bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of ATM Mutation as a Potential Prognostic Biomarker for
Immune Checkpoint Inhibitors Therapy
Authors: Cui Saijin , Chen Tianyu , Zhao Yaning , Xiao Zhuoyun , Liu Meitong , Huang Xi , Cao Shiru , Zhou Rongmiao , Li You , Huo Xiangran , Wang Na 
Published: November 2023

Background:
Ataxia telangiectasia mutated (ATM), an apical DNA damage response
gene, is a commonly mutated gene in tumors, and its mutation could strengthen tumor immunogenicity
and alter the expression of PD-L1, which potentially contributes to immune checkpoint inhibitors
(ICIs) therapy.

Methods:
The characteristics of ATM mutation and its relationship with the ICIs-treated clinical
prognosis have been analyzed comprehensively in this paper. The overall frequency of ATM mutations
has been found to be 4% (554/10953) in the cancer genome atlas (TCGA) cohort.

Results:
Both the TMB and MSI levels in patients with ATM mutations were significantly higher
than those in patients without mutations (P < 0.0001). The median TMB was positively correlated
with the frequency of ATM mutations (r = 0.54, P = 0.003). In the TCGA cohort, patients with
ATM mutations had better clinical benefits in terms of overall survival (OS, hazard ratio (HR) =
0.736, 95% CI = 0.623 - 0.869), progression-free survival (PFS, HR = 0.761, 95% CI = 0.652 -
0.889), and disease-free survival (DFS, HR = 0.686, 95% CI = 0.512 - 0.919)] than patients without
ATM mutations. Subsequently, the verification results showed ATM mutations to be significantly
correlated with longer OS in ICIs-treated patients (HR = 0.710, 95% CI = 0.544 - 0.928).
Further exploration indicated ATM mutation to be significantly associated with regulated anti-tumor
immunity (P < 0.05).

Conclusion:
Our findings highlight the value of ATM mutation as a promising biomarker to predict
ICIs therapy in multiple tumors.
Combined RNAi of CTTN and FGF2 Modulates Cell Migration, Invasion
and G1/S Transition of Hepatocellular Carcinoma through Ras/ERK
Signaling Pathway
Authors: Zhou Jiaming , Liu Jiaxuan , Li Tiejun , Zhong Qiang , Yu Hongyu 
Published: November 2023

Background:
Most patients with hepatocellular carcinoma (HCC) die of rapid progression
and distant metastasis. Gene therapy represents a promising choice for HCC treatment, but
the effective targeted methods are still limited.

Objective:
CTTN/cortactin plays a key role in actin polymerization and regulates cytoskeleton remodeling.
However, the interaction network of CTTN in HCC is not well understood.

Methods:
siRNA was designed for CTTN silencing and Affymetrix GeneChip sequencing was
used to obtain the gene profile after CTTN knockdown in the HCC cell line SMMC-7721. Potential
interacting genes of CTTN were identified using qRT-PCR. The inhibition on HCC by combined
RNA interference (RNAi) of CTTN and fibroblast growth factor 2 (FGF2) was detected.

Results:
A total of 1,717 significantly altered genes were screened out and 12 potential interacting
genes of CTTN were identified. The interaction of CTTN and FGF2 was validated and combined
RNAi of CTTN and FGF2 achieved a synergistic effect, leading to better inhibition of HCC cell
migration, invasion and G1/S transition than single knockdown of CTTN or FGF2. Mechanistically,
combined RNAi of CTTN and FGF2 modulated the Ras/ERK signaling pathway. In addition,
the EMT epithelial marker E-cadherin was upregulated while the mesenchymal marker Vimentin
and cell cycle protein Cyclin D1 were downregulated after combined RNAi of CTTN and FGF2.
Additionally, qRT-PCR and immunohistochemical staining showed that both CTTN and FGF2
were highly expressed in metastatic HCC tissues.

Conclusion:
Combined RNAi of CTTN and FGF2 may be a novel and promising intervention
strategy for HCC invasion and metastasis.
LINC00887 Acts as an Enhancer RNA to Promote Medullary Thyroid
Carcinoma Progression by Binding with FOXQ1
Authors: Liu Daxiang , Wang Wenjing , Wu Yanzhao , Qiu Yongle , Zhang Lan 
Published: November 2023

Background:
Medullary thyroid carcinoma (MTC) is a rare but aggressive endocrine
malignancy that originates from the parafollicular C cells of the thyroid gland. Enhancer RNAs
(eRNAs) are non-coding RNAs transcribed from enhancer regions, which are critical regulators of
tumorigenesis. However, the roles and regulatory mechanisms of eRNAs in MTC remain poorly
understood. This study aims to identify key eRNAs regulating the malignant phenotype of MTC
and to uncover transcription factors involved in the regulation of key eRNAs.

