bluuebunny/crossref_metadata_2025_split huggingface dataset:
Windmills of the Minds: A Hopping Algorithm for Fermat's Two Squares Theorem
Authors: Chan Hing Lun 
Published: May 2024

Abstract

Fermat's two squares theorem asserts that a prime one more than a multiple of 4 is a sum of two squares. There are many proofs of this gem in number theory, including a remarkable one-sentence proof by Don Zagier based on two involutions on a finite set built from such a prime. Applying the two involutions alternatively leads to an iterative algorithm to find the two squares for the prime. Moreover, a detailed analysis of the computation reveals that it is possible to jump through the iteration nodes, leading to a better hopping algorithm. Here is a formalisation of Zagier's proof, deriving the involutions using windmill patterns. Theories developed for the formal proof are used to establish the correctness of both algorithms.
Degradation of PFOA solutions and PFAS-contaminated groundwater using atmospheric non-thermal plasma treatment
Authors: Gyaljen Tamang Sonam , Umlauf Georg , Barz Jakob , Ghomi Mohammad Reza 
Published: May 2024

ABSTRACT
Per- and polyfluoroalkyl substances (PFASs) can be found ubiquitously in the environment due to their large-scale use, and they pose risks to both ecosystems and human health. These pollutants are highly persistent, making them difficult or impossible to break down with standard processing methods. Therefore, the focus of this research is to explore an alternative approach to reduce PFAS-contaminated water by investigating the breakdown of these pollutants using atmospheric non-thermal plasma (NTP) technology. The experiments tested PFOA standard solutions with varying parameters, including different oxygen and nitrogen ratios as feeding air, with or without a cooling system, and at different time exposures. The process showed energy efficiency being ranged from 0.31 to 15.31 mg/kWh. Chemical analysis of treated samples confirmed the reactor's suitability for PFAS degradation, achieving a 63.75% reduction in initial PFOA concentration after 2 h of plasma treatment. Furthermore, degradation products such as PFHpA, PFHxA, PFPeA, and PFBA were identified after plasma treatment. Overall, these results suggest that plasma-based technology is a promising approach for treating PFAS-contaminated water.
Research on nowcasting prediction technology for flooding scenarios based on data-driven and real-time monitoring
Authors: Zheng Yue , Jing Xiaoming , Lin Yonggang , Shen Dali , Zhang Yiping , Yu Mingquan , Zhou Yongchao 
Published: May 2024

ABSTRACT
With the impact of global climate change and the urbanization process, the risk of urban flooding has increased rapidly, especially in developing countries. Real-time monitoring and prediction of flooding extent and drainage system are the foundation of effective urban flood emergency management. Therefore, this paper presents a rapid nowcasting prediction method of urban flooding based on data-driven and real-time monitoring. The proposed method firstly adopts a small number of monitoring points to deduce the urban global real-time water level based on a machine learning algorithm. Then, a data-driven method is developed to achieve dynamic urban flooding nowcasting prediction with real-time monitoring data and high-accuracy precipitation prediction. The results show that the average MAE and RMSE of the urban flooding and conduit system in the deduction method for water level are 0.101 and 0.144, 0.124 and 0.162, respectively, while the flooding depth deduction is more stable compared to the conduit system by probabilistic statistical analysis. Moreover, the urban flooding nowcasting method can accurately predict the flooding depth, and the R2 are as high as 0.973 and 0.962 of testing. The urban flooding nowcasting prediction method provides technical support for emergency flood risk management.
Examining the Mechanism of Treatment for Primary Dysmenorrhea with
Wenjing Huoxue Decoction based on Transcriptomics, Metabolomics, and
Network Pharmacology
Authors: Fan Weisen , Wang Dandan , Yan Liwei , Yuan Zheng 
Published: May 2024

Background:
Wenjing Huoxue Decoction (WJHXD) is a traditional treatment for primary dysmenorrhea
(PD) that can quickly relieve various symptoms caused by PD. Previous clinical studies have shown
that WJHXD has better long-term efficacy than ibuprofen in the treatment of PD and can reverse the disorder
of T cell subsets.

Objective:
To investigate the effect of WJHXD on serum-related factors in the treatment of PD, including the
identification of key targets, pathways, and active ingredients.

Methods:
In order to study the effects of the WJHXD intervention in Parkinson's Disease (PD) rats, we used
transcriptomics and metabolomics methods to examine the differentially expressed genes (DEGs) and differentially
expressed metabolites (DEMs). We also utilized network pharmacology to predict the target and effective
route of WJHXD in treating PD. Finally, we employed molecular docking (MD) technology to confirm
the placement of important targets and metabolites.

