bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study in 404,302 individuals identifies 7 significant loci for reaction time variability
Authors: Wootton Olivia , Shadrin Alexey A. , Mohn Christine , Susser Ezra , Ramesar Raj , Gur Ruben C. , Andreassen Ole A. , Stein Dan J. , Dalvie Shareefa
Published: April 2023

Reaction time variability (RTV), reflecting fluctuations in response time on cognitive tasks, has been proposed as an endophenotype for many neuropsychiatric disorders. There have been no large-scale genome wide association studies (GWAS) of RTV and little is known about its genetic underpinnings. Here, we used data from the UK Biobank to conduct a GWAS of RTV in participants of white British ancestry (n= 404,302) as well as a trans-ancestry GWAS meta-analysis (n= 44,873) to assess replication. We found 161 genome-wide significant single nucleotide polymorphisms (SNPs) distributed across 7 genomic loci in our discovery GWAS. Functional annotation of the variants implicated genes involved in synaptic function and neural development. The SNP-based heritability (h2SNP) estimate for RTV was 3%. We investigated genetic correlations between RTV and selected neuropsychological traits using linkage disequilibrium score regression, and found significant correlations with several traits, including a positive correlation with schizophrenia. We assessed the predictive ability of a polygenic score (PGS) for RTV, calculated using PRSice and PRS-CS, and found that the RTV-PGS significantly predicted RTV in independent cohorts, but that the generalizability to other ancestry groups was poor. These results identify genetic underpinnings of RTV, and support the use of RTV as an endophenotype for neurological and psychiatric disorders.
Validation of a polygenic risk score for Frailty in the Lothian Birth Cohort and English Longitudinal Study of Ageing
Authors: Flint J P , Welstead M , Cox S R , Russ T C , Marshall A , Luciano M
Published: April 2023

Frailty is a complex trait. Twin studies and a high-powered Genome Wide Association Study (GWAS) conducted in the UK Biobank have demonstrated a strong genetic basis of frailty. The present study utilized summary statistics from this GWAS to create and test the predictive power of frailty polygenic risk scores (PRS) in two independent samples – the Lothian Birth Cohort 1936 (LBC1936) and the English Longitudinal Study of Ageing (ELSA) aged 67-84 years. Multiple regression models were built to test the predictive power of frailty PRS at five time points. Frailty PRS significantly predicted frailty at all-time points in LBC1936 and ELSA, explaining 2.1% (β= 0.15, 95%CI, 0.085-0.21) and 1.6% (β= 0.14, 95%CI, 0.10-0.17) of the variance, respectively, at age ∼68/∼70 years (p < 0.001). This work demonstrates that frailty PRS can predict frailty in two independent cohorts, particularly at early ages (∼68/∼70). PRS have the potential to be valuable instruments for identifying those at risk for frailty and could be important for controlling for genetic confounders in epidemiological studies.
Exploring the adoption of digital pathology in clinical settings - Insights from a cross-continent study
Authors: Pinto Daniel Gomes , Bychkov Andrey , Tsuyama Naoko , Fukuoka Junya , Eloy Catarina
Published: April 2023

The last seventy years have been characterized by rapid advancements in computer technology, and the healthcare system has not been immune to this trend. However, anatomic pathology has remained largely an analog discipline. In recent years, this has been changing with the growing adoption of digital pathology, partly driven by the potential of computer-aided diagnosis. As part of an international collaboration, we conducted a comprehensive survey to gain a deeper understanding of the status of digital pathology implementation in Europe and Asia. A total of 127 anatomic pathology laboratories participated in the survey, including 75 from Europe and 52 from Asia, with 72 laboratories having established digital pathology workflow and 55 without digital pathology. Laboratories using digital pathology were thoroughly questioned about their implementation strategies and institutional experiences, including details on equipment, storage, integration with laboratory information system, computer-aided diagnosis, and the costs of going digital. The impact of the digital pathology workflow was also evaluated, focusing on turnaround time, specimen traceability, quality control, and overall satisfaction. Laboratories without access to digital pathology were asked to provide insights into their perceptions of the technology, expectations, barriers to adoption, and potential facilitators. Our findings indicate that while digital pathology is still the future for many, it is already the present for some. This decade may be a time when anatomic pathology finally embraces the digital revolution on a large scale.

HIGHLIGHTS

Larger labs adopt digital pathology more

Full digital transition is still rare nowadays

Many initial concerns have not materialized after implementation

Most non-digital laboratories plan to go digital soon
The effects of a dietary supplement on brain function and structure in Junior A ice hockey players: a prospective randomized trial
Authors: Breuer Logan T. , Fickling Shaun D. , Krause David A. , D’Arcy Ryan C.N. , Frizzell Tory O. , Gendron Tania , Stuart Michael J.
Published: April 2023

Background

Neurocognitive impairment linked to head impact exposure in otherwise healthy, non-concussed athletes may be associated with adverse long-term outcomes. The primary purpose of this study was to evaluate whether a dietary supplement, SynaquellTM, supports brain function and structure in male Junior A ice hockey players over the course of a season.

Methods

Players underwent pre-season testing, were randomized into a placebo or dietary supplement group, then were retested after the season. Objective tests included: NeuroCatch®portable evoked potential platform, King-Devick Test of rapid number naming, and blood biomarker assay for neurofilament light chain (NfL).

