bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Simulation Modeling to Analyze the Impact of Whole Genome Sequencing National Implementation Scenarios in Lung cancer on Time-to-Treatment, Costs and Patient Demand
Authors: van de Ven Michiel , Koffijberg Hendrik , Retèl Valesca P.J. , van Harten Wim H. , IJzerman Maarten J.
Published: November 2023

Background

Although Whole Genome Sequencing (WGS) is increasingly proposed to unravel molecular origins of advanced cancers, it is less clear if and how WGS should be routinely offered in the health service. The objective of this study is to investigate how the cost per patient and time-to-treatment is affected if WGS were implemented in the national health system and how these outcomes differ among subgroups of patients with lung cancer. This first-ever study used health systems simulation modeling to analyze implementation scenarios ensuring sustainable access to cancer treatment.

Methods

A base case and three scenarios (varying stage of disease and hospitals offering WGS) the optimal placement of WGS in the diagnostic pathway was simulated using a dynamic simulation model. The model simulated lung cancer patients undergoing molecular diagnostic procedures in one or multiple hospitals. The model also included patient and healthcare provider heterogeneity as well as referral patterns of lung cancer (LC) patients using patient-level data obtained from the Netherlands Cancer Registry. Model outcomes were the time-to-treatment, total diagnostic cost, and the demand for WGS sequencing capacity including the expertise of a molecular tumor board.

Results

The time-to-treatment ranged between 20-46 days for all four scenarios considered. The cost of molecular diagnostic testing per patient ranged from €621 in the base case to €1930 in the scenario where all LC patients (stage I-IV) receive upfront WGS. Compared to the base case, upfront testing using WGS in all LC patients led to a 33% reduction in the time-to-treatment, a 210% increase in the cost per patient and a six-fold increase in total diagnostic costs.

Conclusions

This first-ever study investigating implementation scenario’s demonstrated that upfront WGS for all lung cancer patients can reduce the time to treatment yet at a higher cost. However, upfront WGS also reduces diagnostic pathway complexity, which may improve care planning and treatment efficiency. The model is versatile in its approach to study the impact of price discounts or the amount of actionable targets tested for and further analysis showed discounts on consumables up to 50% imply WGS would the preferred strategy.
Measures of retention in HIV care: A protocol for a mixed methods study
Authors: Rehman Nadia , Garcia Michael Cristian , Jones Aaron , Ma Jinhui , Mertz Dominik , Mbuagbaw Lawrence
Published: November 2023

Introduction

Retention in HIV care is necessary to achieve adherence to antiretroviral therapy, viral load suppression, and optimal health outcomes. There is no standard definition for retention in HIV care, which compromises consistent and reliable reporting and comparison of retention across facilities, jurisdictions, and studies.

Objective

The objective of this study is to explore how stakeholders involved in HIV care define retention in HIV care and their preferences on measuring retention.

Methods

We will use an exploratory sequential mixed methods design involving HIV stakeholder groups such as people living with HIV, people involved in providing care for PLHIV, and people involved in decision-making about PLHIV. In the qualitative phase of the study, we with conduct 20-25 in-depth interviews to collect perspectives of HIV stakeholders on using their preferred retention measures. The interview guide has being provided as an online Supplementary Appendix 1.The findings from the qualitative phase will inform the development of survey items for the quantitative phase. Survey participants (n=385) will be invited to rate the importance of each approach to measuring retention on a seven-point Likert scale. We will merge the findings from the qualitative and quantitative findings phase to inform a consensus-building framework for a standard definition of retention in care.

Ethical Issues and Dissemination

This study has received ethics approval from the Hamilton Integrated Research Ethics Board. The findings will be disseminated through peer-reviewed publications, conference presentations, and among stakeholder groups.

Limitations

1. This study has limitation, we won’t be able to arrive at a standard definition, a Delphi technique amongst the stakeholders will be utilized using the framework to reach a consensus globally accepted definition.
Transitions of care between jail-based medications for opioid use disorder and ongoing treatment in the community: A retrospective cohort study
Authors: Krawczyk Noa , Lim Sungwoo , Cherian Teena , Goldfeld Keith S. , Katyal Monica , Rivera Bianca D. , McDonald Ryan , Khan Maria , Wiewel Ellen , Braunstein Sarah , Murphy Sean M. , Jalali Ali , Jeng Philip J. , Kutscher Eric , Khatri Utsha G. , Rosner Zachary , Vail William L. , MacDonald Ross , Lee Joshua D.
Published: November 2023

Background and Aims

Offering medications for opioid use disorder (MOUD) in carceral settings can significantly reduce overdose risk. However, it is unknown whether and to what extent individuals in U.S. jail settings continue MOUD once they leave incarceration, and what factors influence treatment continuity.

Design

Retrospective cohort study of linked jail-based electronic health records and community OUD treatment claims.

Setting

New York City Jail

Participants

Incarcerations of individuals with OUD discharged from jail to the community between May 1, 2011 and December 31, 2017

Comparators

Receiving vs. not receiving MOUD (methadone or buprenorphine) at the time of release from jail

Measurements

We measured continuity of community-based MOUD treatment within one month of release, among those with and without MOUD during release from jail. We tested for effect modification based on MOUD receipt prior to incarceration and assessed factors associated with treatment discontinuation upon re-entry.

