bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing a RiskScore Model based on Angiogenesis-related
lncRNAs for Colon Adenocarcinoma Prognostic Prediction
Authors: Li Xianguo , Lei Junping , Shi Yongping , Peng Zuojie , Gong Minmin , Shu Xiaogang 
Published: November 2023

Aim:
We screened key angiogenesis-related lncRNAs based on colon adenocarcinoma
(COAD) to construct a RiskScore model for predicting COAD prognosis and help reveal the
pathogenesis of the COAD as well as optimize clinical treatment

Background:
Regulatory roles of lncRNAs in tumor progression and prognosis have been confirmed,
but few studies have probed into the role of angiogenesis-related lncRNAs in COAD.

Objective:
To identify key angiogenesis-related lncRNAs and build a RiskScore model to predict
the survival probability of COAD patients and help optimize clinical treatment.

Methods:
Sample data were collected from The Cancer Genome Atlas (TCGA) and Gene Expression
Omnibus (GEO) database. The HALLMARK pathway score in the samples was calculated using
the single sample gene set enrichment analysis (ssGSEA) method. LncRNAs associated with
angiogenesis were filtered by an integrated pipeline algorithm. LncRNA-based subtypes were classified
by ConsensusClusterPlus and then compared with other established subtypes. A RiskScore
model was created based on univariate Cox, least absolute shrinkage and selection operator (LASSO)
regression and stepwise regression analysis. The Kaplan-Meier curve was drawn by applying
R package survival. The time-dependent ROC curves were drawn by the timeROC package. Finally,
immunotherapy benefits and drug sensitivity were analyzed using tumor immune dysfunction
and exclusion (TIDE) software and pRRophetic package.

Results:
Pathway analysis showed that the angiogenesis pathway was a risk factor affecting the
prognosis of COAD patients. A total of 66 lncRNAs associated with angiogenesis were screened,
and three molecular subtypes (S1, S2, S3) were obtained. The prognosis of S1 and S2 was better
than that of S3. Compared with the existing subtypes, the S3 subtype was significantly different
from the other two subtypes. Immunoassay showed that immune cell scores of the S2 subtype
were lower than those of the S1 and S3 subtypes, which also had the highest TIDE scores. We recruited
8 key lncRNAs to develop a RiskScore model. The high RiskScore group with inferior survival
and higher TIDE scores was predicted to benefit limitedly from immunotherapy, but it may
be more sensitive to chemotherapeutics. A nomogram designed by RiskScore signature and other
clinicopathological characteristics shed light on rational predictive power for COAD treatment.

Conclusion:
We constructed a RiskScore model based on angiogenesis-related lncRNAs, which
could serve as potential prognostic predictors for COAD patients and may offer clues for the intervention
of anti-angiogenic application. Our results may help evaluate the prognosis of COAD and
provide better treatment strategies.
Integrating Network Pharmacology and In vivo Experimental Validation to Reveal the Mechanism of FuZheng YiLiu Formula on Estrogen Receptor Positive Breast Cancer
Authors: Xu Yuan , Zhang Ying-xuan , Chen Hong-yu , Chang Li-sheng , Gou Xiao-jun , Chen Wen-li 
Published: November 2023

Background and Purpose:
FuZheng YiLiu Formula (FZYL) is a commonly used formula
for postoperative estrogen receptor-positive (ER+) breast cancer and post-radiotherapy
deficiency of both Qi and Yin. FZYL has been used in clinical practice for decades because of its
ability to effectively improve the symptoms of deficiency in cancer patients. However, its mechanism
needs to be further clarified. In this paper, we will observe the effect of FZYL on mice with
ER+ breast cancer and explore the mechanism by which it improves the symptoms of ER+ breast
cancer.

Materials and Methods:
A tumor xenograft mouse model was established to detect tumor growth
in vivo in order to evaluate the pharmacological effects of FZYL on ER+ breast cancer. The main
targets of FZYL were identified by extracting the FZYL components and the corresponding potential
target genes of breast cancer from the established database and constructing a proteinprotein
interaction network of shared genes using the string database. GO functional annotation
and KEGG pathway enrichment analysis were performed, and molecular docking, molecular dynamics
simulations, western blotting analysis, and RT-qPCR were performed to confirm the validity
of targets in the relevant pathways.

