bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model-based cost-effectiveness of the IMPROVE score versus care as usual for risk-based selection of symptomatic patients for carotid revascularization
Authors: Nies Kelly , Ramaekers Bram , Auer Dorothee , Schindler Andreas , Saam Tobias , Bos Daniel , de Jong Pim , Nederkoorn Paul , de Borst Gert J. , Oostenbrugge Robert van , Joore Manuela , Kooi M. Eline , Smits Luc 
Published: January 2025

Abstract

Background. A clinical prediction model (IMPROVE) for ipsilateral ischemic stroke risk in symptomatic patients with carotid artery disease was recently developed and internally validated with good performance. In this decision-analytic study, we evaluated the model-based cost-effectiveness of IMPROVE-based triage versus triage in care-as-usual (CAU) for optimal medical treatment (OMT) alone or carotid revascularization plus OMT.
Methods. A dataset of 678 patients with a recent ipsilateral ischemic stroke, TIA or amaurosis fugax pooled from 4 cohort studies, informed a decision-analytic model. Stratification of patients for carotid revascularization was either based on ≥50% carotid stenosis (CAU arm), or based on a range of 3-year ipsilateral ischemic stroke risk thresholds (IMPROVE arm). The threshold resulting in the lowest number of strokes was selected as the optimal threshold. Patients with <50% stenosis (CAU arm) or an IMPROVE risk score below the threshold were modeled to receive OMT only. Parameter uncertainty was incorporated in probabilistic analyses using 10,000 Monte Carlo simulations for a 3-year and lifetime horizon. Subgroup analyses for mild (<50%), moderate (50-69%), and severe (70-99%) carotid stenosis were performed.
Results. IMPROVE-based triage, as compared to triage in CAU, reduced ipsilateral ischemic strokes and perioperative stroke/death by 34.5% (CAU: 4.3% vs. IMPROVE: 2.8%) over 3 years. Perioperative stroke occurred in 1.8% of the patients in CAU versus 1.4% for IMPROVE. Revascularizations decreased by 20% with IMPROVE, while QALYs slightly increased. Societal costs decreased on average by €1,441/patient for IMPROVE versus CAU for a 3-years time horizon (lifetime cost reduction: €6,101/patient). Subgroup analyses identified IMPROVE as the superior strategy for moderate/ severe stenosis (3-year and lifetime horizon) and mild stenosis (lifetime horizon).
Conclusions. Triage of symptomatic patients with carotid artery disease with the IMPROVE model versus CAU can lead to the prevention of one-third of ipsilateral ischemic strokes, while also reducing societal costs.
Elemene Injection Suppresses Pancreatic Cancer Progress through Regulating Cell Adhesion: A Research Based upon Network Pharmacology and Verification Test
Authors: Zhao Jiangang , Zhang Fenglin , Li Ping 
Published: January 2025

Background:
This study investigates the potential effects of elemene injection
on pancreatic cancer using network pharmacology and experimental validation.

Methods:
GEO database were used to acquire genes which are differentially expressed
between pancreatic cancer tissue and normal tissue. The vigorous energetic ingredients
were identified in research and the object genes were obtained from BATMAN-TCM.
The key targets and signaling pathways of elemene injection were identified using compound-
target network analysis, protein-protein interaction network analysis, and Gene
Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.
in vitro experiments were carried out to confirm the accuracy of the network pharmacology
predictions.

Results:
Two hundred and eleven target genes that may be involved in Elemene's impact
on pancreatic cancer were identified. Bioinformatics analysis was conducted to determine
the two active mixtures and one key target. GO and KEGG enrichment analyses
indicated that elemene injection exerts therapeutic effects on pancreatic cancer, regulating
the cell adhesion by ECM-receptor interaction pathway. The experiments verified
that elemene injection suppressed the growth and movement of pancreatic cancer cell
lines Panc02 and MiaPaca-2 and the mechanism is related to regulating ECM-receptor
interaction pathway-related genes. FN1 was identified as core targets by bioinformatics
analysis. The FN1 was downregulated by elemene injection and was validated by QPCR
and Western Blot.