Findings

Of 28,298 eligible incarcerations, 52.8% received MOUD at release. 30% of incarcerations with MOUD had a community-based MOUD claim within 30 days of release, compared to 7% of incarcerations without MOUD (Risk Ratio: 2.62 (2.44-2.82)). Most (69%) of those with MOUD claims prior to incarceration who received in-jail MOUD continued MOUD in the community, compared to only 9% of those without prior MOUD. Among incarcerations with MOUD at release, those who were younger, Non-Hispanic Black and with no history of MOUD treatment were less likely to continue treatment following release.

Conclusions

MOUD maintenance in jail is strongly associated with MOUD continuity in the community upon release. Still, findings highlight a continued gap in MOUD upon-reentry, especially among those who initiate MOUD in jail. In the wake of worsening overdose deaths and troubling disparities, improving continuty of evidence-based care among this population must be an urgent policy priority.
Inter-phylum circulation of a beta-lactamase - encoding gene: a rare but observable event
Authors: Gschwind Rémi , Petitjean Marie , Fournier Claudine , Lao Julie , Clermont Olivier , Nordmann Patrice , Mellmann Alexander , Denamur Erick , Poirel Laurent , Ruppé Etienne
Published: November 2023

Beta-lactam degradation by beta-lactamases is the most common mechanism of beta-lactam resistance in Gram-negative bacteria. Beta-lactamase encoding genes can be transferred between closely-related bacteria, but spontaneous inter-phylum transfers (between distantly related bacteria) has never been reported. Here, we describe an extended-spectrum beta-lactamase (ESBL)-encoding gene (blaMUN-1) shared between the Peudomonadota and Bacteroidota phyla.

AnEscherichia colistrain was isolated from a patient in Münster (Germany). Its genome was sequenced (Illumina and Nanopore). The ESBL encoding gene was cloned and the corresponding enzyme was characterised. Distribution of the gene among bacteria was studied with BLASTN using RefSeq Genomes databases. Frequency of its closest homolog in the Global Microbial Gene Catalog (GMGC) was also analysed.

TheblaMUN-1gene found in theE. colistrain, encoded for an Ambler subclass A2 beta-lactamase with 82.2% amino acid identity to TLA-1 and it was found to confer an ESBL phenotype.blaMUN-1was found in four copies, two chromosomal copies and two located on a phage-plasmid p0111. Each copy was found on a 7.6kb genomic island associated with mobility.blaMUN-1was found distributed among the Bacteroidales order and inSutterella wardsworthensis(Pseudomonadota). Its closest homolog in the GMGC was found predominantly and frequently in the Human gut sub-catalog (found in 26.8% of the samples).

This is the first reported case of inter-phylum transfer of an ESBL-encoding gene, between the Bacteroidota and Pseudomonadota phyla. While the gene was frequently found in the human gut, inter-phylum transfer was rare, suggesting that inter-phylum barriers are strong but not impassable.
UnderstandingCampylobacter coliisolates from the Vietnamese meat production network; a pilot study
Authors: Lehri Burhan , Navoly Georgina , Corser Abigail , Nashar Fauzy , Willcocks Sam , Ngoc Pham Thi , Wren Brendan W. , Huong Luu Quynh , Stabler Richard A.
Published: November 2023

Changing farming practices and the associated increase in the use of antibiotics are amongst the main drivers shaping the global increase of Campylobacter infections. The effects farming practices have onCampylobacterspecies, need to be studied at the global scale, particularly in emerging middle-income countries, where the demand for low-cost poultry meat is rising. WhileC. jejunicauses the majority of poultry associated diarrhoea,C. colicauses a significant amount of disease but are relatively understudied. In this study we characterised sevenC. colistrains isolated from poultry farms and markets in Hanoi, Vietnam. Comprehensive data sets of bacterial Whole-Genome Sequencing; and phenotypic assays, such as, growth, motility, antimicrobial resistant testing along with virulence testing were performed to reveal the genetic relatedness and pathophysiological characteristics of sevenC. colistrains. Six isolates were classified as multi-drug resistant, with all isolates resistant to ciprofloxacin, nalidixic acid and tetracycline, but susceptible to phenicols. All isolates had similar growth rates, while five were hyper-motile. Lethality of the isolates towards a tractable host-model system, larvae of the greater wax mothGalleria mellonella, often used to determineCampylobactervirulence was demonstrated for the first time forC. coli. Multilocus sequence typing data correlates with North American, European, and Asian isolates from patients suffering from gastroenteritis, emphasising the global spread of these strains. This work demonstrates thatC. coli, with high levels of antimicrobial resistance, is an understudied global threat.

