bluuebunny/crossref_metadata_2025 huggingface dataset:
Outward FDI and productivity promotion of exporting firms: firm-level evidence from China
Authors: Zhang Song , Li Haoze , Chen Chunlai
Published: February 2021

Purpose

The purpose of this paper is to estimate the impact of China's outward foreign direct investment (OFDI) conducted by exporting firms on their productivity.

Design/methodology/approach

This study uses two Chinese firm-level datasets. To reduce the bias when merging the two datasets, this study uses a comprehensive link approach to obtain more observations. The propensity score matching method is employed together with the difference-in-difference and difference-in-difference-in-difference approaches to identify the casual effects.

Findings

The study finds that exporting firms become more productive through learning effect via OFDI, and the positive impact of OFDI on total factor productivity materializes very quickly but subject to diminishing return. The study also finds that state-owned enterprises gain less learning effect via OFDI than private-owned enterprises, and firms with higher export intensity or larger size tend to gain less improvement in productivity via OFDI.

Originality/value

This is one of the first studies to investigate empirically the impact of OFDI conducted by exporting firms on their productivity. In particular, the study analyzes three types of firm heterogeneous factors, namely, ownership, export intensity and size, in affecting exporting firms' learning effect via OFDI.
Quality and reliability studies in software defect management: a literature review
Authors: Pai Anusha R. , Joshi Gopalkrishna , Rane Suraj
Published: February 2021

Purpose

This paper is focused at studying the current state of research involving the four dimensions of defect management strategy, i.e. software defect analysis, software quality, software reliability and software development cost/effort.

Design/methodology/approach

The methodology developed by Kitchenham (2007) is followed in planning, conducting and reporting of the systematic review. Out of 625 research papers, nearly 100 primary studies related to our research domain are considered. The study attempted to find the various techniques, metrics, data sets and performance validation measures used by researchers.

Findings

The study revealed the need for integrating the four dimensions of defect management and studying its effect on software performance. This integrated approach can lead to optimal use of resources in software development process.

Research limitations/implications

There are many dimensions in defect management studies. The authors have considered only vital few based on the practical experiences of software engineers. Most of the research work cited in this review used public data repositories to validate their methodology and there is a need to apply these research methods on real datasets from industry to realize the actual potential of these techniques.

Originality/value

The authors believe that this paper provides a comprehensive insight into the various aspects of state-of-the-art research in software defect management. The authors feel that this is the only research article that delves into the four facets namely software defect analysis, software quality, software reliability and software development cost/effort.
Making better foreign friendships: the effects of increased cultural diversity in alliance portfolios and portfolio configuration decisions on firm performance
Authors: Li Ning , Murphy William Hoggan
Published: February 2021

Purpose

This paper aims to examine the effect of increases in alliance portfolio cultural diversity (IAPCD) on a firm’s performance and how portfolio configuration characteristics moderate this effect, aiming to enable managers to make better partner choice and portfolio configuration decisions to improve performance.

Design/methodology/approach

The sample includes 2,326 focal firms from 93 countries that formed 7,616 alliances between the years 1992 and 2006. This study uses generalized method of moments estimation to examine the effects of portfolio changes on next year’s firm sales performance.

Findings

Results reveal an inverted-U relationship between IAPCD and firm performance. Data limitations led to examining moderating effects only on the upslope portion of the inverted-U, indicating that an increasing percentage of joint ventures in a firm’s alliance portfolio strengthens IAPCD’s contribution to performance. Further, increased numbers of marketing alliances or research and development alliances and increased percentage of horizontal alliances in an alliance portfolio have a negative moderating effect.

Research limitations/implications

The sample mostly covers large companies. The data indicate that nearly all firms are on the upslope of an inverted-U IAPCD–to–performance relationship, allowing testing of moderating effects pre-inflection point only.

Practical implications

Firms can leverage the additions of culturally diverse partners toward improved performance through astute configuration decisions in alliance portfolio composition.

Originality/value

This paper uses the knowledge-based view to contribute to the alliance portfolio literature. This study asserts that capacity constraints affect firms’ ability to realize performance gains when taking on culturally diverse partners, an effect moderated by portfolio configurations. This paper tests hypothesis with longitudinal data.
The impact of ambivalence on recovery from non-suicidal self-injury: considerations for health professionals
Authors: Gray Nicole , Hasking Penelope , Boyes Mark E.
Published: February 2021

Purpose

Non-suicidal self-injury (NSSI) is a growing public health concern. Continued NSSI is often associated with negative outcomes, yet the behaviour usually serves a purpose for individuals who self-injure (e.g. emotional relief). As such, individuals who self-injure often experience ambivalence about the behaviour. The purpose of this paper is to highlight the importance of recognising ambivalence as a natural and expected part of the recovery process.

Design/methodology/approach

This paper draws on literature regarding NSSI recovery, ambivalence towards stopping the behaviour and challenges for both clients and health professionals.

Findings

This paper argues that ambivalence towards self-injury can be challenging for both clients and health professionals. Clients may feel shame and sense of failure if they experience a setback; health professionals may experience frustration towards clients who continue to self-injure despite treatment.

