bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is LPBSA the Future of Cancer Diagnosis? Exploring Machine Learning and Nature-Inspired Algorithms for Liver, Breast, and Lung Cancer Detection
Authors: dana  , Tarik  
Published: January 2025

Abstract

Cancer diseases are remaining a leading cause of death in all over the world, this is encouraging the development of advanced diagnostic systems for reliable and accurate detection. The current study investigates the models of traditional machine learning and nature-inspired algorithms for classifying liver, breast and lung cancer cases utilizing structured datasets. More focuses of this research will be on the performance evaluation of five nature-inspired optimizer algorithms like Learner Performance-Based Behavior with Simulated Annealing (LPBSA), Learner Performance-Based Behavior (LPB), FOX Algorithm (FOX), Genetic Algorithm (GA), Particle Swarm Optimization (PSO), Support Vector Machine (SVM), Random Forest (RF), Decision Tree (DT). Among these models LPBSA performing the best, consistently obtained the highest accuracy of 92%, sensitivity 94% and specificity 90%, with confusion matrices reflecting minimal false negative and positives. This work contributes to growing adoption of popular algorithms for enhancing healthcare diagnosis and LPBSA can be utilized in other field investigations.
The temporal and spatial dynamic characterization of intestinal microbiota in Taihe Silky Fowl
Authors: Li Wentao , Guo Haoneng , Wu Youping , Wang Yizhen , Lu Zeqing 
Published: January 2025

Abstract

Background
Through large-scale sampling and 16S sequencing at 8 timepoints and 3 intestinal regions (288 samples), this study aimed to systematically elucidated the dynamic characterization in intestinal microbiota and core microbiota of Taihe Silky Fowl, providing a theoretical basis for precise regulation of native microbiota in this precious Chinese local breed through nutritional means.
Results
The results showed that the alpha and beta diversity of intestinal microbiota changed significantly with the different age and intestinal regions. In alpha diversity, Ace index and Shannon index: cecum > rectum > duodenum; Simpson index: cecum > rectum and duodenum. In beta diversity, compared to the duodenum and rectum, cecum samples were more concentrated. The core phylum (top 5) of Taihe Silky Fowl was Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Cyanobacteria. The core genus (top 10) was Lactobacillus, Bacillus, Escherichia-Shigella, Alistipes, norank_o__Clostridia_UCG-014, Bacteroides, Faecalibacterium, norank_f__Ruminococcaceae, Enterococcus and Streptococcus. As age increased, the cecal microbiota degree centrality rapidly increased from 0 to 1 weeks old, then rapidly decreased from 1 to 2 weeks old and remained relatively stable from 2 to 21 weeks old, while the betweenness centrality was opposite. Closeness centrality decreased continuously with increasing age. The cecal microbiota function varied at different age, the central functions were nucleic acid metabolism and protein synthesis in 0 weeks old, carbohydrate metabolism and quorum sensing in 9 weeks old.
Conclusions
In conclusion, the structure, composition, and function of intestinal microbiota in Taihe Silky Fowl dynamically changed with age and intestinal regions.
Effect of Fibrates on Lipoprotein-associated Phospholipase A2 Mass and
Activity: A Systematic Review and Meta-analysis of Controlled Clinical Trials
Authors: Simental-Mendía Luis E. , Simental-Mendía Mario , Gamboa-Gómez Claudia I. , Jamialahmadi Tannaz , Sahebkar Amirhossein 
Published: January 2025

Background:
In vascular tissue, macrophages and inflammatory cells produce the enzyme lipoprotein-
associated phospholipase A2 (Lp-PLA2). Treatment with fibrates decreases Lp-PLA2 levels in individuals
with obesity and metabolic syndrome; however, these findings have not been fully clarified.

Objective:
The goal of this study was to investigate the possible effects of fibrate therapy on Lp-PLA2 mass
and activity through a meta-analysis of clinical trials.

Methods:
Web of Science, PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases were searched
using MeSH terms and keywords. Randomized controlled trials (RCT) evaluating the effect of statins on Lp-
PLA2 mass and/or activity were included in the meta-analysis. Quantitative data were analyzed using a random-
effects model and the generic inverse variance method.