Data summary

GenBank database with accession numbers JAKGTW000000000, JAKGTV000000000, JAKGTS000000000, JAKGTU000000000, JAKGTT000000000, JAKGTR000000000 and CP091310

https://www.ncbi.nlm.nih.gov/nuccore/JAKGTW000000000

https://www.ncbi.nlm.nih.gov/nuccore/JAKGTV000000000

https://www.ncbi.nlm.nih.gov/nuccore/JAKGTS000000000

https://www.ncbi.nlm.nih.gov/nuccore/JAKGTU000000000

https://www.ncbi.nlm.nih.gov/nuccore/JAKGTT000000000

https://www.ncbi.nlm.nih.gov/nuccore/JAKGTR000000000

https://www.ncbi.nlm.nih.gov/nuccore/CP091310.1

The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
Robotic process automation and artificial intelligence capabilities driving digital strategy: a resource-based view
Authors: Moderno Osvaldo Braz dos Santos , Braz Antonio Carlos , Nascimento Paulo Tromboni de Souza
Published: November 2023

Purpose

Research of currently limited literature sees Robotic Process Automation (RPA) as an important tool at the tactical level. However, the literature has not considered its potential contribution to creating competitive advantages. This paper aims to link RPA and Resource-based view (RBV) literature, proposing a conceptual framework boosting RPA research as part of an organizational AI strategy.

Design/methodology/approach

This study applied a Systematic Literature Review (SRL), combining bibliometrics and content analysis. This study also built a new framework based on the updated RBV model that was transformed based on the RPA literature review results.

Findings

By bridging the two bodies of literature on RBV and RPA, this study manages to show the strategic side of the technology. Therefore, this study brought to light the most updated fundamental concepts of complementarity and scale-free fungible resources from RBV theory and AI technologies, applied to the domains of RPA, information systems and information technology (IS/IT) through the development of a new theoretical lens. Also, this study was able to elaborate on a new conceptual framework for AI strategy formulation to help organizations on their journey to AI utilization.

Originality/value

The authors did not find any research that has shown the strategic side of RPA, nor any that has used a theoretical lens based on the RBV theory to show this side. To the best of the author’s knowledge, this study seems to be the first to make the case for RPA's strategic potential.
ESG performance and firms' innovation efficiency: the moderating role of state-owned firms and regional market development
Authors: Wan He , Fu Jialiang , Zhong Xi
Published: November 2023

Purpose

Although the impact of environmental, social and governance (ESG) on firms' innovation has attracted attention, the existing research findings diverge. The authors believe that failure to consider both innovation input and output is an important reason for the divergence of conclusions in the extant literature when discussing the impact of ESG and firm innovation. Thus, based on signaling theory, this study aims to reconcile these divergent findings by examining the impact of ESG performance on firms' innovation efficiency.

Design/methodology/approach

To seek empirical evidence to support the authors’ theoretical view, the authors conduct an empirical test based on the Tobit model using 8 years of data from Chinese listed companies.

Findings

Although ESG performance effectively improves firms' innovation efficiency, the institutional-level signaling environment (including state-owned firms and regional market development) weakens the positive effect of ESG performance on firms' innovation efficiency. Further tests suggest that financing constraints partially mediate the relationship between ESG performance and firms' innovation efficiency.

Originality/value

By systematically revealing whether, how and under what circumstances ESG performance improves firms' innovation advantages, this study bridges the gap in the existing literature and highlights important implications to suggest how firms can better capture the value associated with ESG.
Drivers of disaster planning among African-American households
Authors: Pudlo Jason M. , Ellis William Curtis , McGowen Ernest B.
Published: November 2023

Purpose

The paper seeks to explore the drivers of disaster planning in African-American households. While the paper is exploratory, the authors attempt to dialogue with substantial theoretical and applied research around vulnerability and disaster. Race, ethnicity and vulnerability are issues deeply entangled with American disaster preparedness and response. In this study, the authors hope to illuminate the threads which bind them together and contribute to a more nuanced understanding of the relationship between race, ethnicity, class and preparedness.

Design/methodology/approach

Data for this project come from a disaster planning question placed on the 2020 Collaborative Multiracial Post-Election Survey (CMPS). The authors analyze a split sample of around 5,000 African-American households descriptively and with multinomial logistic regression.

Findings

Disaster planning among African-American households is a product of past experiences, concern about other hazards, social trust and gender identity. These results are similar to other findings within the study of household preparedness and help to advance the understanding of predictors within the African-American community. Key drivers such as income, education level, gender identity, social trust and perceptions of other risks are consistent with previous studies.

Originality/value

This project is the first to examine issues of disaster planning utilizing a national sample of African-American households via the one-of-a-kind 2020 CMPS.
A reduced-order Jacobi spectral collocation method for solving the space-fractional FitzHugh–Nagumo models with application in myocardium
Authors: Abbaszadeh Mostafa , Bagheri Salec AliReza , Kamel Abd Al-Khafaji Shurooq
Published: November 2023

Purpose

The space fractional PDEs (SFPDEs) play an important role in the fractional calculus field. Proposing a high-order, stable and flexible numerical procedure for solving SFPDEs is the main aim of most researchers. This paper devotes to developing a novel spectral algorithm to solve the FitzHugh–Nagumo models with space fractional derivatives.

Design/methodology/approach

The fractional derivative is defined based upon the Riesz derivative. First, a second-order finite difference formulation is used to approximate the time derivative. Then, the Jacobi spectral collocation method is employed to discrete the spatial variables. On the other hand, authors assume that the approximate solution is a linear combination of special polynomials which are obtained from the Jacobi polynomials, and also there exists Riesz fractional derivative based on the Jacobi polynomials. Also, a reduced order plan, such as proper orthogonal decomposition (POD) method, has been utilized.

Findings

A fast high-order numerical method to decrease the elapsed CPU time has been constructed for solving systems of space fractional PDEs.