Results:
WJHXD has been found to be effective in prolonging the onset time and decreasing the number of
writhing episodes in PD rats after oxytocin injection. It has also been observed to reduce the levels of PGF2,
COX-2, AVP, and PGE2 in the serum of PD rats to different degrees. Transcriptomics analysis has revealed
that the core targets of WJHXD include KRT1, KRT16, CCL5, F2, NOS2, RAC2, and others, while the core
pathways are Calcium signaling and cAMP signaling. The Estrogen signaling pathway was found to be downregulated
in PD rats compared to normal uterine tissue, but WJHXD was able to up-regulate the pathway. A
combined transcriptomics and metabolomics analysis suggested that WJHXD may be involved in eight
metabolism-related pathways, with the most reliable ones being mucin-type O-glycan biosynthesis and glycolysis
or gluconeogenesis. MD has shown that Hydroxyisocaproic acid may bind to important targets such as SLC6A4,
PTGER3, IGFBP3, and IGF2.

Conclusion:
In WJHXD, the most targeted herbs were Corydalis rhizoma, licorice, and Myrrha. The most targeted
active ingredients include quercetin, 3'-Hydroxy-4'-O-methylglabridin, shinpterocarpin, and isorhamnetin.
Potential targets include PTGS2, NOS2, AR, SCN5A, and GAS6. Analysis revealed 72 highly reliable
relationships between group A and B DEGs and DEMs, with 23 positive correlations and 49 negative correlations
among them. A combined analysis of transcriptomics, metabolomics, and network pharmacology was
used to identify possible targets, pathways, and active ingredients of WJHXD in PD treatment, and the correlation
between DEGs and DEMs was investigated. However, further research is required to confirm the relationship
between active ingredients, targets, and metabolites.
Diagnosis of the Initial Stage of Hepatocellular Carcinoma: A Review
Authors: Sharma Krishana Kumar , Mohsin Mohd. , Mittal Piyush , Ali Zeeshan , Fatma Nishat , Upadhyay Prashant , Gupta Ritu , Verma Anurag , Kumar Gajendra 
Published: May 2024

Abstract:
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide.
There may be more than a million instances of hepatocellular carcinoma by 2025, making it a persistent
concern for global health. The most common form of hepatocellular carcinoma accounts for more than 90% of
cases. There is no known cure for hepatocellular carcinoma, which is usually detected late in life. Unlike most
other common malignancies, such as lung, prostate, and breast cancers, where mortality rates are declining,
rates of death are rising by around 2-3% every year. It is extremely difficult to diagnose hepatocellular carcinoma
in its early stages. Alpha-fetoprotein serology studies and ultrasonography (US) monitoring were historically
the primary methods for early detection of hepatocellular cancer. However, the sensitivity or specificity of
ultrasonography/alpha-fetoprotein (US/AFP) is not high enough to detect hepatocellular carcinoma in its early
stages. Alpha-fetoprotein, or AFP, is an amino acid that is normally produced by the liver or yolk sac of an embryonic
baby. In adults, AFP levels are typically modest. Adults with high levels of AFP have been associated
with several illnesses, the most well-known of which are certain types of cancer. It is still possible to diagnose
hepatocellular carcinoma early because of current technological advancements. We address the advancements
in the diagnosis of hepatocellular carcinoma in this article, with a focus on new imaging techniques and diagnostic
markers for early-stage tumor identification.
MicroRNAs as Key Regulators in RA and SLE: Insights into Biological
Functions
Authors: Li Xiao-Xiao , Zhao Chan-Na , Wei Hai-Fen , Li Sheng , Tang Jian , Zhu Yan-Yu , Cheng Xue-Er , Shi Qian-Qian , Wang Peng , Pan Hai-Feng 
Published: May 2024

Abstract:
MicroRNAs (miRNAs) are non-coding RNA molecules that bind to mRNAs to regulate gene expression.
Since changes in miRNA expression levels have been found in a variety of autoimmune illnesses,
miRNAs are important in autoimmune diseases. MiRNAs serve not only as pathogenic factors and biomarkers
for autoimmune diseases but also as important targets for disease therapeutics. Although miRNA-based treatments
are still in the research stage, in-depth investigations into the biological functions of miRNAs have significantly
enhanced our understanding of their mechanisms in autoimmune diseases. The purpose of this review
is to summarize the biological functions of miRNAs, their roles in rheumatoid arthritis and systemic lupus erythematosus,
therapeutic strategies, and challenges.
Deciphering the Genetic Complexity of Classical Hodgkin Lymphoma: Insights and Effective Strategies
Authors: Lee Chaeyoung , An Yeeun 
Published: May 2024

