bluuebunny/crossref_metadata_2025 huggingface dataset:
Parameter estimation in the age of degeneracy and unidentifiability
Authors: Lederman Dylan , Patel Raghav , Itani Omar , Rotstein Horacio G.
Published: November 2021

Parameter estimation from observable or experimental data is a crucial stage in any modeling study. Identifiability refers to one’s ability to uniquely estimate the model parameters from the available data. Structural unidentifiability in dynamic models, the opposite of identifiability, is associated with the notion of degeneracy where multiple parameter sets produce the same pattern. Therefore, the inverse function of determining the model parameters from the data is not well defined. Degeneracy is not only a mathematical property of models, but it has also been reported in biological experiments. Classical studies on structural unidentifiability focused on the notion that one can at most identify combinations of unidentifiable model parameters. We have identified a different type of structural degeneracy/unidentifiability present in a family of models, which we refer to as the Lambda-Omega (Λ-Ω) models. These are an extension of the classical lambda-omega (λ-ω) models that have been used to model biological systems, and display a richer dynamic behavior and waveforms that range from sinusoidal to square-wave to spike-like. We show that the Λ-Ω models feature infinitely many parameter sets that produce identical stable oscillations, except possible for a phase-shift (reflecting the initial phase). These degenerate parameters are not identifiable combinations of unidentifiable parameters as is the case in structural degeneracy. In fact, reducing the number of model parameters in the Λ-Ω models is minimal in the sense that each one controls a different aspect of the model dynamics and the dynamic complexity of the system would be reduced by reducing the number of parameters. We argue that the family of Λ-Ω models serves as a framework for the systematic investigation of degeneracy and identifiability in dynamic models and for the investigation of the interplay between structural and other forms of unidentifiability resulting on the lack of information from the experimental/observational data.
StabilitySort: assessment of protein stability changes on a genome-wide scale to prioritise potentially pathogenic genetic variation
Authors: Chuah Aaron , Li Sean , Do Andrea , Field Matt A , Andrews T. Daniel
Published: December 2021

Missense mutations that change protein stability are strongly associated with human inherited genetic disease. With the recent availability of predicted structures for all human proteins generated using the AlphaFold2 prediction model, genome-wide assessment of the stability effects of genetic variation can, for the first time, be easily performed. This facilitates the interrogation of personal genetic variation for potentially pathogenic effects through the application of stability metrics. Here, we present a novel algorithm to prioritise variants predicted to strongly destabilise essential proteins, available as both a standalone software package and a web-based tool. We demonstrate the utility of this tool by showing that at values of the Stability Sort Z-score above 1.6, pathogenic, protein-destabilising variants from ClinVar are detected at a 58% enrichment, over and above the destabilising (but presumably non-pathogenic) variation already present in the HapMap NA12878 genome.

Availability and Implementation

StabilitySort is available as both a web service (http://130.56.244.113/StabilitySort/) and can be deployed as a standalone system (https://gitlab.com/baaron/StabilitySort).

Contact

Dan.Andrews@anu.edu.au
Usability of the login authentication process: passphrases and passwords
Authors: Bhana Bhaveer , Flowerday Stephen Vincent
Published: November 2021

Purpose

The average employee spends a total of 18.6 h every two months on password-related activities, including password retries and resets. The problem is caused by the user forgetting or mistyping the password (usually because of character switching). The source of this issue is that while a password containing combinations of lowercase characters, uppercase characters, digits and special characters (LUDS) offers a reasonable level of security, it is complex to type and/or memorise, which prolongs the user authentication process. This results in much time being spent for no benefit (as perceived by users), as the user authentication process is merely a prerequisite for whatever a user intends to accomplish. This study aims to address this issue, passphrases that exclude the LUDS guidelines are proposed.

Design/methodology/approach

To discover constructs that create security and to investigate usability concerns relating to the memory and typing issues concerning passphrases, this study was guided by three theories as follows: Shannon’s entropy theory was used to assess security, chunking theory to analyse memory issues and the keystroke level model to assess typing issues. These three constructs were then evaluated against passwords and passphrases to determine whether passphrases better address the security and usability issues related to text-based user authentication. A content analysis was performed to identify common password compositions currently used. A login assessment experiment was used to collect data on user authentication and user – system interaction with passwords and passphrases in line with the constructs that have an impact on user authentication issues related to security, memory and typing. User–system interaction data was collected from a purposeful sample size of 112 participants, logging in at least once a day for 10 days. An expert review, which comprised usability and security experts with specific years of industry and/or academic experience, was also used to validate results and conclusions. All the experts were given questions and content to ensure sufficient context was provided and relevant feedback was obtained. A pilot study involving 10 participants (experts in security and/or usability) was performed on the login assessment website and the content was given to the experts beforehand. Both the website and the expert review content was refined after feedback was received from the pilot study.

Findings

It was concluded that, overall, passphrases better support the user during the user authentication process in terms of security, memory issues and typing issues.