Originality/value

The spectral collocation method is combined with the POD idea to solve the system of space-fractional PDEs. The numerical results are acceptable and efficient for the main mathematical model.
Oh, the stories we could tell: a conceptual model for building shared entrepreneurial narratives
Authors: Fleck Emma , Pishko Joanna , Verhoeven Betsy
Published: November 2023

Purpose

Prior research has drawn from entrepreneurial practice to conceptualize a variety of discreet narrative types. Research has also demonstrated that narratives are a practical and useful tool for entrepreneurs in many stages of the entrepreneurial process. This paper proposes a new narrative, shared narrative, and a conceptual model for how entrepreneurs might build such a narrative that is strategic in nature.

Design/methodology/approach

First, the authors review the types of narrative and introduce shared narrative as an account that narrativizes both the entrepreneur and relevant stakeholders. Then, integrating theoretical concepts from constitutive rhetoric and value co-creation, the authors introduce a conceptual framework as a three-stage process guide for entrepreneurs to build shared narratives for strategic stakeholder engagement. Leveraging the power of shared roles and salient values as the key to pre-story building process, the intended audience of the story (i.e. consumer, investor) is present from the inception of the story and integral to its success.

Findings

The authors assert that entrepreneurs need to adopt a shared narrative approach for strategic purposes. Further, the development of a shared narrative begins at the pre-story process of co-creation, focused on identifying the roles and values entrepreneurs share with their various stakeholders. Incorporating these shared roles and salient values into the entrepreneurial narrative will result in a narrative that is compelling, authentic and adaptable to different stages of the entrepreneurial process and for multiple stakeholder audiences. Post-story, this authentic narrative will result in higher levels of engagement from both the audience and the entrepreneur in the form of reciprocal action.

Originality/value

This paper proposes a new narrative and provides a structured process to support entrepreneurs in building shared narratives for strategic engagement with a wide range of stakeholders.
Auditor practices and auditee responses to corporate governance audit regulation in Nigeria
Authors: Abdul-Baki Zayyad , Diab Ahmed
Published: November 2023

Purpose

The purpose of this study is to examine both the responses of auditees to corporate governance audit (CGA) regulation and the practices of CGA auditors.

Design/methodology/approach

The study used a mixed method. Content analysis of 200 annual and CGA reports was carried out for 13 years, from 2008 to 2021, split into voluntary disclosure and mandatory disclosure periods. Quantitative analysis was also conducted using Kruskal–Wallis and Dunn's tests. Data gathered were interpreted through the lens of isomorphism and Oliver's (1991) strategic responses to institutional processes.

Findings

The study revealed that in the voluntary disclosure period, auditees responded mainly with acquiescence, motivated by mimetic isomorphic pressure. In the mandatory disclosure period, auditee responses ranged from acquiescence to dismissal of corporate governance regulation (i.e. coercive isomorphic pressure). Auditor reporting of CGA findings was found to be heterogeneous, suggesting that normative and mimetic isomorphism did not homogenize auditor practices.

Practical implications

The absence of uniform auditee responses to CGA regulation during the mandatory disclosure period suggests that the purpose of mandating the regulation has not yet been achieved and may signal inadequate coercive isomorphic pressure from the Financial Reporting Council of Nigeria (FRCN). Similarly, heterogeneous reporting of CGA findings by corporate governance auditors inhibits the comparability of audit findings, limiting their value for information users.

Originality/value

This study examines corporate governance auditor practices and auditee responses to corporate governance audit regulation.
Environmentally friendly practices in Macau hotels before and after the COVID-19 pandemic: hotel executives' perspectives
Authors: Adongo Raymond , Choe Ja Young (Jacey) , Sulemana Sadia Shine
Published: November 2023

Purpose

This study seeks to examine motivations, challenges and strategies implemented to sustain environmentally friendly practices in Macau hotels and the effects of the COVID-19 pandemic on such practices.

Design/methodology/approach

Executives in sustainability departments of hotels in Macau were purposefully targeted for the in-depth interviews. Ten executives were interviewed either face-to-face or via video call.

Findings

The findings revealed that hotels in Macau implement sustainable practices. The main motivation for their implementation was the need to protect the environment, compliance and business-driven reasons. The major challenge involved the implementation costs. The pandemic had a limited impact on the implementation of these practices.

Practical implications

The study recommends that the Macau government should establish clear environmental policies and regulations for hotels with guidelines and support systems. Hotels can also benchmark their performance and collaborate on sustainable practices, develop innovative financing mechanisms and cost-efficient waste recycling practices, organize customer education and engagement programs to promote environmentally friendly practices and incorporate crisis management and resilience strategies into environmental strategies.

Originality/value

The current study denotes that the “sustainable development” concept is crucial in Macau because the largely gaming-driven hospitality industry has been developed over the last decade, significantly impacting environmental degradation. This study examined how hotels respond to these environmental challenges and how their responses can be sustained in the long term. The authors suggest the environmental practice indicators that can be helpful for the hospitality industries in Macau. Social and economic implications are discussed based on the findings.
Microcharity: a promising alternative to microcredit for poverty alleviation
Authors: Hasan Mehedi , Afrin Tania , Misra Vandna
Published: November 2023

Purpose

Microcharity is a non-profit organization promoting social brotherhood through small donations and volunteer services among diverse members, aiming to address poverty through compassion, cooperation and humanitarianism. The study aims to comprehend the role of microcharity as an alternative to microcredit for poverty alleviation. It sheds light on the modus operandi, prospects and problems associated with microcharity.