Results:
The meta-analysis of 10 clinical trials indicated that fibrate treatment has no significant effect on Lp-
PLA2 mass (fibrate vs. placebo/nothing = WMD: -3.29 ng/ml, 95% CI: -21.35, 14.78, p = 0.72; fibrate vs. active
control = WMD: -1.08 ng/ml, 95% CI: -51.38, 49.22, p = 0.97); Lp-PLA2 activity (fibrate vs. active control
= WMD: 0.84 nmol/ml/min, 95% CI: -0.17, 1.84, p = 0.10); HDL-LpPLA2 activity (fibrate vs. active control
= WMD: 0.77 nmol/ml/min, 95% CI: -0.33, 1.88, p = 0.17); and secretory PLA2 (fibrate vs. active control
= WMD: 0.37 ng/ml, 95% CI: -1.22, 1.97, p = 0.65). Also, the results of the sensitivity analysis were robust
for all these parameters.

Conclusion:
In conclusion, fibrate therapy did not reduce the mass and activity of Lp-PLA2.
Exploration of Novel Therapeutic Targets for Breast Carcinoma and Molecular
Docking Studies of Anticancer Compound Libraries with Cyclin-dependent
Kinase 4/6 (CDK4/6): A Comprehensive Study of Signalling Pathways for Drug
Repurposing
Authors: Najmi Asim 
Published: January 2025

Aims:
This study aims to identify and evaluate promising therapeutic proteins and compounds for
breast cancer treatment through a comprehensive database search and molecular docking analysis.

Background:
Breast cancer (BC), primarily originating from the terminal ductal-lobular unit of the breast, is
the most prevalent form of cancer globally. In 2020, an estimated 2.3 million new cases were reported, resulting
in approximately 685,000 deaths. Mutations in the BRCA1 and BRCA2 genes are well-established in hereditary
breast cancer. The identification of effective therapeutic proteins for BC remains a complex and
evolving area of research.

Objective:
This study aims to identify and evaluate promising therapeutic proteins and compounds specific to
breast cancer through a comprehensive database search and molecular docking analysis.

Methods:
A rigorous search was conducted within the National Cancer Institute (NCI), NCI Metathesaurus,
SIGnaling Network Open Resource (SIGNOR), Human Protein Atlas (HPA), and the Human Phenotype Ontology
(HPO) to shortlist proteins linked to BC (CUI C0678222). Recent studies were reviewed to understand
the administration of CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) combined with endocrine therapy
for HR-positive and HER2-negative breast cancer. Anticancer compound libraries available at ZINC and
PubChem were analyzed. Compounds were evaluated based on their binding energies with CDK4 protein, a
rationally selected druggable target.

Results:
Key proteins linked to breast cancer were identified through database searches. Proliferation, apoptosis,
and G1/S transition pathways were frequently found dysregulated in breast cancer. ZINC13152284 exhibited
the strongest binding energy at -10.9 Kcal/mol, followed by ZINC05492794 with a binding energy of
-10.4 Kcal/mol. Preexisting drugs showed lower binding energies with the CDK4 protein.

Conclusion:
The study highlights the importance of drug repurposing as a strategy for the safe and effective
treatment of breast cancer. Synthetic inhibitors often cause severe side effects, emphasizing the need for novel
targets and compounds with better therapeutic profiles. Molecular docking identified promising compounds
from the ZINC database, suggesting potential new avenues for breast cancer therapy.
The Expression Characteristics and Interrelationships of FNDC5 and Pyroptosis-Associated Molecules in the Peripheral Blood of Patients with Coronary Heart Disease
Authors: Pan Yujia , Ou Hangjun , Liu Danan 
Published: January 2025

Objectives:
The aim of this study was to investigate the expression characteristics and
interrelationships of FNDC5 and pyroptosis-associated molecules in peripheral blood mononuclear
cells of patients with coronary heart disease (CHD).

Methods:
Patients were divided into stable angina (SA), unstable angina (UA), and acute myocardial
infarction (AMI) groups based on different clinical symptoms. According to the Gensini
score, they were then divided into mild, moderate, and severe lesion groups. The control (NC)
group was also set. ELISA assay was employed to detect the levels of Irisin, IL-1β, and IL-18, and
the levels of pyroptosis-associated molecules, NF-κB p50, NF-κB p65, and FNDC5 were detected
and compared by qRT-PCR and Western blot (WB). Logistic regression and Spearman's partial
correlation analysis were used to analyze the pathogenic factors of CHD and explore the interrelationships
between FNDC5 and the molecules.