Originality/value

This research aims at promoting the use of a specific type of passphrase instead of complex passwords. Three core aspects need to be assessed in conjunction with each other (security, memorisation and typing) to determine whether user-friendly passphrases can support user authentication better than passwords.
Synergy between sectoral output, energy and CO2 emission: a panel cointegration analysis of South Asia
Authors: Sharmin Mowshumi
Published: November 2021

Purpose

The purpose of this study is to investigate the synergy between sectoral output, energy use and CO2 emission with other factors for a panel of South Asian economies including Afghanistan, Bangladesh, Bhutan, India, Pakistan, Maldives, Nepal and Sri Lanka.

Design/methodology/approach

The analysis is done using annual panel data from 1980–2019 using dynamic ordinary least squares (DOLS), fully modified OLS (FMOLS) and Toda-Yamamoto techniques.

Findings

Empirical findings reveal the existence of a statistically significant long-run cointegrating relationship between energy use, sectoral output such as agricultural, industry and service gross domestic product (GDP), globalization, urbanization and CO2 emission. DOLS and FMOLS result posits that in the case of the South Asian region agriculture GDP does not contribute to increasing CO2 emission while service and industrial GDP is responsible for increasing CO2 emission along with urban population, energy use and to some extent globalization. More remarkably, the contribution of the service GDP is greater than the other two sectoral outputs in increasing CO2 emission with a feedback hypothesis.

Practical implications

As CO2 emission is a global phenomenon with a cross-boundary effect, these empirical findings might contribute to formulating implementable energy and environmental policies to sustain growth, as well as to protect the environment in the regional context.

Originality/value

The study contributes to the literature by providing an empirical investigation of South Asia incorporating the contribution of sectoral output to understand the potential contribution of each sector on energy and emission. This is the first study on the South Asian context from the perspective of sectoral output, energy and emission.
A comparative analysis of employees’ and customers’ attitude towards Islamic banking
Authors: Ali Syed Ahmad , Loussaief Aida , Ahmed Muhammad
Published: November 2021

Purpose

Islamic banking industry with all of its exponential growth and global recognition has been under criticism for the past two decades. However, the problem signifies further when such criticism is made from within the organization and is well supported by outside (the customers). The purpose of this study is to provide a coherent exploration to investigate the factors that polarize its employees and customers across many parts of the world.

Design/methodology/approach

To investigate the phenomenon, a total of 30 responses were taken through interviews 15 each from customers and employees. Afterwards, the data was analysed and summarized into two categories. In doing so, the top five Malaysia’s Islamic banks were shortlisted to collect data from employees and customers.

Findings

A detailed thematic analysis resulted in six themes (Contradiction between theory and practice, Islamic banking knowledge and awareness, inadequate Shariah training, employees’ background, Shariah compliance, Islamic banking benefits) for employees and five (Islamic banking benefits, applying Shariah in Islamic banking, knowledge of Islamic banking, Islamic banking promotion, Islamic banking employees’ behaviour) for customers, respectively.

Research limitations/implications

The results have stronger implications for both practice and theory as organizations can assess stakeholders and their perceptions about Islamic banking. Another implication is the comparative examination of employees and customers which can potentially affect decision and policy making in Islamic banks. Islamic banks can also address employment-related issues related to employees’ behaviour vis-à-vis marketing-related problems faced by its customers that will ultimately improve its global market share and strategic positioning.

Originality/value

The study is based on the importance of Islamic banking in Malaysia and explores the factors that potentially create a positive or negative insight into Islamic banking – both in employees and customers.
Allocation discretion, price discounts and returns in Turkish initial public offerings
Authors: Tutuncu Lokman
Published: November 2021

Purpose

This study aims to investigate whether underwriters exercise their allocation discretion to offer favorable discounts to institutional investors.

Design/methodology/approach

The research covers 173 offerings at Borsa Istanbul between 2010 and September 2021. Two hypotheses related to allocation discretion are developed and tested by means of probit, ordinary least squares and two-stage least squares regressions. Heckman selection regressions are used for robustness tests.

Findings

Allocation discretion is catered toward institutional investors who account for more than 56% of all initial allocations adjusted by gross proceeds. Close to 84% of all gross proceeds come from offerings that allocation discretion is exercised. These discretionary offerings are sold with larger price discounts, yet provide lower initial returns, while evidence points to reallocation to retail investors due to weak demand from institutional investors.

Research limitations/implications

Despite using the population of firms in the research period, the sample size is small relative to more developed markets. The research period cannot be extended because allocation discretion is allowed in 2010.

Practical implications

The research highlights the importance of institutional and foreign investors to the equity markets. This issue is relevant due to the ongoing flight of foreign investors from emerging economies and the increasing participation of small investors in the stock markets.

Social implications

The study cautions retail investors against greater (re)allocations by underwriters who may seek to compensate for the loss of their foreign investor base and urges policymakers to regain foreign investors.

