bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Identification and Anti-Inflammatory Evaluation of T19093 as a TLR4/MD2 Inhibitor
Authors: Chen Kuida , Shi Ke , Jin Tong , Lu Shipeng , Yin Wu 
Published: February 2025

Background:
The TLR4 (Toll-like receptor 4)/MD2 (Myeloid differentiation protein-2)
is a crucial target for developing novel anti-inflammatory drugs. Nevertheless, current inhibitors
often have significant adverse effects, necessitating the discovery of safer alternatives.

Objective:
The investigation aims to identify novel TLR4/MD2 inhibitors with potential antiinflammatory
activity using machine learning and virtual screening technology.

Methods:
A machine-learning model was created using the MACCS (Molecular ACCess Systems)
key fingerprint. Subsequently, virtual screening and molecular docking were used to evaluate candidate
compounds' binding free energy to the TLR4/MD2 complex. Furthermore, ADMET (absorption,
distribution, metabolism, excretion, and toxicity) prediction was used to assess the druggable
properties of compounds. The most promising compound, T19093, was considered for molecular
dynamic simulation. Finally, the anti-inflammatory efficacy of T19093 was further validated using
LPS-treated THP-1 cells.

Results:
T19093, a polyphenolic compound isolated from the Gnaphalium plant genus, showed
strong binding to key residues of the TLR4/MD2 complex, with a docking score of -11.29 kcal/mol.
Furthermore, ADMET predicted that T19093 has good pharmacokinetic properties and balanced
physicochemical properties. Moreover, molecular dynamics simulation confirmed stable binding
between T19093 and TLR4/MD2 complex. Finally, it was found that T19093 alleviated LPSinduced
inflammatory response by inhibiting the activation of TLR4/MD2 downstream signaling
pathways and disrupting the TLR4/MD2 interaction.

Conclusion:
T19093 was discovered as a potential novel TLR4/MD2 inhibitor using machine
learning and virtual screening techniques and showed potent anti-inflammatory activity, which
could provide a new therapeutic alternative for the treatment of inflammation-related diseases.
Over-the-counter Psychosis: A Systematic Review of the Misuse of Antihistamines, Cough Medicines, and Decongestants and the Risk of Developing Psychosis
Authors: Mosca Alessio , Chiappini Stefania , Mancusi Gianluca , Miuli Andrea , Marrangone Carlotta , Allegretti Rita , Panichella Serena , Cavallotto Clara , Corkery John Martin , Pettorruso Mauro , Martinotti Giovanni , Schifano Fabrizio 
Published: February 2025

Background:
The widespread availability and accessibility of over-the-counter (OTC)
medicines play a vital role in modern healthcare systems, enabling individuals to manage minor
health concerns independently. However, certain OTC medications possess pharmacological properties
that render them susceptible to misuse and abuse, including stimulants, laxatives, sedatives, and
opiate-containing products. Misuse involves improper dosage, duration, or indication, while abuse
entails non-therapeutic use to achieve psychoactive effects or other illicit purposes, potentially leading
to dependence and addiction. This review explores the risk of developing psychotic symptoms
associated with OTC drug misuse. Synthesizing existing literature, it comprehensively examines the
relationship between antihistamines, cough medicines, and decongestants misuse, and the onset of
psychotic symptoms.

Methods:
A systematic literature review was carried out using Pubmed, Scopus and Web of Science
databases through the following search strategy: (“diphenhydramine” OR “promethazine” OR
“chlorpheniramine” OR “dimenhydrinate” OR “dextromethorphan” OR “pseudoephedrine” OR codeine-
based cough medicines) AND (“abuse” OR “misuse” OR “craving” OR “addiction”) NOT review
NOT (animal OR rat OR mouse). For data gathering purposes, the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Research methods were registered
on PROSPERO (CRD42024527558).

Results:
We analysed 46 relevant studies out of an initial pool of 2,677 articles. Key findings indicate
that antihistamines, dextromethorphan, and other OTC drugs can induce psychotic symptoms,
such as paranoia, hallucinations, and thought disorders when abused. Dextromethorphan is particularly
associated with a chronic tendency towards psychosis, whereas other substances more commonly
result in acute substance-induced psychosis.