Conclusion:
The findings of the current study emphasized that elemene injection might
control cell attachment, decrease metastasis, and suppresses pancreatic cancer progress.
FN1 might be a therapeutic target for pancreatic cancer.
Network Pharmacology, Molecular Docking, Molecular Dynamics to Explore the Mechanism of Danggui Shaoyao Powder for Hepatic Encephalopathy
Authors: Zhang Miao , Liu Rongxin , Zhao Yusen , Chen Zixin , Zhai Honglin , Si Hongzong 
Published: January 2025

Background:
Patients with hepatic encephalopathy (HE) have many triggers and a high mortality
rate. The protective effect of existing therapeutic drugs on the liver is weak. We found that Danggui Shaoyao
Powder can improve the symptoms of HE and may have a better liver protection effect. And the mechanism
of it is unclear.

Objective:
The research explores the mechanism of Danggui Shaoyao Powder for the treatment of HE through
network pharmacology, molecular docking and molecular dynamics.

Methods:
Targets of Danggui Shaoyao Powder were screened from Traditional Chinese Medicine System
Pharmacology Platform (TCMSP), SwissTargetPrediction, and Uniport. GeneCards was used to gain targets
of HE. Further, core targets and ingredients were screened by protein-protein interaction network (PPI) and
herbs-compounds-targets network. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes
(KEGG) enrichment analysis were completed to screen relative sites and signaling pathways. Molecular docking
and dynamics were used to show the stability of ligand-receptor complexes.

Results:
IL6, SRC and kaempferol, beta-sitosterol were screened as the top two core targets and ingredients.
Dendrites, dendritic trees, and membrane sides were defined as the main sites of action. Core signaling pathways
were screened such as: PI3K-Akt and MAPK. Molecular docking shows well-defined binding sites and
the stability of the binding is demonstrated by molecular dynamics.

Conclusion:
Through this study, Danggui Shaoyao Powder may act on IL6, SRC, and other targets through
ingredients such as kaempferol and beat-sitosterol and regulate signaling pathways such as PI3K-Akt, MAPK
and NF-κB to the treatment of HE.
Herbal Mucoadhesive Gels for Canker Sores: Analysis of Physicochemical Properties, Efficacy, and Safety
Authors: Yapar Evren Algın , İnal Ebrar , Kara Bilge Ahsen , Yıldırım Tuana Seray , Nur Yılmaz Fatıma , Özkanca Cemre , Erdal Meryem Sedef , Döşler Sibel , Kartal Murat 
Published: January 2025

Aim:
The goal of this research was to formulate mucoadhesive gels using hydroglyceric
extracts of Cistus creticus L. and Inula viscosa (L.) Aiton, either separately or in combination,
utilizes carboxymethyl cellulose and detects their physicochemical characteristics and safety
for oromucosal cells and antimicrobial (antibacterial, antifungal, and antiviral) efficacy to assess
their performance.

Methods:
Using LC-HRMS, the extracts of C. creticus and I. viscosa were examined. Evaluations
were conducted on the formulations' viscosity, cytotoxicity-cell proliferation controls, texture,
antibacterial activity, pH, and organoleptic properties. The minimal inhibitory concentrations
and microbroth dilution tests were used to assess the effectiveness of the formulations.

Results:
The pH, organoleptic, and physical characteristics of each formulation have been determined
to be appropriate. The research results demonstrated that I. viscosa contributed antiviral
efficacy to the formulations linked to dose-dependent activities against all examined mouth
pathogens, whereas C. creticus provided antibacterial and antifungal efficacy. The formulation
containing C. creticus extract alone was the most cytotoxic, whereas the formulation including I.
viscosa extract alone was the least cytotoxic against gingival fibroblast cells, according to the
findings of tests on cell proliferation and cytotoxicity.

Conclusion:
The formulation contained a 32% 1:1 mixture of I. viscosa and C. creticus hydroglyceric
extracts was detected as safe with acceptable cytotoxicity along with antibacterial and
antiviral effectiveness, were encouraging for future investigations.
Characterization of Five Natural Anthraquinone Compounds as Potent
Inhibitors against CYP1B1: Implications for Cancer Treatment
Authors: Chen Zujia , Xu Zhixiang , Chen Xiaodong , Guan Xintong , Du Jie , Zhang Jia hui , Wang Chang yuan , Wu Jingjing 
Published: January 2025

Background:
Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic enzyme that is overexpressed
in many tumors and is associated with tumor development and acquired resistance. Few studies have
reported that anthraquinone compounds have inhibitory activity against the CYP1B1 enzyme. Cassiae semen
(Leguminosae) is a well-known traditional Chinese medicine containing more than 70 compounds. The crude
extracts and pure compounds of Cassiae semen have been widely used in preclinical and clinical practice for
their beneficial effects, such as neuroprotective, hepatoprotective, antimicrobial, antioxidant, and hypotensive
effects. Aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin, and rhein are important active natural anthraquinones
in Cassiae semen.