Originality/value

To the best of the authors’ knowledge, this is the first research paper to use actual discounts disclosed in the prospectus to test the predictions related to allocation discretion. The study also contributes to the emerging markets literature by documenting allocation practices of the Turkish underwriters for the first time.
Technological capabilities, technology management and economic performance: the complementary roles of corporate governance and institutional environment
Authors: Wu Weiwei , Liang Zhou , Zhang Qi
Published: November 2021

Purpose

Nowadays, faced with increasingly dynamic and fierce competition, knowledge is considered to be the core to survive and maintain competitive advantages in both managerial practices and academia. Against this background, this study analyzed the influence of technological capabilities (TC) and technology management (TM) on corporate economic performance in the contexts of corporate internal governance mechanisms and external institutional environment from the institutional perspective.

Design/methodology/approach

This study collected data on Chinese publicly listed manufacturing firms in Shenzhen and Shanghai stock markets from 2008 to 2017 and the final data included 3,679 firm-year observations. Ordinary least square regression was used in both regression analysis and robustness tests.

Findings

The empirical results showed that the interaction between TC and TM was positively related to corporate economic performance and both corporate incentives and monitoring mechanisms strengthened this positive relationship; the positive moderating effects of corporate governance were stronger under a more developed corporate external institutional environment.

Originality/value

This research provides a better understanding of the economic effect of TC and TM from the perspective of knowledge integration by indicating that the interaction between TC and TM can enhance corporate economic performance and delimiting the boundaries of this relationship from the institutional perspective.
Does knowledge structure matter? Key factors influencing formal and informal knowledge sharing in manufacturing
Authors: Wen Peihan , Wang Ruiquan
Published: November 2021

Purpose

This study aims to investigate the factors from four dimensions that have an effect both on formal and informal knowledge sharing (FKS and IKS) and the relationship between knowledge sharing (KS) and task performance in Chinese manufacturing.

Design/methodology/approach

The structural equation modeling approach was applied to hypothesis testing according to the data collected from employees of manufacturing companies through the online questionnaire. A total of 530 valid responses were obtained.

Findings

The results indicate that level of knowledge structure, self-efficacy, leadership support and KS culture all have a significant positive effect on both FKS and IKS while trust only positively affects FKS and information technology support positively affects IKS. Both FKS and IKS positively contribute to the task performance of manufacturing companies.

Research limitations/implications

This study merely considered the impact of six factors on KS from four perspectives. Consequently, the relationship between some important other factors and KS is not revealed. In addition, the results of this study indicate that there might be a more complicated relationship between these factors and KS than the model constructed by this study. Therefore, in future research, more influencing factors could be considered in the research framework, and a multilevel model, such as a model considering the mediation effect, could be further explored.

Practical implications

According to the results, both FKS and IKS play a significant role in promoting organizational task performance, which is worthy of attention by the managers of manufacturing companies. In addition, the relationship between the different factors and the FKS and IKS found in this study provides specific guidance for improving the organizational KS practice.

Originality/value

First, previous studies considered the construction of explicit KS and tacit KS models based on the content of KS while this study considered FKS and IKS from the perspective of the process and approach of KS. Second, this research has clearly defined the level of knowledge structure from the perspective of knowledge ontology and verifies the positive effect of this factor on KS, providing a new theoretical perspective for exploring KS factors.
Knowledge management in turbulent times: time-based scenario analysis of vaccinations against COVID-19
Authors: Mennini Francesco Saverio , Magni Domitilla , Daniele Lucia Michela , Favato Giampiero
Published: November 2021

Purpose

This paper aims to estimate the delay or timely effects of the national vaccination strategy for COVID-19 on Italian gross domestic product (GDP). By adopting a knowledge management lens, the study highlights the importance of “time” for Italian recovery. Indeed, recovering an adequate growth rate is crucial for the future of employment, well-being and management of Italian public debt.

Design/methodology/approach

This study applies an epidemiological model of a universal access vaccination programme against COVID-19. The economic model is based on the time-shift of available quarterly projections deriving from the expected delay or acceleration of the national vaccination plan against COVID-19.

Findings

The basic concept underlying the scenario analysis is that the sustainability of the expected recovery of the Italian economy due to the COVID-19 shock, and consequently the growth of the GDP, is time-dependent on the rollout of the national vaccination plan.

Research limitations/implications

A delay in the vaccination campaign could have a twofold negative impact on the growth of the Italian gross product: it reduces the quarterly growth over the previous year in the short term and it delays the quarterly upwards trend over the next two years. Policymakers and practitioners are called to promptly face new dynamic scenarios due to public and economic policies to fight the COVID-19 crisis.

