK19‐positive HCC were more likely to express CDX2 (P = 0.001), CDH17 (P < 0.001) and/or CK20 (P = 0.012). CK20, CDX2 and CDH17 co‐expression was seen in five cases (2.5%). CK19 and SATB2 positivity, tumour size ≥ 5 cm, background cirrhosis, AFP > 400 ng/ml and having no treatment were associated with decreased overall survival by log‐rank test and univariable proportional hazards regression. However, in a multivariable model, CK19 and SATB2 positivity were not independent predictors of decreased survival while their association with known poor prognosticators in HCC was evident.

Conclusions

HCC can express markers of intestinal differentiation. This phenotypical aberrancy correlates with variable clinicopathological parameters, some of which are independent predictors of poor survival.
Excessive caffeine intake increases bone resorption associated with periapical periodontitis in rats
Authors: Dal‐Fabbro Renan , Cosme‐Silva Leopoldo , Capalbo Letícia Cabrera , Chaves‐Neto Antonio Hernandes , Ervolino Edilson , Cintra Luciano Tavares Angelo , Gomes‐Filho João Eduardo
Published: May 2021

Aim

To evaluate the effect of excessive caffeine intake on the inflammation/resorption processes associated with periapical periodontitis (PP) in rats.

Methodology

Sixteen Wistar rats were used. Periapical periodontitis was induced in the four first molars in each animal. The animals were arranged into two groups: control (C)—rats with periapical periodontitis; and caffeine (CAF)—rats with periapical periodontitis under caffeine administration protocol. The CAF animals received 10 mg/100 g of body weight/day of caffeine via gavage starting fifteen days before PP induction and continuing for thirty more days until euthanasia. On the 30th day, the animals were euthanized and the jaws removed for microcomputed tomography, histological and immunohistochemical analysis for RANKL, OPG, TRAP, IL‐10, TNF‐⍺ and IL‐1β. The Mann–Whitney test was performed for nonparametric data, and Student's t test was performed for parametric data, using p < .05.

Results

There was no significant difference in the weight change between the groups. The median score of the inflammatory process was significantly greater in the CAF group (3) compared with the C group (2), p = .0256. Bone resorption was greater in the group consuming caffeine (1.08 ± 0.15 mm3) compared with the C group (0.88 ± 0.10 mm3), p = .0346. The immunolabelling for RANKL, TRAP and IL‐1β was significantly higher in the CAF group when compared to the control, p < .05. No differences were found for the OPG, IL‐10 and TNF‐⍺ immunolabelling.

Conclusion

Excessive caffeine exposure via gavage in rats was able to exacerbate the volume of periapical bone destruction, and the inflammatory pattern deriving from periapical periodontitis altering the expression of RANKL, IL‐1β and TRAP.