Originality/value

Validation of the clients’ experience can have significant positive outcomes in treatment and help-seeking behaviours. Acknowledgement of client ambivalence during the recovery process will serve to validate clients’ experience and facilitate rapport. Health professionals who accept ambivalence as a natural part of the recovery process may experience less frustration with clients who continue to self-injure.
Training as an internal marketing tool within the franchise system
Authors: Domínguez-Falcón Carmen , Fernández-Monroy Margarita , Galván-Sánchez Inmaculada , Ballesteros-Rodríguez José Luis
Published: February 2021

Purpose

The purpose of this paper is to analyse the important role of training (specifically, training relevance and training transfer) in enhancing franchisor-franchisee relationship satisfaction, and its influence upon customer performance (e.g., customer satisfaction, quality service), all driven by an internal marketing (IM) culture.

Design/methodology/approach

An empirical study consisting of a questionnaire was conducted on a final sample of 157 individuals who are members of the franchise system. Structural equation modelling (SEM) was used to test the research hypotheses.

Findings

The results reveal that IM culture has a direct influence on training relevance; likewise, training relevance provides a positive and significant effect on training transfer, which does directly affect franchisor-franchisee relationship satisfaction and at least also impacts indirectly on customer performance.

Practical implications

In order to ensure the success of the franchise system and customer satisfaction, all franchise parties should take a proactive role in the configuration of the training programmes. This proactive role should be conformed based on an IM culture developed properly by the franchise to strengthen a successful long-term relationship.

Originality/value

This paper provides an innovative approach to strengthen the franchisor-franchisee relationship through training based on the IM culture. This exploratory study integrates different theoretical frameworks that, to our knowledge, have not been linked, such as IM culture and franchise literature, considering the franchisee as an internal customer who has an influence on external customer satisfaction, with training and training transfer as essential key factors.
Realistic hardening-to-softening transition effects of metals over the finite strain range up to failure
Authors: Xu Zi-Han , Zhan Lin , Wang Si-Yu , Xi Hui-Feng , Xiao Heng
Published: February 2021

Purpose

A new approach is proposed toward accurately matching any given realistic hardening and softening data from uniaxial tensile test up to failure and moreover, toward bypassing usual tedious implicit trial-and-error iterative procedures in identifying numerous unknown parameters.

Design/methodology/approach

Finite strain response features of metals with realistic hardening-to-softening transition effects up to eventual failure are studied for the first time based on the self-consistent elastoplastic J2-flow model with the logarithmic stress rate. As contrasted with usual approximate and incomplete treatments merely considering certain particular types of hardening effects such as power type hardening, here a novel and explicit approach is proposed to obtain a complete form of the plastic-work-dependent yield strength over the whole hardening and softening range.

Findings

A new multi-axial evolution equation for both hardening and softening effects is established in an explicit form. Complete results for the purpose of model validation and prediction are presented for the finite strain responses of monotonic uniaxial stretching up to failure.

Originality/value

New finite strain elastoplastic equations are established with a new history-dependent variable equivalently in place of the usual plastic work. With these equations, a unified and accurate simulation of both gardening and softening effects up to failure is achieved for the first time in an explicit sense without involving usual tedious implicit trial-and-error iterative procedures.
Finding ourselves as Black women in Eurocentric theory: collaborative biography on learning and reshaping qualitative inquiry
Authors: Summerville Kiara S. , Campbell Erica T. , Flantroy Krystal , Prowell Ashley Nicole , Shelton Stephanie Anne
Published: February 2021

Purpose

Qualitative research consistently centers Eurocentrism through courses' integrations of ontological, epistemological and axiological perspectives. This literal whitewashing was a source of great frustration and confusion for the authors, four Black women, who found their identities omitted and disregarded in qualitative inquiry. Using Collins' outsider-within concept and collective narratives to center their experiences, the authors seek through their writing to actively repurpose and re-engage with qualitative scholarship that generally seeks to exclude Black women.

Design/methodology/approach

Theoretically informed by Collins' outsider-within concept, the authors use Deleuze and Parnet's collective biography to tell the stories of four Black doctoral students negotiating race, gender, class and intellectual identity, while critiquing Eurocentric theory, through coursework. The collaborative writing process provided shared space for the engagement of individual thoughts and experiences with(in) others' narratives.

Findings

Black women can interpret qualitative inquiry outside of the Eurocentric norm, and qualitative courses can provide spaces for them to do so by repositioning Black women philosophers as central to understanding qualitative inquiry.

Originality/value

Through collective biography (Deleuze and Parnet, 2007), this paper centers the voices of four Black women scholars who use a creative writing approach to think with/through theory as Black women (Jackson and Mazzei, 2012). The paper offers new discussions of and ways in which qualitative researchers might decolonize Eurocentric ways of knowing in qualitative inquiry and qualitative pedagogy from students' perspectives.
From prose to poetry: retelling the experiences of children with autism navigating around a school to promote empathy and understanding
Authors: Irish Julie E.N.
Published: February 2021

Purpose

The purpose of this paper was to describe the experiences of four children with autism spectrum disorder navigating around the corridors of an unfamiliar school and translate the findings into poetic format. Poetry could provide a more accessible format to a nonacademic audience and promote empathy and understanding about this population.