Results

Multivariate analysis revealed significant differences in neurocognitive changes between groups from pre to postseason after controlling for covariates related to head impact exposure. Post-hoc tests showed significant within-subject differences between groups from pre- to post-season in both N100 latency (p = 0.005) and King-Devick score (p = 0.043). Univariate tests of the NeuroCatch results replicated prior findings of a N400 amplitude decrease (p = 0.017) and N100 latency increase (p = 0.049) in the placebo group, but not in the dietary supplement group.

Conclusions

This prospective, randomized trial showed that, compared to the placebo group, a multi-ingredient dietary supplement significantly affected objective measures of brain function and structure in Junior A ice hockey players from pre- to post-season. Further investigation into the effects of dietary supplementation on the contact athlete’s brain is warranted.
Chemo-phosphoproteomic profiling with ATR inhibitors berzosertib and gartisertib uncovers new biomarkers and DNA damage response regulators
Authors: Jadav Rathan , Weiland Florian , Noordermeer Sylvie M. , Carroll Thomas , Gao Yuandi , Wang Jianming , Zhou Houjiang , Lamoliatte Frederic , Muñoz Ivan , Toth Rachel , Macartney Thomas , Brown Fiona , Hastie C. James , Alabert Constance , van Attikum Haico , Zenke Frank , Masson Jean-Yves , Rouse John
Published: April 2023

The ATR kinase protects cells against DNA damage and replication stress and represents a promising anti-cancer drug target. The ATR inhibitors (ATRi) berzosertib and gartisertib are in clinical trials for treatment of advanced solid tumours as monotherapy or in combination with genotoxic agents. However, the pharmacodynamic ATR biomarker phospho-CHK1 has shown limited sensitivity in for quantitative assessment of ATR activity in clinical trials. Therefore, better biomarkers are needed, and with this in mind we carried out quantitative phospho-proteomic screening for ATR biomarkers that are highly sensitive to berzosertib and gartisertib. Screening identified novel ATR-dependent targets in three broad classes: i) targets whose phosphorylation is highly sensitive to ATRi; ii) novel targets with known genome maintenance roles; iii) novel targets whose cellular roles are unclear, including SCAF1. We show that SCAF1 interacts with RNAPII in a phospho-dependent manner and suppresses homologous recombination in cells lacking theBRCA1tumour suppressor. Taken together these data reveal potential new ATR biomarkers and new genome maintenance factors.
A hybrid CNN-Random Forest algorithm for bacterial spore segmentation and classification in TEM images
Authors: Qamar Saqib , Öberg Rasmus , Malyshev Dmitry , Andersson Magnus
Published: April 2023

We present a new approach to segment and classify bacterial spore layers from Transmission Electron Microscopy (TEM) images using a hybrid Convolutional Neural Network (CNN) and Random Forest (RF) classifier algorithm. This approach utilizes deep learning, with the CNN extracting features from images, and the RF classifier using those features for classification. The proposed model achieved 73% accuracy, 64% precision, 46% sensitivity, and 47% F1-score with test data. Compared to other classifiers such as AdaBoost, XGBoost, and SVM, our proposed model demonstrates greater robustness and higher generalization ability for non-linear segmentation. Our model is also able to identify spores with a damaged core as verified using TEMs of chemically exposed spores. Therefore, the proposed method will be valuable for identifying and characterizing spore features in TEM images, reducing labor-intensive work as well as human bias.
A dirofilariasis mouse model for heartworm preclinical research
Authors: Marriott A E , Dagley J L , Hegde S , Steven A , Fricks C , DiCosty U , Mansour A , Campbell E J , Wilson C M , Gusovsky F , Ward S A , Hong W D , O’Neill P , Moorhead A , McCall S , McCall J W , Taylor M J , Turner J D
Published: April 2023

Use of experimental cats and dogs in veterinary heartworm preclinical drug research is increasing. As a potential alternative primaryin vivoheartworm preventative drug screen, we assessed lymphopenic mice with ablation of the interleukin-2/7 common gamma chain (γc) as susceptible to the larval development phase ofD. immitis. Non-obese diabetic (NOD) Severe Combined ImmunoDeficient (SCID)γc-/-(NSG / NXG) mice consistently yielded viableD. immitislarvae at 2-4 weeks post-infection across multiple experiments, different batches of infectious larvae inoculates, different isolates ofD. immitisand at independent laboratories. Mice did not display any overt clinical signs associated with infection up to 4 weeks. Developing larvae were found in subcutaneous and muscle fascia tissues, the natural site of this stage of heartworm in dogs. Larvae retrieved from NSG / NXG mice were mid-L4 stage of development. Compared with 14-dayin vitropropagated larvae,in vivoderived L4 were significantly larger and contained expandedWolbachiaendobacteria titres, determined by QPCR and Fluorescentin situHybridisation (FISH). We established anex vivo6-day L4 paralytic screening system against nematodicidal agents (moxidectin, levamisole) which highlighted discrepancies in relative drug sensitivities in comparison within vitroreared L4D. immitis.We demonstrated effective depletion ofWolbachiaby 70-90% inD. immitisL4 following 2-7 day oralin vivoexposures of NSG / NXG infected mice with doxycycline or the rapid-acting investigational anti-Wolbachiadrug, AWZ1066S. We validated the NSG / NXG mouse model as a filaricide drug screen byin vivotreatments with single injections of moxidectin, which mediated 60-88% reduction in L4 larvae at 14-28 days. Future adoption of the mouse model as a first-line efficacy screen will benefit end-user laboratories conducting research and development of novel heartworm preventatives via increased access, rapid turnaround and reduced costs whilst simultaneously decreasing need for experimental cat or dog use.
Antimicrobial resistance level and conjugation permissiveness shape plasmid distribution in clinical enterobacteria
Authors: Alonso-del Valle Aida , Toribio-Celestino Laura , Quirant Anna , Tardio Pi Carles , DelaFuente Javier , Canton Rafael , Rocha Eduardo , Ubeda Carles , Peña-Miller Rafael , San Millan Alvaro
Published: April 2023