Results:
FZYL was able to significantly reduce the size of tumors in vivo and had a significant
therapeutic effect on tumor xenograft mice. GO and KEGG pathway enrichment analyses indicated
that the effects of FZYL may be mediated by oxidative stress levels, apoptotic signaling pathways,
and cell cycle proliferation. By RT-qPCR and protein blotting assays, FZYL targeted the
key targets of TP53, JUN, ESR1, RELA, MYC, and MAPK1 to exert its effects. The key active
components of FZYL are quercetin, luteolin, stigmasterol, and glycitein. Molecular docking and
molecular dynamics simulation results further demonstrated that the key active components of
FZYL are stably bound to the core targets.

Conclusion:
In this study, the potential active ingredients, potential core targets, key biological
pathways, and signaling pathways involved in the treatment of breast cancer with FZYL were
identified, providing a theoretical basis for further anti ER+ breast cancer research.
Denosumab Induces Neoplastic Stromal Cell Apoptosis Via p62
Downregulation Dependent on Autophagy Pathway in Giant Cell Tumour
of Bone
Authors: Chen Xianwei , Ye Fan , He Hao , Chen Gong , Chen Zhifu , Ye En , He Bingjan , Yang Yuqi , Zhang Jing 
Published: November 2023

Background:
As the only humanized monoclonal antibody against receptor activator of
nuclear factor-κB ligand (RANKL) for giant cell tumour of bone (GCTB) therapy, denosumab has
limited antitumour effect on neoplastic stromal cells. Nevertheless, its mechanism of action has
not yet been clarified. A previous study has revealed that p62 may play an important role in the antitumour
activity of denosumab.

Objective:
The study aimed to investigate if the mechanism by which denosumab inhibits GCTB
neoplastic stromal cells growth is via p62 modulation and other related mechanisms.

Methods:
p62 expression before and after denosumab therapy was analysed by RT‒qPCR, western
blot, ELISA, and immunohistochemical assays. Two primary neoplastic stromal cells were isolated
from fresh GCTB tumour tissue (L cell) and metastatic tissue (M cell). Cell proliferation, migration,
apoptosis, and autophagy were investigated in p62 knockdown neoplastic stromal cells
transfected by short hairpin RNA lentivirus in vitro. Tumor growth was evaluated in the chick chorioallantoic
membrane model in vivo.

Results:
p62 expression was found to be downregulated following denosumab therapy. The patients
with a decrease in p62 expression had lower recurrence-free survival rates. The proliferation
of M cells was not inhibited by denosumab therapy, but it was restored by p62 knockdown. Moreover,
p62 knockdown inhibited tumour growth in vivo. Denosumab induced M cell apoptosis and
arrested the cell cycle at the G1/G0 transition and these effects were also enhanced by p62 knockdown.
Autophagic flux assays revealed p62 modulation to be dependent on autophagy following
denosumab incubation.

Conclusion:
Denosumab induced neoplastic stromal cells apoptosis via p62 downregulation dependent
on autophagy pathway. The combination of p62 and RANKL knockdown might be a better
strategy than RANKL knockdown alone for GCTB targeted therapy.
A Comparative Study on BRAFV600E Mutation, Sonographic Findings,
and Pathologic Characteristics in Non-invasive Follicular Thyroid
Neoplasm with Papillary-like Nuclear Features (NIFTP) and Invasive
Follicular Variant of Papillary Thyroid Carcinoma (IFVPTC)
Authors: Mohebbi Masoud , Yaghoubi Mohammad Ali , Moradi Ali , Mousavi Zohreh , Dadgar Maliheh , Sahebkar Amirhossein , Gholamimoallem Zeinab 
Published: November 2023

Objective:
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features
(NIFTP) comprise a new subgroup of thyroid tumors of follicular origin with borderline histologic
features that lack evidence of either capsular or vascular invasion. In contrast to the invasive follicular
variant of papillary thyroid carcinoma (IFVPTC), adverse events such as cancer-related death,
distant or regional metastases, and structural or biochemical recurrence do not occur in patients with
NIFTP. Many studies have been done to elucidate these two specific types of papillary thyroid cancer
(PTC) and reduce aggressive therapeutic actions. This study compares molecular, cytological, and
radiologic features of NIFTP and IFVPTC.

Materials and Methods:
Two groups of patients with NIFTP and IFVPTC (n = 18 in each group)
who were referred to the endocrine clinic, at Imam Reza Hospital, were enrolled in this crosssectional
study. Molecular analysis for BRAFV600E mutation of thyroid tissue was evaluated for all
cases. Patient data included: age, sex, type of surgery, thyroid sonographic findings, and prior cytological
diagnosis with the Bethesda system for reporting thyroid cytopathology.