Design/methodology/approach

Each participant was shown a route from the start point to the destination by the researcher then asked to lead the way there. Post-study, participants were interviewed for their perceptions and feelings about navigating.

Findings

Participants' responses and behaviors differed, e.g. some were stimulated by colors, some noticed small details and some were distracted. Poetic translation vividly emphasized these behaviors and emotions.

Originality/value

Few studies have described how children with autism navigate the built environment or asked their opinion about navigating. None in the field have used poetic translation to explore data.
The heterogeneous impact of leverage on firm performance: empirical evidence from Bangladesh
Authors: Das Nirmol Chandra , Chowdhury Mohammad Ashraful Ferdous , Islam Md. Nazrul
Published: February 2021

Purpose

The purpose of this study primarily is to investigate the heterogeneous effect of leverage on performance of the listed nonfinancial joint stock companies in Bangladesh.

Design/methodology/approach

A large panel sample of 165 listed nonfinancial firms under different industries of Bangladesh studied for the period 2007–2016 employing the dynamic panel approaches, namely, differenced generalized method of moments (GMM) and system GMM. The asymmetric relationship between leverage and performance is also examined by quantile regression approach.

Findings

GMM showed that the leverage indicators have the negative impact on the performance of the firms in terms of return on equity and return on asset while the quantile regressions revealed the heterogeneous relationship between leverage and profitability. It showed that greater negative impact of leverage on performance in high-profitable firms than low-profitable firms.

Research limitations/implications

The study is confined to only the listed nonfinancial joint-stock companies of Bangladesh.

Practical implications

The asymmetric relationship between leverage and financial performance identified in this study would be the helpful tool for financial managers for optimal capital structure decisions.

Originality/value

This is one of the first in-depth attempts to find the nonlinear heterogeneous effect of leverage on firms' performance.
Playing piggy(bank) in the middle: Philanthropic foundations’ roles as intermediaries
Authors: Williamson Alexandra Kate , Leat Diana
Published: February 2021

Philanthropic foundations are often described as ‘intermediaries’ yet the term is neither defined nor de‐constructed. This short paper identifies and briefly discusses 14 dimensions of the intermediary roles played by foundations, and groups them into four major themes: bringing parties together, capacity development and relationship building, temporal bridging, and sector‐level or institutional intermediation.
Ethephon foliar application: Impact on the phenolic and technological Tempranillo grapes maturity
Authors: López Rosa , Portu Javier , González‐Arenzana Lucía , Garijo Patrocinio , Gutiérrez Ana Rosa , Santamaría Pilar
Published: February 2021

In recent years, there has been increasing concern about the impact of climate change on viticulture, in particular regarding its influence on grape maturity and quality. Extensive research has shown that the rise of temperatures during grape ripening accelerates the accumulation of sugars while reducing the synthesis of phenolic and aromatic compounds. The aim of this study was to investigate whether the foliar application of the plant growth regulator ethephon might delay technological grape maturity and increase grape phenolic content, improving wine quality. For this, different concentrations of ethephon were applied during two vintages to the Tempranillo grape variety at the onset of veraison. Results showed that grape sugar accumulation was delayed in one of the two vintages, whereas the treatment favored the accumulation of phenolic compounds in both vintages. In conclusion, the application of ethephon at the onset of veraison to Tempranillo grapevines helped to couple grape phenolic and technological maturity, leading to more balanced wines, either by delaying sugar accumulation or by enhancing the synthesis of anthocyanins and phenolic compounds.

Practical Application

Due to the current climate change, phenolic maturity of grapes does not match with their technological maturity, which means that harvested grapes are usually very sweet but without enough color and aroma. The foliar application of the plant growth regulator—ethephon—delays technological grape maturity and increases grape phenolic content, improving wine quality and creating wines that are more balanced.
Open chest and pericardium facilitate transpulmonary passage of venous air emboli
Authors: Storm Benjamin S. , Halvorsen Per Steinar , Skulstad Helge , Dybwik Knut , Schjalm Camilla , Christiansen Dorte , Wisløff‐Aase Kristin , Fosse Erik , Braaten Tonje , Nielsen Erik W. , Mollnes Tom E.
Published: February 2021

Background

Transpulmonary passage of air emboli can lead to fatal brain‐ and myocardial infarctions. We studied whether pigs with open chest and pericardium had a greater transpulmonary passage of venous air emboli than pigs with closed thorax.

Methods

We allocated pigs with verified closed foramen ovale to venous air infusion with either open chest with sternotomy and opening of the pleura and pericardium (n = 8) or closed thorax (n = 16). All pigs received a five‐hour intravenous infusion of ambient air, starting at 4‐6 mL/kg/h and increased by 2 mL/kg/h each hour. We assessed transpulmonary air passage by transesophageal M‐mode echocardiography and present the results as median with inter‐quartile range (IQR).