Objective:
Aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin, and rhein have a wide range of pharmacological
activities and have been found to have good anti-tumor and antioxidant effects. However, the underlying
mechanisms of these pharmacological activities remain poorly understood. This study aimed to investigate
the inhibitory effects of five natural anthraquinones on the activity of CYP1B1 and to analyze the structure-
activity relationship of these compounds.

Materials and Methods:
In this study, 7-ethoxyresorufin O-deethylation (EROD) was used as the fluorescent
substrate of CYP1B1 to investigate the inhibition effect, and molecular docking was performed to further determine
the structural-activity relationship of the compound molecules.

Results:
We found that aloe-emodin and chrysophanol had strong inhibitory effects on CYP1B1 with IC50 values
of 0.28 and 0.34μM, respectively, while obtusifolin and aurantio-obtusin had IC50 values of 0.77μM and
9.11μM, respectively. The structural activity analysis showed that the inhibition strength was related to the position
of the hydroxyl group substitution and the number of methoxy group substitutions. Rhein containing one
carboxyl group showed the weakest inhibition of 23.72μM. The inhibition kinetics showed that all five compounds
belonged to the non-competitive inhibition model. The inhibition kinetics revealed that all five compounds
exhibited the non-competitive inhibition model.

Conclusion:
The present study provided a comprehensive analysis of the inhibitory effects of five natural anthraquinones,
namely aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin and rhein, on CYP1B1 activity,
and elucidated the structure-activity relationship. Molecular docking simulations further revealed the specific
amino acid residues within the active site of CYP1B1, where these compounds exerted their actions. These
findings offer novel insights into investigating the potential antitumor properties of natural anthraquinones.
New Advances in Drug Research for Myopia Control in Adolescents
Authors: Liu Yu , Dang Yalong 
Published: January 2025

Background:
Myopia is one of the most common eye diseases worldwide, with an increasing
incidence observed in recent years. Globally, effective treatments for myopia have been
extensively explored. In recent years, research on drugs for the treatment of myopia has become a
popular topic in ophthalmology, with some breakthroughs having been achieved. Compared with
surgical treatment, drug treatment is easier for people to accept. Although the efficacy of some
drugs in delaying the development of myopia has been confirmed, the mechanism and site of action
of some drugs are still not completely clear.

Objective:
In this study, we review the recent related research on drug therapy for myopia at home
and abroad, describe the mechanism of various drugs in treating myopia, evaluate their clinical application
value, and identify existing problems.

Results:
These drugs include atropine, a series of anticholinergic drugs, dopamine agonists, 7-
methylxanthine, and intraocular pressure-lowering drugs.

Conclusion:
Results highlight the efficacy of atropine in myopia treatment with minimal side effects.
Anticholinergic medications, such as atropine, have demonstrated efficacy in managing the
progression of myopia with a reduced incidence of adverse effects. The emphasis is placed on
achieving better long-term effectiveness and minimizing the rebound effect after treatment is
stopped. Furthermore, participating in outdoor activities and reducing eye strain are proven strategies
for preventing myopia.
TCF19 Enhances Glioma Cell Proliferation via Modulating the Β-Catenin Signaling Pathway through Accelerating DHX32 Transcription
Authors: Tan Jing , lian Haiping , Zheng Qi , Yang Tingting , Wang Tuo 
Published: January 2025

Background:
Transcription factor 19 (TCF19) is considered a crucial transcription factor and acts as an oncogene in a few cancers. Nevertheless, the effect and mechanism of TCF19 on glioma remain unknown.

Objective:
This research aimed to explore the function of TCF19 on glioma progression and clarify the potential mechanism.

Methods:
TCF19 and DHX32 expressions in glioma were determined using bioinformatics, Quantitative real-time PCR, and immunohistochemistry. MTT assay was
carried out to detect the biological function of TCF19 and DHX32 in glioma cell multiplication. Cell-cycle distri-bution and apoptosis were measured by using
FACS. The function of TCF19 on glioma growth was examined using tumor xenografts assay. Bioinformatics analysis, ChIP-qRT-PCR, and reporter gene assay were
employed to illustrate the TCF19 target regulating DHX32 tran-scription.

