bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOE genotype and the effect of statins: a systematic review and meta-analysis
Authors: Asiimwe Innocent G. , Gebru Tsegay , Jorgensen Andrea L. , Pirmohamed Munir 
Published: December 2024

AbstractIntroductionTheAPOEgenotype may affect statin therapy response. We conducted a systematic review and meta-analysis to update and quantify this association across various outcomes.MethodsWe searched seven databases (MEDLINE, Scopus, Web of Science, The Cochrane Library, APA PsycINFO, CINAHL Plus, andClinicalTrials.gov) on 9thMay 2024. Screening and data extraction were performed by two reviewers and a machine learning tool (ASReview).ResultsFrom 4,352 de-duplicated records, 68 studies were included in the systematic review and 52 in the meta-analysis. Biomarkers analysed included Low-Density Lipoprotein Cholesterol (LDLC), Total Cholesterol (TC), Triglycerides (TG), and High-Density Lipoprotein Cholesterol (HDLC). Compared toε3carriers,ε2carriers showed greater reductions in LDLC (mean difference: −2.98%, 95% CI: −5.88% to −0.08%) and similar reductions in TC (−2.73%, −5.62% to 0.16%), and TG (−4.95%, −11.93% to 2.04%) with no significant difference in HDLC (−0.09%, −3.10% to 2.91%). After adjusting for publication bias,ε4carriers showed less pronounced statin effects, with smaller reductions in LDLC (mean difference: 10.04%, 6.04% to 14.04%), TC (8.99%, 5.08% to 12.90%), and TG (8.24%, 2.15% to 14.33%), along with a smaller increase in HDLC (−10.08%, −15.30% to −4.85%) compared toε3carriers. Study quality was uncertain, and heterogeneity (partly explained by sex and Familial Hypercholesterolemia) was high, especially for the percentage changes. A stronger genotype effect was seen in males.ConclusionOur meta-analysis shows thatAPOEgenotype can significantly influence statin response, emphasizing the need to incorporate known genetic factors into personalized treatment regimes.
APOEGenotype and Statin Response: Evidence from Electronic Health Records in the UK Biobank and All of Us Research Program
Authors: Asiimwe Innocent G. , Jorgensen Andrea L. , Pirmohamed Munir ,   Mechanism and Therapeutic Research Collaborative
Published: December 2024

AbstractIntroductionAPOE genotype may affect statin response. We investigated the relationship betweenAPOEgenotype and key outcomes in statin users using UK Biobank (UKB) and All of Us (AoU) data.MethodsWe analysed electronic health records from up to 45,515 UKB participants and 35,562 AoU participants. Using multivariable linear regression and Cox proportional hazards models, we assessed associations betweenAPOEgenotype and outcomes, including lipid biomarkers, all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE).ResultsAfter Bonferroni correction, significant changes in HDLC and triglyceride levels were observed in both cohorts (P< 0.01) following statin initiation. For all-cause mortality, significant associations were found in the UKB cohort, withε3ε4(HR: 1.08, 95% CI: 1.01–1.15) andε4ε4(HR: 1.54, 1.33–1.78) carriers showing higher risk compared to the referenceε3ε3genotype. In the AoU cohort, onlyε4ε4carriers showed an increased risk (HR: 1.64, 1.08–2.49). Cardiovascular-related mortality was assessed in only the UKB cohort, withε4ε4carriers having an increased risk (HR: 1.30, 1.01–1.68). In the AoU cohort, lipid level changes were significantly associated with reduced all-cause mortality risk: HDLC (median increase of 0.03 mmol/L, HR: 0.26 [0.16–0.41] per mmol/L), LDLC (median reduction of 0.82 mmol/L, HR: 0.82 [0.69–0.97] per mmol/L), and triglycerides (median reduction of 0.10 mmol/L, HR: 0.79 [0.72–0.87] per mmol/L). No significant associations with MACE were observed in either cohort.ConclusionThis study re-affirms thatAPOEgenotype significantly impacts statin response, highlighting the need to integrate genetics into personalized treatment regimens.
CSF pharmacokinetics-pharmacodynamics of linezolid in critically brain injured patients, with or without central nervous system healthcare-associated infection. The PK-Pop-LCR Study: A Multicenter Pharmacokinetics and Pharmacodynamics Population Study
Authors: Dahyot-Fizelier Claire , Chauzy Alexia , Chalard Kévin , Bernard Fanny , Courson Hugues de , Leblanc Pierre-Etienne , Francony Gilles , Chabanne Russel , Lakhal Karim , Cinotti Raphaël , Gregoire Charles , Pottecher Julien , Bouhemad Belaid , Merlaud Assil , Adier Christophe , Lecron Jean-Claude , Remy Ombeline , Couet William , Gregoire Nicolas , Marchand Sandrine ,   the PK-Pop-LCR Study Group
Published: December 2024

