bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Gross Alpha, Gross Beta Activity, Heavy Metal Concentrations, and Cancer Risk Assessment in IspartaDrinking Tap Water
Authors: MANAV Ramazan 
Published: September 2024

Abstract

In this study, tap water samples were collected from different locations in the city center of Isparta. Gross alpha and gross beta activity concentrations were determined according to the Environmental Protection Agency (EPA) protocol. The annual effective dose and lifetime cancer risk were calculated. The gross alpha activity concentrations ranged from 37 mBq/L to 136 mBq/L, and the gross beta activity ranged from 111 mBq/L to 181 mBq/L. These values are below the World Health Organization (WHO) limits of 500 mBq/L for alpha and 1000 mBq/L for beta activities. The lifetime cancer risk assessment for adults, based on these concentrations, ranged from 0.59x10-4 to 2.36x10-4 (mean 1.37x10-4), with the highest value being lower than the UNSCEAR standard of 0.29x10-3. Additionally, the concentrations of several heavy metals, including arsenic (As), barium (Ba), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), lead (Pb), selenium (Se), and thallium (Tl), were measured at 0.0016, 0.0417, 0.0002, 0.0027, 0.005, 0.0016, 0.0088, 0.0028, and 0.0043 ppm, respectively. The concentrations of As, Ba, Cd, Cr, Cu, Pb, and Se were below the recommended limits of the WHO and EPA standards. However, the Hg and Tl concentrations were below the WHO limits but exceeded the EPA standards. The cancer risk assessment was performed based on the concentrations of As, Pb, Cd, and Cr using the EPA's cancer slope factors. The calculated hazard indices (HIs) for these heavy metals were lower than the EPA's critical level.
A Circadian Rhythm-related Signature to Predict Prognosis, Immune Infiltration, and Drug Response in Breast Cancer
Authors: Chu Mingyu , Huang Jing , Wang Qianyu , Fang Yaqun , Cui Dina , Jin Yucui 
Published: September 2024

Purpose:
Circadian rhythm-related genes (CRRGs) play essential roles in cancer
occurrence and development. However, the prognostic significance of CRRGs in
breast cancer (BC) has not been fully elucidated. Our study aimed to develop a prognostic
gene signature based on CRRGs that can accurately and stably predict the prognosis
of BC.

Methods:
The transcriptome data and clinical information for BC patients were obtained
from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.
A consensus unsupervised clustering analysis was carried out to investigate the roles
of CRRGs in BC. A CRRGs-related prognostic risk model was established by using logistic
least absolute shrinkage and selection operator (LASSO) Cox regression and univariate
Cox regression analyses. Kaplan-Meier (KM) curves analysis, time-dependent receptor
operation characteristics (ROC) curves analysis, and nomogram were plotted to
evaluate the predictive efficacy of the model. The relevance of risk score to the immune
cell infiltration, tumor burden mutation (TMB), and therapeutic response was assessed.

Results:
risk model comprising six CRRGs (SLC44A4, SLC16A6, TPRG1, FABP7,
GLYATL2, and FDCSP) was constructed and validated, demonstrating an effective predictor
for the prognosis of BC. The low-risk group displayed a higher expression of immune
checkpoint genes and a lower burden of tumor mutation. Additionally, drug sensitivity
analysis demonstrated that the prognostic signature may serve as a potential chemosensitivity
predictor.

Conclusion:
We established 6 CRRGs-related risk signatures for the prognosis of BC,
which is of great value in predicting the prognosis of patients with BC and guiding the
treatment for BC.
A Comprehensive Pan-Cancer Analysis Identified that TRIB3 was Associated with Immune Cell Infiltration and Poor Prognosis
Authors: Yu Ke Xun , Yuan Wei Jie , Li Jing , Wang Hui Zhen , Li Yong Xiang 
Published: September 2024

Background:
Previous studies have demonstrated that TRIB3 plays a carcinogenic
role in tumor progression. However, the exploration of TRIB3 at the pan-cancer level has not
been reported.

Aims:
This study aimed to conduct a comprehensive pan-cancer analysis of TRIB3.

Objective:
We explored the expression pattern and functional mechanism of TRIB3 on the basis
of multiple databases.

