bluuebunny/crossref_metadata_2025 huggingface dataset:
Culture media, DMSO and efflux affect the antibacterial activity of cisplatin and oxaliplatin
Authors: Gupta Arya , Bernacchia Lorenzo , Kad Neil M.
Published: March 2022

Cisplatin was originally discovered through its antibacterial action, and subsequently has found use as a potent broad spectrum anticancer agent. This study determines the effect of growth media and solvent on the antibacterial activity of cisplatin and its analogue, oxaliplatin.E. coliMG1655 or MG1655ΔtolCwere treated with the platinum compounds under different conditions and susceptibility was determined. Our results showed that DMSO reduced the activity of cisplatin by 4-fold (MIC 12.5 mg/L) compared with 0.9% NaCl-solubilized cisplatin (MIC 3.12 mg/L) when tested in MOPS. Surprisingly, complete loss of activity was observed in Mueller Hinton Broth II (MHB II). By supplementing MOPS with individual components of MHB II such as the sulphur containing amino acids, L-cysteine and L-methionine, individually or in combination reduced activity by ≥8-fold (MIC ≥25 mg/L). Oxaliplatin was less active againstE. coli(MIC 100 mg/L) but exhibited similar inactivation in the presence of DMSO, MHBII or MOPS spiked with L-cysteine and L-methionine (MIC ≥400 mg/L). Our data suggest that the antibacterial activity of cisplatin and oxaliplatin is modulated by both choice of solvent and composition of growth media. We demonstrate that this is primarily due to sulphur-containing amino acids cysteine and methionine, an essential component of the recommended media for testing antimicrobial susceptibility, MHBII.

Significance and impact of the study

As well as an anticancer treatment, cisplatin possesses antibacterial activity and is active against AMR resistant persister cells, opening the possibility of renewed use against resistant bacterial strains. Our findings provide evidence on how the composition of growth media and choice of solvent modulate the antibacterial activity of cisplatin and its analogue, oxaliplatin. These observations provide a necessary, consistent standard for assessing the antibacterial activity of platinum-based compounds, as a precursor towards their application against bacterial infection.

Graphical abstract
On the theory of synchrotron radiation nanofocusing with planar compound refractive lenses
Authors: Kohn V. G.
Published: March 2022

Two new methods of computer simulation of synchrotron radiation nanofocusing with planar compound refractive lenses (PCRLs) are presented. The methods are based on the results of analytical theory. In contrast to previous works, the new methods take into account the PCRL aperture. It is especially important at high photon energies, when absorption is low and the calculations based on analytical theory, i.e. without taking into account the aperture, give incorrect results. A computer program was created and specific results were obtained for a silicon PCRL having an aperture of 50 µm, element length of 102 µm and minimum thickness of 2 µm. For an energy of 50 keV and number of elements 300, it focuses the beam to 31 nm size at a distance of one and a half times its length. Analysis of the calculation accuracy for the proposed methods is performed, as well as a demonstration of the capabilities of the computer program.
Towards sustainable supply strategy in the food industry: the case of Finland
Authors: Kähkönen Anni-Kaisa , Lintukangas Katrina
Published: March 2022

Purpose

This paper investigates how sustainability requirements modify supply strategies at different levels in the food industry companies. The paper integrates single supply decisions into firm-level supply strategy and views supply strategy as one coherent strategy in which the decision-making is based on the values and principles of a firm.

Design/methodology/approach

The paper captures the decade of change and studies the renewal of supply strategy by utilising two qualitative data sets with a ten years of difference. The data contain 41 interviews from a retailer and 5 of its food supplier companies.

Findings

Results confirm that a decade ago only minor attention was channelled towards sustainability whereas today sustainability is a key driver behind supply decisions and supply strategies because firms need to respond to sustainability requirements and challenges. The study presents a framework for analysing different levels (firm, category and supply market levels) of changes and sustainability requirements faced by food companies and their supply strategies.

Originality/value

Previously, sustainability has rarely been connected to firm-level supply strategy. This study presents the supply strategy elements that were important for Finnish food industry companies over a decade ago and matches these elements to the needs of today’s firms. As a result, the study incorporates the concept of sustainability with the supply strategy frameworks.
Olympic Games, media coverage and brand image/performance from fan and gender perspectives
Authors: Smith-Ditizio Amber , Smith Alan David
Published: March 2022

Purpose

The purpose of this paper is to explore and test certain assumptions concerning the role of the media in its coverage of the Olympic Games, US men's and women's basketball in particular, and its perceived impact on brand image of the athletes' performance from a fan's motivational and financial perspective.

Design/methodology/approach

Uses and gratifications theory and sport fan motivation scales were used to identify potential impacts of media coverage and branding on athletic performance. Based on a study of 143 working professionals that identified themselves as Olympic sport fans in the Pittsburgh, PA metropolitan area, several hypotheses were tested.