Design/methodology/approach

The current study used a qualitative research design to investigate a social phenomenon while involving the researchers directly. The study applied participatory action research by involving participants and researchers to comprehend social challenges and evaluate their experiences. The study made considerable use of participant-observer data and field observations.

Findings

It has been revealed that microcharity has potential to address social challenges faced by the marginalized and vulnerable section of society.

Research limitations/implications

This study is based on participatory action research, and therefore, it suffers from academic standardization and heavily depends on researchers. On the other hand, it offers practical approach to solve social problems and would bring forth realistic resolution by offering insights of those making use of micro charity for philanthropic activities.

Practical implications

The article is especially helpful for communities that must respond to emergencies and will be beneficial to individuals and institutions working for social welfare.

Social implications

It will bring forth various facets of micro charity as an alternate for fundraising to rescue sufferers of social exigencies through collective efforts.

Originality/value

The article represents original scholarly research, leveraging the researchers' personal experience to enrich the understanding of microcharity. Its implications are valuable for communities involved in social welfare and can benefit individuals working for charitable institutions, cooperative societies, NGOs and social welfare programmes of government. Additionally, the study's insights can aid researchers in designing new methodologies to explore microcharity and its impact on social welfare initiatives.
Antimicrobial resistance and biotechnological potential of plastic‐associated bacteria isolated from an urban estuary
Authors: Canellas Anna Luiza Bauer , Abdon Beatriz Balthazar , Diniz Matheus Nunes , da Silva Oliveira Alves Gabrielle , de Paula Lourenço Marcos Felipe , Machado Wilson Thadeu Valle , Giambiagi‐deMarval Marcia , de Oliveira Bruno Francesco Rodrigues , Laport Marinella Silva
Published: November 2023

Plastics have quickly become one of the major pollutants in aquatic environments worldwide and solving the plastic pollution crisis is considered a central goal of modern society. In this study, 10 different plastic samples, including high‐ and low‐density polyethylene and polypropylene, were collected from a deeply polluted urban estuary in Brazil. By employing different isolation and analysis approaches to investigate plastic‐associated bacteria, a predominance of potentially pathogenic bacteria such as Acinetobacter, Aeromonas, and Vibrio was observed throughout all plastic samples. Bacteria typically found in the aquatic environment harboured clinically relevant genes encoding resistance to carbapenems (blaKPC) and colistin (such as mcr‐3 and mcr‐4), along with genetic determinants associated with potentially active gene mobilization. Whole genome sequencing and annotation of three plastic‐associated Vibrio strains further demonstrated the carriage of mobile genetic elements and antimicrobial resistance and virulence genes. On the other hand, bacteria isolated from the same samples were also able to produce esterases, lipases, and bioemulsifiers, thus highlighting that the plastisphere could also be of special interest from a biotechnological perspective.
Efficacy of baricitinib for the treatment of systemic lupus erythematosus patients: A meta‐analysis of randomized controlled trials
Authors: Panda Aditya K. , Ranjan Shovit , Sahu Jayanta K.
Published: November 2023

Background

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal autoantibody production, inflammation, and organ damage. Most SLE treatment strategies aim to induce remission or reduce disease activity while avoiding flares. Baricitinib has been used effectively to manage various inflammatory diseases, and some randomized controlled trials (RCT) have shown that it is beneficial in treating SLE. The current study aims to assess the efficacy of baricitinib in treating SLE patients.

Materials and Methods

Various databases such as PubMed, Scopus, and Science Direct were searched to obtain eligible studies for the present meta‐analysis. Data such as baseline characteristics of patients, doses of the baricitinib, follow‐up duration, and treatment outcome in the form of SLE responder index‐4 (SRI‐4) and lupus low disease activity state (LLDAS) were extracted. Combined odds ratio, 95% confidence interval, and probability values were calculated to study the efficacy of baricitinib in treating SLE patients. A p‐value less than .05 was taken as significant. Comprehensive meta‐analysis v3 was used for all analyses.

Results

Three articles were found eligible for the present meta‐analysis comprising 614 patients with placebo, 614 SLE patients receiving 4 mg, and 621 patients with 2 mg of baricitinib. Meta‐analysis revealed a beneficial effect of 4 mg baricitinib in SLE patients compared to placebo, as measured by an increase in the SRI‐4 (p = .006, OR = 1.370) and LLDAS (p = .083, OR = 1.252) rates. In contrast to the placebo group, however, patients receiving 2 mg of baricitinib exhibited no significant improvement. The trial sequential analysis revealed the need for additional RCTs to determine the role of baricitinib in treating SLE patients.