Results

Transpulmonary air passage occurred in all pigs with open chest and pericardium and in nine pigs with closed thorax (56%). Compared to pigs with closed thorax, pigs with open chest and pericardium had a shorter to air passage (10 minutes (5‐16) vs. 120 minutes (44‐212), P < .0001), a smaller volume of infused air at the time of transpulmonary passage (12 mL (10‐23) vs.170 mL (107‐494), P < .0001), shorter time to death (122 minutes (48‐185) vs 263 minutes (248‐300, P = .0005) and a smaller volume of infused air at the time of death (264 mL (53‐466) vs 727 mL (564‐968), P = .001). In pigs with open chest and, infused air and time to death correlated strongly (r = 0.95, P = .001).

Conclusion

Open chest and pericardium facilitated the transpulmonary passage of intravenously infused air in pigs.
Barriers to prescribing of long‐acting reversible contraception (LARC) by general practitioner registrars: A cross‐sectional questionnaire
Authors: Turner Rachel , Tapley Amanda , Sweeney Sally , Magin Parker
Published: February 2021

Long‐acting reversible contraception (LARC) is highly effective but uptake in Australia is low. We aimed to establish general practitioner (GP) registrars’ (vocational trainees’) perspectives on barriers to prescribing LARC. We conducted a cross‐sectional questionnaire‐based study of 191 GP registrars in NSW and ACT. Outcome factors were levels of agreement with eight barriers to prescribing LARC. We found the most‐reported barriers to prescribing LARC were limited access to training and limited opportunities to maintain skills. Registrars perceived greater barriers to the use of intrauterine devices, compared to contraceptive implants, regarding indemnity insurance, difficulty accessing training, and insufficient insertion opportunities to maintain skills.
A quantitative global review of species population monitoring
Authors: Moussy Caroline , Burfield Ian J. , Stephenson P. J. , Newton Arabella F. E. , Butchart Stuart H. M. , Sutherland William J. , Gregory Richard D. , McRae Louise , Bubb Philip , Roesler Ignacio , Ursino Cynthia , Wu Yanqing , Retief Ernst F. , Udin Jihad S. , Urazaliyev Ruslan , Sánchez‐Clavijo Lina M. , Lartey Eric , Donald Paul F.
Published: February 2021

Species monitoring, defined here as the repeated, systematic collection of data to detect long‐term changes in the populations of wild species, is a vital component of conservation practice and policy. We created a database of nearly 1200 schemes, ranging in start date from 1800 to 2018, to review spatial, temporal, taxonomic, and methodological patterns in global species monitoring. We identified monitoring schemes through standardized web searches, an online survey of stakeholders, in‐depth national searches in a sample of countries, and a review of global biodiversity databases. We estimated the total global number of monitoring schemes operating at 3300–15,000. Since 2000, there has been a sharp increase in the number of new schemes being initiated in lower‐ and middle‐income countries and in megadiverse countries, but a decrease in high‐income countries. The total number of monitoring schemes in a country and its per capita gross domestic product were strongly, positively correlated. Schemes that were active in 2018 had been running for an average of 21 years in high‐income countries, compared with 13 years in middle‐income countries and 10 years in low‐income countries. In high‐income countries, over one‐half of monitoring schemes received government funding, but this was less than one‐quarter in low‐income countries. Data collection was undertaken partly or wholly by volunteers in 37% of schemes, and such schemes covered significantly more sites and species than those undertaken by professionals alone. Birds were by far the most widely monitored taxonomic group, accounting for around half of all schemes, but this bias declined over time. Monitoring in most taxonomic groups remains sparse and uncoordinated, and most of the data generated are elusive and unlikely to feed into wider biodiversity conservation processes. These shortcomings could be addressed by, for example, creating an open global meta‐database of biodiversity monitoring schemes and enhancing capacity for species monitoring in countries with high biodiversity.

Article impact statement: Species population monitoring for conservation purposes remains strongly biased toward a few vertebrate taxa in wealthier countries.
Endocrine mucin‐producing sweat gland carcinoma and associated primary cutaneous mucinous carcinoma: Review of the literature
Authors: Au Rebecca Tian Mei , Bundele Manish M.
Published: February 2021

Background

Endocrine mucin‐producing sweat gland carcinoma (EMPSGC) is a rare, low‐grade, cutaneous adnexal carcinoma with neuroendocrine differentiation. It is considered to be a precursor of invasive neuroendocrine type primary cutaneous mucinous carcinoma (PCMC).

Objective

To review clinicopathological literature summary of EMPSGC and associated neuroendocrine PCMC from all reported cases and compare its behavior vs non‐neuroendocrine PCMC data reported in the literature.

Methods

A review of English literature of all EMPSGC cases with and without associated PCMC was carried out.

Results

EMPSGC was associated with invasive neuroendocrine type PCMC in 35.7% of cases. We found the recurrence rate of PCMC associated with EMPSGC of about 12.3%, which is much less than the 30% recurrence rate reported for the non‐neuroendocrine subtype of PCMC. The non‐neuroendocrine subtype of PCMC shows a 4% and 11% rate of distant and lymph node metastasis, respectively, vs EMPSGC‐associated neuroendocrine type of PCMC, which is very indolent and only one recent case of locoregional metastasis out of 190 EMPSGC cases has been reported so far.

Limitation

Limitation of our study includes data derivation from case reports and case series in the literature.