Findings

The most to least important factor-based constructs found from a PCA (Principal Components Analysis)/factor analysis included competitiveness, fan commitment, media connections, media impacts, demographics and financial impacts. When using the construct athletic performance at the Olympic level as the dependent variable, results suggested that competitiveness, media connections and fan commitment were significant for males only, while only media connections for significant for females. Males were found to be more player-centric than females, willing to be more focused on the competitive nature of the Olympic Games and to dedicate more money for such activities.

Originality/value

Focusing on Olympic Games and associated athletes' competitive nature opens a unique perspective from fan's gender perspective.
Exploring the inclusive leadership and employee change participation relationship: the role of workplace belongingness and meaning-making
Authors: Katsaros Kleanthis K.
Published: March 2022

Purpose

By drawing on the need to belong theory, the paper aims to propose a moderated mediation model to examine the role of workplace belongingness and meaning-making in the positive relationship between inclusive leadership and employee change participation.

Design/methodology/approach

Participants were 155 employees from 31 teams from a branch of a multinational pharmaceutical company located in an EU country. The company faces constant legal, regulatory and technology-related changes after the coronavirus disease 2019 (COVID-19) pandemic outbreak. Data were collected in three waves, approximately three weeks apart between March 2020 and May 2020. To test the mediating effect of workplace belongingness were performed first – a series of regression analyses – and second, bootstrapping to assess the statistical significance of the indirect effect (Preacher and Hayes, 2008).

Findings

Workplace belongingness mediates the relationship between inclusive leadership and employees change participation. Further, the research findings provide support that meaning-making moderates the relationship between workplace belongingness and change participation as well as the indirect relationship between inclusive leadership and change participation through workplace belongingness such that the positive relationships are stronger when meaning-making is higher.

Practical implications

The results indicate that should leaders and change management practitioners manage to influence positively employees' workplace belongingness by employing inclusive practices and procedures; leaders and change management practitioners will increase the level of participation during change and further the results note from an applied perspective the importance of mean-making as a facilitating factor during change in organizational settings. Relevant suggestions are made.

Originality/value

The findings provide new insights into how inclusive leadership and workplace belongingness can affect employees' change participation. Further, the research findings note the significant moderating role of meaning-making regarding both the relationship between workplace belongingness and change participation as well as the indirect relationship between inclusive leadership and change participation through workplace belongingness.
Quantile analysis of the aspirational middle class in Malaysia: spending behaviour emulation or dissociation?
Authors: Soon Jan-Jan
Published: March 2022

Purpose

This paper focusses on how the educated and less-educated middle class react differently to income increases, against an intertwined literature backdrop of Engel's law, quality of life, aspirational and conspicuous consumption. The paper seeks to answer two main questions: Is there evidence of the middle class, particularly the educated, trying to emulate the upper class by shifting towards aspirational consumption? Is there any distinct expenditure behaviour amongst the middle class?

Design/methodology/approach

Combining the Malaysian 2016 Household Expenditure Survey (HES) and the 2016 Consumer Price Indices datasets, quantile estimations are applied on the merged dataset of 14,326 households.

Findings

There is evidence of the educated middle class emulating the upper class in terms of food share, home furnishing and starchy produce expenditure behaviour. The less-educated middle class exhibits a predilection for home furnishing expenditures when income increases, whilst the educated shows signs of dissociating themselves from such material acquisitions. The paper concludes that the middle class is collectively an aspirational class, but with diverging paths towards upward social mobility between the educated and less-educated households.

Originality/value

Aspirational consumption of the middle class has not been given detailed empirical treatment at the household micro-level in the literature, especially for upper-middle income countries like Malaysia. The paper starts off by detecting an anomaly in the Engel's food share coefficients, where the middle class sees unexpected larger declines in food share than those of the upper class. This is the paper's departure point from the literature.
Determinants of financial inclusion across gender in Saudi Arabia: evidence from the World Bank's Global Financial Inclusion survey
Authors: Shabir Suheela , Ali Jabir
Published: March 2022

Purpose

This paper investigates the magnitude of financial inclusion in terms of ownership and usage of financial products across gender in Saudi Arabia based on the World Bank's Global Financial Inclusion (GFI) survey data.

Design/methodology/approach

This study derives the data from the GFI survey, covering 1,009 respondents from Saudi Arabia. The data on ownership and usage of financial products along with demographic characteristics of the surveyed respondents have been extracted for the analysis. The data have been analyzed with the help of statistical techniques, such as the chi-square test, and marginal effects for identifying the factors affecting financial inclusion across gender.

Findings

There is a significant association between financial inclusion and gender in terms of ownership and usage. About 82% of males have reported having a bank account with financial institutions, whereas only 60% females have reported ownership of a bank account in Saudi Arabia. The ownership and usage of financial products are comparatively more among males than females. The analysis of the marginal effect of gender shows a significant and positive impact on financial inclusion, implying that males are 10 and 13% more likely to own and use financial products, respectively, as compared to females. Further, marginal effect estimates for ownership and usage for males and females indicate that a set of independent variables related to age, level of education, occupation and income level of the respondents have a significant impact on financial inclusion.

Practical implications

Financial inclusion across gender is the first step of creating an inclusive society and empowering both males and females equally. Findings indicated an inclination of financial inclusion towards males. The research findings provide key policy insights for achieving the Vision 2030 of Saudi Arabia by strengthening gender inclusion in its growth story and ensuring the participation of females at workplaces.