Method:
We first explored the expression level of TRIB3 in the TCGA database. Then, the receiver
operation characteristic curve (ROC), Kaplan-Meier plotter, and Cox regression were used
to estimate the diagnostic and prognostic value of TRIB3, respectively. We also explored the
relationship between TRIB3 and the infiltration of tumor immune cells, as well as the expression
of immune checkpoint molecules. Gene enrichment and protein interaction network analysis
were carried out to identify possible carcinogenic molecular mechanisms and functional pathways.
Finally, we compared the non-promoter region methylation of TRIB3 in normal and tumor
tissues and explored potential systems with unique functions in TRIB3-mediated tumorigenesis.

Result:
The expression level of TRIB3 was elevated in multiple tumor types, and the high expression
of TRIB3 was associated with poor prognosis. TRIB3 had a higher frequency of genetic
changes in several tumors and showed varying trends in TRIB3 methylation levels. Additionally,
high expression of TRIB3 was also associated with infiltration of cancer-related fibroblasts and
different types of immune cells and was positively correlated with the expression of immune
checkpoint molecules. Furthermore, gene enrichment analysis suggested that TRIB3 may play a
role in the malignant progression of cancer by participating in protein post-translational modifications
and activating transcription initiation factors.

Conclusion:
Our pan-cancer analysis provided the potential carcinogenic role of TRIB3 in tumors
and verified a promising target for clinical immune treatment.
COL12A1 Promotes Osteosarcoma Progression via the
FAK/PI3K/AKT/mTOR Pathway
Authors: Zhang Yun-Pu , Wang Hai-xia , Gao Zhi-chao , Xu Li-zhe , Fu Yu 
Published: September 2024

Background:
Osteosarcoma (OS) is a common malignancy among
adolescents and children, characterized by a high propensity for metastasis and
resistance to chemotherapy.

Aims:
This study aimed to investigate the role of COL12A1, a gene often
overexpressed in various cancers and associated with poor prognosis, in the
progression of OS and explore the underlying mechanisms.

Methods:
The expression pattern and potential function of COL12A1 in OS were
evaluated using bioinformatics analyses, clinical sample examination, and OS cell
lines. Various assays, including transwell, CCK-8, flow cytometry, and wound healing,
were performed to assess the impact of COL12A1 on OS cell growth, cell cycle
progression, apoptosis, invasion, and migration. Western blot analysis was conducted
to investigate markers associated with the FAK/PI3K/AKT/mTOR pathway.

Results:
COL12A1 expression was significantly elevated in OS tissues and cells.
Upregulation of COL12A1 promoted cell growth, accelerated cell cycle progression,
and enhanced migration and invasion while inhibiting apoptosis. Conversely, the
knockdown of COL12A1 had the opposite effect. Additionally, COL12A1
overexpression increased the phosphorylation of components in the
FAK/PI3K/AKT/mTOR pathway. The FAK inhibitor Y15 mitigated the effects of
COL12A1 overexpression on cell apoptosis, invasion, proliferation, and the
FAK/PI3K/AKT/mTOR pathway in OS.

Conclusion:
Our findings indicated that COL12A1 enhanced OS development by
activating the FAK/PI3K/AKT/mTOR pathway, suggesting that COL12A1 could serve
as a valuable biomarker for the prediction and identification of OS patients.
Role of Circadian Rhythm Changes on Functional Dependence Despite
Successful Repercussion in Patients with Endovascular Treatment
Authors: Zhang Mengke , Wang Xian , Chen Xi , Xu Jiali , Guo Wenting , Ren Changhong , Li Sijie , Zhao Wenbo , Wu Chuanjie , Ji Xunming 
Published: September 2024

Background:
Increasing evidence of circadian biology may influence the physiopathologic
mechanism, progression, and recovery of stroke. However, few data have shown about circadian
rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT).

Methods:
From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients
with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure
to achieve functional independence in patients at 90 days after EVT, although the occluded vessels
reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic
regression model.

Results:
Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318
patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered from stroke
during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of
intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT
in patients who had a stroke between 15:00-22:59 was significantly higher than in those with
stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of
stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04)
was an independent predictor of FR.

Conclusion:
Circadian rhythm can directly or indirectly affect the occurrence, development, and
prognosis of AIS. More studies may be needed in the future to validate the results of our study and
to explore the potential mechanisms behind the effects of circadian rhythms on FR.
Using Entropy as the Convergence Criteria of Ant Colony Optimization and the Application at Gene Chip Data Analysis
Authors: Gao Chonghao , Pang Xinping , Wang Chongbao , Huang Jingyue , Liu Hui , Zhu Chengjiang , Jin Kunpei , Li Weiqi , Zheng Pengtao , Zeng Zihang , Wei Yanyu , Pang Chaoyang 
Published: September 2024

Introduction:
When Ant Colony Optimization algorithm (ACO) is adept at identifying
the shortest path, the temporary solution is uncertain during the iterative process. All temporary
solutions form a solution set.