Conclusion

In treating SLE patients, administrating a higher dose of baricitinib (4 mg) may be effective. However, additional RCTs in different populations with larger sample sizes are required to validate our findings.
The etherase system of Novosphingobium sp. MBES04 functions as a sensor of lignin fragments through phenylpropanone production to induce specific transcriptional responses
Authors: Kumagawa Eri , Katsumata Madoka , Nishimura Hiroshi , Watanabe Takashi , Ishii Shun'ichi , Ohta Yukari
Published: November 2023

The MBES04 strain of Novosphingobium accumulates phenylpropanone monomers as end‐products of the etherase system, which specifically and reductively cleaves the β‐O‐4 ether bond (a major bond in lignin molecules). However, it does not utilise phenylpropanone monomers as an energy source. Here, we studied the response to the lignin‐related perturbation to clarify the physiological significance of its etherase system. Transcriptome analysis revealed two gene clusters, each consisting of four tandemly linked genes, specifically induced by a lignin preparation extracted from hardwood (Eucalyptus globulus) and a β‐O‐4‐type lignin model biaryl compound, but not by vanillin. The most strongly induced gene was a 2,4′‐dihydroxyacetophenone dioxygenase‐like protein, which leads to energy production through oxidative degradation. The other cluster was related to multidrug resistance. The former cluster was transcriptionally regulated by a common promoter, where a phenylpropanone monomer acted as one of the effectors responsible for gene induction. These results indicate that the physiological significance of the etherase system of the strain lies in its function as a sensor for lignin fragments. This may be a survival strategy to detect nutrients and gain tolerance to recalcitrant toxic compounds, while the strain preferentially utilises easily degradable aromatic compounds with lower energy demands for catabolism.
Cognitive deficits among people with schizophrenia and prediabetes or diabetes
Authors: John Alexander Panickacheril , Mya Thynn , Haywood Darren
Published: November 2023

Introduction

Both type 2 diabetes mellitus (T2DM) and schizophrenia are known to be associated with cognitive deficits. The impact of the comorbidities of T2DM or prediabetes (PD) on cognition among people with schizophrenia has been poorly researched. We evaluated the cognitive functioning of patients with schizophrenia and PD or T2DM and compared them to patients with schizophrenia with normal blood sugar.

Methods

We retrospectively collated data on cognition, fasting blood glucose (FBG), lipids and other selected demographic and clinical variables of 171 patients with schizophrenia and 16 patients with schizoaffective disorder who were admitted to an inpatient rehabilitation facility in Western Australia from 2011 to 2018. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to evaluate cognitive functioning. Parametric and non‐parametric analyses were used to examine the study's aims.

Results

Sixty‐six percent of the patients had normal blood sugar, 25% had PD and 9% had T2DM. The BACS composite score revealed an increasing gradient of cognitive deficits, ranging from mild to severe, between the normal, PD and T2DM groups, respectively. The T2DM group had a significantly lower composite score compared with the PD (p = 0.026) and normal groups (p < 0.001). On the BACS subtests, the scores of T2DM and PD patients were similar except for the token motor task, in which the T2DM group had significantly lower scores (p < 0.001). The T2DM group also had lower scores on the subtests of BACS, except memory tests, compared with those with normal blood sugar. There was no significant difference in the composite and subtest cognitive scores between the PD and normal groups.

Conclusions

Our study revealed more pronounced cognitive deficits among patients with schizophrenia and dysglycaemia, particularly those with T2DM, compared with those with schizophrenia with normal blood sugar.
Association of daily steps on lipid and glycaemic profiles in children: The mediator role of cardiorespiratory fitness
Authors: Sequí‐Domínguez Irene , Martínez‐Vizcaíno Vicente , Rodríguez‐Gutiérrez Eva , Bizzozero‐Peroni Bruno , Martinez‐Madrid Vanesa , Prada de Medio Enrique , Martínez‐García Irene , Cavero‐Redondo Ivan
Published: November 2023

Aim

To analyse, in schoolchildren, the relationship between daily steps with metabolic parameters; and to examine whether this association is mediated by cardiorespiratory‐fitness (CRF).

Methods

A cross‐sectional analysis of baseline data from a feasibility trial was performed in children from two primary schools in Cuenca, Spain. Daily steps were measured using the Xiaomi MI Band 3. Lipid and glycaemic profiles were analysed from blood samples. CRF was assessed using the 20‐m shuttle run test. ANCOVA models were used to test the mean differences by daily steps quartiles. Mediation analyses were conducted to examine whether CRF mediates the association between daily steps and lipid and glycaemic parameters.

Results

A total of 159 schoolchildren (aged 9–12 years, 53% female) were included in the analysis. Schoolchildren in the highest daily steps quartiles (>10 000 steps) showed significantly lower triglycerides and insulin levels (p = 0.004 and 0.002, respectively). This association did not remain after controlling for CRF. In mediation analyses, a significant indirect effect was observed through CRF in the relationship between daily steps with triglycerides and insulin.

Conclusion

Children who daily accumulate more than 10 000 steps have better lipid and metabolic profile, and CRF mediated their relationship in schoolchildren.
Self‐perceived learning outcomes of virtual and in‐person academic detailing among general practitioners in Norway
Authors: Schjøtt Jan , Steen Ingrid Lunde , Espnes Ketil Arne , Riedel Bettina
Published: November 2023