Originality/value

Most of the studies have included bank account ownership in a financial institution as an indicator of financial inclusion. The authors have included ownership and usage of a variety of financial products for assessing the determinants of financial inclusion across gender, which provides empirical evidence on the magnitude of financial inclusion.
The impact of individual and team professional capital on physicians’ performance in online health-care communities: a cross-level investigation
Authors: Wang Jian-Jun , Liu Huiyuan , Ye Jiao
Published: March 2022

Purpose

Online medical teams (OMTs) are gaining popularity as a new form of online health service to provide patients with prompt and guaranteed treatment. While the effective development of an OMT depends on physicians’ active participation, there is insufficient research on how a doctor gains from the OMT, especially from the multilevel and cross-level perspectives. In attempting to narrow this knowledge gap, the authors hypothesize multilevel and cross-level professional capital determinants of physicians’ performance in online health-care communities (OHCs) through the lens of social exchange theory.

Design/methodology/approach

This study develops a cross-level model to explain the effects of individual and team professional capital on physicians’ performance. To test the research model and hypotheses, the authors leverage data of 10,398 physicians engaged in 2,611 popular OMTs in China in conjunction with the hierarchical linear model approach.

Findings

The results indicated that physicians’ status capital (SC) and decisional capital (DC) are positively related to their performance. The SC and DC of an OMT not only increase physicians’ performance but also indirectly strengthen the positive effect of physicians’ SC on their performance. In contrast, OMTs’ SC and DC lessen the importance of physicians’ DC in promoting their performance.

Originality/value

By studying the mechanism between professional capital and physicians’ performance, this study provides several contributions to theory and practice. Specifically, this study contributes to the extant professional capital research by uncovering the influencing pathways of professional capital on physicians’ performance from a cross-level perspective. These findings suggest physicians pay close attention to the strength and mechanism of OMTs’ professional capital in improving their online performance.
Stock lending and short-selling: evidence from national pension service in Korea
Authors: Lee Kuan-Hui , Wang Shu-Feng
Published: March 2022

The National Pension Service (NPS) of Korea suddenly announced that they would suspend their stock lending business from October 22, 2018. Using this ideal setting, the authors investigate the effects of this suspension on market quality and short-selling activities. The authors find that stock return does not increase after the suspension of stock lending for both the KOSPI and KOSDAQ markets. However, the returns of stocks with NPS ownership decline less than those without NPS ownership. The authors also find that the institutional and foreign investors' short sales did not increase in both markets after the lending business suspension by the NPS. In addition, the effect of suspension of stock lending on market quality is mixed, so the authors cannot conclude that market quality has improved. Overall, the authors’ results indicate that the stock market, especially for short-sales activity, has not been affected by the suspension of the stock lending service by the NPS.
Energy‐based step selection analysis: Modelling the energetic drivers of animal movement and habitat use
Authors: Klappstein Natasha J. , Potts Jonathan R. , Michelot Théo , Börger Luca , Pilfold Nicholas W. , Lewis Mark A. , Derocher Andrew E.
Published: March 2022

The energetic gains from foraging and costs of movement are expected to be key drivers of animal decision‐making, as their balance is a large determinant of body condition and survival. This fundamental perspective is often missing from habitat selection studies, which mainly describe correlations between space use and environmental features, rather than the mechanisms behind these correlations.

To address this gap, we present a novel parameterisation of step selection functions (SSFs), that we term the energy selection function (ESF). In this model, the likelihood of an animal selecting a movement step depends directly on the corresponding energetic gains and costs, and we can therefore assess how moving animals choose habitat based on energetic considerations.

The ESF retains the mathematical convenience and practicality of other SSFs and can be quickly fitted using standard software. In this article, we outline a workflow, from data gathering to statistical analysis, and use a case study of polar bears Ursus maritimus to demonstrate application of the model.

We explain how defining gains and costs at the scale of the movement step allows us to include information about resource distribution, landscape resistance and movement patterns. We further demonstrate this process with a case study of polar bears and show how the parameters can be interpreted in terms of selection for energetic gains and against energetic costs.

The ESF is a flexible framework that combines the energetic consequences of both movement and resource selection, thus incorporating a key mechanism into habitat selection analysis. Further, because it is based on familiar habitat selection models, the ESF is widely applicable to any study system where energetic gains and costs can be derived, and has immense potential for methodological extensions.
Romance Genitives: Agreement, Definiteness, and Phases*
Authors: Massaro Angelapia
Published: March 2022