Conjugative plasmids play a key role in the dissemination of antimicrobial resistance (AMR) genes across bacterial pathogens. AMR plasmids are widespread in clinical settings, but their distribution is not random, and certain associations between plasmids and bacterial clones are particularly successful. For example, the globally spread carbapenem resistance plasmid pOXA-48 can use a wide range of enterobacterial species as hosts, but it is usually associated with a small number of specificKlebsiella pneumoniaeclones. These successful associations represent an important threat for hospitalized patients. However, knowledge remains limited about the factors determining AMR plasmid distribution in clinically relevant bacteria. Here, we combinedin vitroandin vivoexperimental approaches to analyze pOXA-48-associated AMR levels and conjugation dynamics in a collection of wild type enterobacterial strains isolated from hospitalized patients. Our results reveal significant variability in these traits across different bacterial hosts, withKlebsiellaspp. strains showing higher pOXA-48-mediated AMR and conjugation frequencies thanEscherichia colistrains. Using experimentally determined parameters, we developed a simple mathematical model to interrogate the contribution of AMR levels and conjugation permissiveness to plasmid distribution in bacterial communities. The simulations revealed that a small subset of clones, combining high AMR levels and conjugation permissiveness, play a critical role in stabilizing the plasmid in different polyclonal microbial communities. These results help to explain the preferential association of plasmid pOXA-48 withK. pneumoniaeclones in clinical settings. More generally, our study reveals that species- and strain-specific variability in plasmid-associated phenotypes shape AMR evolution in clinically relevant bacterial communities.

Significance statement

Conjugative plasmids disseminate AMR genes across bacterial pathogens. Understanding the rules governing plasmid dynamics in bacterial communities is therefore crucial to controlling the global AMR crisis. In this study, we analyzed the dynamics of an AMR plasmid of great clinical relevance, pOXA-48, in a collection of wild type bacteria recovered from hospitalized patients. We reported a high degree of variability in two key plasmid-associated phenotypes, AMR level and conjugation ability, across the collection of clinical bacteria. Using simulations based on the experimental results, we studied how successful associations between AMR plasmids and clinical strains can arise in bacterial communities. Our results revealed that accounting for variability in plasmid-associated phenotypes help to understand the evolution of AMR in clinical settings.
Cross-species communication viaagrcontrols phage susceptibility inStaphylococcus aureus
Authors: Yang Jingxian , Bowring Janine Zara , Krusche Janes , Bejder Benjamin Svejdal , Silva Stephanie Fulaz , Bojer Martin Saxtorph , Grunert Tom , Peschel Andreas , Ingmer Hanne
Published: April 2023

Bacteria and their viruses (phages) use quorum sensing (QS) systems to coordinate group behavior. InStaphylococcus aureus, QS plays a critical role in the transition from colonization to infection and involves the accumulation of auto-inducing peptides (AIPs). Humans and animals are also colonized by non-aureus staphylococci (NAS) that produce AIPs, many of which inhibitS. aureusQS. We found that QS induction is necessary forS. aureussusceptibility to the lytic phage, Stab20 and that in mixed communities with NAS producing inhibitory AIPs,S. aureusis protected from phage infection. The primary phage receptors inS. aureusare wall teichoic acids (WTA) substituted with α- and/or β-linked N- acetylglucosamine (GlcNAc). We show that QS induction reduces α-GlcNAc substitutions and enables Stab20 infection through binding to β-glycosylated WTA. However, in the presence of inhibitory AIPs or during co-culture with NAS, QS induction and Stab20 infection are impeded. Our results highlight how cross-species communication can significantly impact bacterial susceptibility to phages and may explain occasional failures observed when phages are used as antimicrobials in for example phage therapy.
IS1-related large-scale deletion of chromosomal regions harbouring oxygen-insensitive nitroreductase genenfsBcauses nitrofurantoin heteroresistance inEscherichia coli
Authors: Wan Yu , Sabnis Akshay , Mumin Zaynab , Potterill Isabelle , Jauneikaite Elita , Brown Colin S. , Ellington Matthew J. , Edwards Andrew , Sriskandan Shiranee
Published: April 2023

Nitrofurantoin is a broad-spectrum first-line antimicrobial used for managing uncomplicated urinary tract infection. Loss-of-function mutations in chromosomal genesnfsA, nfsB, andribEofEscherichia coliare known to reduce nitrofurantoin susceptibility. Here, we report monoclonal nitrofurantoin heteroresistance inE. coliand a novel genetic mechanism associated with this phenomenon.