Methods:
GSE32662 and GSE114068 were used for the identification of differentially expressed
genes, eRNAs, enhancers and enhancer-regulated genes in MTC. Metascape and the transcription
factor affinity prediction method were used for gene function enrichment and transcription factor
prediction, respectively. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was
used to assess the binding of histone H3 lysine 27 acetylation (H3K27ac)-enriched regions to anti-
H3K27ac. RIP-qPCR was used to detect the binding between FOXQ1 and LINC00887. CCK8
and Transwell were performed to measure the proliferation and invasion of MTC cells, respectively.
Intracellular reactive oxygen species (ROS) levels were quantified using a ROS assay kit.

Results:
Four eRNAs (H1FX-AS1, LINC00887, MCM3AP-AS1 and A1BG-AS1) were screened,
among which LINC00887 was the key eRNA promoting the proliferation and invasion of MTC
cells. A total of 135 genes controlled by LINC00887-regulated enhancers were identified; among
them, BCL2, PRDX1, SFTPD, TPO, GSS, RAD52, ZNF580, and ZFP36L1 were significantly enriched
in the “ROS metabolic process” term. As a transcription factor regulating genes enriched in
the “ROS metabolic process” term, FOXQ1 could recruit LINC00887. Overexpression of FOXQ1
restored LINC00887 knockdown-induced downregulation of GSS and ZFP36L1 transcription in
MTC cells. Additionally, FOXQ1 overexpression counteracted the inhibitory effects of
LINC00887 knockdown on the proliferation and invasion of MTC cells and the promotion of intracellular
ROS accumulation induced by LINC00887 knockdown.

Conclusion:
LINC00887 was identified as a key eRNA promoting the malignant phenotype of
MTC cells. The involvement of FOXQ1 was essential for LINC00887 to play a pro-tumorigenic
role in MTC. Our findings suggest that the FOXQ1/LINC00887 axis is a potential therapeutic target
for MTC.
Comparison of Surgical and Colonoscopy Tissue to Establish Colorectal
Patient-derived Organoids
Authors: Chen Hong , Yang Yuping , Shi Jinsen , Yan Ting , Wang Jun , Yang Yuning , Lu Qin , Feng Hailan , Du Jian , Cao Zhiyun , Weygant Nathaniel 
Published: November 2023

Background:
Patient-derived organoids (PDOs) are ex vivo models that retain the functions
and characteristics of individualized source tissues, including a simulated tumor microenvironment.
However, the potential impact of undiscovered differences between tissue sources on
PDO growth and progression remains unclear.

Objective:
This study aimed to compare the growth and condition of PDO models originating
from surgical resection and colonoscopy and to provide practical insights for PDO studies.

Methods:
Tissue samples and relevant patient clinical information were collected to establish
organoid models. PDOs were derived from both surgical and colonoscopy tissues. The growth of
the organoids, including their state, size, and success rate of establishment, was recorded and analyzed.
The activity of the organoids at the end stage of growth was detected using calcein-AM fluorescence
staining.

Results:
The results showed that the early growth phase of 2/3 colonoscopy-derived organoids
was faster compared to surgical PDOs, with a growth difference observed within 11-13 days of
establishment. However, colonoscopy-derived organoids exhibited a diminished growth trend after
this time. There were no significant differences observed in the terminal area and quantity between
the two types of tissue-derived organoids. Immunofluorescence assays of the PDOs revealed
that the surgical PDOs possessed a denser cell mass with relatively higher viability than
colonoscopy-derived PDOs.

Conclusion:
In the establishment of colorectal patient-derived organoids, surgically derived
organoids require a slightly longer establishment period, while colonoscopy-derived organoids
should be passaged prior to growth inhibition to preserve organoid viability.
Bioinformatics and Experimental Study Revealed LINC00982/
miR-183-5p/ABCA8 Axis Suppresses LUAD Progression
Authors: Ding Defang , Zhong Jingyu , Xing Yue , Hu Yangfan , Ge Xiang , Yao Weiwu 
Published: November 2023

Background::
Lung adenocarcinoma (LUAD) is a major health challenge worldwide
with an undesirable prognosis. LINC00982 has been implicated as a tumor suppressor in diverse
human cancers; however, its role in LUAD has not been fully characterized.