In this paper, which discusses data from Gargano Apulian Italo‐Romance, I propose that prepositional and non‐prepositional genitives are fundamentally two different types of phrases, and that the interpretation of a non‐prepositional noun as the possessor is not due to a silent preposition or head‐modifier inversion, but rather to an agreement mechanism taking place between the modifier and its head. We propose that, just as a genitive can agree with its head for gender and number features so it can for definiteness, and that agreement for definiteness yields a genitival interpretation of the non‐prepositional noun. I.e., definiteness can externalize the syntactic relation between head and modifier. We also propose that in this Apulian variety, non‐prepositional genitives are syntactic phases (Chomsky 2001), and that the same holds for non‐prepositional ‘qualitative’ predicative phrases in the same language. This would explain the impossibility of accessing the phrase through syntactic operations such as extraction.
Can the use of minipublics backfire? Examining how policy adoption shapes the effect of minipublics on political support among the general public
Authors: VAN DIJK LISA , LEFEVERE JONAS
Published: March 2022

Academics and practitioners are increasingly interested in deliberative minipublics and whether these can address widespread dissatisfaction with contemporary politics. While optimism seems to prevail, there is also talk that the use of minipublics may backfire. When the government disregards a minipublic's recommendations, this could lead to more dissatisfaction than not asking for its advice in the first place. Using an online survey experiment in Belgium (n = 3,102), we find that, compared to a representative decision‐making process, a minipublic tends to bring about higher political support when its recommendations are fully adopted by the government, whereas it generates lower political support when its recommendations are not adopted. This study presents novel insights into whether and when the use of minipublics may alleviate or aggravate political dissatisfaction among the public at large.
Predicting Future Earnings Changes Using Machine Learning and Detailed Financial Data
Authors: CHEN XI , CHO YANG HA (TONY) , DOU YIWEI , LEV BARUCH
Published: March 2022

We use machine learning methods and high‐dimensional detailed financial data to predict the direction of one‐year‐ahead earnings changes. Our models show significant out‐of‐sample predictive power: the area under the receiver operating characteristics curve ranges from 67.52% to 68.66%, significantly higher than the 50% of a random guess. The annual size‐adjusted returns to hedge portfolios formed based on the prediction of our models range from 5.02% to 9.74%. Our models outperform two conventional models that use logistic regressions and small sets of accounting variables, and professional analysts’ forecasts. Analyses suggest that the outperformance relative to the conventional models stems from both nonlinear predictor interactions missed by regressions and the use of more detailed financial data by machine learning.
Tonian–Ediacaran Tectonometamorphic History of the Sa'al Complex, Sinai (Egypt): Implications for the Tectonostratigraphic Framework of the Northern Arabian–Nubian Shield
Authors: ALI‐BIK Mohamed W. , GHOSH Suranjan , PRABHAKAR N. , RAHIM Said H. Abd El , MOUSSA Hilmy E.
Published: March 2022

The Sa'al Metamorphic Complex (SMC; southern Sinai) encompasses the oldest arc rocks in the Arabian–Nubian Shield, comprising two non‐consanguineous metavolcanic successions (the Agramiya Group and the Post‐Ra'ayan Formation) separated by the metasediments of the Ra'ayan Formation. It experienced three distinct deformational events (D1–D3) and two low‐medium grade regional metamorphic events (M1–M2). The Agramiya Group and the Ra'ayan Formation experienced all tectonometamorphic events (D1–D3 and M1–M2), whereas the Post‐Ra'ayan volcanic rocks were only affected by the D3 and M2 events. D1 is an extensional event and is connected to the late Rodinia break‐up (∼Tonian; 900–870 Ma). The M1 metamorphism variably affected the older Agramiya Group, the rhyolitic tuffs experiencing lower to upper greenschist facies conditions and the basic and intermediate volcanic rocks undergoing amphibolite facies metamorphism. The Ra'ayan Formation metasediments experienced upper greenschist to amphibolite facies metamorphism. The upper greenschist facies M2 affected the youngest Post‐Ra'ayan volcanic rocks and other stratigraphic successions. The compressive D2 and D3 events were coeval with the accretion of dismembered terranes in the assembly of Gondwana. D2 can be linked to the Tonian–Cryogenian arc‐arc assembly (∼880–760 Ma; in Elat and Sinai), whereas D3 and the accompanying M2 is constrained to 622–600 Ma (Ediacaran).
A New Species of Septuconularia (Hexangulaconulariidae, Cnidaria) from Cambrian Stage 2, South China
Authors: SONG Zuchen , GUO Junfeng , HAN Jian , VAN ITEN Heyo , QIANG Yaqin , PENG Jiaxin , SUN Jie , ZHANG Zhifei
Published: March 2022

Hexangulaconulariids, an extinct family of medusozoan small shelly fossils (SSFs), were a conspicuous component of early Cambrian, shallow marine platform communities in South China. Described herein is Septuconularia crassiformis sp. nov. from Bed 5 of the Yanjiahe Formation (Cambrian Stage 2) in the Three Gorges area of Hubei Province. The new species differs from the type and only other known species, S. yanjiaheensis, in the shape of the abapical portion and in the degree of curvature of the adapertural margin. The anatomy of the apical portion of the new species is unknown. The diagnosis of the genus Septuconularia is emended and the spatio‐temporal distribution of hexangulaconulariids in South China is summarized. Finally, S. yanjiaheensis, with its slit‐like aperture and very narrow transverse cross‐section, may have been better adapted to the shallow platform environment than the broader S. crassiformis, which appears to have been less common than the type species.
Rutile to Titanite Transformation in Eclogites and its Geochemical Consequences: An Example from the Sumdo Eclogite, Tibet
Authors: ZHAO Linghao , ZENG Lingsen , GAO Li'e , HU Mingyue , SUN Dongyang , ZHANG Lifei
Published: March 2022