Subpopulations with reduced nitrofurantoin susceptibility in cultures of twoE. coliblood strains were identified using population analysis profiling. Four colonies of each strain growing on agar with 0.5×MIC nitrofurantoin were sub-cultured in broth with 0.5×MIC nitrofurantoin (n=2) or without nitrofurantoin (n=2). Moreover, one colony of each strain growing without nitrofurantoin exposure was selected as a reference for genomic comparison. Whole-genome sequencing of all isolates were conducted on Illumina and Nanopore MinION systems.

Both strains had a nitrofurantoin MICs of 64 mg/L. The proportion of cells grown at 0.5×MIC was two and 99 per million, respectively, which is distinct to that of a homogeneously susceptible or resistant isolate. All isolates grown at 0.5×MIC had 11–66 kbp deletions in chromosomal regions harbouringnfsB, and all these deletions were immediately adjacent to IS1-family insertion sequences.

Although this study is limited toE. coliand nitrofurantoin, our findings suggest IS1-associated genetic deletion represents a hitherto unrecognised mechanism of heteroresistance that could compromise infection management and impact conventional antimicrobial susceptibility testing.

Impact statement

Nitrofurantoin is widely used for treating and preventing urinary tract infection. Prevalence of nitrofurantoin resistance generally is low inE. coli. Here, we report nitrofurantoin heteroresistance in twoE. coliblood strains and attribute this phenotype to IS1-associated deletion of chromosomal regions harbouring oxygen-insensitive nitroreductase genenfsB. Our discoveries demonstrate a novel genetic mechanism of heteroresistance and suggest detecting nitrofurantoin heteroresistance inE. coliurinary isolates for improving prescribing.

Data summary

Whole-genome sequencing reads and genome assemblies generated in this study have been deposited under BioProject PRJEB58678 in the European Nucleotide Archive (ENA). Accession numbers are listed in Supplementary Table 1. Previously generated Illumina whole-genome sequencing reads of parental isolates EC0026B and EC0880B are available under ENA accessions ERR3142418 and ERR3142524, respectively.
Assessing Brain Involvement in Fabry Disease with Deep Learning and the Brain-Age Paradigm
Authors: Montella Alfredo , Tranfa Mario , Scaravilli Alessandra , Barkhof Frederik , Brunetti Arturo , Cole James , Gravina Michela , Marrone Stefano , Riccio Daniele , Riccio Eleonora , Sansone Carlo , Spinelli Letizia , Petracca Maria , Pisani Antonio , Cocozza Sirio , Pontillo Giuseppe
Published: April 2023

Background

While neurological manifestations are core features of Fabry disease (FD), quantitative neuroimaging biomarkers allowing to measure brain involvement are lacking. We used deep learning and the brain-age paradigm to assess whether FD patients’ brains appear older than normal and to validate brain-predicted age difference (brain-PAD) as a possible disease severity biomarker.

Methods

MRI scans of FD patients and healthy controls (HC) from a single Institution were retrospectively studied. The Fabry stabilization index (FASTEX) was recorded as a measure of disease severity. Using minimally preprocessed 3D T1-weighted brain scans of healthy subjects from 8 publicly available sources (N=2160; mean age=33y[range 4-86]), we trained a model predicting chronological age based on a DenseNet architecture and used it to generate brain-age predictions in the internal cohort. Within a linear modeling framework, brain-PAD was tested for age/sex-adjusted associations with diagnostic group (FD vs HC), FASTEX score, and both global and voxel-level neuroimaging measures.

Results

We studied 52 FD patients (40.6±12.6y; 28F) and 58 HC (38.4±13.4y; 28F). The brain-age model achieved accurate out-of-sample performance (mean absolute error=4.01y, R2=0.90). FD patients had significantly higher brain-PAD than HC (estimated marginal means: 3.1vs-0.1, p=0.01). Brain-PAD was associated with FASTEX score (B=0.10, p=0.02), brain parenchymal fraction (B=-153.50, p=0.001), white matter hyperintensities load (B=0.85, p=0.01), and tissue volume reduction throughout the brain.

Conclusions

We demonstrated that FD patients’ brains appear older than normal. Brain-PAD correlates with FD-related multi-organ damage and is influenced by both global brain volume and white matter hyperintensities, offering a comprehensive biomarker of (neurological) disease severity.

Summary Statement

Using deep learning and the brain-age paradigm, we found that Fabry disease is associated with older-appearing brains. The gap between brain-predicted and chronological age correlates with multi-organ disease severity, offering a novel quantitative neuroimaging biomarker.

Key Points

Patients with Fabry disease show significantly higher brain-predicted age difference values compared to healthy controls (estimated marginal means: 3.1 vs -0.1, p=0.01).

Brain-predicted age difference correlates with multi-organ disease severity and is associated with brain parenchymal fraction, white matter hyperintensities load, and tissue volume throughout the brain.