Conclusion

The prognostic benefits for this cohort of patients may be considered in their overall management.
Clinical significance of early systolic reverse flow in left anterior descending coronary artery on transthoracic echocardiography in patients with acute myocardial infarction
Authors: Watanabe Shingo , Usui Michio
Published: February 2021

Background

Predicting the cardiac function in chronic phase of acute myocardial infarction (AMI) patients is important. Previous studies showed that the presence of early systolic reverse flow (ESRF) in coronary flow measured with a Doppler guide wire is a predictor of worsening chronic phase function in patients with anterior AMI. We routinely examined the coronary flow velocity (CFV) of the distal left anterior descending artery (LAD) using transthoracic echocardiography (TTE) in AMI patients. The aim of this study is to investigate whether the ESRF in TTE is associated with the chronic cardiac function, recovery of cardiac function, and the incidence of major adverse cardiac events (MACE) in patients with anterior AMI.

Methods

We enrolled 84 patients with their first anterior AMI. Using TTE, we recorded the CFV of distal LAD within 5 days after primary percutaneous coronary intervention. Patients were divided into two groups, ESRF + group (ESRF was detected in TTE: 21 cases) and ESRF‐ group (ESRF was not detected in TTE: 63 cases). We compared chronic cardiac function in TTE, changes in cardiac function in acute and chronic phase (ΔLVEF, ΔLVDd), and the incidence of MACE.

Results

The incidence of MACE in ESRF‐group was lower than that in ESRF + group (3.3% vs 19.1% P = .02). LVEF in chronic phase in ESRF‐ group was higher than that in ESRF + group (54.1 ± 5.6% vs 40.4 ± 6.2% P < .001). ΔLVDd was smaller in ESRF‐group than ESRF + group (−0.62 ± 4.0 mm vs +5.06 ± 3.4 mm P = .003).

Conclusion

Early systolic reverse flow in TTE is a predictor of chronic cardiac function and incidence of MACE in patients with anterior AMI.
Age‐dependent messenger RNA expression of toll‐like receptor 4 and intercellular adhesion molecule‐1 in peripheral blood mononuclear cells
Authors: Wen Chiung‐Jung , Chang Chin‐Hao , Chen Chin‐Ying , Peng Jen‐Kuei , Huang Hsien‐Liang , Chuang Pei‐Ni , Chen Ching‐Yu , Tsai Jaw‐Shiun
Published: February 2021

Background

Inflammation plays an important role in the ageing process in which monocytes/macrophages are important players. Intercellular adhesion molecule‐1 (ICAM‐1), tumour necrosis factor‐α (TNF‐α) and Toll‐like receptor 4 (TLR4) are well‐known inflammatory markers. This study aimed to investigate the relationship between age and the expression and correlation of ICAM‐1, TNF‐α and TLR4 mRNA in peripheral blood mononuclear cells (PBMCs).

Methods

A total of 239 participants were recruited in a medical centre in Taiwan. The mRNA isolated from the PBMCs was used to determine the levels of ICAM‐1, TNF‐α and TLR4 mRNAs with real‐time polymerase chain reaction (PCR). The propensity‐matched analysis was also applied for subgroup analysis.

Results

When compared 189 older adults (≧65 years) to 50 younger adults (<65 years), the ICAM‐1, TNF‐α and TLR4 mRNA levels in PBMCs were significantly higher in older adults (2.00 ± 0.72 vs 0.87 ± 0.34 for ICAM‐1, 2.32 ± 0.69 vs 1.15 ± 0.44 for TNF‐α and 1.56 ± 0.47 vs 1.05 ± 0.51 for TLR4, and all P < .0001). Also, both age and TLR4 were independent factors affecting mononuclear cell ICAM‐1 in the multiple linear regression analysis (P < .0001).

Conclusion

The mRNA levels of ICAM‐1 and TLR4 in PBMCs are higher in older adults than those in younger adults. TLR4 is an independent factor affecting ICAM‐1 expression in PBMCs, especially in older adults. This may suggest that ICAM‐1 and TLR4 in PBMCs are potential biomarkers and their relationship may shed some light on the ageing process.
Eicosanoid‐induced calcium signaling mediates cellular immune responses of Tenebrio molitor
Authors: Roy Miltan Chandra , Kim Yonggyun
Published: February 2021

Calcium signaling is associated with actin cytoskeleton rearrangement. It is required for expressing cellular immune responses of insect hemocytes. Eicosanoids mediate immune responses by cytoskeleton rearrangement against various pathogen infections in insects. The objective of this study was to investigate cellular immune responses of a mealworm, Tenebrio molitor L. (Coleoptera: Tenebrionidae). The hypothesis tested was that immune responses would be mediated by calcium signaling associated with eicosanoid mediation. Larvae of T. molitor possessed at least four morphological types of hemocytes, most (almost 75%) of which were granulocytes and plasmatocytes. They all exhibited a hemocyte‐spreading behavior by F‐actin extension. Upon bacterial infection, hemocytes exhibited phagocytosis and formed hemocytic nodules. Intracellular calcium was detected in hemocytes. Its amount increased with increasing incubation time after bacterial infection. Inhibition of calcium influx or release from endoplasmic reticulum using specific inhibitors prevented cellular immune responses. Interestingly, treatment with an eicosanoid biosynthesis inhibitor suppressed calcium signals induced by bacterial challenge. Furthermore, treatment with naproxen, a prostaglandin (PG) synthesis inhibitor, or esculetin, a leukotriene synthesis inhibitor, also inhibited the increase of calcium concentration in hemocytes. Among eicosanoids, PGE2 highly stimulated the increase of calcium signals. These results suggest that cellular immune responses of T. molitor are triggered by calcium signaling, which is up‐regulated by eicosanoids.
Heat shock alters pea aphid–Buchnera interactions: negative allometry of gene densities
Authors: Parven Nousheen , Yao Izumi , Kanbe Takashi , Akimoto Shin‐ichi
Published: February 2021