Methods::
Expression level and prognostic value of LINC00982 were investigated in pan-cancer
and lung cancer from The Cancer Genome Atlas (TCGA) project. Differential expression analysis
based on the LINC00982 expression level was performed in LUAD followed by gene set enrichment
analysis (GSEA) and functional enrichment analyses. The association between LINC00982
expression and tumor immune microenvironment characteristics was evaluated. A potential ceRNA
regulatory axis was identified and experimentally validated.

Results::
We found that LINC00982 expression was downregulated and correlated with poor prognosis
in LUAD. Enrichment analyses revealed that LINC00982 could inhibit DNA damage repair
and cell proliferation, but enhance tumor metabolic reprogramming. We identified a competing endogenous
RNA network involving LINC00982, miR-183-5p, and ATP-binding cassette subfamily
A member 8 (ABCA8). Luciferase assays confirmed that miR-183-5p can interact with
LINC00982 and ABCA8. Forced miR-183-5p expression reduced LINC00982 transcript levels
and suppressed ABCA8 expression.

Conclusions::
Our findings revealed the LINC00982/miR-183-5p/ABCA8 axis as a potential therapeutic
target in LUAD.
Diabetic Retinopathy Diagnosis based on Convolutional Neural Network in
the Russian Population: A Multicenter Prospective Study
Authors: Gognieva Daria , Durzhinskaya Madina , Vorobyeva Irina , Chomakhidze Petr , Suvorov Alexander , Kuznetsova Natalia , Bektimirova Alina , Al-Dwa Baraah , Abdullaev Magomed , Yusef Yusef , Pavlov Vladislav , Budzinskaya Maria , Sychev Dmitry , Moshetova Larisa , Kopylov Philipp 
Published: November 2023

Background::
Diabetic retinopathy is the most common complication of diabetes
mellitus and is one of the leading causes of vision impairment globally, which is also relevant
for the Russian Federation.

Objective::
To evaluate the diagnostic efficiency of a convolutional neural network trained for the
detection of diabetic retinopathy and estimation of its severity in fundus images of the Russian
population.

Methods::
In this cross-sectional multicenter study, the training data set was obtained from an
open source and relabeled by a group of independent retina specialists; the sample size was
60,000 eyes. The test sample was recruited prospectively, 1186 fundus photographs of 593 patients
were collected. The reference standard was the result of independent grading of the diabetic
retinopathy stage by ophthalmologists.

Results::
Sensitivity and specificity were 95.0% (95% CI; 90.8-96.4) and 96.8% (95% CI; 95.5-
99.0), respectively; positive predictive value – 98.8% (95% CI; 97.6-99.2); negative predictive
value – 87.1% (95% CI, 83.4-96.5); accuracy – 95.9% (95% CI; 93.3-97.1); Kappa score – 0.887
(95% CI; 0.839-0.946); F1score – 0.909 (95% CI; 0.870-0.957); area under the ROC-curve –
95.9% (95% CI; 93.3-97.1). There was no statistically significant difference in diagnostic accuracy
between the group with isolated diabetic retinopathy and those with hypertensive retinopathy
as a concomitant diagnosis.

Conclusion::
The method for diagnosing DR presented in this article has shown its high accuracy,
which is consistent with the existing world analogues, however, this method should prove its
clinical efficiency in large multicenter multinational controlled randomized studies, in which the
reference diagnostic method would be unified and less subjective than an ophthalmologist.
Recurred Uterine Cervical Cancer Initially Manifesting as Hemorrhagic Cyst: A
Case Report
Authors: Jung Yoon Kyung , Park Sung Bin , Park Hyun Jeong , Lee Eun Sun 
Published: November 2023

Background::
Recurrence of uterine cervical cancer is common and often shows a dismal prognosis. Local recurrence usually manifests as solid soft tissue
lesions and has rarely been reported to have cystic lesions.

Case Presentation::
Herein, we report a case of recurrent uterine cervical cancer with initial manifestation as a hemorrhagic cyst, assessed using strain
sonoelastography, CT, and MRI.