Results:
IL-1β and IL-18 of CHD patients were increased, while the Irisin was decreased. With
the aggravation of symptoms and severity of coronary artery stenosis, the former increased, and
the Irisin gradually decreased (P<0.05). About qRT-PCR and WB: With the aggravation of symptoms,
the levels of pyroptosis-associated molecules and other indicators were increased, and FNDC5
was decreased (P<0.05). NLRP3, Caspase-1, and NF-κB p50 protein were positively correlated
with the incidence of CHD, and FNDC5 was also negatively correlated with that of CHD.

Spearman's Partial Correlation Analysis:
Even when common risk factors for CHD were taken
into account, FNDC5 and NLRP3 were still found to be negatively connected.

Conclusion:
The decreased expression level of FNDC5 and the increased level of pyroptosis-associated
molecules may be related to CHD.
Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery
Authors: Shukla Shruti , Kushwah Shikha , Mani Ashutosh 
Published: January 2025

Abstract:
The global rise of drug-resistant malaria parasites is becoming an increasing threat to
public health, emphasizing the urgent need for the development of new therapeutic strategies. Artimisinin-
based therapies, once the backbone of malaria treatment, are now at risk due to the resistance
developed in parasites. The lack of a universally accessible malaria vaccine exacerbates
this crisis, underscoring the need to explore new antimalarial drugs. A more comprehensive understanding
of the parasites’s life cycle has revealed several promising targets, including enzymes,
transport proteins, and essential metabolic pathways that the parasite relies on for its survival and
proliferation. This review provides an in-depth analysis of the vulnerabilities displayed by Plasmodium
and recent advances that highlight potential drug targets and candidate molecules.
Delineating CYP2C19-Mediated Interactions: Network Pharmacology Investigation of Ilaprazole and Clopidogrel versus Conventional Proton
Pump Inhibitors
Authors: Ananthathandavan Priyadharshini , Narayanasamy Damodharan 
Published: January 2025

Background:
Clopidogrel, an antiplatelet drug commonly used in cardiovascular disease,
is metabolized by the liver mainly through CYP2C19. Concomitant use of Proton pump inhibitors
along with clopidogrel may affect the potency of clopidogrel by CYP2C19 inhibition. However, a
novel PPI, ilaprazole is known to differ in its pharmacokinetic features, given the potential differences
between ilaprazole’s interactions and their metabolism with clopidogrel. Network pharmacology investigation
could be a useful tool to evaluate the drug-drug interaction between them.

Methodology:
The molecular structures and targets were retrieved from PubChem and SwissTargetPrediction
to establish the information related to the identified drugs. The possible shared targets
between the clopidogrel and PPIs were explored by a Venn analysis. Subsequently, Protein-Protein
Interaction networks were established using the STRING database. Hub genes were also determined
using the Cytoscape cytoHubba plugin.

Results & Discussion:
Ilaprazole (13.6%) and pantoprazole (13.6%) were characterized by fewer
targets being shared with clopidogrel compared to conventional PPIs (14.9%). Moreover, CYP2C19
was not a hub gene in ilaprazole and pantoprazole interactions, which indicated no significant
CYP2C19 involvement. On the other hand, CYP2C19 functioned as a hub gene in the interactions
with rabeprazole, lansoprazole, dexlansoprazole, omeprazole, and esomeprazole. As a result, patients
receiving pantoprazole and ilaprazole would be at a lower risk for developing adverse cardiovascular
events by maintaining the clopidogrel therapeutic effect.

Conclusion:
The application of the network pharmacology technique allows us to consider the potential
for different effects of PPIs on clopidogrel and its metabolism via CYP2C19. There is a lower
chance of experiencing adverse effects from an interaction between ilaprazole and clopidogrel as
ilaprazole has not been linked to CYP2C19. More research is necessary to confirm these results and
provide clinical guidance for patients undergoing clopidogrel and PPI combination therapy.
Ultrasound-assisted and Efficient Multicomponent Synthesis of 4H-Pyran Derivatives catalyzed by LiOH.H2O in Water
Authors: Masmoudi Nihel , Chtourou Manef 
Published: January 2025

Aim and Objective:
It is well established that 4H-pyran derivatives hold a sig-nificant position in synthetic organic chemistry due to their diverse biological and phar-macological properties. This work aims to introduce a novel synthetic pathway for highly functionalized 4H-pyran derivatives, achieved through a 1,4-Michael addition followed by a cascade cyclization. This reaction is catalyzed by LiOH·H2O under ultrasonic irradiation in water, offering an efficient and environmentally friendly approach.