Self‐perceived learning outcomes of virtual academic detailing (AD) are poorly studied. We compared self‐perceived learning outcomes of virtual and in‐person AD among general practitioners (GPs). GPs from the Western region of Norway received a questionnaire before and after AD concerning rational pharmacotherapy of migraine in the autumn 2022. Five statements addressing specific knowledge and two statements addressing general knowledge and skills in pharmacotherapy of migraine were rated in both questionnaires. A 7‐point Likert scale ranging from 1: Strongly disagree to 7: Strongly agree was applied to all the statements. Histograms that showed the difference in the mean composite scores before and after AD were used to compare learning outcomes of virtual and in‐person AD. Positive self‐perceived learning outcomes were observed among 80%–88% of the GPs. No significant differences between virtual and in‐person AD were observed.
Pay transparency intervention and the gender pay gap: Evidence from research‐intensive universities in the UK
Authors: Gamage Danula K. , Kavetsos Georgios , Mallick Sushanta , Sevilla Almudena
Published: November 2023

This study investigates the impact of a pay transparency intervention in reducing the gender pay gap in the UK university sector. Introduced in 2007, the initiative enabled public access to average annual earnings disaggregated by gender in UK universities. We use a detailed matched employee‐employer administrative dataset that follows individuals over time, allowing us to adopt a quasi‐experimental approach based on event studies around the intervention. We find that the earnings of female academics increased by around 0.62 percentage points compared to their male counterparts as the control group, whose earnings remained constant after the pay transparency intervention, reducing the gender pay gap by 4.37 per cent. Further evidence suggests that the main mechanism for the fall in the pay gap is driven by female employees negotiating higher wages, particularly among senior female academics.
Development of a therapeutic monoclonal antibody against circulating adipocyte fatty acid binding protein to treat ischaemic stroke
Authors: Liao Boya , Yang Shilun , Geng Leiluo , Zong Jiuyu , Zhang Zixuan , Jiang Mengxue , Jiang Xue , Li Simeng , Xu Aimin , Chang Junlei , Hoo Ruby Lai Chong
Published: November 2023

Background and Purpose

Adipocyte fatty acid‐binding protein (A‐FABP) exacerbates cerebral ischaemia injury by disrupting the blood–brain barrier (BBB) through inducing expression of MMP‐9. Circulating A‐FABP levels positively correlate with infarct size in stroke patients. We hypothesized that targeting circulating A‐FABP by a neutralizing antibody would alleviate ischaemic stroke outcome.

Experimental Approach

Monoclonal antibodies (mAbs) against A‐FABP were generated using mouse hybridoma techniques. Binding affinities of a generated mAb named 6H2 towards various FABPs were determined using Biacore. Molecular docking studies were performed to characterize the 6H2‐A‐FABP complex structure and epitope. The therapeutic potential and safety of 6H2 were evaluated in mice with transient middle cerebral artery occlusion (MCAO) and healthy mice, respectively.

Key Results

Replenishment of recombinant A‐FABP exaggerated the stroke outcome in A‐FABP‐deficient mice. 6H2 exhibited nanomolar to picomolar affinities to human and mouse A‐FABP, respectively, with minimal cross‐reactivities with heart and epidermal FABPs. 6H2 effectively neutralized JNK/c‐Jun activation elicited by A‐FABP and reduced MMP‐9 production in macrophages. Molecular docking suggested that 6H2 interacts with the “lid” of the fatty acid binding pocket of A‐FABP, thus likely hindering the binding of its substrates. In mice with transient MCAO, 6H2 significantly attenuated BBB disruption, cerebral oedema, infarction, neurological deficits, and decreased mortality associated with reduced cytokine and MMP‐9 production. Chronic 6H2 treatment showed no obvious adverse effects in healthy mice.

Conclusion and Implications

These results establish circulating A‐FABP as a viable therapeutic target for ischaemic stroke, and provide a highly promising antibody drug candidate with high affinity and specificity.
Kaempferol‐3‐O‐sophoroside (PCS‐1) contributes to modulation of depressive‐like behaviour in C57BL/6J mice by activating AMPK
Authors: Wang Rong , Hu Xiaolong , Liu Shumeng , Wang Jingjin , Xiong Fei , Zhang Xiaoqi , Ye Wencai , Wang Hao
Published: November 2023

Background and Purpose

Kaempferol‐3‐O‐sophoroside (PCS‐1) is the main component in Crocus sativus (Saffron), a herb with mood‐enhancing properties. AMP‐activated protein kinase (AMPK) is a potential therapeutic target for depression. This study explores the antidepressive‐like properties of PCS‐1 and its AMPK activation to confirm AMPK as a target for antidepression.

Experimental Approach

Corticosterone (CORT)‐induced PC12 cell injury served as an in vitro model to evaluate the neuroprotective effect of PCS‐1. Neuro‐2a cells and primary neurons were utilized to evaluate the synaptogenesis role of PCS‐1. CORT‐induced mouse depression model and chronic unpredictable mild stress (CUMS) model were used to assess the antidepressive‐like properties of PCS‐1 through behavioural tests, magnetic resonance imaging, and biochemical index measurements. Western blot and immunofluorescence assays were used to study the mechanisms of PCS‐1. Cellular thermal shift assay was used to confirm the binding target.

Key Results

PCS‐1 (12.5–50 μM) ameliorated CORT‐induced PC12 cell damage, oxidative stress and inflammation. PCS‐1 alone promoted an increase in synapses in Neuro‐2a cells and primary neurons. Oral administration of PCS‐1 (10 and 20 mg·kg−1) ameliorated weight loss, dyskinesia, and hippocampal volume reduction induced by CORT and CUMS. PCS‐1 bound to AMPK to improve the expression of brain‐derived neurotrophic factor (BDNF) and induce autophagy.