:
Understanding the genetics of susceptibility to classical Hodgkin lymphoma (cHL) is
considerably limited compared to other cancers due to the rare Hodgkin and Reed-Sternberg
(HRS) tumor cells, which coexist with the predominant non-malignant microenvironment. This article
offers insights into genetic abnormalities in cHL, as well as nucleotide variants and their associated
target genes, elucidated through recent technological advancements. Oncogenomes in HRS
cells highlight the survival and proliferation of these cells through hyperactive signaling in specific
pathways (e.g., NF-kB) and their interplay with microenvironmental cells (e.g., CD4+ T cells).
In contrast, the susceptibility genes identified from genome-wide association studies and expression
quantitative trait locus analyses only vaguely implicate their potential roles in susceptibility
to more general cancers. To pave the way for the era of precision oncology, more intensive efforts
are imperative, employing the following strategies: exploring genetic heterogeneity by gender and
cHL subtype, investigating colocalization with various types of expression quantitative trait loci,
and leveraging single-cell analysis. These approaches provide valuable perspectives for unraveling
the genetic complexities of cHL.
Recent Advances in Fluorescent Probes for G-quadruplex DNAs / RNAs
Authors: Yang Hongyan , Xu Ping , Pan Fei , Gao Jinhong , Yuan Libo , Lu Kui 
Published: May 2024

:
Guanine-quadruplexes (G4s) are high-level structures formed by the folding of guaninerich
nucleic acid sequences. G4s play important roles in various physiological processes, such as
gene transcription, replication, recombination, and maintenance of chromosomal stability. Specific
and sensitive monitoring of G4s lays the foundation for further understanding the structure, content,
distribution, and function of G4s in organisms, which is important for the treatment and diagnosis of
diseases. Moreover, visualization of G4s will provide new ideas for developing antitumor strategies
targeting G4s. The design and development of G4-specific ligands are challenging due to the subtle
differences in the structure of G4s. This review focuses on the progress of research on G4 fluorescent
probes and their binding mechanisms to G4s. Finally, the challenges and future prospects for
better detection and targeting of G4s in different organisms are discussed. This paper provides ideas
for the development of novel G4 fluorescent probes.
CircRNA Interference Pathway: A New Target for Intervention in
Different Stages of Heart Failure
Authors: Wang Yuli , Chen Qiaoling , Zhang Jiaqi , Deng Yun , Liu Changyu , Wang Shuangcui , Guo Maojuan , Song Lili 
Published: May 2024

Abstract:
Cardio-cerebrovascular disease has seen a rapid rise in recent years, with Heart Failure
(HF) -- a terminal stage of various cardiovascular diseases -- also on the rise. HF has a complex
pathogenesis involving multiple factors, such as inflammation, fibrosis, and oxidative stress. Due
to its unique reverse shear mechanism, HF exhibits distinct expression patterns across different diseases.
CircRNA has been linked to conditions like cancer, diabetes, and osteoarthritis. This article
briefly introduces the mechanisms of circRNA biogenesis and its associated biological functions,
focusing on CircSLC8A1-1, CircRNA_000203, and others at the early stage of HF, CircRNA
PAN3, CircRNA (ACR), and others during the progression of HF, and CircHIPK3, CircNfix, and
others at the end stage of HF. These circRNAs play a participatory role in the exact mechanism.
As a research method, circRNA can be utilized to study the pathogenesis of heart failure and serve
as a target for drug discovery and development. Therefore, circRNA's ability to mark the disease
at different stages has significant guiding implications for HF monitoring, treatment, and prognosis.
Rational Drug Discovery for Isoxazole Based VEGFR2 Inhibition
Authors: Patil Shital M. , Mahadik Indrani , Bhandari Shashikant V. , Asgaonkar Kalyani D. , Randive Vrushali D. , Edake Aishwarya M. 
Published: May 2024

Background:
Inhibiting receptor-tyrosine-kinase (RTK) signalling pathways has emerged
as a key focus of novel cancer therapy development. Vascular endothelial growth factor receptor
(VEGFR) is a member of the RTK family and is required for vasculogenesis and angiogenesis. Because
VEGFR 2 is the subtype responsible for cellular angiogenesis and vasculogenesis, blocking it
will impair tumour cell blood supply, reducing their development, proliferation, and metastasis.

Aim & Objective:
The aim of this study is to obtain an optimised pharmacophore as a VEGFR2
inhibitor using QSAR investigations. This aids in determining the link between structure and activity
in new chemical entities (NCEs).