Originality/value

To the best of the authors’ knowledge, this is the first attempt of research that focuses attention on the synchrony between the economic time necessary for recovery and the real-time necessary to achieve vaccination coverage for the restart of production activities.
Technological entrepreneurship: present conditions and future perspectives for Latin America
Authors: Yáñez-Valdés Claudia
Published: November 2021

Purpose

Technological entrepreneurship is distinguished from other types of initiatives by its innovative characteristics and rapid growth, as well as by the high uncertainty it faces, both in terms of investment cost and capacity for continuous adaptation. The purpose of this study is to investigate the definitions, measures and methods that have been used to investigate the phenomenon and to define the process of the “entrepreneurial journey” and the associated typologies according to the technological level.

Design/methodology/approach

This paper provides a systematic review of the literature on technological entrepreneurship focusing on emerging economies in Latin America. Based on the review of 62 papers, it analyses the current state and future research perspectives on the topic.

Findings

The authors can conclude that technological entrepreneurship in Latin America has great opportunities, especially linked to growth, but faces the threats of an uncertain and dynamic environment. Taking advantage of technologies allows the formulation of unique value propositions linked to the environment through innovation that improves the quality of life of the population.

Research limitations/implications

This study is a starting point for the development of research on resilient technology ventures. Latin America represents a limited location but offers insight into the developing phenomenon to measure the impacts that this phenomenon generates in society.

Originality/value

Considering the possibilities offered by technology and its continuous evolution, the impact that this type of entrepreneurship generates on the environment can be on a global scale. However, high growth and success are as likely as a failure and this is part of the improvement process.
Does environmental proactivity make a difference? The critical roles of green operations and collaboration in GSCM
Authors: Kitsis Aleksandr M. , Chen Injazz J.
Published: November 2021

Purpose

This paper aims to examine the complex links between environmental proactivity, collaboration with suppliers and customers, green operations and firm performance.

Design/methodology/approach

Based on a sample of 208 US companies, five main effects and two mediation effects were tested using structural equation modeling analysis.

Findings

This study reveals that environmental proactivity exerts positive effects on green operations and that collaboration mediates the above relationship. Further, green operations are a powerful driver of a firm’s economic and environmental performance. Findings also demonstrate the critical mediating role of green operations in linking collaboration with performance.

Research limitations/implications

This research contributes to a scholarly debate by offering novel insights into the extent to which proactivity improves firm performance may be influenced by multiple supply chain practices. To managers, this study highlights the strategic value of environmental proactivity as it fosters collaboration and green operations in boosting a firm’s environmental and economic performance.

Originality/value

This study addresses a gap in the literature by investigating the links between environmental proactivity, collaboration, green operations and corporate performance.
Outcomes to measure the effects of pharmacological interventions for pain management for women during labour and birth: a review of systematic reviews and randomised trials
Authors: Tan A , Wilson AN , Eghrari D , Clark H , Tse WC , Bohren MA , Homer CSE , Vogel JP
Published: November 2021

Background

Pharmacological pain management options can relieve women’s pain during labour and birth. Trials of these interventions have used a wide variety of outcomes, complicating meaningful comparisons of their effects. To facilitate better assessment of the effectiveness of labour pain management in trials and meta‐analyses, consensus about key outcomes and the development of a core outcome set is essential.

Objective

To identify all outcomes used in studies of pharmacological pain management interventions during labour and birth.

Design

A review of systematic reviews and their included randomised controlled trials was undertaken.

Search strategy

Cochrane CENTRAL was searched to identify all Cochrane systematic reviews describing pharmacological pain management options for labour and birth. Search terms included ‘pain management’, ‘labour’ and variants, with no limits on year of publication or language.

Selection criteria

Cochrane reviews and randomised controlled trials contained within these reviews were included, provided they compared a pharmacological intervention with other pain management options, placebo or no treatment.

Data collection and analysis

All outcomes reported by reviews or trials were extracted and tabulated, with frequencies of individual outcomes reported.

Main results

Nine Cochrane reviews and 227 unique trials were included. In total, 146 unique outcomes were identified and categorised into maternal, fetal, neonatal, child, health service, provider’s perspective or economic outcome domains.

Conclusions

Outcomes of pharmacological pain management interventions during labour and birth vary widely between trials. The standardisation of trial outcomes would permit the assessment of meta‐analyses for best clinical practice.

Tweetable abstract

Outcomes to measure pharmacological pain management options during labour are highly variable and require standardisation.
Contributions of side effects to contraceptive discontinuation and method switch among Kenyan women: a prospective cohort study
Authors: Rothschild CW , Richardson BA , Guthrie BL , Kithao P , Omurwa T , Mukabi J , Callegari LS , Lokken EL , John‐Stewart G , Unger JA , Kinuthia J , Drake AL
Published: November 2021

Objective

To determine the contribution of specific contraceptive side effects to method switch and modern‐method discontinuation among Kenyan women.

Design

A prospective cohort study.

Setting

Five counties in Western Kenya.

Participants

Women aged ≥18 years old and emancipated female minors ≥14 years old using modern, reversible contraception were recruited while attending 10 public health facilities.