Brain-predicted age difference might represent a sensitive quantitative biomarker of brain involvement in Fabry disease, with potentially relevant implications for patient stratification and treatment response monitoring.
From trash to cash: the effect of product construal and benefit appeals on consumer evaluations of rescued meals
Authors: de Visser-Amundson Anna , Kleijnen Mirella , Aydinli Aylin
Published: April 2023

Purpose

Hospitality companies increasingly sell their unsold, or so-called rescued meals, on food waste reduction applications (e.g. Too Good To Go [TGTG]). The purpose of this research is to explore the influence of product construal and benefit appeals on consumer evaluations.

Design/methodology/approach

Study 1 (N = 277 participants) is an online experiment with a 2 × 3 between subject design analyzed using ANOVA and planned contrast analysis. Study 2 is a 2 × 2 field experiment (N = 147 sold rescued food boxes) using chi-square tests for the main analysis.

Findings

This study finds that an abstract product description (e.g. a magic box with an opaque content) matched with an environmental benefit appeal renders significantly higher consumer evaluations in comparison to when the same product is paired with financial benefits. In contrast, a concrete product presentation featuring financial benefits as opposed to environmental benefits increases consumer purchase intentions and willingness to pay.

Research limitations/implications

We empirically show how the interaction and congruency between product construal and benefit appeals affect evaluations in a last-minute purchase context.

Originality/value

To the best of the authors’ knowledge, this is the first study to look at the interactive effect between product construal and benefit appeals in a food waste and technology context.
Investigating pension choice factors among the faculty of public sector universities in Pakistan
Authors: Wahab Muhammad , Khan Muhammad Aamir , Siddique Muhammad , Hasan Fakhrul
Published: April 2023

Purpose

This research designed, optimized and tested a context-specific scale to evaluate public sector employees' pension choices.

Design/methodology/approach

The authors developed the scale using a comprehensive process of interviews and focus groups with experts across academia and finance. The authors used the refined scale to collect data from 564 faculty members in public sector universities following a multistage systematic cluster sampling technique. The findings revealed diversity in choice across different socio-economic and demographic variables.

Findings

The results revealed that items related to the defined benefit pension system explain most of the data variance and are preferred widely. This is followed by a preference for monetizing pension benefits and a defined contribution system. These findings indicated the need for flexible pension plans.

Practical implications

Therefore, the progressive movement towards monetization and the shift from defined benefit to a defined contribution pension system due to economic pressures must be accurately calculated and introduced where it is suitable.

Originality/value

Although the theory of introducing a defined contribution pension system and monetization system is appealing, its practical implementation may not be encouraging for all employees.
Consumer animosity: the mitigating effect of perceived brand globalness
Authors: Mandler Timo , Bartsch Fabian , Krüger Tinka , Kim Kyung Ae , Han C. Min
Published: April 2023

Purpose

This research investigates if perceived brand globalness (PBG) can help mitigate the adverse effects of consumer animosity on brand evaluations and purchase intentions.

Design/methodology/approach

The authors analyze survey data from Chinese consumers (N = 395) and South Korean consumers (N = 420) using multi-group structural equation modeling. In both countries, the authors use Japanese products as stimuli, ensuring high comparability levels between the studies.

Findings

The authors empirically demonstrate that PBG can mitigate the negative consequences of consumer animosity by weakening the spillover effect between product–country image and brand evaluations. However, the authors find the mitigating effect of PBG only in China, not in South Korea.

Originality/value

By highlighting PBG's role as an actionable moderator that firms can manipulate to attenuate the negative consequences of consumer animosity toward a brand's country of origin, this work adds to the much-needed debate about how animosity-induced effects can be mitigated in times of global conflicts and tensions.
Origin, development and evolution: the space construction and cultural motivations of Shi Gandang temple in Macau
Authors: Huang Linsheng , Chen Yashan , Chen Yile
Published: April 2023

Purpose

This study aims to explore the relationship between folk religious place-making and the development of urban public spaces and summarize its influence on community network construction and daily behavior to discover the authentic practices and role of folk faith culture in social space.

Design/methodology/approach

Taking Macau's Shi Gandang Temple and its belief culture as an example, on-site research, historical evidence and interviews were used to elaborate and analyze the processes of place-making, social functions, management mechanisms and folk culture to establish a new perception of folk religious place-making in contemporary urban spaces.

Findings

The article argues that the culture of folk beliefs profoundly influences urban spaces and the social management system of Macau and has a positive significance in building the local community and geopolitical relations. In addition, it suggests that the participation of folk religious places in local practices is important as key nodes and emotional hubs of local networks, reconciling conflicts between communities of different backgrounds and driving urban spaces toward diversity while forming a positive interaction and friendly cooperation between regional development and self-contained management mechanisms, governance models and cultural orientations.

Originality/value

This study takes an architectural and anthropological perspective of the impact of faith on urban spaces and local governance, using the Shi Gandang Temple in Macau as an example, to complement related studies.
The nonlinear effect of executive compensation on corporate social responsibility performance
Authors: Pareek Ritu , Sahu Tarak Nath
Published: April 2023

Purpose

Taking cues from the fact that there remains a dearth in the establishment of theoretical and empirical relationship between executive compensation and corporate social responsibility (CSR) performance of the firms, this study attempts to explore the non-linear relationship between the said variables.

Design/methodology/approach

The study utilizes a strongly balanced panel data set of 179 non-financial National Stock Exchange (NSE) 500 listed firms for the study period of 2015–2020. The study further employs both static as well as Arellano-Bond dynamic panel model under generalized method of moments (GMM) framework to establish the relationship between executive compensation and CSR performance of the sampled firms.