AbstractLinezolid is an alternative to vancomycin for treating Gram-positive central nervous system (CNS) healthcare-associated infections. The recommended dosing regimen remains debated. PK-Pop-LCR is a prospective population pharmacokinetic-pharmacodynamic multicenter study which included brain injured patients with an external ventricular drainage receiving linezolid at different dosing regimens. The cerebrospinal fluid (CSF) penetration of linezolid was investigated and a population pharmacokinetic model developed using plasma and CSF data. Monte Carlo simulations were conducted to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR) in CSF against methicillin-resistantStaphylococcus aureus(MRSA) and methicillin-resistantStaphylococcus epidermidis(MRSE), for different dosing regimens. The plasma pharmacodynamic target, AUC/MIC > 100, was used in CSF.Over 25 patients included, blind adjudication confirmed 14 cases of CNS infections. The mean AUCCSF/fAUCplasmaratio was close to 80% with no difference between patients with and without CNS infection, despite higher CSF cytokines levels in CNS-infected patients. The recommended dose of 1200 mg/24h allowed to reach PTAs ≥ 90% only for MICs ≤ 0.5 mg/L, and CFR of 3.2% and 40% for MRSA and MRSE, respectively. 2 700 mg/24h would allow to achieve PTA > 90% for MIC up to 1 mg/L and CFR of 90% for MRSE but none of dosing regimens tested was appropriate for MRSA infections.We confirmed the extensive CSF distribution of linezolid. Higher doses than those recommended should be considered to treat CNS infection in critically brain injured patients. However, pharmacodynamic target for CNS infections should be further investigated to confirm these findings.FundingsFrench Ministry of Health.
Greater lesion damage is bidirectionally related with accelerated brain aging after stroke
Authors: Khan Mahir H. , Marin-Pardo Octavio , Chakraborty Stuti , Borich Michael R. , Castillo Mayerly , Cole James H. , Cramer Steven C. , Donnelly Miranda R. , Fokas Emily E. , Fullmer Niko H. , Gumarang Jeanette R. , Hayes Leticia , Kim Hosung , Kumar Amisha , Marks Emily A. , Rosario Emily R. , Schambra Heidi M. , Schweighofer Nicolas , Song Grace C. , Taga Myriam , Tavener Bethany P. , Winstein Carolee J. , Liew Sook-Lei 
Published: December 2024

AbstractRegional neuron loss following stroke can result in remote brain changes due to diaschisis and secondary brain atrophy. Whole brain changes post-stroke can be captured by the predicted brain age difference (brain-PAD), a neuroimaging-derived biomarker of global brain health previously associated with poorer chronic stroke outcomes. We hypothesized that greater lesion damage would be longitudinally associated with worsening brain-PAD during subacute stroke, and conversely, that poorer baseline brain-PAD would be associated with enlarged lesion damage.We prospectively collected MRIs from 47 stroke patients across three sites within 3 weeks (baseline) and at 3 months (follow-up) post-stroke. Predicted brain age was estimated via a pretrained ridge regression model using 77 morphological features. Brain-PAD was calculated as predicted age minus chronological age. Robust linear mixed effects regression models were used to examine relationships between infarct volume and brain-PAD, adjusting for age, sex, time, and intracranial volume at baseline.Larger baseline infarct volume was associated with accelerated brain aging at 3 months (β=0.87, p=0.023). Conversely, larger baseline brain-PAD predicted larger increase in infarct volume at 3 months (β=0.02, p=0.009). These findings reveal a bidirectional relationship between focal stroke damage and global brain health during the subacute period, underscoring the importance of assessing both.
Mechanistic Insights into Periplasmic Chaperones as Regulators of Protein Folding and Translocation in Gram-Negative Bacteria
Authors: Chaudhuri Deep , Bhatt Madhu , Haldar Shubhasis 
Published: December 2024