Methods

Patient‐reported adverse effect symptoms, method switch and discontinuation were reported through weekly text message‐based surveys for 24 weeks.

Main outcome measurements

Prevalence, hazards ratio (HR).

Results

Among 825 women, 44% were using implants, 43% injectables, 7% an intrauterine device and 6% oral contraceptive pills at enrolment. Most (61%) women were continuing a method used in the previous month. During the 24‐week follow up, incidence of contraceptive switch was 61.3 per 100 person‐years (95% confidence interval [CI] 52.4–71.8) and incidence of discontinuation was 38.5 per 100 person‐years (95% CI 31.6–47.0). On average, one‐quarter (prevalence [Pr] 0.24, 95% CI 0.22–0.26) of participants reported side effects or method problems weekly, with sexual side effects the most prevalent symptom (Pr 0.15, 95% CI 0.13–0.16). Lack of expected bleeding was associated with higher risk of method switch (adjusted hazard ratio [aHR] 2.36, 95% CI 1.22–4.57). Risk of all‐modern method discontinuation was higher among women experiencing irregular bleeding (aHR 2.39, 95% CI 1.20–4.77), weight changes (aHR 2.72, 95% CI 1.47–4.68) and sexual side effects (aHR 2.42, 95% CI 1.40–4.20).

Conclusions

Addressing irregular bleeding, weight changes and sexual side effects through development of new products that minimise these specific side effects and anticipatory counseling may reduce method‐related discontinuation.

Tweetable abstract

Bleeding, weight changes, sexual problems associated with discontinuation of #contraception, but many continue despite side effects.
Phylogenomic analyses of the genusDrosophilareveals genomic signals of climate adaptation
Authors: Li Fang , Rane Rahul V. , Luria Victor , Xiong Zijun , Chen Jiawei , Li Zimai , Catullo Renee A. , Griffin Philippa C. , Schiffer Michele , Pearce Stephen , Lee Siu Fai , McElroy Kerensa , Stocker Ann , Shirriffs Jennifer , Cockerell Fiona , Coppin Chris , Sgrò Carla M. , Karger Amir , Cain John W. , Weber Jessica A. , Santpere Gabriel , Kirschner Marc W. , Hoffmann Ary A. , Oakeshott John G. , Zhang Guojie
Published: November 2021

ManyDrosophilaspecies differ widely in their distributions and climate niches, making them excellent subjects for evolutionary genomic studies. Here, we have developed a database of high‐quality assemblies for 46Drosophilaspecies and one closely relatedZaprionus. Fifteen of the genomes were newly sequenced, and 20 were improved with additional sequencing. New or improved annotations were generated for all 47 species, assisted by new transcriptomes for 19. Phylogenomic analyses of these data resolved several previously ambiguous relationships, especially in themelanogasterspecies group. However, it also revealed significant phylogenetic incongruence among genes, mainly in the form of incomplete lineage sorting in the subgenusSophophorabut also including asymmetric introgression in the subgenusDrosophila. Using the phylogeny as a framework and taking into account these incongruences, we then screened the data for genome‐wide signals of adaptation to different climatic niches. First, phylostratigraphy revealed relatively high rates of recent novel gene gain in three temperatepseudoobscuraand five desert‐adapted cactophilicmullerisubgroup species. Second, we found differing ratios of nonsynonymous to synonymous substitutions in several hundred orthologues between climate generalists and specialists, with trends for significantly higher ratios for those in tropical and lower ratios for those in temperate‐continental specialists respectively than those in the climate generalists. Finally, resequencing natural populations of 13 species revealed tropics‐restricted species generally had smaller population sizes, lower genome diversity and more deleterious mutations than the more widespread species. We conclude that adaptation to different climates in the genusDrosophilahas been associated with large‐scale and multifaceted genomic changes.
The behavioral economics of alcohol demand in Greek‐affiliated college students
Authors: Ortelli Olivia A. , Martinetti Margaret P.
Published: November 2021

Background

College students affiliated with fraternity and sorority, or “Greek” life represent a known high‐risk group for alcohol consumption and related consequences, but little is known about demand for alcohol in this population. The current study examined behavioral economic demand for alcohol in a sample of Greek life‐affiliated undergraduate students using the alcohol purchase task (APT) and a novel variation of the APT that included a fixed‐price, nonalcoholic alternative (APT Choice).

Methods

Participants (n = 229) completed the APT, APT Choice, Alcohol Use Disorders Identification Test (AUDIT), and Daily Drinking Questionnaire (DDQ). Group demand indices were calculated for the entire sample and then separately for participants who met or did not meet the legal drinking age (21+ or underage, respectively). Independent‐sample t tests assessed whether there were any significant differences between the two age cohorts in the percent change in each behavioral economic index from the APT to APT Choice. Tests of correlation evaluated the construct validity of the demand indices from both hypothetical purchase tasks.