Results:
Only two cases in the IFVPTC group were positive for BRAFV600E mutation. The majority of
NIFTP cases were diagnosed as benign lesions (8/18). In contrast, the majority of IFVPTC cases were
diagnosed as suspicious for malignancy on cytology (7/18). The mean nodule size in ultrasound in the
NIFTP group (41.81 ± 20.43 mm) was larger than the IFVPTC group (36.72 ± 20.73 mm) (p =0.47).
Most cases in the IFVPTC group had significantly multiple nodules (72.2%), while most cases in the
NIFTP group (81.3%) had solitary nodules. Nodule composition in both groups was solid and complex;
however, no cystic nodules were detected in ultrasound examinations. Furthermore, no calcification or
lymphadenopathy was seen in the majority of cases in ultrasound. In the IFVPTC group, 47.1% and
35.3% of nodules were hyperechoic and hypoechoic, respectively, while 23.1%, 38.5%, and 23.1% of
nodules in the NIFTP group were heterogenic, hyperechoic, and hypoechoic, respectively.

Conclusion:
According to our findings, only 11.1% of IFVPTC cases were BRAFV600E-positive,
while none of the patients in the NIFTP group showed this mutation. However, IFVPTC was predominantly
associated with a preceding diagnosis of PTC on FNA, and NIFTP was associated with the
preceding diagnosis of benign lesions and follicular neoplasm. Sonographic findings failed to distinguish
NIFTP from IFVPTC.
The miR-210 Primed Endothelial Progenitor Cell Exosomes Alleviate
Acute Ischemic Brain Injury
Authors: Wang Jinju , Chen Shuzhen , Sawant Harshal , Chen Yanfang , Bihl Ji Chen 
Published: November 2023

Background::
Stem cell-released exosomes (EXs) have shown beneficial effects on regenerative
diseases. Our previous study has revealed that EXs of endothelial progenitor cells
(EPC-EXs) can elicit favorable effects on endothelial function. EXs may vary greatly in size, composition,
and cargo uptake rate depending on the origins and stimulus; notably, EXs are promising
vehicles for delivering microRNAs (miRs). Since miR-210 is known to protect cerebral endothelial
cell mitochondria by reducing oxidative stress, here we study the effects of miR-210-loaded
EPC-EXs (miR210-EPC-EXs) on ischemic brain damage in acute ischemic stroke (IS).

Methods::
The miR210-EPC-EXs were generated from EPCs transfected with miR-210 mimic.
Middle cerebral artery occlusion (MCAO) surgery was performed to induce acute IS in C57BL/6
mice. EPC-EXs or miR210-EPC-EXs were administrated via tail vein injection 2 hrs after IS. To
explore the potential mechanisms, inhibitors of the vascular endothelial growth factor receptor 2
(VEGFR2)/PI3 kinase (PI3K) or tyrosine receptor kinase B (TrkB)/PI3k pathways were used. The
brain tissue was collected after treatments for infarct size, cell apoptosis, oxidative stress, and protein
expression (VEGFR2, TrkB) analyses on day two. The neurological deficit score (NDS) was
evaluated before collecting the samples.

Results::
As compared to EPC-EXs, miR210-EPC-EXs profoundly reduced the infarct volume
and improved the NDS on day two post-IS. 2) Fewer apoptosis cells were detected in the peri-infarct
brain of mice treated with miR210-EPC-EXs than in EPC-EXs-treated mice. Meanwhile, the
oxidative stress was profoundly reduced by miR210-EPC-EXs. 3) The ratios of p-PI3k/PI3k, p-
VEGFR2/VEGFR2, and p-TrkB/TrkB in the ipsilateral brain were raised by miR210-EPC-EXs
treatment. These effects could be significantly blocked or partially inhibited by PI3k, VEGFR2, or
TrkB pathway inhibitors.

Conclusion::
These findings suggest that miR210-EPC-EXs protect the brain from acute ischemia-
induced cell apoptosis and oxidative stress partially through the VEGFR2/PI3k and TrkB/PI3k
signal pathways.
Differentiation of Human Adipose-derived Stem Cells to Exosome-affected
Neural-like Cells Extracted from Human Cerebrospinal Fluid Using
Bioprinting Process
Authors: Cheravi Mojtaba , Baharara Javad , Yaghmaei Parichehreh , Roudbari Nasim Hayati 
Published: November 2023

Background:
Advancement in tissue engineering has provided novel solutions for creating
scaffolds as well as applying induction factors in the differentiation of stem cells. The present
research aimed to investigate the differentiation of human adipose-derived mesenchymal
stem cells to neural-like cells using the novel bioprinting method, as well as the effect of cerebrospinal
fluid exosomes.