Materials and Methods:
The multi-linear regression approach (MLR) method was utilised to generate
the QSAR Model using the programme QSARINS v.2.2.4.

Results and Discussion:
For 2D QSAR, the best models produced has correlation coefficients of R2=
0.9396. The 3D-QSAR model obtained with R2= 0.9121 and Q2 = 0.8377. Taking docking observations,
pharmacological behaviour, and toxicity analyses into account, most of the derivatives demonstrated
VEGFR2 inhibitory competence.

Conclusion:
According to QSAR studies, more electron-donating groups on the benzene ring linked
to the isoxazole were shown to be necessary for activity. In molecular docking studies, most compounds
have shown stronger affinity for the crucial amino acids Cys:919, Asp:1046, and Glu:885,
which are found in typical drugs. All NCEs passed the Lipinski screening.
Integrating Tumor and Nodal Radiomics to Predict the Response to
Neoadjuvant Chemotherapy and Recurrence Risk for Locally Advanced Gastric
Cancer
Authors: Han Shimei , Han Xiaomeng , Song Yaolin , Liu Ruiqing , Wang Hexiang , Zhang Zaixian , Yu Bohua , Li Zhiming , Liu Shunli 
Published: May 2024

Aims:
To develop and evaluate machine learning models using tumor and nodal radiomics features for predicting the response to neoadjuvant
chemotherapy (NAC) and recurrence risk in locally advanced gastric cancer (LAGC).

Background:
Early and accurate response prediction is vital to stratify LAGC patients and select proper candidates for NAC.

Objective:
A total of 218 patients with LAGC undergoing NAC followed by gastrectomy were enrolled in our study and were randomly divided into a
training cohort (n = 153) and a validation cohort (n = 65).

Methods:
We extracted 1316 radiomics features from the volume of interest of the primary lesion and maximal lymph node on venous phase CT images. We
built 3 radiomics signatures for distinguishing good responders and poor responders based on tumor radiomics (TR), nodal radiomics (NR), and a
combination of the two (TNR), respectively. A nomogram was then developed by integrating the radiomics signature and clinical factors. Kaplan-
Meier survival curves were used to evaluate the prognostic value of the nomogram.

Results:
The TNR signature achieved improved predictive value, with AUCs of 0.755 and 0.744 in the training and validation cohorts. Our proposed
nomogram model (TNRN) showed a good performance for GR prediction in the prediction efficacy, calibration ability, and clinical benefit, with
AUCs of 0.779 and 0.732 in the training and validation cohorts, superior to the clinical model. Moreover, the TNRN could accurately classify the
patients into high-risk and low-risk groups in both training and validation cohorts with regard to postoperative recurrence and metastasis.

Conclusion:
The TNRN performed well in identifying good responders and provided valuable information for predicting progression-free survival time (PFS)
in patients with LAGC who underwent NAC.
Aberrant Intra- and Inter-Network Connectivity in Idiopathic Sudden
Sensorineural Hearing Loss with Tinnitus
Authors: Zhang Yawen , Feng Chengyan , Qian Jinjia , Zhu Genxu , Xu Xiaomin , Xu Jin-Jing , Chen Yu-Chen , Che Zigang 
Published: May 2024

Background::
Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) is related to alterations in brain cortical and subcortical structures, and changes in brain
functional activities involving multiple networks, which is often accompanied by tinnitus. There have been many in-depth research studies
conducted concerning ISSNHL. Despite this, the neurophysiological mechanisms of ISSNHL with tinnitus are still under exploration.

Objective::
The study aimed to investigate the neural mechanism in ISSNHL patients with tinnitus based on the alterations in intra- and inter-network
Functional Connectivity (FC) of multiple networks.

Methods::
Thirty ISSNHL subjects and 37 healthy subjects underwent resting-state functional Magnetic Resonance Imaging (rs-fMRI). Independent
Component Analysis (ICA) was used to identify 8 Resting-state Networks (RSNs). Furthermore, the study used a two-sample t-test to calculate the
intra-network FC differences, while calculating Functional Network Connectivity (FNC) to detect the inter-network FC differences.

Results::
By using the ICA approach, tinnitus patients with ISSNHL were found to have FC changes in the following RSNs: CN, VN, DMN, ECN, SMN,
and AUN. In addition, the interconnections of VN-SMN, VN-ECN, and ECN-DAN were weakened.