Results:
TCF19 was observably upregulated in glioma and has important clinical significance. Overexpressing TCF19 expedited glioma cell multiplication and
cell-cycle transition, mean-while preventing apoptosis. TCF19 knockdown inhibited cell proliferation, cell-cycle transi-tion, and tumour growth, simultaneously
accelerating apoptosis. TCF19 expressions had a positive correlation with DHX32 expressions in glioma. It was demonstrated that TCF19 acti-vated DHX32
transcriptional activity in glioma by combining it with the promoter of DHX32. DHX32 promoted glioma cell growth and cell-cycle transition while restraining
apoptosis. Overexpressing DHX32 eliminated the function of TCF19 knockdown on cell multiplication, cell-cycle transition, and apoptosis. Moreover,
TCF19 activated the β-catenin pathway by en-hancing DHX32 transcriptional activity.

Conclusion:
TCF19 promotes glioma cell multiplication and cell-cycle transition while sup-pressing apoptosis by modulating the β-catenin signaling pathway
via accelerating DHX32 transcription. These findings provide a promising therapeutic target for glioma.
Synthesis and Evaluation of Coumarin Clubbed Sulfanilamide and
2-Aminobenzothiazole Hybrids for Antibacterial Applications
Authors: Lata Suman , Mehmi Gagandeep , Kaur Hardeep , Sharma Anuradha , Pandit Amit , Abbot Vikrant 
Published: January 2025

Background:
The increasing prevalence of drug-resistant bacterial infections poses a
significant challenge to global healthcare, necessitating the development of novel antibacterial
agents. Coumarin-based derivatives are well-recognized for their diverse biological activities, and
hybridization with other pharmacophores offers a promising strategy for enhancing therapeutic
efficacy and overcoming resistance.

Objective:
This study aimed to synthesize and evaluate a novel series of coumarin hybrids by integrating
the coumarin scaffold with sulfanilamide (9a-e) and 2-aminobenzothiazole (10a-e), targeting
bacterial pathogens through a dual pharmacophoric approach.

Methods:
The synthesized hybrids were characterized using mass spectrometry, FTIR, and NMR
(1H and 13C) to confirm their structural integrity. Antibacterial activity was assessed in vitro
against Escherichia coli and Staphylococcus aureus at concentrations of 100, 250, and 500 μg/ml,
with ciprofloxacin as the standard. The molecular binding mechanism was explored using molecular
docking and pharmacophore-based analysis.

Results:
Among the synthesized derivatives, compounds 9e and 10e exhibited the highest antibacterial
activity, with inhibition zones of 22 mm and 21 mm against E. coli and 25 mm and 22 mm
against S. aureus at 500 μg/ml, demonstrating comparable efficacy to ciprofloxacin. Molecular
docking studies revealed strong interactions of these compounds with bacterial enzymes, supporting
the in vitro results and highlighting their potential as protein-inhibitor candidates.

Conclusion:
The novel hybrid derivatives demonstrated significant antibacterial activities, suggesting
their potential as promising therapeutic agents. Their effectiveness against various bacterial
strains indicated that these compounds could serve as a foundation for the development of new
antibacterial drugs. Further research and optimization are needed to enhance their potency and
ensure their safety, paving the way for future clinical applications.

other:
NA
Physicochemical, Pharmacognostical, Phytochemical, Heavy Metal and
Pesticidal Residue Analysis of Angelica glauca Edgew roots: An Approach
to Establish Quality Standards Using Advanced Analytical Techniques
Authors: Mishra Arun Kumar , Paliwal Sarvesh Kumar 
Published: January 2025

Background:
Angelica glauca (AG) (family Apiaceae) is used by tribes as a spice and to
treat various diseases. Before consumption, effective measures must be used for quality control tests.
This study establishes quality standards for A. glauca. The study analyses A. glauca roots for
physico-chemical, pharmacognostic, phytochemical, heavy metals, pesticidal residue, microbial load,
and aflatoxin

Methods:
The standard procedure was used for powder microscopy and physiochemical parameters.
Multiple culture media were used to measure microbial load. Aflatoxins were estimated using HPLC.
Mercury, arsenic, lead, cadmium, chromium, and nickel were estimated using graphite furnace
atomic absorption spectrometry. To identify 87 pesticide residues in A. glauca roots, LC-MS was
used

Results:
On root powder microscopy, parenchymatous cells packed with yellow material, capillaries
with reticulate thickenings, and simple oval to circular starch grains were found. Foreign matter,
LOD, total ash, and extractive values were all within range. Salmonela, Pseudomnas, and Coliform
(E. coli) were absent. The total viable aerobic bacterial count was 1.14 x 103 cfu/ml, compared to 1.0
x 105 permitted. Aflatoxins were absent in all samples. Heavy metal levels met the FSSR 2011
maximum residue standard for foods not specified. All 87 pesticides in the crude sample were below
detection limits, indicating the safety and quality of the A. glauca root sample.