Methods:
In the present study, the extent of neuronal proliferation and differentiation of adipose-
derived stem cells were explored using the MTT method, immunocytochemistry, and real--
time PCR in the scaffolds created by the bioprinting process. Furthermore, in order to investigate
the veracity of the identity of the CSF (Cerebrospinal fluid) derived exosomes, after the isolation
of exosomes, dynamic light scattering (DLS), scanning electron microscopy (SEM), and atomic
force microscopy (AFM) techniques were used.

Results:
MTT findings indicated survivability and proliferation of cells in the scaffolds created by
the bioprinting process during a 14-day period. The results obtained from real-time PCR showed
that the level of MAP2 gene (Microtubule Associated Protein 2) expression increased on days 7
and 14, while the expression of the Nestin gene (intermediate filament protein) significantly decreased
compared to the control. The investigation to confirm the identity of exosomes indicated
that the CSF-derived exosomes had a spherical shape with a 40-100 nm size.

Conclusion:
CSF-derived exosomes can contribute to the neuronal differentiation of adipose-
derived stem cells in alginate hydrogel scaffolds created by the bioprinting process.
Anti-lung Cancer Activity of Synthesized Substituted 1,4-Benzothiazines: An Insight
from Molecular Docking and Experimental Studies
Authors: Amin Andleeb , Zubaid-Ul-Khazir  , Ji Arfa , Bhat Basharat Ahmad , Murtaza Dar , Hurrah Aaqib A. , Bhat Imtiyaz A. , Parveen Shaheena , Nisar Syed , Sharma Praveen Kumar 
Published: November 2023

Background:
Thiazine, a 6-membered distinctive heterocyclic motif with sulfur and nitrogen atoms, is
one of the heterocyclic compounds that functions as a core scaffold in a number of medicinally significant molecules.
Small thiazine-based compounds may operate simultaneously on numerous therapeutic targets and by
employing a variety of methods to halt the development, proliferation, and vasculature of cancer cells. We have,
herein, reported a series of substituted 1,4 benzothiazines as potential anticancer agents for the treatment of lung
cancer.

Methods:
In order to synthesize 2,3-disubstituted-1,4 benzothiazines in good yield, a facile green approach for
the oxidative cycloaddition of 2-amino benzenethiol and 1,3-dicarbonyls employing a catalytic amount of ceric
ammonium nitrate has been devised. All the molecules have been characterized by spectral analysis and tested for
anticancer activity against the A-549 lung cancer cell line using various functional assays. Further in silico
screening of compound 3c against six crucial inflammatory molecular targets, such as Il1-α (PDB ID: 5UC6), Il1-
β (PDB ID: 6Y8I), Il6 (PDB ID: 1P9M), vimentin (PDB ID: 3TRT), COX-2 (PDB ID: 5KIR), Il8 (PDB ID:
5D14), and TNF-α (PDB ID: 2AZ5), was done using AutoDock tool.

Results:
Among the synthesized compounds, propyl 3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazine-2-
carboxylate (3c) was found to be most active based on cell viability assays using A-549 lung cancer cell line and
was found to effectively downregulate various pro-inflammatory genes, like Il1-α, Il1-β, Il6, vimentin, COX-2,
Il8, and TNF-α in vitro. The ability of the molecule to effectively suppress the proliferation and migration of lung
cancer cells in vitro has been further demonstrated by the colony formation unit assay and wound healing assay.
Molecular docking analysis showed the maximal binding affinity (− 7.54 kcal/mol) to be exhibited by compound
3c against IL8.

Conclusion:
A green unconventional route for the synthesis of 2,3-disubstituted-1,4 benzothiazines has been
developed. All the molecules were screened for their activity against lung cancer and the data suggested that the
presence of an additional unbranched alkyl group attached to the thiazine ring increased their activity. Also, in
vitro and in silico modeling confirmed the anti-cancer efficiency of compound 3c, encouraging the exploration of
such small molecules against cancer.
Evaluation of Urban Sprawl and Land Surface Temperature along with Vegetation and Built-up Index for Nagpur City, Maharashtra
Authors: Ansari Tauseef Ahmad , Bade Rashmi G. , Shende A. M. , Pathan Mohd Gulfom , Kadam Anjali D. , Mendhe Ajay M. , Katre Fanindra F. , Deshmukh Abhilasha G. , Khan Farhan , Ghaffar Abdul 
Published: November 2023

Introduction:
Land use and Land cover (LULC) are now major worldwide issues. The
need for land is growing due to urbanisation and industrialisation, thus to meet this need, forest
and vegetation land are transformed to open land that is either utilised for colonisation of urban
areas or industrial usage. Patents are done on the calculation of LST.