Materials and Methods:
In this study, lithium hydroxide monohydrate (LiOH·H2O) was used as the catalyst. To explore environmentally friendly methods, two novel approaches utilizing pure water were investigated (Method 1 and Method 2). The first method in-volves the use of alkylidene reagents malononitrile and ethyl acetoacetate in an aqueous medium. The second method features a multi-component cyclocondensation of aromatic aldehydes, malononitrile, and ethyl acetoacetate, activated by ultrasound waves and con-ducted in pure water. The impact of various substituents on the formation of 4H-pyrans, including both electron-poor and electron-rich aromatic aldehydes, was also evaluated.

Results:
Most products were obtained in high yield and as very pure crystals with distinct colors. Generally, aromatic aldehydes with electron-withdrawing groups (Cl) exhibited greater reactivity than those with electron-donating groups (OMe). This trend is clearly demonstrated when comparing entries 3 and 4 with entries 5 and 6 in Tables 1-6.

Conclusion:
Compared to other procedures, this method is simple, fast, eco-compatible since it uses water as a solvent. In addition, the products are obtained in good yields in the pure state after simple recrystallization without the need for other purification techniques, such as column chromatography. These factors make this novel approach highly attractive for the synthesis of 4H-pyrans.
The Exploration of TCM Therapeutic Mechanism as Evidenced by Houpusanwu Decoction on GI Disorders Treatment using Systems Pharmacology
Authors: Wang Shuailong , Zhao Xulong , Li Yan 
Published: January 2025

Background:
Gastrointestinal (GI) disorders are a kind of common, but complicated disease
that may be triggered by many factors. In Asia, many traditional Chinese herbs are prominent in
treating GI disorders, but the pharmacological mechanism still remains vague or unknown due to the
multiple-component characteristics of traditional Chinese medicine (TCM).

Objective:
In order to investigate the therapy mechanism of traditional Chinese medicine (TCM) for
Gastrointestinal (GI) diseases, a typical TCM prescription, Houpusanwu Decoction, for the treatment
of ileus, a severe GI disease, is used as a probe presently.

Method:
We performed data mining on all components in Houpusanwu Decoction (HD), established
a corresponding component database, and then conducted ADME screening of potentially active
compounds in the database. Next, we identify potential targets of HD candidate compounds, followed
by the establishment of a series of pharmacological networks. Finally, we conducted SP analysis
and mechanism analysis.

Results:
Through pathway analysis, we found that HD treats ileus mainly through four pathways,
i.e., GI motility-related Calcium, inflammation-related SCF/c-kit and p38/MAPK, and thrombosis
and diabetes-related JAK2/STAT3 signaling pathways, which indicated that HD is a typical prescription
with multichannel and multifunction of TCM characteristics.

Conclusion:
This study not only expounds the pathogenesis of ileus and, at the same time systematically
illuminates the curative mechanism of HD, but also provides a novel SP method to explore the
therapeutic mechanism of TCM in treating complicated GI diseases.
A Current Review on Transdermal Delivery of Protein and Peptides: Possibilities and Challenges
Authors: Thakur Nishant , Thakur Shivani , SINGH YASH PAL , Prasad Sonima , Kaur Bhupinder , Sharma Chandan 
Published: January 2025

Abstract:
Transdermal drug administration has become increasingly popular in pharmaceutical research
due to its potential to enhance drug bioavailability, patient compliance, and therapeutic effectiveness.
Transdermal administration of proteins and peptides has proven to be a viable method for
enhancing the therapeutic efficacy and patient adherence to biologic medications. Administering
proteins and peptides through the gastrointestinal route exposes them to stomach acid and enzymes,
causing denaturation and resulting in poor bioavailability. Moreover, to address these issues, various
research groups are focusing on transdermal delivery systems as an alternative route of administration.
Therefore, in this article, we tried to cover the recent developments in formulation strategies,
transdermal delivery systems, and regulatory issues for protein and peptide medicines. The main
approaches for peptide administration, including nanoparticle carriers, biophysical enhancement
techniques, and microneedle-based devices, have been discussed to overcome the difficulties of delivering
macromolecular medications through the skin barrier. Furthermore, we analyse the regulatory
environment that oversees the creation and authorization of transdermal peptide and protein delivery
systems, highlighting the significance of quality control, safety, and efficacy, while also focusing
on clinical advancements and recent research findings.. This review attempts to offer insights delivery
of peptides and proteins. This study focuses on transdermal methods, summarizing recent advancements
in protein and peptide drug delivery. The transdermal route is favored over oral administration
due to its numerous advantages, including non-invasiveness, high patient compliance, and
avoidance of the first-pass effect. Consequently, it highlights the development of an efficient carrier
system that demonstrates these benefits effectively.
Impact of the Extraction Method and Solvent on the Phenolic Compound Content and Antioxidant Potential of the Aerial Part of Ephedra altissima: In vitro and In silico Studies
Authors: Houhou Dalal , Saad Somia , Menacer Rafik , Ferroudj Sana , Zeraib Azzeddine , Karoune Samira , Fadlaoui Haroun , Bendjemana Katia 
Published: January 2025