Results

Descriptive statistics on alcohol use in this Greek‐affiliated sample revealed “hazardous” drinking scores, with AUDIT‐C scores exceeding the threshold of alcohol misuse. These measures were significantly correlated with demand indices from both APT conditions, and demand was inversely related to price; however, demand for alcohol was reduced when a nonalcoholic alternative was available. Both age cohorts reported a reduction in BP1 (highest price of nonzero consumption) and an increase in α (rate of change in elasticity), but these changes were significantly greater among underage participants.

Conclusions

Although Greek life‐affiliated students demonstrate high demand for alcohol, the concurrent availability of a nonalcoholic alternative reduces alcohol demand, particularly for underage students. These findings suggest that nonalcoholic options may enhance the effectiveness of increasing alcohol prices to reduce alcohol consumption among students at higher risk for alcohol use.
Chloride intracellular channel 4 (CLIC4) expression profile in the mouse medial prefrontal cortex and its regulation by ethanol
Authors: Bogenpohl James W. , Weston Rory M. , Foreman Taylor N. , Kitchen Kaitlyn E. , Miles Michael F.
Published: November 2021

Background

Chloride intracellular channel 4 (CLIC4) is a multifunctional metamorphic protein for which a growing body of evidence supports a major role in the brain's molecular and behavioral responses to ethanol (EtOH). Although key to understanding the functional biology underlying this role, little is known about the cellular and subcellular expression patterns of CLIC4 in brain and how they are affected by EtOH.

Methods

We used qRT‐PCR to assess Clic4 mRNA expression in the medial prefrontal cortex (mPFC) of C57BL/6J mice in the absence and presence of acute EtOH exposure. Two complementary immunohistochemical techniques were employed to assess the subcellular localization of the CLIC4 protein and its pattern of expression across brain cell types in the mPFC in the absence and presence of acute EtOH.

Results

Through immunohistochemical and stereological techniques, we show that CLIC4 protein is robustly expressed by oligodendrocytes (most abundant), microglia, and astrocytes, with minimal expression in neurons. Following acute EtOH exposure, we observed a rapid increase in Clic4 mRNA expression in female but not male mice and an overall increase in the number of oligodendrocytes and astrocytes expressing the CLIC4 protein.

Conclusions

These findings suggest that Clic4 functions as an early response gene for acute EtOH in brain, which likely underlies its ability to modulate EtOH behavior. Our results also suggest that the role of CLIC4 in the brain's response to EtOH is mediated through oligodendrocytes.
Understanding uncontrolled severe allergic asthma by integration of omic and clinical data
Authors: Delgado‐Dolset María Isabel , Obeso David , Rodríguez‐Coira Juan , Tarin Carlos , Tan Ge , Cumplido José A. , Cabrera Ana , Angulo Santiago , Barbas Coral , Sokolowska Milena , Barber Domingo , Carrillo Teresa , Villaseñor Alma , Escribese María M.
Published: November 2021

Background

Asthma is a complex, multifactorial disease often linked with sensitization to house dust mites (HDM). There is a subset of patients that does not respond to available treatments, who present a higher number of exacerbations and a worse quality of life. To understand the mechanisms of poor asthma control and disease severity, we aim to elucidate the metabolic and immunologic routes underlying this specific phenotype and the associated clinical features.

Methods

Eighty‐seven patients with a clinical history of asthma were recruited and stratified in 4 groups according to their response to treatment: corticosteroid‐controlled (ICS), immunotherapy‐controlled (IT), biologicals‐controlled (BIO) or uncontrolled (UC). Serum samples were analysed by metabolomics and proteomics; and classifiers were built using machine‐learning algorithms.

Results

Metabolomic analysis showed that ICS and UC groups cluster separately from one another and display the highest number of significantly different metabolites among all comparisons. Metabolite identification and pathway enrichment analysis highlighted increased levels of lysophospholipids related to inflammatory pathways in the UC patients. Likewise, 8 proteins were either upregulated (CCL13, ARG1, IL15 and TNFRSF12A) or downregulated (sCD4, CCL19 and IFNγ) in UC patients compared to ICS, suggesting a significant activation of T cells in these patients. Finally, the machine‐learning model built including metabolomic and clinical data was able to classify the patients with an 87.5% accuracy.

Conclusions

UC patients display a unique fingerprint characterized by inflammatory‐related metabolites and proteins, suggesting a pro‐inflammatory environment. Moreover, the integration of clinical and experimental data led to a deeper understanding of the mechanisms underlying UC phenotype.
A prehabilitation programme implemented before robot‐assisted radical prostatectomy improves peri‐operative outcomes and continence recovery
Authors: Rahota Razvan‐George , Salin Ambroise , Gautier Jean‐Romain , Almeras Christophe , Garnault Valérie , Tollon Christophe , Loison Guillaume , Beauval Jean‐Baptiste , Ploussard Guillaume
Published: December 2021

Objectives

To assess the impact of a routine, on‐site, 1‐day prehabilitation (PreHab) programme on peri‐operative and continence recovery after robot‐assisted radical prostatectomy (RARP).