In the face of global climate change, the understanding of how aphid‐symbiont relationships are affected by heat shock is critical. We evaluated the effects of heat shock on the pea aphid, Acyrthosiphon pisum Harris (Hemiptera: Aphididae), and its obligate endosymbiont Buchnera aphidicola Munson et al. by means of quantitative PCR in treated aphids and their offspring. First‐instar aphids received a single heat shock (35 °C for 6 h), repetitive heat shocks (repeat of the single heat shock for 3 days), or a control treatment (constant 20 °C). We evaluated the impacts on aphid body length and Buchnera and aphid gene densities, estimated from the number of copies of bacterial 16S‐rRNA and nuclear elongation factor 1‐alpha (EF1α) genes, respectively. Heat shock negatively affected aphid body length and Buchnera and EF1α gene densities. Heat‐shocked aphids contained lower densities of Buchnera and EF1α genes than control aphids when body length was kept constant. When Buchnera and EF1α gene densities were represented on a log–log scale, Buchnera densities increased with EF1α densities in all treatments, but Buchnera densities showed negative allometry with EF1α densities. Compared to control aphids, heat‐shocked aphids contained lower Buchnera densities relative to EF1α densities. Some heat‐shocked aphids became sterile if their Buchnera gene density was lower than a threshold (ca. 42 000 copies). The offspring of aphids subjected to a single heat shock recovered the number of Buchnera, but the offspring of aphids subjected to repetitive heat shocks exhibited markedly lower Buchnera and EF1α densities. Thus, heat shock negatively affects both aphid and Buchnera cell proliferation, in the heat shock‐treated generation as well as in their offspring, but the impact is more severe on Buchnera. Because the symbiont supplies essential amino acids, vitamins, and an essential protein, this could reduce aphid development and reproduction and possibly leads to extinction of local populations.
The guardian's choice: how p53 enables context‐specific decision‐making in individual cells
Authors: Friedel Laura , Loewer Alexander
Published: February 2021

p53 plays a central role in defending the genomic integrity of our cells. In response to genotoxic stress, this tumour suppressor orchestrates the expression of hundreds of target genes, which induce a variety of cellular outcomes ranging from damage repair to induction of apoptosis. In this review, we examine how the p53 response is regulated on several levels in individual cells to allow precise and context‐specific fate decisions. We discuss that the p53 response is not only controlled by its canonical regulators but also controlled by interconnected signalling pathways that influence the dynamics of p53 accumulation upon damage and modulate its transcriptional activity at target gene promoters. Additionally, we consider how the p53 response is diversified through a variety of mechanisms at the promoter level and beyond to induce context‐specific outcomes in individual cells. These layers of regulation allow p53 to react in a stimulus‐specific manner and fine‐tune its signalling according to the individual needs of a given cell, enabling it to take the right decision on survival or death.
Concurrent giant sialoliths within the submandibular gland parenchyma and distal segment of Wharton’s duct: Novel case report
Authors: Brooks John K. , Macauley Meriam R. , Price Jeffery B.
Published: February 2021

Objective

This article discusses the clinical significance of an unusual case of the simultaneous occurrence of 2 giant sialoliths within the ipsilateral submandibular gland and distal aspect of Wharton's duct in a 63‐year‐old patient.

Background

The majority of submandibular gland sialoliths are found in Wharton's duct, with fewer within the gland parenchyma. Giant sialoliths (exceeding 15 mm in size) are rare.

Materials and methods

An asymptomatic, otherwise healthy older patient sought dental care and underwent a comprehensive oral and radiographic examination.

Results

A panoramic radiograph revealed 2 incidental radiopaque structures, representing giant sialoliths within the submandibular gland and along the distal segment of Wharton's duct. This synchronous finding apparently represents the first case reported in the geriatric literature.

Conclusions

The detection of 1 salivary stone should heighten the scrutiny for additional stones. Practitioners should carefully weigh the risk of sialolith removal versus deferment of treatment in older medically compromised patients.
Late‐career unemployment and risk of frailty among older adults in Taiwan: An 8‐year population‐based cohort study
Authors: Chu Wei‐Min , Ho Hsin‐En , Yeh Chih‐Jung , Tsan Yu‐Tse , Lee Shu‐Hsin , Lee Meng‐Chih
Published: February 2021

Aim

To evaluate whether late‐career unemployment is associated with increased physical frailty among older adults in Taiwan by the design of a population‐based cohort study.