Findings

The study acknowledges an inverted U-shaped relationship between executive compensation and environmental, social and governance (ESG) score of the firms. According to the robust estimator, an increase in the level of executive compensation is said to affect CSR performance positively until it surpasses a threshold level of 18.7 percent.

Practical implications

One of the major takeaways that the study provides for the corporate policymakers is that the level of compensation can only motivate the executives to take up socially responsible work up to a certain level surpassing which the executives becomes resistant towards any benefits provided by the CSR performance and get inclined towards economical performances of the firm. At the later stage, the economical expansionary investment benefits overweigh the personal career benefit gained by the executives from the CSR performances of the firm.

Originality/value

The nonlinearity relationship between executive compensation and CSR performance and the threshold level providing the two-fold effect of compensation on the CSR performance of the firms attempted by this study is a rare attempt in an emerging economy like India.
The impact of institutions' quality and information availability on capital inflows volatility in selected MENA countries
Authors: Al Sayed Ola , Omar Noha Sami , Khaled Abdelmoneam
Published: April 2023

Purpose

This paper aims to discuss the main characteristics of the Middle East North Africa (MENA) region's capital inflows volatility. It also examines the effect of institutional quality and information availability on capital inflows volatility in selected MENA countries (Bahrain, Egypt, Israel, Jordan, Kuwait, Libya, Morocco, Oman, Saudi Arabia and Tunisia) in the period 1996–2017.

Design/methodology/approach

The study's assessments are based on the International Country Risk Guide (ICRG) and globalization indices. It also employs an updated data set of balance of payments indicators released by the International Monetary Fund. Moreover, the study uses econometric panel modeling of random effect model, with Driscoll-Kraay robust standard error, to analyze the relationship between capital inflows volatility, institutional quality and information availability.

Findings

The paper finds that both institutional quality and information availability are in an inverse relationship with the total capital inflows volatility in the MENA region. However, the findings vary across the different components of total capital inflows. For example, the volatility of foreign direct investment (FDI) declines, like total capital flows, as the two factors improve. However, the volatility of foreign portfolio investment (FPI) is negatively related to institutional quality but does not have any significant relationship with information availability. While the volatility of foreign other investments (FOI) decreases with the availability of information, but does not have any significant relationship with institutional quality.

Originality/value

This paper expands the limited literature regarding the determinants of capital inflows volatility. Furthermore, it is the first study that investigates the effect of institutional quality and information availability on capital inflows volatility in the MENA region.
Hysterectomy on benign indication and risk of pelvic organ prolapse surgery: A national matched cohort study
Authors: Aagesen Andreas Höier , Klarskov Niels , Gradel Kim Oren , Husby Karen Ruben
Published: April 2023

Introduction

Hysterectomy is a frequently performed gynecological procedure but long‐term effects remain understudied. Pelvic organ prolapse reduces life quality significantly. The lifetime risk of undergoing pelvic organ prolapse surgery is 20% and parity is known to be the largest risk factor. Studies have shown an increased risk of pelvic organ prolapse surgery after hysterectomy; however, few have studied the compartments which are affected and how this association is affected by surgical route and parity.

Material and methods

In this Danish nationwide cohort study, we identified women born in 1947–2000 who underwent hysterectomy during 1977–2018 who were indexed on the day of hysterectomy. We excluded women who immigrated when older than 15 years, who underwent pelvic organ prolapse surgery prior to index, and who were diagnosed with a gynecological cancer prior to or within 30 days of index. Women who underwent hysterectomy were matched 1:5 to references on age and year of hysterectomy. Women were censored at the time of death, emigration, a gynecological cancer diagnosis, radical or unspecified hysterectomy or December 31, 2018, whichever came first. The risk of pelvic organ prolapse surgery after hysterectomy was computed using Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, calendar year, parity, income and educational level.

Results

We included 80 444 women who underwent hysterectomy and 396 303 reference women. Women who underwent hysterectomy had a significantly higher risk of undergoing pelvic organ prolapse surgery: HRadjusted 1.4 (95% CI 1.3–1.5). In particular, the risk of a posterior compartment prolapse operation was increased: HRadjusted 2.2 (95% CI 2.0–2.3). The risk of prolapse surgery increased with increased parity and by an additional 40% after hysterectomy. Cesarean sections did not seem to increase the risk of prolapse surgery.

Conclusions

This study shows that hysterectomy, regardless of surgical route, leads to an increased risk of pelvic organ prolapse surgery, especially in the posterior compartment. The risk of prolapse surgery increased with the number of vaginal births, and not cesarean sections. Women should be thoroughly informed about the risk of pelvic organ prolapse and other treatment options should be considered before choosing hysterectomy to treat benign gynecological diseases –particularly women who have had numerous vaginal births.
The prevalence and burden of Rome IV faecal incontinence in ulcerative colitis: A cross‐sectional study
Authors: Vasant Dipesh H. , Nigam Gaurav B. , Bate Sebastian , Hamdy Shaheen , Limdi Jimmy K.
Published: April 2023

Background

Despite advances in ulcerative colitis (UC) therapies, a relatively undefined proportion of patients experience faecal incontinence (FI) in the absence of active inflammation. For this group, there remains a significant unmet need with a limited evidence base.