The formation of titanite coronae after rutile is common in retrograde high‐ to ultrahigh‐pressure meta‐mafic rocks, which provides a good opportunity to address the geochemical behavior of HFSE in crustal environments. In the Sumdo eclogite, titanite occurs either as a corona around rutile grains or as semi‐continuous veins cross‐cutting the major foliation, whereas rutile grains occur either as inclusions in garnet or omphacite or as a relict core surrounded by titanite. Textural relationships and trace elements characteristics of rutile and titanite with different occurrences indicate that both minerals preferentially incorporate Nb and Hf over Ta and Zr in aqueous fluid. Moreover, the breakdown of omphacite and epidote could release substantial amounts of aqueous fluids enriched in Ca, Si, Fe and REE, which would react with rutile to form titanite coronae and veins. During this process, water‐insoluble elements, like HFSE and HREE, behave like mobile elements, but they do not migrate substantially out of the system, instead, tending to react in situ. This suggests that the aqueous fluids released during the retrograde metamorphic reactions in mafic rocks could not substantially transfer fluid‐immobile elements into the overlying mantle wedge in subduction environments.
Sustainable Development Goals and Sustainability Governance: Norms, Implementation Pathways and Caribbean Small Island Developing States
Authors: Scobie Michelle
Published: March 2022

Small Island Developing States (SIDS) ambitiously pursue their development agendas while facing resource and governance constraints. Global processes like the Sustainable Development Goals (SDGs) include governance norms with the potential to influence national institutional arrangements and policy. National implementation processes are dynamic and contest, reinterpret, and/or apply external norms in varied ways. Although much of the success in SDG implementation depends on understanding these dynamic processes, surprisingly, the question has received little scholarly attention. This study explores the power of SDGs to act as a broker for sustainability governance. First, I construct a framework of five governance norms with nine implementation pathways that characterise the SDG governance. Second, using national reports to the United Nations, I provide evidence of how SIDS applied this framework in the years immediately following the launch of the Agenda 2030. In most cases, although recognising their value, states had not incorporated the implementation pathways. The findings suggest that greater attention should be given to governance capacity‐building to support SIDS‐led sustainable development national agendas. This study contributes to discourses on the ability of global processes to improve national governance, to the constructivists’ norm penetration debates, and to debates and policy on SDGs and governance.
Fool Me Once, Shame on You; Fool Me Twice, Shame on Me: The Long‐Term Impact of Arthur Andersen's Demise on Partners' Audit Quality*
Authors: Guo Feng , Lisic Ling Lei , Pittman Jeffrey , Seidel Timothy A. , Zhou Mi , Zhou Ying
Published: March 2022

Although recent evidence suggests that individual audit partners explain a substantial portion of the variation in audit quality proxies, much less is known about what determines an audit partner's quality. Psychology and behavioral economics theories hold that an individual's experiences can have enduring impacts on subsequent behavior. We examine whether auditors' direct exposure to Arthur Andersen's collapse has a long‐term impact on the quality of their audits. Our evidence implies that audit partners who directly experienced Andersen's demise impose stricter monitoring evident in their clients exhibiting a lower propensity for misstatements and small profits, and paying higher audit fees. Importantly, these findings reconcile with research in finance and economics implying that firsthand experiences matter more to subsequent behavior than general economic conditions or secondhand or thirdhand experiences. Collectively, the results shed light on one facet of how partners' audit quality evolves over time. Our findings suggest that major failures associated with the audit firm in which an auditor works can ultimately result in these affected individuals later delivering higher audit quality, which should benefit audit committees in partner selection decisions and audit firms in designing partner assignment policies.
Iron production along the Great Wall Belt of the Han Empire: A metallurgical study of an iron smelting site in the Northern Shaanxi, China
Authors: Zhang Mengyi , Xi Tongyuan , Shao Jing , Pei Xuesong , Zhu Yingpei , Feng Dan , Xue Cheng , Liu Ruiliang
Published: March 2022

Ironworks of the Han dynasty in Yangqiaopan ancient city are so far the only discovered iron smelting site in Northern Shaanxi. A total of 27 slag samples from the site were analysed. The results of metallographic and elemental analyses suggest that both cast iron smelting and the fining process were employed at the site. In addition, this paper suggests that under the iron monopoly policy, iron production was carried out in prefectures along the Great Wall Belt where iron offices (tieguan) were not set up, and iron industry not only satisfied the local demands but also supplied iron to the neighbouring cities.
Being part of history, being part of activism: Exploring the lives and experiences of Black people with learning disabilities
Authors: Christian Paul , Ledger Sue
Published: March 2022