AbstractIn Gram-negative bacteria, periplasmic chaperones mediate the transport and folding of outer membrane proteins. While their substrate interaction mechanisms are well studied, their functional cycle during periplasmic translocation remains unclear. Using single-molecule force spectroscopy, we demonstrate that SecYEG-associated chaperones PpiD and DsbC act as foldases, delivering up to 45.5 zJ of mechanical work. This activity facilitates substrate extraction from the SecYEG translocation tunnel, reducing ATP consumption during SecA-mediated translocation. In contrast, chaperones such as Spy and Skp function as holdases, stabilizing unfolded substrates to prevent misfolding during translocation. Our findings reveal a unique mechanism by which chaperones adapt to mechanical constraints, optimizing protein folding and translocation in the periplasm.
Engineering the MarinePseudoalteromonas haloplanktisTAC125 via pMEGA Plasmid Targeted Curing Using PTasRNA Technology
Authors: Severino Angelica , Lauro Concetta , Calvanese Marzia , Riccardi Christopher , Colarusso Andrea , Fondi Marco , Parrilli Ermenegilda , Tutino Maria Luisa 
Published: December 2024

AbstractMarine bacteria that have adapted to thrive in extreme environments, such asPseudoalteromonas haloplanktisTAC125 (PhTAC125), offer a unique biotechnological potential. The discovery of an endogenous megaplasmid (pMEGA) raised questions about its metabolic impact and functional role in this strain. This study aimed at streamlining the host genetic background by curingPhTAC125 from the pMEGA plasmid using a sequential genetic approach. We combined homologous recombination by exploiting a suicide vector with the PTasRNA gene silencing technology to interfere with pMEGA replication machinery. This approach led to the construction of the novelPhTAC125 KrPL2strain, cured from the pMEGA plasmid, which exhibited no significant differences in the growth behaviour, though showcasing enhanced resistance to oxidative stress and a reduced capability of biofilm formation. These findings represent a significant achievement for understanding of the role of pMEGA plasmid and for the biotechnological applications ofPhTAC125 in recombinant protein production. This opens up the possibility to exploit pMEGA valuable genetic elements and further advancing the genetic tools forPhTAC125.
Sustainable development goals, culture and advertising: tracing the roots to stride forward
Authors: Soni Pavleen , Vohra Jyoti , Ghuman Mandeep Kaur , Polsa Pia 
Published: December 2024

PurposeGrowing concern about sustainability, which focuses on the triple bottom line, namely people, planet and profits, must integrate with local culture to ensure inclusive growth. Localized advertising themes adapted to suit a country’s culture borrow from that country’s culture. Global advertising themes, on the other side, influence and modify the existing culture of a nation. The present study looks at the potential of using traditional Indian sustainable themes to promote sustainability as a way of life, which can be used to craft advertising messages that contribute to the achievement of sustainable development goals (SDGs).Design/methodology/approachA content analysis of 395 advertisements displayed on Indian television during primetime has been done. Data have been analyzed using descriptive statistics.FindingsThe findings reveal that 4 SDGs (achieve gender equality, ensure affordable and clean energy, ensure good health and well-being and promote industry, innovation and infrastructure) out of a total of 17 SDGs find a place in 395 advertisements. They mostly appear for beauty and personal care products and automotive. Depictions of a frugal lifestyle, natural/green surroundings and women empowerment in advertisements “together” exemplify opportunities to use culture creatively in crafting advertising messages.Research limitations/implicationsAs the multinational companies embrace the trends towards globalization in advertising, they can also extend the traditional cultural values and lifestyle from a country like India, which tremendously and conspicuously contribute to sustainability to appeal “differently” to buyers. It would offer an opportunity to synergize the growth outcomes in a thoughtful manner.Originality/valueThis is an original piece of research, as no such study has already been conducted in India (to the best of researchers' knowledge).
Toward BPM maturity assessment integrated with BPM implementation and use
Authors: Szelągowski Marek , Sliż Piotr 
Published: December 2024