Methods

Data were retrieved from the Taiwan Longitudinal Study on Aging. The study examined data from the period 1999 to 2007. A total of 652 subjects were included in the final analysis, and they were categorized as normally employed or unemployed depending on their employment status in 1999. Frailty was defined using the Fried criteria. Multiple confounding factors were adjusted in a multilevel analysis.

Results

The average age of the participants in 1999 was 59.0 years. A total of 491 participants were normally employed, and 161 participants were unemployed. After adjustment for gender, age, level of education, income, marital status, and number of chronic diseases, late‐career unemployment was associated with increased frailty [odds ratio (OR) = 1.61; 95% confidence interval (CI) = 1.00–2.59]. The risk of developing frailty was higher for participants who were unemployed during late career and had poor self‐rated health [OR = 3.54; 95% CI = 1.37–9.20].

Conclusions

Late‐career unemployment is associated with increased frailty, especially for those who also have poor self‐rated health. Older adults should be encouraged to maintain normal employment during the later stages of their career before retirement. Employers should apply strategies to prevent possible late‐career unemployment, and the government should provide resources and help to unemployed older workers so that they can minimize poor health outcomes in late life. Geriatr Gerontol Int 2021; 21: 353–358.
Sonic hedgehog signals hinder the transcriptional network necessary for pancreatic endoderm formation from human embryonic stem cells
Authors: Dumasia Niloufer P. , Khanna Aparna P. , Pethe Prasad S.
Published: February 2021

Hedgehog morphogens govern multiple aspects of pancreas organogenesis and functioning with diverse outcomes across species. Although most current differentiation protocols repress Sonic hedgehog (SHH) signals during in vitro endocrine specification, the role and mechanisms through which the SHH pathway antagonizes pancreas development during in vitro human embryonic stem (hES) cell differentiation remain unclear. We modulated SHH signaling at transitory stages of hES cell‐derived pancreatic progenitors and analyzed the effect on cellular fate decisions. We identify the Hedgehog pathway as a negative regulator of pancreatic endoderm formation through up‐regulation of a set of pancreatobiliary markers required for ductal specification, including SOX17, FOXA2, HNF1β, HNF6, PDX1, and SOX9. Surprisingly, active Hedgehog signals impeded a group of pancreatic epithelium markers, including HNF4α, HHEX, PAX6, and PTF1α. To understand how SHH signals repress the transcription of these specific markers, we analyzed Polycomb group proteins. We found differential expression of Polycomb Repressive Complex 1 subunit, BMI1 upon Shh pathway modulation in the pancreatic progenitors. Ectopic activation of Sonic hedgehog results in over‐expression of BMI1 and its associated repressive histone mark, H2AK119Ub1, in the multipotent progenitors. Our data suggest that Sonic hedgehog restricts the pancreatic differentiation program by limiting progenitor cells acquiring pancreatic epithelial fates and instead promotes pancreatobiliary differentiation. We further provide mechanistic cues of an association between Hedgehog signaling and epigenetic silencers during pancreatic lineage decisions.
A simple digital image analysis system for automated Ki67 assessment in primary breast cancer
Authors: Alataki Anastasia , Zabaglo Lila , Tovey Holly , Dodson Andrew , Dowsett Mitch
Published: February 2021

Aims

Ki67 is a well‐established immunohistochemical marker associated with cell proliferation that has prognostic and predictive value in breast cancer. Quantitative evaluation of Ki67 is traditionally performed by assessing stained tissue slides with light microscopy. Automated image analysis systems have become available and, if validated, could provide greater standardisation and improved precision of Ki67 scoring. Here, we aimed to evaluate the use of the Cognition Master Professional Suite (CogM) image analysis software, which is a simple system for scoring Ki67 in primary breast cancer samples.

Methods and results

Sections from 94 core‐cut biopsies, 20 excision specimens and 29 pairs of core‐cut biopsies and excision specimens were stained for Ki67 with MIB1 antibody and the Dako EnVision FLEX Detection System. Stained slides were scanned to convert them to digital data. Computer‐based Ki67 scoring was performed with CogM. Manual Ki67 scoring assessment was conducted on previously stained sections from the same biopsies with a clinically validated system that had been calibrated against the risk of recurrence. A high correlation between manual and digital scores was observed [rCores = 0.92, 95% confidence interval (CI) 0.87–0.94, P < 0.0001; rExcisions = 0.95, 95% CI 0.86–0.98, P < 0.0001] and there was no significant bias between them (P = 0.45). There was also a high correlation of Ki67 scores between paired core‐cut biopsies and excision specimens when CogM was used (r = 0.78, 95% CI 0.59–0.89, P < 0.0001).

Conclusions

CogM image analysis allows for standardised automated Ki67 scoring that accurately replicates previously clinically validated and calibrated manual scores.
The human‐in‐the‐loop: an evaluation of pathologists’ interaction with artificial intelligence in clinical practice
Authors: Bodén Anna C S , Molin Jesper , Garvin Stina , West Rebecca A , Lundström Claes , Treanor Darren
Published: February 2021

Aims

One of the major drivers of the adoption of digital pathology in clinical practice is the possibility of introducing digital image analysis (DIA) to assist with diagnostic tasks. This offers potential increases in accuracy, reproducibility, and efficiency. Whereas stand‐alone DIA has great potential benefit for research, little is known about the effect of DIA assistance in clinical use. The aim of this study was to investigate the clinical use characteristics of a DIA application for Ki67 proliferation assessment. Specifically, the human‐in‐the‐loop interplay between DIA and pathologists was studied.