My name is Paul Christian. I am a Black British man with learning disabilities. The lives and experiences of Black people with learning disabilities are under ‐ represented in the UK history of learning disability. This article explains my involvement in activism to change this and shares the learning from these projects. It discusses the process of co‐writing and why research is needed to record and share the experiences of Black people admitted to the former institutions and the importance of accessible information about Black history, race and racism.
The political economy of trade and international labour mobility
Authors: Galiani Sebastian , Torrens Gustavo
Published: March 2022

We explore the political economy of trade and migration policies in several models of international trade. We show that in a Ricardian world, free trade and no international labour mobility is a Nash equilibrium outcome, but free trade and free international labour mobility is not. The result holds under different assumptions about the set of goods, preferences and the number of countries. An analogous result also holds in multifactor economies such as a version of the standard two‐sector Heckscher–Ohlin model, the Ricardo–Vinner specific factors model and a three‐sector model with a non‐tradeable sector. We also study several extensions of our model in which free trade and at least partial labour mobility is a Nash equilibrium outcome. One extension introduces increasing returns to scale. Another an extractive elite. Finally, we allow the recipient country to charge an immigration fee in the form of an income tax and distribute the proceeds among domestic workers, which induces a Pareto improvement for the global economy.
Clinical impact of genetic alterations of CTNNB1 in patients with grade 3 endometrial endometrioid carcinoma
Authors: Kobayashi Kato Mayumi , Asami Yuka , Takayanagi Daisuke , Matsuda Maiko , Shimada Yoko , Hiranuma Kengo , Kuno Ikumi , Komatsu Masaaki , Hamamoto Ryuji , Matsumoto Koji , Ishikawa Mitsuya , Kohno Takashi , Kato Tomoyasu , Shiraishi Kouya , Yoshida Hiroshi
Published: March 2022

To identify prognostic factors in patients with grade 3 (high‐grade) endometrial endometrioid carcinoma, we evaluated the spectrum of genomic alterations and examined whether previously reported molecular subtypes of endometrial carcinoma were adapted to clinical outcome prediction. Seventy‐five Japanese patients with grade 3 endometrial endometrioid carcinoma, who underwent a potentially curative resection procedure between 1997 and 2018 at the National Cancer Center Hospital, were included. We classified the patients into four risk groups of the disease based on the Proactive Molecular Risk Classifier for Endometrial Cancer. Genomic alterations in PTEN, ARID1A, TP53, and PIK3CA were detected in more than 30% of the patients. Overall survival and recurrence‐free survival of patients with genomic alterations in CTNNB1 were poorer than those of patients with wild‐type CTNNB1 (p = 0.006 and p = 0.004, respectively). Compared with that of alterations prevalent in Caucasians, the frequency of genomic alterations in POLE and TP53 was higher in our study than in The Cancer Genome Atlas dataset (p = 0.01 and p = 0.01, respectively). The tendency for recurrence‐free survival in the POLE exonuclease domain mutation group was better than that in the TP53 mutation and mismatch repair‐deficient groups (p = 0.08 and p = 0.07, respectively), consistent with the Proactive Molecular Risk Classifier for Endometrial Cancer risk classifier definition. The CTNNB1 mutation is a potential novel biomarker for the prognosis of patients with grade 3 endometrial endometrioid carcinoma, and prognosis classification using Proactive Molecular Risk Classifier for Endometrial Cancer may help screen Japanese patients with the disease.
Pharmacophore screening, denovo designing, retrosynthetic analysis, and combinatorial synthesis of a novel lead VTRA1.1 against RecA protein of Acinetobacter baumannii
Authors: Tiwari Vishvanath
Published: March 2022

Antibiotics and disinfectants resistance is acquired by activating RecA‐mediated DNA repair, which maintains ROS‐dependent DNA damage caused by the antimicrobial molecules. To increase the efficacy of different antimicrobials, an inhibitor can be developed against RecA protein. The present study aims to design a denovo inhibitor against RecA protein of Acinetobacter baumannii. Pharmacophore‐based screening, molecular mechanics, molecular dynamics simulation (MDS), retrosynthetic analysis, and combinatorial synthesis were used to design lead VTRA1.1 against RecA of A. baumannii. Pharmacophore models (structure‐based and ligand‐based) were created, and a phase library of FDA‐approved drugs was prepared. Screening of the phase library against these pharmacophore models selected thirteen lead molecules. These filtered leads were used for the denovo fragment‐based design, which produced 253 combinations. These designed molecules were further analyzed for its interaction with active site of RecA that selected a hybrid VTRA1. Further, retrosynthetic analysis and combinatorial synthesis produced 1000 analogs of VTRA1 by more than 100 modifications. These analogs were used for XP docking, binding free energy calculation, and MDS analysis which finally select lead VTRA1.1 against RecA protein. Further, mutations at the interacting residues of RecA with VTRA1.1, alter the unfolding rate of RecA, which suggests the binding of VTRA1.1 to these residues may alter the stability of RecA. It is also found that VTRA1.1 had reduced interaction of RecA with LexA and ssDNA polydT, showing the lead's efficacy in controlling the SOS response. Further, it was also observed that VTRA1.1 does not contain any predicted human off‐targets and no cytotoxicity to cell lines. As functional RecA is involved in antimicrobial resistance, denovo designed lead VTRA1.1 against RecA may be further developed as a significant combination for therapeutic uses against A. baumannii.
Pharmacological suppression of the kallikrein kinin system with KVD900: An orally available plasma kallikrein inhibitor for the on‐demand treatment of hereditary angioedema
Authors: Duckworth Edward J. , Murugesan Nivetha , Li Lily , Rushbrooke Louise J. , Lee Daniel K. , De Donatis Gian Marco , Maetzel Andreas , Yea Christopher M. , Hampton Sally L. , Feener Edward P.
Published: March 2022