Conclusion:
The study underscores the necessity for increased awareness and specific interventions
to address the misuse of OTC drugs and their potential to cause significant psychiatric disorders, emphasizing
the broader public health implications of such misuse.
Virtual Screening and Identification of Novel Oxindole Derivatives as Potential Antimicrobial Agents
Authors: P. Sowmiya , G. Revathi , K. Girija 
Published: February 2025

Introduction:
Antimicrobial resistance (AMR), according to the World Health Organi-zation, is one of the most serious risks to global public health and development. It is a serious health hazard, with over 10 million deaths expected by 2050. New treatment materials and ways to remove AMR pathogens are in great demand to combat illnesses caused by such bacteria. Hence, the current work focused on virtual screening of the therapeutic potential of new oxindole derivatives against the targeted enzymes for antibacterial activity.

Materials and Methods:
A series of 120 novel 3-substituted-2-oxindole derivatives were designed based on the literature and SAR study, which were screened for their binding affinity against tar-geted enzymes, such as methionyl-tRNA synthetase (1PFV) and tyrosyl-tRNA synthetase (1JIL) using AutoDock Vina software. Compounds with significant binding energy were identified and filtered for appropriate ADME properties using the SwissADME program. Furthermore, the top fifteen hit compounds were evaluated for toxicity risk and drug score with the pkCSM online tool and OSIRIS Property Explorer, respectively.

Results and Discussion:
The docking analysis of the top two hits revealed that compounds 4 and 6 had a binding affinity of -10.1 Kcal/mol and -10.0 Kcal/mol against the targeted enzymes, respec-tively, compared to the standard (Tetracycline -9.3 Kcal/mol and Mupirocin -7.5 Kcal/mol).

Conclusion:
Hence, the best-hit compound 4 underwent MD simulation, validating its stability and successfully satisfying all in silico parameters, necessitating further synthesis and screening for in-vitro antimicrobial activity. These novel oxindole scaffolds could thus serve as promising leads for effective antibacterial drugs.
A Human Embryonic Stem Cell-derived Neural Stem Cell Senescence Model Triggered By Oxidative Stress
Authors: Pan Hui , Bao Li , Ji Meng , Lyu Zhengbing , Qi Nianmin , Wu Yuehong 
Published: February 2025

Introduction:
Neural stem cells (NSCs) are vulnerable to oxidative stress, which triggers
aging and subsequently leads to a reduced regenerative capacity of the central nervous system
(CNS). Due to the challenges in acquiring aged human NSCs and the lack of an oxidative stressinduced
aging model specifically designed for human NSCs, research related to the aging mechanisms
and the screening of anti-aging drugs have been limited. Here, we aimed to establish an oxidative
stress-induced senescence model of NSCs by using D-galactose (D-gal).

Methods:
Human embryonic stem cells (hESC) were differentiated into hESC-NSCs using a type I
collagen method. hESC-NSCs were characterized by flow cytometry combined with immunofluorescence.
A senescence model of hESC-NSCs was established using D-gal and characterized by CCK-8
assay, neurosphere formation, crystal violet staining, DNA damage assay, SA-β-gal staining and
ROS levels measurement. To further explore the profile of gene expression in D-gal-induced hESCNSCs
senescence model, transcriptome sequencing was performed and analysed by bioinformatics
method, following verified by qPCR.

Results:
The hESC-derived NSCs senescence model demonstrated reduced proliferation and elevated
β-galactosidase activity, accompanied by DNA damage and increased levels of reactive oxygen
species. Furthermore, transcriptome analysis unveiled the potential central role of the MAPK signaling
pathway in D-gal-induced senescence, which involves the key genes including DDIT3, ATF3,
CEBPB, JUN, and CCND1.

Conclusion:
We presented an oxidative stress-induced senescence model of hESC-NSCs and identified
key pathways and genes related to D-gal-induced senescence. Our study might offer an alternative
approach for investigating human NSC aging and provide valuable data for understanding the
underlining mechanisms of oxidative stress-induced aging.
Empagliflozin and Arterial Stiffness in Patients with Type 2 Diabetes: A Real-World Case-Control Study
Authors: Tassone Francesco , Ferreri Cinzia , Rossi Arianna , Borretta Giorgio , Pastorini Guido , Anastasio Fabio , Feola Mauro 
Published: February 2025

Background:
Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated
beneficial cardiovascular and renal effects in patients with type 2 diabetes mellitus (T2DM).

Objective:
The objective of this case-control study was to evaluate the efficacy of empagliflozin
in modifying the arterial stiffness in type 2 diabetic patients.