Conclusion and Implications

PCS‐1 binds to AMPK to promote BDNF production and autophagy enhancement, ultimately achieving antidepressant effects. This study provides support for the clinical application of saffron petals and provides further evidence for AMPK as a potential target for antidepression.
A splice donor variant of GAS8 induces structural disorganization of the axoneme in sperm flagella and leads to nonsyndromic male infertility
Authors: Kherraf Zine‐Eddine , Barbotin Anne‐Laure , Martinez Guillaume , Mazet Aurélien , Cazin Caroline , Coutton Charles , Arnoult Christophe , Thierry‐Mieg Nicolas , Rives Nathalie , Rives‐Feraille Aurélie , Ray Pierre F.
Published: November 2023

Motile cilia and flagella are closely related organelles structured around a highly conserved axoneme whose formation and maintenance involve proteins from hundreds of genes. Defects in many of these genes have been described to induce primary ciliary dyskinesia (PCD) mainly characterized by chronic respiratory infections, situs inversus and/or infertility. In men, cilia/flagella‐related infertility is usually caused by asthenozoospermia due to multiple morphological abnormalities of the sperm flagella (MMAF). Here, we investigated a cohort of 196 infertile men displaying a typical MMAF phenotype without any other PCD symptoms. Analysis of WES data identified a single case carrying a deleterious homozygous GAS8 variant altering a splice donor consensus site. This gene, also known as DRC4, encodes a subunit of the Nexin‐Dynein Regulatory Complex (N‐DRC), and has been already associated to male infertility and mild PCD. Confirming the deleterious effect of the candidate variant, GAS8 staining by immunofluorescence did not evidence any signal from the patient's spermatozoa whereas a strong signal was present along the whole flagella length in control cells. Concordant with its role in the N‐DRC, transmission electron microscopy evidenced peripheral microtubule doublets misalignments. We confirm here the importance of GAS8 in the N‐DRC and observed that its absence induces a typical MMAF phenotype not necessarily accompanied by other PCD symptoms.
Psychiatric disorders associated with PCSK9 inhibitors: A real‐world, pharmacovigilance study
Authors: Deng Zhifang , Liu Jue , Gong Hongjian , Cai Xiaonan , Xiao Han , Gao Wenqi
Published: November 2023

Background

The relationship between Protein Convertase Subtilisin Kexin Type 9 inhibitor (PCSK9i) and psychiatric adverse events (AEs) remains unclear due to the limitations of clinical trials. In this study, PCSK9i‐related psychiatric AEs were realistically observed and systematically summarized in the real world by data mining the FDA AE Reporting System (FAERS).

Method

Total AEs between the third quarter of 2015 and the first quarter of 2023 were obtained from FAERS. Psychiatric AEs were identified using disproportionality analysis and clinical prioritization of signals using a rating scale, followed by univariate logistic regression to explore factors influencing psychiatric AEs.

Results

Psychiatric AEs accounted for 6.7% of the total number of PCSK9i reports. Eighteen psychiatric AEs were defined as PCSK9i‐related psychiatric adverse events (ppAEs) (lower 95% CI of both ROR >1 and IC025 > 0). The median age of ppAE reports was 68 years, and female patients accounted for 22.67% of reports, including 41.40% of reports with a serious outcome. Eleven (61.11%) and seven (38.89%) ppAEs were classified as weak and moderate clinical priority, respectively. The median time to onset of ppAEs was 149 and 196 days after treatment with evolocumab and alirocumab, respectively. Patients weighing ≥80 kg were 1.59 times more likely to experience ppAEs.

Conclusion

The results of this study facilitate the prioritization of psychiatric AE signals by healthcare professionals with the goal of mitigating the risk of PCSK9i‐related psychiatric AEs. However, as an exploratory study, our findings need to be confirmed in large‐scale prospective studies.
Expectations of Processing Ease, Informativeness, and Accuracy Guide Toddlers’ Processing of Novel Communicative Cues
Authors: Aguirre Marie , Brun Mélanie , Morin Olivier , Reboul Anne , Mascaro Olivier
Published: November 2023

Discovering the meaning of novel communicative cues is challenging and amounts to navigating an unbounded hypothesis space. Several theories posit that this problem can be simplified by relying on positive expectations about the cognitive utility of communicated information. These theories imply that learners should assume that novel communicative cues tend to have low processing costs and high cognitive benefits. We tested this hypothesis in three studies in which toddlers (N = 90) searched for a reward hidden in one of several containers. In all studies, an adult communicated the reward's location with an unfamiliar and ambiguous cue. We manipulated the processing costs (operationalized as inferential chain length) and cognitive benefits (operationalized as informativeness) of the possible interpretations of the cues. Toddlers processing of novel communicative cues were guided by expectations of low processing costs (Study 1) and high cognitive benefits (Studies 2 and 3). More specifically, toddlers treated novel cues as if they were easy to process, informative, and accurate, even when provided with repeated evidence to the contrary. These results indicate that, from toddlerhood onward, expectations of cognitive utility shape the processing of novel communicative cues. These data also reveal that toddlers, who are in the process of learning the language and communicative conventions of people around them, exert a pressure favoring cognitive efficiency in communicative systems.