Methods:
Where each solution is random. That is, the solution set has entropy. When the solution
tends to be stable, the entropy also converges to a fixed value. Therefore, it was proposed in this
paper that apply entropy as a convergence criterion of ACO. The advantage of the proposed criterion
is that it approximates the optimal convergence time of the algorithm.

Results:
In order to prove the superiority of the entropy convergence criterion, it was used to cluster
gene chip data, which were sampled from patients of Alzheimer’s Disease (AD). The clustering
algorithm is compared with six typical clustering algorithms. The comparison shows that the
ACO using entropy as a convergence criterion is of good quality.

Conclusion:
At the same time, applying the presented algorithm, we analyzed the clustering characteristics
of genes related to energy metabolism and found that as AD occurs, the entropy of the
energy metabolism system decreases; that is, the system disorder decreases significantly.
What is the Link between Lung Involvement and Anti-CCP Antibodies in Rheumatoid Arthritis: A Cross-sectional Study
Authors: El-Kasmi Hind , Harzy Taoufik , Akasbi Nessrine 
Published: September 2024

Background:
In Rheumatoid Arthritis (RA), pulmonary involvement is one of the most
frequent extra-articular manifestations. Several studies have demonstrated an association between
RA-related lung disease and the positivity of anti-cyclic citrullinated peptide (anti-CCP) antibodies.

Objective:
Our aim is to describe the frequency of pulmonary involvement in the RA population
and investigate the association between anti-CCP antibodies and diverse lung compartment involvement in RA patients.

Methods:
An observational retrospective cross-sectional study was conducted, during which data
were collected from the medical records of the patients with RA who had been tested for anti-CCP
antibodies and had thoracic high resolution computerized tomography (HRCT) evaluation from
January 2011 to March 2022. The univariate and multivariate analyses using logistic regression
models was performed to calculate odds ratios (ORs) with 95% CIs.

Result:
A total of 390 patients with RA were included, the mean age of patients was 58.99 ±
12.44 years, with a predominance of females (85.9%). Two hundred and fifty-two (64.6%) patients were positive for anti-CCP antibodies. The frequency of RA-related lung diseases was
14.4% (n=56). The different manifestations observed in the thoracic HRCT included Nodules
(67.9%), Interstitial lung disease (ILD) (28.6%), bronchiectasis (25%), fibrosis (21.4%), obliterative bronchiolitis (7.1%), and pleuritis (1.8%). In univariate and multivariate analysis, pulmonary
involvement was associated with positive anti-CCP antibodies with an odds ratio (OR) of 5.25
(95% CI: 2.17-12.70, p < 0.0001).

Conclusion:
The study demonstrated a positive association between anti-CCP antibodies and pulmonary involvement in RA and highlighted the importance of tight monitoring in RA patients
with positive anti-CCP for pulmonary complications.
Investigating the Effects of Simultaneous Administration of Melatonin
and Atorvastatin against High Glucose-Induced Oxidative Stress and
Apoptosis in Cultured Chondrocytes
Authors: Mehrzadi Saeed , Safa Majid , Hosseinzadeh Azam 
Published: September 2024

Objective:
Osteoarthritis (OA) is a prevalent joint disorder categorized into phenotypic
subtypes, including those associated with age, traumatic events, and metabolic syndrome. In the
aging population, type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) frequently coexist.
This can result in higher rates of disability and a greater financial burden. This study aimed to investigate
the protective effects of melatonin and atorvastatin together against oxidative stress and
apoptosis induced by high glucose in C28I2 human chondrocytes.

Material and Methods:
After being pretreated for 6 hours with melatonin (10 and 100 μM) and
atorvastatin (0.01 and 0.1 μM), C28I2 cells were exposed to a high concentration of D-glucose (75
mM) for 72 hours. The impact of a high D-glucose concentration (75 mM), with or without melatonin
and/or atorvastatin, on cell viability, intra-cellular ROS generation, lipid peroxidation level,
antioxidant activities, and the expression of proteins, including Bax, Bcl-2, and caspase-3, was analyzed.