Conclusion::
Although cystic recurrence is uncommon, newly detected simple or complex cystic lesions should be closely monitored.
Perspective of Secondary Metabolites in Respect of Multidrug Resistance
(MDR): A Review
Authors: Kaushik Aditi , Kaushik Manish , Kaur Gagandeep , Gupta Vrinda 
Published: November 2023

Abstract:
Aberrant and haphazard use of antibiotics has created the development of antimicrobial
resistance which is a bizarre challenge for human civilization. This emerging crisis of antibiotic resistance
for microbial pathogens is alarming all the nations posing a global threat to human health. It
is difficult to treat bacterial infections as they develop resistance to all antimicrobial resistance. Currently
used antibacterial agents inhibit a variety of essential metabolic pathways in bacteria, including
macro-molecular synthesis (MMS) pathways (e.g. protein, DNA, RNA, cell wall) most often by targeting
a specific enzyme or subcellular component e.g. DNA gyrase, RNA polymerase, ribosomes,
transpeptidase. Despite the availability of diverse synthetic molecules, there are still many complications
in managing progressive and severe antimicrobial resistance. Currently not even a single antimicrobial
agent is available for which the microbes do not show resistance. Thus, the lack of efficient
drug molecules for combating microbial resistance requires continuous research efforts to overcome
the problem of multidrug-resistant bacteria. The phytochemicals from various plants have the potential
to combat the microbial resistance produced by bacteria, fungi, protozoa and viruses without
producing any side effects. This review is a concerted effort to identify some of the major active
phytoconstituents from various medicinal plants which might have the potential to be used as an
alternative and effective strategy to fight against microbial resistance and can promote research for
the treatment of MDR.
Diagnosis and Management of Latent Tuberculosis Infection: Updates
Authors: Swain Satish , Kumar Arvind , Vishwakarma Vishal Kumar , Aayilliath K Adarsh , Mittal Ankit , Wig Naveet 
Published: November 2023

Abstract:
India has the largest problem of tuberculosis (TB) infection globally (estimated at about
35-40 crores cases), and around 18-36 lakh develop active tuberculosis annually. Latent TB is defined
as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with
no evidence of clinically manifested active TB. The progression of a latent infection to active tuberculosis
increases several-fold in children < 5 years of age and in people with some or the other form
of an immunocompromising condition. Therefore, to cater to this gigantic problem of tuberculosis, it
is necessary to have awareness about latent tuberculosis infection (LTBI) amongst clinicians and to
prioritise its diagnosis and treatment in high-risk groups. India plans to end TB well before the deadline
set by the World Health organisation (WHO). However, this can only be achieved with effective
strategies targeting LTBI. Multiple treatment regimens have been approved for LTBI treatment, and
all have comparable efficacy. The selection of one regimen over the other depends on various factors,
such as availability, risk of adverse events, age, and drug interactions. Recently, the WHO, as well as
the Revised National TB Control Programme (RNTCP), have updated their guidelines on TB preventive
treatment in 2020 and 2021, respectively. This review has been especially prepared to
acknowledge the differences in approach to LTBI in developed and developing countries.
The Effect of Metformin Treatment on Disease Control in Patients with
Acromegaly
Authors: Sahin Humeyra Rekali , Sahin Serdar , Sarac Betul , Sulu Cem , Kadioglu Pinar , Ozkaya Hande Mefkure 
Published: November 2023

Background:
The increase in portal insulin levels has been shown to upregulate
growth hormone receptor expression in the liver, leading to increased insulin-like growth hormone-
1 levels. Metformin inhibits hepatic gluconeogenesis and reduces fasting insulin.

Objective:
We evaluated the effect of metformin treatment in patients with acromegaly on
growth hormone, insulin-like growth hormone-1, and pituitary adenoma size.

Methods:
Patients who were followed up with the diagnosis of acromegaly in Istanbul University-
Cerrahpaşa, Cerrahpaşa Medical Faculty were evaluated. The patients were divided into three
groups after pituitary adenectomy as those who received somatostatin receptor ligand and metformin
treatment (group A), somatostatin receptor ligand treatment only (group B), and those
who received metformin treatment only (group C). Groups A and B were compared with each
other, and patients in group C were compared among themselves.