Aims

We aimed to estimate the prevalence and impact of FI in UC.

Methods

In a prospective cross‐sectional study, patients with UC completed a series of validated questionnaires, including Rome IV FI criteria, an inflammatory bowel disease (IBD)‐specific FI questionnaire (ICIQ‐IBD), Hospital Anxiety and Depression Scale and IBD‐Control. UC remission was defined as faecal calprotectin (FCP) ≤250 μg/g, or IBD‐control 8 score ≥13 and IBD‐Control‐VAS ≥ 85.

Results

Of 255 patients with UC, overall, 20.4% fulfilled Rome IV criteria for FI. Rome IV FI prevalence did not differ between active and quiescent UC regardless of whether disease activity was defined by IBD‐Control scores ± FCP (p = 0.25), or objectively with FCP thresholds of 250 μg/g (p = 0.86) and 100 μg/g (p = 0.95). Most patients (75.2%) reported FI when in ‘remission’ and during ‘relapse’ (90.6%) according to ICIQ‐IBD. Those who reported FI according to both ICIQ‐IBD and Rome IV definitions had higher anxiety, depression and worse quality‐of‐life (QoL) scores (p < 0.05). In those with Rome IV FI, there was a strong correlation between FI symptom severity and impaired QoL (r = 0.809, p < 0.001).

Conclusions

The prevalence of FI in UC is high, even in remission, and associated with significant psychological distress, symptom burden and impaired QoL. These findings highlight the urgent need for further research and development of evidence‐based treatments for FI in UC.
Patient preference for commonly‐used, head and neck cancer‐specific quality of life questionnaires in the follow‐up setting (Determin): A multi‐centre randomised controlled trial and mixed methods study
Authors: Mehanna Hisham , Carter Ben , Hartley Andrew , Abou‐Foul Ahmad K. , Brooks Jill , Jones June , Fresco Lydia , Moss Laura , Jones Terence M. , Rogers Simon N. , Morton Randall P. ,   And DETERMIN Study Management Group
Published: April 2023

Background

Quality of life (QoL) assessment forms an integral part of modern cancer care and research. The aim of this study is to determine patients' preferences and willingness to complete commonly used head‐and‐neck cancer (HNC) QoL questionnaires (QLQs) in routine follow‐up clinics.

Methods

This is a randomised control trial of 583 subjects from 17 centres during follow‐up after treatment for oral, oropharyngeal or laryngeal cancer. Subjects completed three structured validated questionnaires: EORTC QLQ‐HN35; FACT‐HN and UW‐QOL, and an unstructured patient‐generated list. The order of questionnaire presentation was randomised, and subjects were stratified by disease site and stage. Patients self‐rated the questionnaires they found most helpful to communicate their health concerns to their clinicians.

Results

Of the 558 respondents, 82% (457) found QLQs useful to communicate their health concerns to their clinician (OR = 15.76; 95% CI 10.83–22.94). Patients preferred the structured disease‐specific instruments (OR 8.79; 95% CI 5.99–12.91), while the open list was the most disliked (OR = 4.25; 95% CI 3.04–5.94). There was no difference in preference by treatment modality. More women preferred the FACT‐HN (OR = 3.01, 95% CI 1.05–8.62), and patients under 70 preferred EORTC QLQ‐HN35 (OR = 3.14, 95% CI 1.3–7.59). However, only 55% of patients expressed preference to complete questionnaires routinely at the clinic.

Conclusions

Most patients found QLQs helpful during their follow‐up and 55% supported routine questionnaires in follow‐up clinics. Males and people over 70 years old were the least willing to complete the routine questionnaires and preferred shorter questionnaires (e.g., UW‐QOL). Women preferred FACT‐HN, and younger patients preferred EORTC QLQ‐HN35. Reasons for the reluctance to complete questionnaires require elucidation.
Structure and epitope of a neutralizing monoclonal antibody that targets the stem helix of β coronaviruses
Authors: Deshpande Ashlesha , Schormann Nobert , Piepenbrink Mike S. , Martinez Sobrido Luis , Kobie James J. , Walter Mark R.
Published: April 2023

Monoclonal antibodies that retain neutralizing activity against multiple coronavirus (CoV) lineages and variants of concern (VoC) must be developed to protect against future pandemics. These broadly neutralizing MAbs (BNMAbs) may be used as therapeutics and/or to assist in the rational design of vaccines that induce BNMAbs. 1249A8 is a BNMAb that targets the stem helix (SH) region of CoV spike (S) protein and neutralizes Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) original strain, delta, and omicron VoC, Severe Acute Respiratory Syndrome CoV (SARS‐CoV), and Middle East Respiratory Syndrome CoV (MERS‐CoV). To understand its mechanism of action, the crystal structure of 1249A8 bound to a MERS‐CoV SH peptide was determined at 2.1 Å resolution. BNMAb 1249A8 mimics the SARS‐CoV‐2 S loop residues 743–749, which interacts with the N‐terminal end of the SH helix in the S post‐fusion conformation. The conformation of 1249A8‐bound SH is distinct from the SH conformation observed in the post‐fusion SARS‐CoV‐2 S structure, suggesting 1249A8 disrupts the secondary structure and refolding events required for CoV post‐fusion S to initiate membrane fusion and ultimately infection. This study provides novel insights into the neutralization mechanisms of SH‐targeting CoV BNMAbs that may inform vaccine development and the design of optimal BNMAb therapeutics.
N‐glycosylation mediated folding and quality control in serine proteases of the hepsin family
Authors: Bergeron John J. M. , Thomas David Y.
Published: April 2023