Background

Hereditary angioedema (HAE) is a rare genetic disease that leads to recurrent episodes of swelling and pain caused by uncontrolled plasma kallikrein (PKa) activity. Current guidelines recommend ready availability of on‐demand HAE treatments that can be administered early upon attack onset. This report describes the pharmacological and pharmacodynamic properties of the novel oral small‐molecule PKa inhibitor KVD900 as a potential on‐demand treatment for HAE.

Methods

Pharmacological properties of KVD900 on PKa and closely related serine proteases were characterized using kinetic fluorogenic substrate activity assays. Effects of KVD900 on PKa activity and kallikrein kinin system activation in whole plasma were measured in the presence of dextran sulphate (DXS)‐stimulation using a fluorogenic substrate and capillary immunoassays to quantify high molecular weight kininogen (HK), plasma prekallikrein and Factor XII cleavage. Pharmacodynamic effects of orally administered KVD900 were characterized in plasma samples from six healthy controls in a first in human phase 1 clinical trial and from 12 participants with HAE in a phase 2 clinical trial.

Results

KVD900 is a selective, competitive and reversible inhibitor of human PKa enzyme with a Ki of 3.02 nM. The association constant (Kon) of KVD900 for PKa is >10 × 106 M−1 s−1. Oral administration of KVD900 in a first‐in‐human clinical trial achieved rapid and near complete inhibition of DXS‐stimulated PKa enzyme activity and HK cleavage and reduced plasma prekallikrein and Factor XII activation in plasma. In individuals with HAE, orally administered KVD900 inhibited DXS‐stimulated PKa activity in plasma by ≥95% from 45 min to at least 4 h post‐dose and provided rapid protection of HK from cleavage.

Conclusion

KVD900 is a fast‐acting oral PKa inhibitor that rapidly inhibits PKa activity, kallikrein kinin system activation and HK cleavage in plasma. On‐demand administration of KVD900 may provide an opportunity to halt the generation of bradykinin and reverse HAE attacks.
Clinical and histological evaluation of the use of acellular dermal matrix (ADM) membrane in peri‐implant vertical soft tissue augmentation: A controlled clinical trial
Authors: Zang Jing , Su Li , Luan Qingxian , Liu Guojing , Li Shiyi , Yu Xiaoqian
Published: March 2022

Objectives

The aim of this study was to clinically and histologically evaluate the efficacy of using acellular dermal matrix (ADM) for peri‐implant vertical soft tissue augmentation at implant placement.

Materials and methods

Twenty patients were enrolled in this study. According to the initial thickness of vertical soft tissue, patients were assigned into the ADM group (≤2 mm) or the control group (>2 mm) prior to implant surgery +ADM grafting or implant surgery alone. Second‐stage surgery was carried out 3 months later, and a small piece of ridge membrane was harvested for histological and immunohistochemical evaluation. Vascular endothelial growth factor (VEGF) and platelet‐derived growth factor (PDGF)‐BB in peri‐implant crevicular fluid (PICF) were also assessed 1 week, 1 month, and 5 months after second‐stage surgery. Clinical parameters were recorded to evaluate peri‐implant health at 1 week and 3 months after implant restoration.

Results

All 20 implants healed uneventfully and successfully. Soft tissue thicknesses were comparable in the two groups at second‐stage surgery (3.20 ± 0.42 mm vs. 3.50 ± 0.58 mm). In the ADM group, the mean increase in soft tissue thickness was 1.85 ± 0.34 mm. Histological and immunohistochemical outcomes showed no differences between the two groups. VEGF and PDGF‐BB levels in PICF were significantly lower in the ADM group 1 week after second‐stage surgery (p < .01), yet they decreased in both groups later. The difference between the groups had disappeared by 5 months after second‐stage surgery. The clinical peri‐implant parameters were good and stable by the end of the study (3 months after restoration).