Method:
The study aims to provide a detailed analysis of land and temperature change with variation
in Normalized difference vegetation index (NDVI) and normalized difference build-up index
(NDBI) for the study area using a geospatial technique. The LULC classification is performed
based on four classes which are Bare land, Built-up, Vegetation, and Waterbodies from the year
2000 to 2020. The classified data is further used to extract the Land Surface Temperature (LST)
data from the thermal band to generate LST maps. The NDVI and NDBI maps are also generated
using the land sat imageries. From the above-mentionedanalysis, it is found that Nagpur city temperature
has risen by 3.67 °C in two decades. Whereas, LULC results show that bare land and
vegetation decreased by 11.88% and 14.93% respectively, while an increase is seen for built-up
and water bodies by 25.62% and 0.19% respectively.

Result:
Regression analysis between temperature and NDVI, NDBI shows that temperature and
NDVI have a negation relation and NDBI has a positive relation with temperature (Pearson’s r:
between -0.89 to -0.81and between 0.90 to 0.81respectively) for both the years. The increased
temperature is a result of urbanization in the study area. The study reveals that for assessment of
LULC and LST with the incorporation of GIS and Remote sensing can be effective and swift.

Conclusion:
This study recommends that policymakers develop policies that should minimize the
transition of different classes and check the outcome of industries and the temperature of the
surroundings.
App-Based Hearing Screenings in Preschool Children With Different Types of Headphones: Diagnostic Study
Authors: Tananuchittikul Pornsek , Yimtae Kwanchanok , Chayaopas Nichtima , Thanawirattananit Panida , Kasemsiri Pornthep , Piromchai Patorn 
Published: November 2023

Abstract

Background
Hearing disability in preschool children can delay or impact oral communication and social skills. Provision of hearing screening tests by standard audiometry in low- to middle-income countries is problematic due to a lack of pediatric audiologists, standard hearing equipment, and standard soundproof rooms. Therefore, an innovative hearing screening tool that is easily accessible and inexpensive such as a mobile app should be considered. Headphones have been a crucial part of hearing screenings. Audiometric headphones, which serve as the reference standard, have been used in most studies. However, since audiometric headphones are not accessible in rural areas, we hypothesized that generic headphones can also be used in hearing screenings.

Objective
This study aimed to determine the sensitivity, specificity, κ coefficiency, and time consumption of the PASS-Pro (Preschool Audiometry Screening System–Pro) app when using TDH39 headphones, Beyerdynamic DT 770 PRO headphones, and generic earmuff headphones compared to standard conditioned play audiometry.

Methods
We recruited preschool children aged 4 to 5 years to participate in this study. The children received 3 PASS-Pro screening tests using different types of headphones in a quiet room and 1 standard conditioned play audiometry in a soundproof room. All tests were administered in random order. The agreement coefficient, sensitivity, specificity, and mean test duration were determined.

Results
A total of 44 children participated in this study. For mild hearing loss screening, the κ coefficients between standard conditioned play audiometry and the PASS-Pro app using TDH39 headphones, Beyerdynamic DT 770 PRO headphones, and generic earmuff headphones were 0.195, 0.290, and 0.261 (P=.02, P=.002, and P=.004), respectively. The sensitivity for all headphones was 50% and the specificity was more than 88%. For moderate hearing loss screening, the κ coefficients were 0.206, 0.272, and 0.235 (all Ps=.001), respectively. The sensitivity for all headphones was 100% and the specificity was more than 92%. There were no statistical differences in sensitivity and specificity between the reference headphone (TDH39), Beyerdynamic DT 770 PRO headphone, and generic earmuff headphones (all Ps >.05). The PASS-Pro app used significantly less time to carry out hearing tests than conditioned play audiometry (P<.001).

Conclusions
The PASS-Pro app, used with generic headphones, is effective for conducting hearing screening tests in preschool children with high sensitivity and specificity.