N‐linked glycans are specifically attached to asparagine residues in a N‐X‐S/T motif of secretory pathway glycoproteins. N‐glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein‐folding enzymes and glycosidases of the endoplasmic reticulum (ER). Misfolded glycoproteins are retained in the ER by the same lectin chaperones. The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. The authors deduce that spatial positioning of N‐glycans on one side of a conserved domain of hepsin, known as the scavenger receptor‐rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. If N‐glycosylation is elsewhere on hepsin, then it is misfolded and has a prolonged accumulation with calnexin and BiP. This association coincides with the engagement of stress response pathways that sense glycoprotein misfolding. The topological considerations of N‐glycosylation dissected by Sun et al. may help unravel how key sites of N‐glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control.
Drivers of the microbial metabolic quotient across global grasslands
Authors: Risch A. C. , Zimmermann S. , Schütz M. , Borer E. T. , Broadbent A. A. D. , Caldeira M. C. , Davies K. F. , Eisenhauer N. , Eskelinen A. , Fay P. A. , Hagedorn F. , Knops J. M. H. , Lembrechts J. J. , MacDougall A. S. , McCulley R. L. , Melbourne B. A. , Moore J. L. , Power S. A. , Seabloom E. W. , Silviera M. L. , Virtanen R. , Yahdjian L. , Ochoa‐Hueso R.
Published: April 2023

Aim

The microbial metabolic quotient (MMQ; mg CO2‐C/mg MBC/h), defined as the amount of microbial CO2 respired (MR; mg CO2‐C/kg soil/h) per unit of microbial biomass C (MBC; mg C/kg soil), is a key parameter for understanding the microbial regulation of the carbon (C) cycle, including soil C sequestration. Here, we experimentally tested hypotheses about the individual and interactive effects of multiple nutrient addition (nitrogen + phosphorus + potassium + micronutrients) and herbivore exclusion on MR, MBC and MMQ across 23 sites (five continents). Our sites encompassed a wide range of edaphoclimatic conditions; thus, we assessed which edaphoclimatic variables affected MMQ the most and how they interacted with our treatments.

Location

Australia, Asia, Europe, North/South America.

Time period

2015–2016.

Major taxa

Soil microbes.

Methods

Soils were collected from plots with established experimental treatments. MR was assessed in a 5‐week laboratory incubation without glucose addition, MBC via substrate‐induced respiration. MMQ was calculated as MR/MBC and corrected for soil temperatures (MMQsoil). Using linear mixed effects models (LMMs) and structural equation models (SEMs), we analysed how edaphoclimatic characteristics and treatments interactively affected MMQsoil.

Results

MMQsoil was higher in locations with higher mean annual temperature, lower water holding capacity and lower soil organic C concentration, but did not respond to our treatments across sites as neither MR nor MBC changed. We attributed this relative homeostasis to our treatments to the modulating influence of edaphoclimatic variables. For example, herbivore exclusion, regardless of fertilization, led to greater MMQsoil only at sites with lower soil organic C (< 1.7%).

Main conclusions

Our results pinpoint the main variables related to MMQsoil across grasslands and emphasize the importance of the local edaphoclimatic conditions in controlling the response of the C cycle to anthropogenic stressors. By testing hypotheses about MMQsoil across global edaphoclimatic gradients, this work also helps to align the conflicting results of prior studies.
Participation in health and frailty check‐ups predicted functional outcomes and mortality in older adults in Japan
Authors: Ogita Mihoko , Okura Mika , Katayose Ryo , Miyamatsu Naomi , Arai Hidenori
Published: April 2023

Aim

This study aimed to examine the association between participation in health and frailty check‐ups and functional outcomes and mortality, controlling for physical and cognitive function, or self‐rated health among Japanese community‐dwelling older adults.

Methods

A cohort of 5093 participants aged ≥65 years (not disabled or institutionalized), completed the baseline survey in April 2013. Functional outcomes and mortality served as follow‐up data from April 2013 to March 2018. However, the data did not include events, such as certified cases for long‐term care and death for 12 months from the start of follow‐up. We collated data on the use of the annual health check system in 2012 and frailty check‐ups using the postal Kihon Checklist in 2013. Cox proportional hazards regression models were used to determine the association between participation in the check‐ups, and functional outcomes and mortality, adjusting for potential confounders.

Results

Long‐term care and mortality risks were significantly lower among those aged <75 years who used health screening than among those who did not, despite adjusting for confounding factors (hazard ratios: 2.1–3.5). In those aged ≥75 years, the risk for long‐term care was lower in individuals participating in both health and frailty check‐ups and in those who participated in the frailty check‐ups only, than in those who did not participate.

Conclusions

The association between participation in health and frailty check‐ups and adverse health outcomes differed among the age groups, indicating the potential benefit of health and frailty check‐ups in older adults. Geriatr Gerontol Int 2023; 23: 348–354.