Results:
Melatonin and atorvastatin combination effectively inhibited high glucose-induced cytotoxicity,
ROS production, and MDA and mitochondrial membrane potential levels. The combination
of melatonin and atorvastatin was more successful in reducing ROS production compared to
each of the drugs alone. Melatonin, but not atorvastatin, reversed high glucose-induced alteration
in the catalase activity. Furthermore, the combination of melatonin and atorvastatin significantly
enhanced the ability of each medication to lower the expression of pro-apoptotic protein Bax.

Conclusion:
The combination of melatonin and atorvastatin exerted greater protective effects
against hyperglycemia-induced toxicity in chondrocytes.
TP53 Gene Polymorphism (Rs1042522) in Rheumatoid Arthritis and
Systemic Lupus Erythematosus: An Updated Systematic Review and
Meta-Analysis
Authors: Ebrahimiyan Hamidreza , Madreseh Elham , Akhtari Maryam , Farhadi Elham , Jamshidi Ahmadreza , Mahmoudi Mahdi 
Published: September 2024

Background:
The p53 protein has important roles in apoptosis, proliferation, and prevention
of DNA damage. Several studies have reported that TP53 gene polymorphism is associated
with various autoimmune diseases, including Rheumatoid arthritis (RA) and Systemic lupus
erythematosus (SLE).

Objective:
Evaluation of the correlation between TP53 gene rs1042522 polymorphism and RA
and SLE risk by meta-analysis.

Methods:
Databases, including PubMed and Scopus, were searched to find studies assessing the
association between TP53 gene polymorphism and RA and SLE risk in different populations up to
August 2022. The protocol of this article was registered on the International Prospective Register
Of Systematic Reviews (PROSPERO number: CRD42022309655).

Results:
Herein, 7 case-control studies, including 2498 cases and 3799 controls in the SLE group,
and 6 case-control studies comprising 1593 cases and 4460 controls in the RA group that investigated
rs1042522 SNP were included in the meta-analysis. Herein, CG genotypes were more frequent
in healthy participants compared to SLE patients and may associated with a decreased SLE
risk (OR=0.85, CI: 0.76-0.95, P-value <0.006). Besides, dominant and recessive models of CC+
CG vs. GG were also protective for SLE risk (OR=0.85, CI: 0.76-0.95, P-value <0.004).

Conclusion:
In summary, this study discloses a weak correlation between rs1042522 and a decreased
risk of SLE. However, no significant association was found in RA.
Cost-effectiveness and Accuracy Analysis of Different Screening Strategies for COVID-19
Authors: Cheng Chih-Chien , Liu Chia-Chen , Liu Hao-Yu , Chou Yi-Chang , Yen Yung-Feng , Chiu Yi-Chun , Fann Li-Yun , Chou Chuan-Yi 
Published: September 2024

Background:
Coronavirus disease 2019 (COVID-19) is mainly confirmed through reverse
transcription polymerase chain reaction (RT-PCR), which is both expensive and time-consuming
and requires specific equipment. Thus, demand for rapid diagnostic methods, such as rapid
antigen detection (RAD) tests, has emerged. Here, we assessed the efficiency and reliability of
RAD for early diagnosis of COVID-19.

Methods:
We performed a retrospective study based on systemic COVID-19 screening and diagnosis
using RAD and RT-PCR at Taipei City Hospital during the first COVID-19 outbreak week
in Taiwan (28 May-6 June 2021). We postulated five strategies for COVID-19 screening in the
general population: one RAD test, one RT-PCR test, one RAD test (negative) followed by one
RT-PCR, one RAD test (positive) followed by one RT-PCR test, and two RAD tests and calculated
their cost and accuracy. We also conducted a cost-effectiveness analysis to identify the most
economically efficient strategy for COVID-19 diagnosis. This study included 6368 cases in total.

Results:
Although RAD exhibited low sensitivity (mean 66%), other values were acceptable:
mean specificity, positive predictive value, negative predictive value, and accuracy were 99%,
82.8%, 97.5%, and 94.2%, respectively. RAD was the most cost-effective method. Additionally,
it may be an effective diagnostic strategy in the later stages of the epidemic, warranting further research.