PurposeThe aim of this article is to develop an efficient method for the assessment of business process management (BPM) maturity, which identifies the present maturity level in the organization, as well as integrates itself with the methodology of implementing BPM and systemically eliminates the identified limitations of existing BPM maturity models (BPM MMs).Design/methodology/approachThe methodological underpinning of this research involves a comprehensive review and critique of existing BPM MMs, dissecting their theoretical foundations and methodological constructs. Grounded in established research methodologies, the study integrates perspectives from Industry 4.0 and Industry 5.0.FindingsThe presented BPM maturity assessment (BPM MA) is targeted at showing the actions that lead to raising BPM maturity by drawing upon the potential of the organization in a way which is harmonious with methodologies of implementing and using BPM. It focuses on practical usability and, thanks to this, eliminates one of the most often discussed flaws of BPM MMs.Research limitations/implicationsThe limitation of this study is, at this stage, the lack of empirical verification and the lack of postulated BPM MA tools, integrated with the BPM software available on the market. Though the proposed BPM MA offers a systematic approach, targeted at practical use, it will, however, in the further perspective, require tailoring to the specific nature of different sectors of the economy in order to reach its full potential by, e.g. adapting the evaluation surveys and adding dedicated recommendations.Practical implicationsPractitioners may reap the benefits of the presented BPM MA thanks to its harmonization with methodologies of implementing BPM and the possibility of its use as an element of the standard BPM lifecycle. Accounting for the requirements of Industry 4.0/5.0 in both assessment criteria and recommendations provides managers support in the rapidly changing business environment.Originality/valueThe originality of this study rests in the synthesis of theoretical and methodological rigor with a singular focus on the practical usability of the proposed BPM MA. Apart from conceptual progress, the contribution of this study rests in removing the theoretical-practical gap and accounting for the requirements of Industry 4.0 and the upcoming Industry 5.0.
Insights into CEO duality in corporate governance: a bibliometric and systematic analysis approach
Authors: Javed Maryam , Nasir Nadia , Bashir Adnan , Mehmood Kashif , Akhtar Hammad 
Published: December 2024

Purpose
This study aims to analyze chief executive officer (CEO) duality in corporate governance by using Scopus data. It explores CEO duality research trends across diverse corporate governance contexts and disciplines, shaping the future research agenda, and proposing recommendations for further investigations in this area.

Design/methodology/approach
This analysis is conducted through VOSviewer software and Biblioshiny by extracting the bibliometric network from the output files of the Scopus bibliographic database.

Findings
Research on CEO duality centers on keywords such as corporate governance, agency theory, board of directors, board size and firm performance. Word tree maps uncover various research areas and gaps. Top authors are Elsyed K. & Rashid K, with the University of Utara Malaysia as the leading organization. Main disciplines are “Business Management and Accounting” followed by “Economics.” “Corporate Governance: An International Review” tops the journals with 1,120 citations. Quantitative methods using secondary data dominate (94%), mostly from nonfinancial industries (96%). Theoretical lenses include agency theory, stewardship theory, stakeholder theory, resource dependence theory and institutional theory. Firm performance is the most researched aspect (38% of studies) concerning CEO duality.

Practical implications
Bibliometric and systematic analysis offer researchers a general overview and in-depth insights into current CEO duality research trends, influential articles and keywords in corporate governance. This study’s findings benefit research institutions, professional bibliometric users and funding agencies alike.

Originality/value
By visualizing bibliometric networks and conducting systematic analysis of top-cited articles, this study not only advances the academic understanding of CEO duality in corporate governance but also provides actionable recommendations for researchers, practitioners and policymakers to enhance governance practices and contribute to the field’s evolving body of knowledge.
BIM adoption predictors for health and safety management among construction SMEs
Authors: Sila Nosabelo , Agumba Justus Ngala , Adebowale Oluseyi Julius 
Published: December 2024

Purpose
Health and safety (H&S) management remains a significant global challenge in the construction industry. Small and medium enterprises (SMEs) particularly struggle to comply with H&S regulations, resulting in high accident records. To address this poor performance, experts suggest that SMEs adopt H&S management technologies, particularly building information modeling (BIM), due to their potential to improve H&S practices. This study aims to determine the key predictors of construction SMEs’ intentions to adopt BIM for H&S management. The study also explores the potential impact of selected demographic variables on construction SMEs’ adoption intentions.