Conclusions

Our results suggested that using ADM at implant placement was effective in increasing the thickness of peri‐implant vertical soft tissue and achieved comparable clinical and histological performance to the control group. However, the incremental soft tissue showed inferior angiogenic ability in the early stage of wound healing.
A deep reinforcement learning based decision‐making approach for avoiding crowd situation within the case of Covid'19 pandemic
Authors: Abdallah Wejden , Kanzari Dalel , Sallami Dorsaf , Madani Kurosh , Ghedira Khaled
Published: March 2022

Individuals' flow's fluidifcation in the same way as the thinning of the population's concentration remains among major concerns within the context of the pandemic crisis situations. The recent COVID‐19 pandemic crisis is a typical example of the aforementioned where on despite of the containment phases that radically isolate the population but are not applicable persistently, people have to adapt their behavior to new daily‐life situations tempering Individuals' stream, avoiding tides, and watering down population's concentration. Crowd evacuation is one of the well‐known research domains that can play a pertinent role to face the challenge of the COVID‐19 pandemic. In fact, considering the population's concentration thinning within the slant of the “crowd evacuation” paradigm allows managing the flow of the population, and consequently, decreasing the probable number of infected cases. In other words, crowd evacuation modeling and simulation with the aim of better‐exploiting individuals' flow allow the study and analysis of different possible outcomes for designing population's concentration thinning strategies. In this article, a new decision‐making approach is proposed in order to cope with the aforesaid challenges, which relies on an independent Deep Q Network with an improved SIR model (IDQN‐I‐SIR). The machine‐learning component (i.e., IDQN) is in charge of the agent's movements control and I‐SIR (improved “susceptible‐infected‐recovered” individuals) model is responsible to control the virus spread. We demonstrate the effectiveness of IDQN‐I‐SIR through a case‐study of individuals' flow's management with infected cases' avoidance in an emergency department (often overcrowded in context of a pandemic crisis).
Penile extramammary Paget disease associated with urothelial carcinoma in situ: Case report and literature review
Authors: Al Qa’qa’ Shifaa’ , Tiwari Raj , van der Kwast Theodorus
Published: March 2022

Background

Extramammary Paget disease (EMPD) is an uncommon disease affecting older men and women. Clinically, it appears as a plaque lesion with an erythematous or leukoplakic background in regions with abundant apocrine glands such as female external genitalia, perineum, scrotum, and penis.

Methods

We are presenting an 85‐year‐old patient with recurrent erythematous plaque lesions involving the penis and known to have urothelial carcinoma (UC) in situ of the bladder. A literature review of EMPD secondary to UC has been conducted through PubMed and Google Scholar search engines.

Results

The histopathologic examination revealed a proliferation of Paget cells within the surface squamous epithelium. The lesional cells displayed vesicular nuclei, clear cytoplasm, and a positive staining for CK7, CK20, HER2, GATA3 as well as p40, and negative staining for SOX10, CK5/6, and CDX2. The literature review revealed 18 more cases of EMPD associated with UC, including 4 with non‐invasive UC. Most of them were treated surgically, but the disease recurred in nine cases and death of disease was reported in at least four patients, all of them associated with invasive UC.

Conclusion

The prognosis of penile EMPD seems to be dictated by the stage of the underlying UC.
Elevational patterns of phylogenetic structure of angiosperms in a biodiversity hotspot in eastern Himalaya
Authors: Li Lijuan , Xu Xiaoting , Qian Hong , Huang Xianhan , Liu Pengju , Landis Jacob B , Fu Quansheng , Sun Lu , Wang Hengchang , Sun Hang , Deng Tao
Published: March 2022

Aims

The tropical niche conservatism (TNC) hypothesis and the out of the tropics (OTT) hypothesis propose mechanisms generating patterns of species diversity across warm‐to‐cold thermal gradients at large spatial scales. These two hypotheses both integrate ecological and biogeography‐related evolutionary factors, but they predict opposite patterns for phylogenetic structure. Mount Namjagbarwa possesses one of the longest elevational gradients for flowering plant diversity in the world. We aim to analyse the elevational patterns of the phylogenetic structure of flowering plants in this mountain, and investigate underlying causes for the emergence of the patterns.

Location

Mt. Namjagbarwa located at the eastern edge of the Himalaya.

Methods

Species distribution data of Mt. Namjagbarwa were extracted from specimen records in online sources, literature, herbarium and our fieldwork. Bioclimatic data were extracted from the CHELSA database. Mt. Namjagbarwa was divided into 100‐m elevational belts, which were grouped into three elevation segments (100–2000 m, 2000–4000 m and 4000–5200 m) for data analysis. We calculated phylogenetic metrics for each belt. The relationships of phylogenetic metrics with elevation and climatic factors were analysed using generalized additive models and structural equation models.

Results

A typical hump‐shaped pattern of species richness was observed along the elevational gradient of Mt. Namjagbarwa. However, the phylogenetic structure showed a zig‐zag pattern with the three elevation segments, each of which has different formation mechanisms. Temperature tolerance played important roles throughout the entire elevational gradient in species richness and phylogenetic structure.

Main conclusions

Neither TNC nor OTT alone can fully explain the patterns of floristic assembly of the entire elevational gradient of Mt. Namjagbarwa. OTT and TNC are better explanation for the patterns of low and middle elevations respectively. Potential mechanisms for species assembly of different elevation segments in Mt. Namjagbarwa region alternate between niche convergence and niche conservatism. The patterns observed in this study are likely to be common across the entire Himalaya. This is important for preserving the evolutionary potential of mountain biodiversity. However, more studies are needed to determine the underlying mechanisms generating the zig‐zag pattern of the phylogenetic structure in the Himalaya.