Materials and Methods

All 303 consecutive RARPs performed between March 2018 and February 2020 since the routine implementation of PreHab were included in our study. PreHab was carried out according to the availability of the 1‐day programme before the planned date of surgery (two sessions per month including four patients per session). The PreHab programme was implemented in 165 patients (54.5%). The primary endpoint was continence recovery, strictly defined as no safety pad use at 1 and 6 months. Secondary endpoints were peri‐operative variables (blood loss, operating time, length of stay, transfusion, complications, and readmission rates). Comparisons were made according to whether the PreHab pathway was applied or not (PreHab+ vs PreHab−) in univariable and multivariable models.

Results

The PreHab pathway was implemented for a stable proportion of patients over time (54.5%). The two cohorts were comparable in terms of preoperative and pathological features (P > 0.05). Length of stay was significantly shorter in the PreHab+ group (1.3 vs 1.9 days; P = 0.001). There was a trend towards fewer complications in the PreHab+ group (P = 0.061). Use of the PreHab pathway was independently correlated with higher continence rates at 1 month (37% vs 60%; P < 0.001) and 6 months (67.4% vs 87.3%; P < 0.001), even after controlling for age, body mass index, prostate volume, type of apical reconstruction, nerve‐sparing surgery and lymph node dissection. The main limitation of the study was the absence of randomization.

Conclusions

Our experience demonstrates that the PreHab programme is the major predictor of improved peri‐operative outcomes and continence recovery after RARP, with sustainable benefits 6 months after surgery.
E239K mutation abolishes the suppressive effects of lysine‐specific demethylase 1 on migration and invasion of MCF7 cells
Authors: Zhang Yu , Wu Tong , Zhao Bo , Liu Ziyu , Qian Rui , Zhang Jing , Shi Yueru , Wan Youzhong , Li Zhe , Hu Xin
Published: November 2021

Lysine‐specific demethylase 1 (LSD1) is an important histone demethylase that mediates epithelial to mesenchymal transition (EMT). The E239K mutation of LSD1 was identified in a luminal breast cancer patient from the COSMIC Breast Cancer dataset. To investigate the functional effects of the E239K mutation of LSD1, a stable LSD1 knockdown MCF7 cell line was generated. Rescue with WT LSD1, but not E239K mutated LSD1, suppressed the invasion and migration of the LSD1 knockdown cells, indicating that the E239K mutation abolished the suppressive effects of LSD1 on the invasion and migration of MCF7 cells. Further analysis showed that the E239K mutation abolished LSD1‐mediated invasion and migration of MCF7 cells through downregulation of estrogen receptor α (ERα). Most importantly, the E239K mutation disrupted the interaction between LSD1 and GATA3, which reduced the enrichment of LSD1 at the promoter region of the ERα gene; the reduced enrichment of LSD1 at the promoter region of the ERα gene caused enhanced histone H3K9 methylation, which subsequently suppressed the transcription of the ERα gene. In summary, the E239K mutation abolishes the suppressive function of LSD1 on migration and invasion of breast cancer cells by disrupting the interaction between LSD1 and GATA3.
Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma
Authors: Nakano Tomoyuki , Fujimoto Kenji , Tomiyama Arata , Takahashi Masamichi , Achiha Takamune , Arita Hideyuki , Kawauchi Daisuke , Yasukawa Mami , Masutomi Kenkichi , Kondo Akihide , Narita Yoshitaka , Maehara Taketoshi , Ichimura Koichi
Published: November 2021

Meningioma is the most common intracranial tumor, with generally favorable patient prognosis. However, patients with malignant meningioma typically experience recurrence, undergo multiple surgical resections, and ultimately have a poor prognosis. Thus far, effective chemotherapy for malignant meningiomas has not been established. We recently reported the efficacy of eribulin (Halaven) for glioblastoma with a telomerase reverse transcriptase (TERT) promoter mutation. This study investigated the anti–tumor effect of eribulin against TERT promoter mutation‐harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines, IOMM‐Lee and HKBMM, were used in this study. The strong inhibition of cell proliferation by eribulin via cell cycle arrest was demonstrated through viability assay and flow cytometry. Apoptotic cell death in malignant meningioma cell lines was determined through vital dye assay and immunoblotting. Moreover, a wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. Intraperitoneal administration of eribulin significantly prolonged the survival of orthotopic xenograft mouse models of both malignant meningioma cell lines implanted in the subdural space (P < .0001). Immunohistochemistry confirmed apoptosis in brain tumor tissue treated with eribulin. Overall, these results suggest that eribulin is a potential therapeutic agent for malignant meningiomas.
SUMOylation regulates Rb hyperphosphorylation and inactivation in uveal melanoma
Authors: Meng Fengxi , Yuan Yiqun , Ren Hui , Yue Han , Xu Binbin , Qian Jiang
Published: November 2021