Conclusion:
The current findings can be utilized in quality control procedures and to assess the
quality of A. glauca samples before incorporating them into formulations. Phytochemical tests,
heavy metal analysis, and pesticide residue contents can be used to assess quality before using A.
glauca raw materials.
Sorption Preconcentration of Heavy Metals on Graphene Oxide for Analysis of Waters by Electrothermal Vaporization ICP-OES
Authors: Medvedev Nikolay S. , Frolova Alexandra O. , Kurbatova Valeriya D. , Guselnikova Tatiana Ya. , Makotchenko Viktor G. , Saprykin Anatolij I. 
Published: January 2025

Background:
Heavy metals (HMs) such as Cr, Hg, Pb, etc., are major threats to human
health due to their toxic and carcinogenic properties. So, the determination of HMs concentrations in
waters is an actual and important task.

Methods:
In this paper, the method includes a preliminary concentration of HMs and other analytes
(Ag, Au, Ba, Be, Bi, Cr, Hg, In, Pb, Sn, and Zn) from water solutions on the graphene oxide and
subsequent analysis of slurries of sorbent by electrothermal vaporization inductively coupled plasma
optical emission spectrometry (ETV-ICP-OES) is developed for the first time.

Results:
The high efficiency of analytes sorption on graphene oxide made it possible to significantly
increase the sensitivity of the analysis. The limits of detection of Ag, Au, Ba, Be, Bi, Cr, Hg, In, Pb,
Sn, and Zn from 0.7 to 300 ng L-1 are achieved for ETV-ICP-OES analysis. The use of electrothermal
vaporization for sample introduction allows the analysis of sorbent suspensions and avoids the
desorption stage, reduces sample dilution, increases the preconcentration factor, and improves limits
of detection (LODs) of analytes by 2-33 times compared to routine inductively coupled plasma optical
emission spectrometry analysis (ICP-OES) with sorption preconcentration.

Conclusion:
For Ba, Be, Bi, Cr, In, Pb, Sn, and Zn ETV-ICP-OES provides LODs from 2 to 33
times lower compared to conventional ICP-OES analysis with sorption preconcentration due to higher
preconcentration factor and transport efficiency of introducing of the analytes concentrates into
the ICP. The developed method was applied to the analysis of real tap and mineral water samples.
The results of analysis by ETV-ICP-OES with preconcentration of trace elements and ICP-OES were
in good agreement. As a result of lower LODs of analytes, ETV-ICP-OES analysis provides the determination
of concentrations of Ba, Bi, Sn, and Pb in tap and mineral water samples.
Remimazolam in Modern Anaesthesia Practice: From Pharmacokinetics to Clinical Outcomes
Authors: Kateel Ramya , Bhat Ravitej 
Published: January 2025

Abstract:
Remimazolam, a novel ultra-short-acting benzodiazepine, has emerged as a promising
agent in the field of anaesthesia and sedation. This comprehensive review examines the pharmacological
properties, clinical applications, and safety profile of remimazolam. Its unique pharmacokinetic
profile, characterised by rapid onset and offset of action, organ-independent metabolism, and
availability of a specific reversal agent, offers potential advantages over traditional sedatives. Clinical
studies have demonstrated its efficacy in procedural sedation, particularly in gastrointestinal
endoscopy and bronchoscopy, as well as in the induction and maintenance of general anaesthesia.
Emerging evidence also suggests its potential utility in intensive care sedation. Remimazolam has
shown a favourable safety profile, with studies indicating comparable or improved hemodynamic
stability and potentially reduced respiratory depression compared to propofol. The availability of
flumazenil as a reversal agent enhances its safety profile. However, as with any relatively new
medication, ongoing research is needed to fully characterise its long-term safety and optimal use
in various clinical scenarios. This review synthesises current knowledge on remimazolam, providing
insights into its potential to optimise sedation and anaesthesia practices across diverse patient
populations and clinical settings, while highlighting areas for future research.