Conclusion:
Although RT-PCR remains the standard method for diagnosing COVID-19, RAD is
faster and a more cost-effective, convenient, and globally available method, allowing for early detection
of SARS-CoV-2.

conclusion:
We propose that RAD could be a fast and feasible method for diagnosing SARS-CoV-2 infection, allowing for early detection. Although RT-PCR remains the standard method for diagnosing SARS-CoV-2 infection, RAD is a more cost-effective, convenient, fast, and globally available method.
High-throughput Approaches to Detect Cytokines and Chemokines Secretion by Both Autophagy and Endosome Vesicle Fusion of HBMEC by Knocking Down the NLRP2 Gene
Authors: Feng Yingzhu , Huang Mengjun , Ma Dengke , Ou Kepeng , Qiu Juhui , Li Yong , Peng Zitian , Lei Jie , Chen Zhongzhu , Shao Jingwei , Desai Prashant , Zhu Heng , Wang Bochu 
Published: September 2024

Background:
Given the rapid increase in serious infectious and inflammatory diseases in
the general population worldwide, it is vital to advance our understanding of the process of infection
and inflammation.

Objective:
These illnesses can be treated by diverse cytokines, chemokines, and chemical compounds,
but how to find and identify effective protein drugs is unknown. In this study, large–scale
analytical approaches, such as high–throughput chips with RNA-Seq that construct the protein regulatory
networks, were established.

Methods:
NLRP2:shRNA (1–3) and GFP: Control lentivirus were fabricated to infect Human Brain
Microvascular Endothelial Cells (HBMEC) to knock down NLRP2 gene that not only possesses biochemical
activity but also bio-mechanical properties. Once HBMEC was loaded on the
18mmX18mm circular soft cover slip, by knocking down NLRP2 gene processing and adding puromycin,
a large number of cytokines were secreted to activate both autophagy and endosome vesicle
signaling by KEGG pathway analysis, which was successfully detected by both ELISA approach and
QAH-Neu-1 chip. However, no secretion from GFP: Control was reported.

Results:
It was demonstrated that the NLRP2 gene was highly responsive to cytokines.
The protein regulatory network from RNA–Seq platform demonstrated that the secretion by knocking
down the NLRP2 gene was highly correlated with autophagy, endosome, multivesicular body,
phosphatidylinositol, and necrosis signalling pathway. Furthermore, most of the cytokines expressed
were found to be specific for intracellular vesicle–dependent secretion, leading to obvious cell swelling
and shedding, membrane protein dotting to nucleation, and actin dynamics. Interestingly, it was
also found that autophagy, together with endosome signalling, was collectively activated to boost
the secretion to cause a “cytokine storm”, which led to lipid phase separation.

Conclusion:
This study proposed high throughput approaches centered on the NLRP2 gene network
for many severe diseases, providing novel insight into biological pathways influencing infection and
inflammation (e.g., COVID-19/E.coli). They can be modulated as potential therapeutic targets and used
as biomarkers in the diagnosis and treatment of many diseases to promote human health. This increases
our interest in developing new leadless-peptides at the genomics and proteomics levels to obtain cytokines
and chemokines for micro-array constructions (VirD‒cytokines, VirD‒enzymes), antibody and
vaccine development for infections, diabetes, cardiovascular disease, atherosclerosis, non–alcoholic
fatty liver, auto-immune, neurodegenerative disorder, and even cancer-related disease therapy. They
have the most valuable applications in molecular diagnosis, protein marker discovery, and bio-therapy.
The Potential Role of Curcumin as a Regulator of microRNA in Colorectal Cancer: A Systematic Review
Authors: Salehi Amir Mohammad , Torogi Fatemeh , Jalilian Farid Azizi , Amini Razieh 
Published: September 2024

Introduction:
Curcumin is known as a bioactive component that is found in the rhizomes
of Curcuma longa. Curcumin is well known for its chemo-preventive and anticancer properties.
However, its anticancer mechanism in colorectal cancer treatment is unclear, and some
studies have shown that many microRNAs (miRs) could be potential targets for curcumin in colorectal
cancer (CRC) treatment, so there is a need for their integration and clarification.

Methods:
We systematically searched international databases, including PubMed, Scopus, and
Web of Science, until July 2021 by using some relevant keywords.

Results:
The search resulted in 87 papers, among which there were 18 related articles. Curcumin
was found to cause the upregulation of miR-497, miR-200c, miR-200b, miR-409-3p, miR‐34,
miR‐126, miR-145, miR-206, miR-491, miR-141, miR-429, miR-101, and miR-15a and the
downregulation of miR-21, miR-155, miR‐221, miR‐222, miR-17-5p, miR-130a, miR-27, and
miR-20a.

Conclusion:
The present review study suggests that curcumin may be useful as a novel therapeutic
agent for CRC by altering the expression level of miRs.