Design/methodology/approach
Quantitative research was used using a questionnaire distributed to 357 randomly sampled SMEs. The questionnaire collected data regarding SMEs’ intention to adopt BIM for H&S management. Binary logistic regression analysis was used to analyze the research data.

Findings
The findings reveal specific “relative advantages”, which include “BIM for H&S management will be preferable to the manual use of the H&S file” and “BIM for H&S management will make it easier to comply with H&S regulations” as significant predictors of the intention to adopt BIM for H&S management. The study also underscores the significance of educational qualifications and professional affiliation as predictors of BIM adoption.

Research limitations/implications
The study’s sample population consisted of SMEs registered with the Construction Industry Development Board register of contractors in Gauteng province, South Africa. This regional focus limits the generalizability of the findings to the entire country. Further research is recommended to investigate the adoption of BIM for H&S management among SMEs in other South African provinces. Additionally, a comparative study exploring BIM adoption for H&S between large construction enterprises and SMEs within the South African context could provide valuable insights.

Practical implications
This study presents a novel approach, leveraging the diffusion of innovation (DOI) theory and demographic analysis, to determine the key predictors of SMEs’ intentions to adopt BIM for H&S management.

Social implications
Socially, the study promotes the adoption of BIM for H&S. Digital technology is advancing and upgrades social standard, it is crucial for the society to adopt BIM for H&S.

Originality/value
Existing BIM for H&S management research has neglected SMEs’ adoption intentions, focusing instead on broader adoption enablers. This study presents a novel approach, leveraging the DOI theory and demographic analysis, to determine the key predictors of SMEs’ intentions to adopt BIM for H&S management.
Aerodynamic characteristics of the race car in pitch and roll attitude
Authors: Ma Xiaojing , Li Jie , Zhao Jun , Chen Jiliang 
Published: December 2024

Purpose
Aerodynamics plays a crucial role in enhancing the performance of race cars. Due to the low ride height, the aerodynamic components of race cars are affected by ground effects. The changes in pitch and roll attitudes during the car’s movement impact its ride height. This study aims to analyze the aerodynamic characteristics of race cars under specific pitch and roll attitudes to understand the underlying aerodynamic mechanisms. This paper focuses on the aerodynamic characteristics of racing cars under variations in body posture associated with different vehicle ride heights. It examines not only the force and pressure distribution resulting from changes in the overall vehicle posture but also the flow field behavior of both surface flow and off‑body flow. Analyzing individual components reveals the impact of the front wing on the overall aerodynamic performance and aerodynamic balance of the racing car under these posture variations.

Design/methodology/approach
The grid strategy for the computational fluid dynamics (CFD) method was established under baseline conditions and compared with the results from wind tunnel experiments. The CFD approach was further employed to investigate the aerodynamic characteristics of the racing car under varying body postures associated with different vehicle ride heights. Emphasis is placed on the overall aerodynamic performance of the vehicle and the various components’ influence on the changing trends of aerodynamic forces. By considering the surface pressure distribution of the car, the primary reasons behind the changes in aerodynamic forces for each component are investigated. In addition, the surface flow and detached flow (wake and vortex distributions) of the car were observed to gain insights into the overall flow field behavior under different attitudes.

Findings
The findings indicate that both pitch and roll attitudes result in a considerable loss of downforce on the front wing compared with other components, thereby affecting the overall downforce and aerodynamic balance of the vehicle.

Originality/value
This paper focuses on the aerodynamic characteristics of racing cars under variations in body posture associated with different vehicle ride heights. It examines not only the force and pressure distribution resulting from changes in the overall vehicle posture but also the flow field behavior of both surface flow and off-body flow. Analyzing individual components reveals the impact of the front wing on the overall aerodynamic performance and aerodynamic balance of the racing car under these posture variations.