Results:
While the median insulin-like growth factor-1 level decreased to 170 ng/ml in Group A
after the treatment, the median insulin-like growth factor-1 level decreased to 229 ng/ml in
Group B, and a statistically significant difference was found between the two groups (p =0.020).
There was no significant difference in post-treatment growth hormone levels and residual adenoma
sizes between groups A and B (p >0.005). In group C, there was no significant difference
in growth hormone values pre-and post-metformin treatment (p =0.078); however, the median
insulin-like growth factor-1 level decreased from 205 ng/ml to 168 ng/ml during metformin
treatment and was found to be statistically significant (p =0.027).

Conclusion:
Due to the effect of metformin treatment on insulin-like growth factor-1 values in
patients with acromegaly, it can be used in disease control, as well as diabetes treatment.
Hypoparathyroidism Associated with Benign Thyroid Nodules in
DiGeorge-like Syndrome: A Rare Case Report and Literature Review
Authors: Spinelli Claudio , Ghionzoli Marco , Guglielmo Carla , Baroncelli Giampiero , Tyutyusheva Nina , Frega Alessia , Patrizio Armando , Fallahi Poupak , Ferrari Silvia Martina , Antonelli Alessandro 
Published: November 2023

Background:
DiGeorge-like syndrome (DGLS) is a rare genetic disorder due to the
presence of the same classical clinical manifestations of DiGeorge syndrome (DGS) without its
typical deletion. In the DGLS phenotype, hypoparathyroidism seldom occurs and is considered
rare. In DGS, hypocalcemia affects up to 70% of patients, and a considerable share often has
asymptomatic thyroid abnormalities.

Case Presentation:
In this study, we describe an unusual case of a 16-year-old patient with
DGLS due to a duplication of 365 kb in the 20p11.22 region, affected by hypoparathyroidism
associated with thyroid nodule. The intraoperative parathyroid evaluation ruled out agenesis as a
cause of hypoparathyroidism. In addition, we carried out a thorough literature review from 2010
to 2023 of DGLS cases using specific keywords, such as “22q11.2 deletion syndrome”, “Di-
George-like Syndrome”, “hypoparathyroidism”, “thyroid”, and “children”, analyzing 119 patients
with DGLS.

Conclusion:
Interestingly enough, the present case represents, to our knowledge, the first report
of a patient with DGLS associated with hypoparathyroidism and the presence of thyroid nodules
where an intraoperative observation reported a non-functional parathyroid gland.
The Anti-ulcer Potential of Weissella cibaria Assisted
Bio-fermented Product of Citrus limetta Waste Peel in Wistar
Albino Rats
Authors: Singh Monika , Singh Shreshtha , Puri Dinesh , Sawhney Shalini Kapoor , Kumar Nitin , Yasir Mohd. , Nainwal Pankaj 
Published: November 2023

Background:
There are patents available related to fermented food and beverages
which enhance to human health. Citrus limetta (Mosambi) has a high content of flavonoids
and exhibits antioxidant activity, which could stimulate the digestive system and
be useful for gastroprotective activity. It supports digestion by neutralizing the acidic digestive
juices and reducing gastric acidity.

Objective:
This study explored the potential of using waste peel extract from Citrus
limetta to prevent ulcers. The study specifically sought to assess the anti-ulcer properties
of fermented and non-fermented extracts and compare them. Further, the study looked at
the potential benefits of treating or preventing ulcers with Citrus limetta waste peels and
whether fermentation affected the efficacy of the treatment.

Methods:
Thirty female Wistar albino rats were equally distributed into five different
groups. Group 1 received distilled water (20 ml/kg/b.w); Group 2 received indomethacin
(mg/kg/b.w); Group 3 received omeprazole (20 mg/kg/b.w); Group 4 received aqueous
extract of Mosambi peel (400 mg/kg/b.w) and Group 5 received fermented product of extract
of Mosambi peel (400 mg/kg/b.w).

Results:
Findings explored that, compared to non-fermented citrus fruit juice, biofermented
exhibited less gastric volume (1.58 ± 0.10 ml vs. 1.8 ± 0.14 ml), reduced MDA
levels (355.23 ± 100.70 μmol/mg protein vs. 454.49 ± 155.88 μmol/mg protein), and low
ulcer index (0.49 ± 0.07 vs. 0.72 ± 0.14).

Conclusion:
The results suggest that the bio-fermented product of Citrus limetta peel has
better anti-ulcer potential against peptic ulcer induced by indomethacin in Wistar albino
rats compared to non-fermented.