Methods:
Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed at
baseline and after three months of empagliflozin treatment in 16 consecutive outpatients with type
2 diabetes mellitus (T2DM) exhibiting normal left ventricular function and no signs of heart failure.
A control group of 16 T2DM outpatients not treated with SGLT2 inhibitors was used for comparison.

Results:
Duration of diabetes mellitus and sex distribution did not differ between groups. Patients
in the empagliflozin group were younger compared to controls (64.1 ± 8.68 vs 74.45 ± 8.13, p <
0.05). At 3-month follow-up, empagliflozin treatment significantly reduced HbA1c (7.9 ± 0.78 vs
7.04 ± 1.09%, p < 0.008). Empagliflozin significantly improved PWV compared to controls (from
13.2 ± 2.0 m/sec to 12.3 ± 1.8 m/sec; P = 0.001; in the control group 12.8 ± 2.3m/s to 13.2 ± 2.4,
p = ns, with age and HbA1c as covariates) as well as body weight that significantly reduced
(86.75 ± 16.16 kg vs 81.71 ± 16.5 kg, p =0.001) and BMI (30.48 ± 5.4 versus 28.75 ± 5.66 kg/m2,
p < 0.002) in comparison to controls. Estimated glomerular filtration rate (eGFR) remained
unchanged whereas a significant improvement of urine Albumin to Creatinine ratio with empagliflozin
emerged (17.8 ± 46.8 vs 12.2 ± 35.7 mg/mmol, p = 0.049).

Conclusion:
In this clinical study, mid-term treatment with empagliflozin in patients with type 2
diabetes mellitus (T2DM) resulted in a significant reduction in arterial stiffness. Additionally, the
improvement in the urine albumin-to-creatinine ratio suggests a potential enhancement in endothelial
function.
The Beauty of Auditor Selection: The Effects of Auditor Attractiveness and Auditee Goals on Procuring Governmental Audit Services
Authors: Messina Marena M. , Schafer Jennifer K. , Stefaniak Chad M. 
Published: February 2025

ABSTRACT
Baugh, Hallman, and Kachelmeier (2022) archivally find audit committees with no Big 4-experienced members are more likely to favor attractive partners, suggesting attractiveness influences auditor selection. We extend Baugh et al. (2022) by investigating the conditions in which attractiveness influences auditor selection. Using 140 finance directors as participants, we experimentally examine if auditor attractiveness affects hiring recommendations, and whether auditee goals moderate the effects of attractiveness. We find when the auditee’s goal is “meticulous,” recommendations are similar across conditions. However, when the goal is “check-the-box,” participants are more (less) likely to recommend more (less) attractive auditors. In the “check-the-box” condition we also find attractive auditors are more likely to be recommended compared to the baseline (no photo), indicating a “beauty premium.” Our study has implications for audit firms, auditees, and regulators by identifying a factor that contributes to auditees’ susceptibility to beauty bias, which can ultimately affect audit quality.
Comparative Efficacy of Glucagon-Like Peptide 1 Receptor Agonists for Cardiovascular Outcomes in Asian Versus White Populations: Systematic Review and Meta-analysis of Randomized Trials of Populations With or Without Type 2 Diabetes and/or Overweight or Obesity
Authors: Lee Matthew M.Y. , Ghouri Nazim , Misra Anoop , Kang Yu Mi , Rutter Martin K. , Gerstein Hertzel C. , McGuire Darren K. , Sattar Naveed 
Published: February 2025

BACKGROUND
Cardiovascular outcome trials (CVOTs) suggest glucagon-like peptide 1 receptor agonists (GLP-1RAs) provide greater cardiovascular (CV) benefits in Asian compared with White individuals.

PURPOSE
Compare CV efficacy of GLP-1RAs between Asian and White individuals.

DATA SOURCES
Systematic review of PubMed and ClinicalTrials.gov (1 January 2015 to 1 November 2024).

STUDY SELECTION
Randomized placebo-controlled CVOTs of GLP-1RAs. Risk of bias was assessed (RoB 2).

DATA EXTRACTION
Ethnicity-specific hazard ratios (HRs) for major adverse cardiovascular events (MACE).

DATA SYNTHESIS
Random-effects meta-analyses per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines included eight trials (5,909 Asian individuals, 55,855 White individuals). GLP-1RA–associated MACE HR was 0.69 (95% CI 0.58, 0.83) in Asian people and 0.85 (95% CI 0.79, 0.91) in White people (Pinteraction = 0.045). Absolute MACE risk reduction was 2.9% (95% CI 1.5, 4.2) in Asian people versus 1.4% (0.9, 1.9) in White people.