Small ubiquitin‐like modifier (SUMO)ylation is one of the posttranslational modifications and is implicated in many tumor types. Modulation of SUMOylation can affect tumor progression, but the underlying mechanisms remain unclear. Here, we show that, for the first time, in uveal melanoma (UM), the most common intraocular malignancy in adults, global SUMOylation is upregulated and participates in tumor growth. Inhibition of SUMOylation in UM is sufficient to reduce tumor growth both in vitro and in vivo. Furthermore, we found that retinoblastoma protein (Rb) is a target protein and a critical downstream effector of the upregulated SUMOylation activity in UM. Increased SUMOylation of the Rb protein leads to its hyperphosphorylation and inactivation in UM cells, promoting UM cell proliferation. In summary, our results provide novel insight into the mechanism underlying SUMOylation‐regulated tumor growth in UM.
Hardware Adaptive High‐Order Interpolation for Real‐Time Graphics
Authors: Lin D. , Seiler L. , Yuksel C.
Published: November 2021

Interpolation is a core operation that has widespread use in computer graphics. Though higher‐order interpolation provides better quality, linear interpolation is often preferred due to its simplicity, performance, and hardware support.

We present a unified refactoring of quadratic and cubic interpolations as standard linear interpolation plus linear interpolations of higher‐order terms and show how they can be applied to regular grids and (triangular/tetrahedral) simplexes Our formulations can provide significant reduction in computation cost, as compared to typical higher‐order interpolations and prior approaches that utilize existing hardware linear interpolation support to achieve higher‐order interpolation. In addition, our formulation allows approximating the results by dynamically skipping some higher order terms with low weights for further savings in both computation and storage. Thus, higher‐order interpolation can be performed adaptively, as needed.

We also describe how relatively minor modifications to existing GPU hardware could provide hardware support for quadratic and cubic interpolations using our approach for both texture filtering operations and barycentric interpolation.

We present a variety of examples using triangular, rectangular, tetrahedral, and cuboidal interpolations, showing the effectiveness of our higher‐order interpolations in different applications.
A Halfedge Refinement Rule for Parallel Catmull‐Clark Subdivision
Authors: Dupuy J. , Vanhoey K.
Published: November 2021

We show that Catmull‐Clark subdivision induces an invariant one‐to‐four refinement rule for halfedges that reduces to simple algebraic expressions. This has two important consequences. First, it allows to refine the halfedges of the input mesh, which completely describe its topology, concurrently in breadth‐first order. Second, it makes the computation of the vertex points straightforward as the halfedges provide all the information that is needed. We leverage these results to derive a novel parallel implementation of Catmull‐Clark subdivision suitable for the GPU. Our implementation supports non‐quad faces, extraordinary vertices, boundaries and semi‐sharp creases seamlessly. Moreover, we show that its speed scales linearly with the number of processors, and yields state‐of‐the‐art performances on modern GPUs.
Evaluation of the implementation of the sigmoid take‐off landmark in the Netherlands
Authors: Hazen Sanne‐Marije J. A. , Sluckin Tania C. , Horsthuis Karin , Lambregts Doenja M. J. , Beets‐Tan Regina G. H. , Tanis Pieter J. , Kusters Miranda ,   the Dutch Snapshot Research Group
Published: November 2021

Aim

The sigmoid take‐off (STO), the point on imaging where the sigmoid sweeps ventral from the sacrum, was chosen as the definition of the rectum during an international Delphi consensus meeting and has been incorporated into the Dutch guidelines since October 2019. The aim of this study was to evaluate the implementation of this landmark 1 year after the guideline implementation and to perform a quality assessment of the STO training.

Method

Dutch radiologists, surgeons, surgical residents, interns, PhD students and physician assistants were asked to complete a survey and classify 20 tumours on MRI as ‘below’, ‘on’ or ‘above’ the STO. Outcomes were agreement with the expert reference, inter‐rater variability and accuracy before and after the training.

Results

Eighty‐six collaborators participated. Six radiologists (32%) and 11 surgeons (73%) used the STO as the standard landmark to distinguish between rectal and sigmoidal tumours during multidisciplinary meetings. Overall agreement with the expert reference improved from 53% to 70% (p < 0.001) after the training. The positive predictive value for diagnosing rectal tumours was high before and after the training (92% vs. 90%); the negative predictive value for diagnosing sigmoidal tumours improved from 39% to 63%.

Conclusion

Approximately half of the represented hospitals have implemented the new definition of rectal cancer 1 year after the implementation of the Dutch national guidelines. Overall baseline agreement with the expert reference and accuracy for the tumours around the STO was low, but improved significantly after training. These results highlight the added value of training in implementation of radiological landmarks to ensure unambiguous assessment.