Background:
Despite the widespread use of Ephedra altissima plant in traditional Algerian
medicine, the biological potential of this species has still not been well explored.

Objective:
This study, for the first time, focused on determining the effect of extraction methods and
solvents on the phenolic content and antioxidant ability of the aerial part of Ephedra altissima.

Methods:
Extraction was carried out by maceration and Soxhlet using the solvents H2O, Methanol/
H2O and Petroleum ether. The chemical profile of E. altissima was determined by a qualitative
HPLC/UV–Visible, and the antioxidant potential was evaluated by in vitro and in-silico studies.

Results:
The aqueous extract obtained by maceration exhibited the greatest total phenol content,
while the petroleum ether prepared by Soxhlet extraction demonstrated the highest total flavonoid
and condensed tannin contents. The HPLC profile showed the presence of a variety of phenolic compounds.
The in-vitro assay results indicated good antioxidant potential. Gallic acid and sinapic acid
were highlighted as the most potent antioxidants in the Soxhlet hydro-methanolic and petroleum
ether extracts, respectively, according to the machine learning model. Molecular docking predicted
the possible antioxidant potential of E. altissima phytocompounds by the interaction with human
peroxiredoxin 5, and epicatechin was the most effective ligand. Molecular dynamics simulations
confirmed the stability of the epicatechin-Prdx5 complex. Multivariate analysis was used to categorize
the Ephedra altissima extracts into three groups according to their phenolic compound content
and in vitro antioxidant ability.

Conclusion:
Overall, the results of the present study revealed that the choice of solvent and extraction
technique directly influence the biomolecule content and bioactivity of Ephedra altissima aerial
part extracts.
Synergistic Anti-tumorigenic Effects of Cabazitaxel and Usnic Acid Combination on
Metastatic Castration-Resistant Prostate Cancer Cells
Authors: Bergel Ceyda Colakoglu , Eryilmaz Isil Ezgi , Bulut Ebrucan , Balaban Rumeysa Fatma , Egeli Unal , Cecener Gulsah 
Published: January 2025

Background:
Prostate cancer (PC) affects millions of men, causing high mortality rates. Despite the
treatment approaches, the options for metastatic castration-resistant prostate cancer (mCRPC), a lethal form of
advanced PC, are still limited. Cabazitaxel (Cbx) is the last taxane-derived chemotherapeutic approved for Docetaxel-
resistant mCRPC patients. However, its effects are limited due to the activation of several pathways. Therefore,
new approaches are needed to increase the efficacy of Cbx. Usnic acid (UA) is a natural product with wellknown
anti-tumorigenic and synergistic effects with various chemotherapeutics. Although the cytotoxicity of UA
and Cbx has been evaluated on mCRPC cells, the anti-tumorigenic effect of UA combination with any taxane has
not been investigated yet. Thus, we aimed to evaluate the possible synergistic effect of Cbx+UA in mCRPC cells.

Methods:
Cell viability and apoptosis were analyzed using WST-1 and Annexin-V. Morphological changes were
visualized by fluorescent staining. Finally, cell cycle, mitochondrial health, and ROS levels were determined.

Results:
Based on WST-1 results, 25 μM UA exhibited significant additive and synergistic effects with the use of
Cbx. Annexin V and cell cycle results showed that UA significantly enhanced the Cbx efficacy at increasing
doses compared to using only Cbx (**p<0.01). Moreover, combined treatment significantly increased ROS levels
and mitochondrial membrane depolarization compared with Cbx alone (**p<0.01).

Conclusions:
Thus, the results suggest that UA increased the anti-tumorigenic effects of Cbx on mCRPC cells by
increasing apoptosis, causing an increase in intracellular ROS and disrupting mitochondrial health. Consequently,
combining UA and Cbx offers a new combined therapeutic strategy for mCRPC treatment.