LIMITATIONS
Lack of individual patient-level data precluded detailed subclassification of the Asian group.

CONCLUSIONS
GLP-1RAs may offer greater MACE reductions in Asian compared with White individuals.
Myocarditis and pericarditis during COVID-19 pandemic: a study of the Italian Society of Cardiology
Authors: Birtolo Lucia Ilaria , Di Pietro Gianluca , D’Ascenzo Fabrizio , Cuccuru Giuditta , Fabris Enrico , Merlo Marco , Andreis Alessandro , Cameli Matteo , Improta Riccardo , Campo Gianluca , De Ferrari Gaetano Maria , Emdin Michele , Galassi Alfredo Ruggero , Iliceto Sabino , Imazio Massimo , D’Agata Mottolese Biancamaria , Porto Italo , Montisci Roberta , Novo Giuseppina , Pavan Daniela , Vizza Carmine Dario , Maestrini Viviana , Basso Cristina , Perrone Filardi Pasquale , Sinagra Gianfranco , Mancone Massimo 
Published: February 2025

Aims
Some studies about myocarditis and pericarditis following COVID-19 vaccination raised concerns worldwide. However, the heterogeneous diagnostic criteria for postvaccination inflammatory heart diseases may result in overestimating incidence rates. The aim of this multicentre Italian registry is to evaluate the impact of COVID-19 vaccines on the incidence of myocarditis and pericarditis in the Italian population.

Methods
Consecutive patients admitted to Italian hospitals for endomyocardial biopsy and/or cardiac magnetic resonance proven acute myocarditis and/or pericarditis in the same period (1 June–31 October) of 2019 and 2021 were enrolled, irrespective of the potential association with the COVID-19 vaccines. Acute pericarditis and/or myocarditis were defined as ‘vaccine-related’ if clinical presentation occurred within 15 days after COVID-19 vaccination, independently of the dose.

Results
There was a comparable incidence rate ratio (IRR) for inflammatory heart diseases in 2019 and 2021 (2019: IRR 0.67 versus 2021: IRR 0.74, P = 0.45). In particular, the IRR did not differ in myocardial involvement (2019: IRR 0.33 versus 2021: IRR 0.33, P = 1) and pericarditis (2019: IRR 0.37 versus 2021: IRR 0.49, P = 0.09) in both periods. Among 125 cases registered in 2021, 32 (25.6%) were ‘vaccine-related’. Among those who experienced ‘vaccine-related’ myocarditis and/or pericarditis, men with age under 40 years were over-represented (53.12%, P = 0.021).

Conclusion
In a nationwide Italian survey comparing pandemic with prepandemic periods, the overall data do not indicate significant concerns about an increased incidence of pericarditis and myocarditis, suggesting that the vaccine is generally well tolerated for these specific conditions.
Critical approach to the 2023 European Society of Cardiology guidelines on cardiomyopathies: a document by the Working Group on Myocardial and Pericardial Diseases of the Italian Society of Cardiology
Authors: Merlo Marco , Pio Loco detto Gava Carola , Perotto Maria , Aimo Alberto , Autore Camillo , Bauce Barbara , Biagini Elena , Cappelli Francesco , Castelletti Silvia , D’Ascenzi Flavio , de Gregorio Cesare , Limongelli Giuseppe , Marzo Francesca , Musumeci Beatrice , Tini Giacomo , Pedrinelli Roberto , Perrone Filardi Pasquale , Sinagra Gianfranco , Imazio Massimo 
Published: February 2025

Last year, the European Society of Cardiology (ESC) published the first guidelines to comprehensively address the management of cardiomyopathies.
This document by the Working Group on Myocardial and Pericardial Diseases of the Italian Society of Cardiology aims at highlighting the most relevant messages and novelties introduced by these guidelines for the management of patients affected by cardiomyopathies.
Five main messages are summarized: the key role of the phenotype, the new classification of cardiomyopathies provided in the ESC guidelines, the importance given to new techniques such as cardiac magnetic resonance (CMR) and genetic testing, the newly provided recommendations given on sport activities and finally how the importance of follow-up evaluations is highlighted.
These five main messages are then further analyzed more in depth so as to inform the reader on all the main novelties of the guidelines and to provide a critical approach to this important document.
Road Rescue: Decentralized Cross-Platform Service Orchestration Based on Blockchain for Roadside Assistance Application
Authors: Somvanshi Vinayak , Walavekar Gandharvi , Thakkar Kevin , Kumbhar Yogesh , Deshmukh Neha , Deshpande Kiran 
Published: February 2025