Methods and results

We retrospectively investigated breast cancer Ki67 areas assessed with human‐in‐the‐loop DIA and compared them with visual and automatic approaches. The results, expressed as standard deviation of the error in the Ki67 index, showed that visual estimation (‘eyeballing’) (14.9 percentage points) performed significantly worse (P < 0.05) than DIA alone (7.2 percentage points) and DIA with human‐in‐the‐loop corrections (6.9 percentage points). At the overall level, no improvement resulting from the addition of human‐in‐the‐loop corrections to the automatic DIA results could be seen. For individual cases, however, human‐in‐the‐loop corrections could address major DIA errors in terms of poor thresholding of faint staining and incorrect tumour–stroma separation.

Conclusion

The findings indicate that the primary value of human‐in‐the‐loop corrections is to address major weaknesses of a DIA application, rather than fine‐tuning the DIA quantifications.
Increasing ferritin predicts early death in adult hemophagocytic lymphohistiocytosis
Authors: Abou Shaar Rand , Eby Charles S. , van Dorp Suzanne , de Witte Theo , Otrock Zaher K.
Published: February 2021

Introduction

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation. Most studies on adult HLH have evaluated prognostic factors for overall survival; factors predicting early mortality have not been sufficiently investigated.

Methods

This was a collaborative study between Henry Ford Hospital and Barnes‐Jewish Hospital. We identified all adult HLH patients with at least 2 ferritin levels within 30 days from admission.

Results

One‐hundred twenty‐four patients were identified. There were 77 males and 47 females; the median age at diagnosis was 48 years. Multivariate analysis showed that age (OR = 11.41; 95% CI:2.71‐48.04; P = .001), hepatomegaly (OR = 15.68; 95% CI:3.24‐75.96; P = .001), hyponatremia (OR = 5.94; 95% CI:1.76‐20.1; P = .004), hypoalbuminemia (OR = 7.47; 95% CI:2.08‐26.85; P = .002), and increasing ferritin levels (OR = 19.46; 95% CI:4.69‐80.71; P < .001) were significant predictors of 30‐day mortality. Patients with declining ferritin by more than 35% from the ferritin peak were more likely to survive the first 30 days of admission (OR = 4.33; 95% CI:1.04‐18.1; P = .033). By risk stratifying our cohort, we identified changes in ferritin levels to be the most significant prognostic factor of 30‐day mortality among other risk factors. Further investigating the prognostic utility of ferritin showed that increasing ferritin during the 1st week of admission (data available for 44 patients) was the only significant predictor of 30‐day mortality.

Conclusions

To the best of our knowledge, this is the first study reporting changes in ferritin to be a predictor for early death in adult HLH. Changes in ferritin might be a useful indicator of adult HLH disease activity and early prognosis.
Periodontitis and the outcome of atrial fibrillation ablation: Porphyromonas gingivalis is related to atrial fibrillation recurrence
Authors: Miyauchi Shunsuke , Tokuyama Takehito , Shintani Tomoaki , Nishi Hiromi , Hamamoto Yuta , Ouhara Kazuhisa , Furusho Hisako , Miyauchi Mutsumi , Komatsuzawa Hitoshi , Nakano Yukiko
Published: February 2021

Introduction

Inflammation is one of the main causes of atrial fibrillation (AF) recurrence after ablation. Porphyromonas gingivalis is a key periodontal pathogen in the oral–systemic disease connection and serum immunoglobulin G (IgG) antibody titers against P. gingivalis reflect the clinical status of periodontitis. This study aimed to investigate the relationship between late recurrence of AF after radiofrequency catheter ablation (RFCA) and serum IgG antibody titers against P. gingivalis.

Methods

A total of 596 AF patients (mean age, 64.9 ± 10.0 years; 69% male; 61% paroxysmal AF) who underwent a first session of RFCA were enrolled. Patients were carefully examined for late recurrence during a mean follow‐up period of 17.1 ± 14.5 months. Serum IgG antibody titers against P. gingivalis (types I–IV) were measured using enzyme‐linked immunosorbent assay. The results of serum antibody titers were divided into a high‐value and a low‐value group.

Results

Among the five P. gingivalis subtypes, serum antibody titer against P. gingivalis type IV was associated with late recurrence (odds ratio, 1.937; 95% confidence interval [CI], 1.301–2.884; p = .002). Multivariate Cox proportional‐hazards regression analysis revealed that high‐value serum antibody titer against P. gingivalis type IV independently predicted late recurrence (paroxysmal AF: adjusted hazard ratio [HR], 1.569; 95% CI, 1.010–2.427; p = .04; non‐paroxysmal AF: adjusted HR, 1.909; 95% CI, 1.213–3.005; p = .004).

Conclusion

Periodontitis was related to the late recurrence of AF after RFCA. P. gingivalis type IV may be pathogenic for AF recurrence after RFCA.