Conclusion::
The present study has demonstrated changes in FC within and between networks in ISSNHL with tinnitus, providing ideas for further study on the
neuropathological mechanism of the disease.
New Thieno[2,3-d]pyrimidines as Anticancer VEGFR-2 Inhibitors with Apoptosis Induction: Design, Synthesis, and Biological and In Silico Studies
Authors: Sobh Eman A. , Dahab Mohammed A. , Elkaeed Eslam B. , Alsfouk Bshra A. , Ibrahim Ibrahim M. , Metwaly Ahmed M. , Eissa Ibrahim H. 
Published: May 2024

Background:
Vascular endothelial growth factor receptor-2 (VEGFR-2) is a critical
protein involved in tumor progression, making it an attractive target for cancer therapy.

Objective:
This study aimed to synthesize and evaluate novel thieno[2,3-d]pyrimidine analogues as
potential anticancer VEGFR-2 inhibitors.

Methods:
The thieno[2,3-d]pyrimidine analogues were synthesized following the pharmacophoric
features of VEGFR-2 inhibitors. The anticancer potential was assessed against PC3 and HepG2 cell
lines. The VEGFR-2 inhibition was evaluated through IC50 determination. Cell cycle analysis and
apoptosis assays were performed to elucidate the mechanisms of action. Molecular docking, molecular
dynamics simulations, MM-GBSA, and PLIP studies were conducted to investigate the
binding affinities and interactions with VEGFR-2. Additionally, in silico ADMET studies were
performed.

Results:
Compound 8b demonstrated significant anti-proliferative activities with IC50 values of
16.35 μM and 8.24 μM against PC3 and HepG2 cell lines, respectively, surpassing sorafenib and
exhibiting enhanced selectivity indices. Furthermore, compound 8b showed an IC50 value of 73 nM
for VEGFR-2 inhibition. Cell cycle analysis revealed G2-M phase arrest, while apoptosis assays
demonstrated increased apoptosis in HepG2 cells. Molecular docking and dynamic simulations
confirmed the binding affinity and interaction of compound 8b with VEGFR-2, supported by MMGBSA
and PLIP studies. In silico ADMET studies indicated the drug development potential of the
synthesized thieno[2,3-d]pyrimidines.

Conclusion:
The study highlights compound 8b as a promising VEGFR-2 inhibitor with potent
anti-proliferative activities. Its mechanism of action involves cell cycle arrest and induction of
apoptosis. Further, molecular docking and dynamic simulations support the strong binding affinity
of compound 8b to VEGFR-2.
Structural Insight into the Binding Pattern and Interaction Mechanism of
Antagonist MCC950 and Agonist BMS986299 with NLRP3 by Molecular
Dynamics Simulation
Authors: Zhang Ruifeng , Xiong Xin , Min Zhenli 
Published: May 2024

Objective::
The NLRP3 inflammasome mediates a range of inflammatory responses
that are associated with an increasing number of pathological mechanisms. Over-activation of
NLRP3 can exacerbate many diseases. However, NLRP3 antagonists have significant therapeutic
potential. Moreover, NLRP3 plays an important role in limiting the growth and spread of
some tumors, and NLRP3 agonists also have clinical value. MCC950 and BMS986299 are an
antagonist and agonist of NLRP3, respectively. In light of the important clinical applications of
NLRP3, especially for NLRP3 inhibitors, a computational method was used to investigate the
interaction modes of MCC950 and BMS986299 with NLRP3 in order to design and develop
more potent NLRP3 regulators.

Methods::
In this study, the conformational behaviors of NLRP3 bound to the antagonist
MCC950 in an inactive state and the agonist BMS986299 in an active state were investigated
using 200 ns equilibrium all-atom molecular dynamics (MD) simulations, and then the analyses
of the MD trajectories (RMSD, Rg, RMSF, SASA, PCA, and DCCM) were carried out to explore
the mechanism of the antagonist and agonist on NLRP3 in the two different states.

Results::
The RMSD, RMSF, Rg, SASA, and PCA analyses indicated that NLRP3 was more
dispersive and less energetically stable in the active state than in the inactive state and that
MCC950 significantly reduced the fluctuations of the interactive residues while BMS986299
did not. The antagonist MCC950 interacted with residues mainly in the NBD, HD1, WHD, and
HD2 domains of NLRP3, whereas the agonist BMS986299 mainly in the NBD and WHD of
NLRP3. Additionally, both compounds did not interact with residues located in the FISNA domain.
The conformation of the FISNA domain appeared to change significantly when NLRP3
was translated from an inactive state to an active state.

Conclusion::
The antagonist may interact with residues mainly in the NBD, HD1, WHD, and
HD2 domains, and the agonist may interact in the NBD and WHD domains. Our study provided
new insights into the development of NLRP3 regulators.