Abstract
Amid the rapid expansion of the vehicular network, the autonomous design of numerous roadside assistance systems, often involving third-party intermediaries, has raised significant concerns about security and reliability. In response, blockchain technology has emerged as a groundbreaking solution, effectively decentralizing these systems and enhancing their dependability and security. The initiative is singularly dedicated to crafting a cross-platform application for roadside assistance, aiming not only to streamline the assistance process but also to empower mechanics to broaden their service horizons. It bifurcates the system into distinct components tailored for mechanics and customers. Programmed in Dart on the Flutter framework, the application seamlessly connects with Firebase as the database, ensuring efficient data management and retrieval. Within this comprehensive application, we have integrated user-centric features, robust data security measures, and real-time service tracking capabilities, all contributing to heightened transparency and user control. Users can request assistance by identifying their precise locations and service requirements, and mechanics can verify their availability, promptly providing clients with well-informed alternatives. The blockchain is intricately connected through endpoints on the cloud, contributing to the overall efficiency of the application. The integration of smart contracts and thorough mechanic verification collectively fortify the reliability and security of the assistance process, establishing a robust foundation for the successful execution of requested services; this not only ensures data integrity and security but also optimizes the performance of the blockchain in facilitating seamless transactions.
Blockchain-Powered Smart System Platform Development: Use Case – Water Meter Readings
Authors: Mohamed Shams Adhouha Ben , Talha Amira , Ktari Jalel , Taleb Youssef Ben , Frikha Tarek , Hamam Habib 
Published: February 2025

Abstract
Today, blockchain technology represents a significant advancement in the field of data management, providing promising opportunities to transform various sectors. Indeed, it offers innovative solutions and builds trust within multi-stakeholder business networks. This article looks at multiple concrete applications of blockchain, highlighting its potential for optimizing water meter reading processes. Moreover, there’s a growing trend toward incorporating Artificial Intelligence (AI) for more accurate and efficient water meter readings. This integration enhances the precision and efficiency of water meter readings, providing valuable insights into water consumption. More specifically, it explores how this technology can be integrated into the development of a dedicated Android application. Thanks to this application, users can now easily and quickly take water meter readings from their smartphone. The data is then secured on the Ethereum blockchain, using smart contracts to guarantee the integrity and transparency of the information recorded. This revolutionary approach opens new perspectives for efficient and secure data management in the field of water resources management.
Electromechanical Integration For Hybrid Solar and Wind Energy Systems: A Case For Maximized Renewable Energy Capture
Authors: Imon Kazi Abdullah Al , Newaz Abdullah Al Hossain , Uddin Nasir , Tanvir Imran Khan 
Published: February 2025

Objectives: This research focuses on the development of a novel electromechanical integration mechanism for hybrid solar and wind energy systems to maximize renewable energy capture. The primary goal is to enhance energy conversion efficiency through the combination of optimized electromechanical components. Additionally, the study aims to bridge gaps in existing hybrid energy system designs and integration techniques.

Methods: The study begins with an extensive literature review to identify gaps in current hybrid energy system designs and integration strategies. Based on these findings, a novel system architecture is proposed that incorporates advanced electromechanical components. To assess the performance of this proposed system, MATLAB/Simulink and COMSOL are used to model and simulate the hybrid system under various environmental conditions. A small-scale prototype is developed to validate the simulation results and analyze real-world performance. Control systems are also integrated into the design for load balancing, power management, and operational optimization. Additionally, a comprehensive environmental and economic analysis is carried out to evaluate the system's cost-effectiveness and ecological impact.

Results: The simulation results demonstrate significant improvements in energy conversion efficiency and system performance compared to existing hybrid energy systems. The small-scale prototype further validates these findings, providing real-world data on energy generation, efficiency, and sustainability. The control systems successfully optimize performance by balancing loads and managing power distribution under different operating conditions. Environmental and economic analyses show that the proposed system is more cost-effective and has a lower ecological impact than current alternatives.

Conclusion: The research concludes with a discussion on the key findings, emphasizing the improvements in efficiency, sustainability, and economic viability of the proposed hybrid energy system. The results suggest that the integration of electromechanical components and advanced control systems can significantly enhance the performance of hybrid solar and wind energy systems. Future work will explore further optimization of the system and its scalability for larger applications.