bluuebunny/crossref_metadata_2025_split huggingface dataset:
iRGD Tumor Penetrating Peptide-Modified NK Cells Exhibit Enhanced Tumor Immune Infiltration Ability and Anti-Tumor Efficacy
Authors: Song Ge , Qi Xueyong , Zhao Yi 
Published: February 2025

Background:
Natural killer (NK) cells, as part of the group I innate lymphocytes (ILCs)
are essential for tumor immune surveillance. NK cells can recognize and eliminate target cells
without the need for prior sensitization or restriction of major histocompatibility complexes
(MHCs) and antigens. However, the limited infiltration of metastatic NK cells poses significant
challenges for advancing adoptive cell immunotherapy for solid tumors.

Objective:
This study aimed to explore the potential of using tumor penetrating peptide (TPP)
iRGD to promote the delivery of activated NK cells to deeper layers of tumor tissue.

Methods:
Flow cytometry was performed to evaluate the activation, inhibition, and expression of
other receptors involved in cytotoxicity. High-pressure liquid chromatography (HPLC) and mass
spectrometry were used to detect the purity of iRGD. 1,2-distearoyl-sn-glycero-3-
phosphoethanolamine-poly(ethylene glycol)-iRGD (DSPE-PEG-iRGD) was synthesized. Surface
modification of cells was performed using DSPE-PEG-iRGD. Multicellular tumor spheroids
(MCTSs) were established to evaluate permeability. In addition, in order to better simulate the
physiological characteristics of solid tumors in vivo, we generated 3D spheroids from HGC27
gastric cancer cell line and BXPC-3 pancreatic cancer cell line to study the anti-tumor effect of NK
cells with combination iRGD in vitro. The mouse models of gastric cancer and pancreatic cancer
were used. In addition, the synergistic anti-tumor effects were evaluated in vivo based on the tumor
volume and body weight of mice.

Results:
Initially, we treated NK cells with interleukin-2 (IL-2), resulting in significant activation
as indicated by upregulation of CD56. On the 15th day, the proliferation of CD3-/56+cell
population in NK cell culture containing IL-2 significantly increased, and the NK cell amplification
factor was greater than 300. In addition, NK cells exhibited increased cytotoxicity towards cancer
cell lines. When the ratio of effect to target was 10:1, the killing rate of NK cells against BXPC-3
was 83.1%. iRGD modification enabled NK cells to penetrate MCTSs, resulting in cytotoxicity
against target HGC27 and BXPC-3 cells. In addition, NK cells modified with iRGD significantly
reduced tumor growth in the xenotransplantation model of gastric cancer and pancreatic cancer
mice model.

Conclusion:
In summary, our results indicated that NK cells exhibited higher efficacy and lifespan
against cancer cell lines in vitro. Furthermore, the integration of iRGD into NK cells led to
improved infiltration and targeted elimination of MCTSs. Moreover, the application of iRGDmodified
NK cells has shown significant anti-tumor efficacy against solid tumors in vivo. This joint
strategy may significantly improve the efficacy of NK cell immunotherapy in treating various solid
tumors.
Anti-Cancer Bioactive Peptide Induces Apoptosis in Gastric Cancer Cells through TP53 Signaling Cascade
Authors: Suyila Qimuge , Li Xian , Su Xiulan 
Published: February 2025

Introduction:
Gastric cancer has emerged as one of the major diseases threatening human
health. Our previous studies indicated that the anti-cancer bioactive peptide (ACBP) inhibits
the initiation and progression of gastric cancer through apoptosis and cell cycle arrest, yet the
mechanisms remain unclear. To elucidate the relationships between the effects of ACBP and the
levels of cell differentiation, as well as the functional mechanisms of ACBP, we conducted a
study using three human gastric cancer cell lines: NCI-N87, MGC-803, and another unspecified
line.

Method:
We investigated the impact of ACBP on the survival and morphology of these cancer
cell lines, examined apoptosis and cell cycle progression, and detected the expression of TP53,
TP63, and TP73 in cancer cells, as well as the expression of Bax, PUMA, and Mcl-1 in a xenograft
mouse model. ACBP inhibited the proliferation of all three cancer cell lines in a dose-dependent
manner, similar to the positive control and 5-fluorouracil (5-FU). The effect of ACBP correlated
with the degree of differentiation of the cancer cells; the lower the differentiation degree, the
stronger the inhibitory effect.

Result:
After ACBP treatment, the expression of TP53, TP63, and TP73 increased in all cell lines.
In the xenograft mouse model, ACBP inhibited the growth of MGC-803 cells in vivo. The apoptotic-
related genes Bax and PUMA were upregulated, while Mcl-1 was downregulated. ACBP inhibited
tumor cell growth by inducing apoptosis through the TP53 signaling cascade, upregulating
TP53, TP63, and TP73 and their downstream apoptosis-promoting genes Bax and PUMA while
downregulating the anti-apoptotic gene Mcl-1.

Conclusion:
Notably, after ACBP treatment, Mcl-1 expression was significantly reduced in the tumor
tissue of the xenograft model, indicating that ACBP induced apoptosis through the TP53 signaling
cascade. This project provides a scientific basis for exploring the antitumor mechanism of
ACBP in gastric cancer therapy.

other:
This project provides a scientific basis for exploring the antitumor mechanism of ACBP in gastric cancer therapy.
A Pharmacological Update of Oxadiazole Derivatives: A Review
Authors: Mohan Magesh , Rathinasamy Gandhimathi , Devarajan Bharathi , Byran Gowramma , Lakshmanan Kaviarasan 
Published: February 2025

Background:
Recent advancements in the synthesis of novel heterocyclic compounds,
particularly oxadiazole derivatives, have garnered significant interest due to their broad pharmacological
activities. Despite the oxadiazole ring being a relatively small structure, its derivatives have
shown considerable therapeutic potential across a range of diseases. These compounds have been
explored for a variety of biological effects, including anti-inflammatory, anticonvulsant, hypoglycemic,
antitubercular, anxiolytic, antimicrobial, antitumor, and anticancer properties. The growing
issue of drug resistance has further fueled research into the therapeutic promise of oxadiazolebased
compounds, particularly for their ability to target resistant diseases

Objective:
This review aims to highlight the pharmacological profiles of oxadiazole derivatives,
with a focus on how structural modifications can enhance their activity against specific therapeutic
targets. Additionally, the review seeks to explore strategies for overcoming resistance mechanisms
associated with these compounds, underscoring their potential in addressing emerging drugresistant
diseases.

Conclusion:
Oxadiazole derivatives represent a promising class of compounds with significant
therapeutic potential, particularly in the face of increasing drug resistance. Their diverse pharmacological
activities and ability to be structurally optimized for specific therapeutic targets position
them as valuable candidates for further research. Continued exploration of oxadiazole derivatives,
with an emphasis on overcoming resistance, may lead to the development of novel treatments for a
variety of challenging diseases.
Discovery of the PARP1 Inhibitors from Natural Compounds Using Structure-Based Virtual Screening and Bioactivity Evaluation
Authors: Pan Dabo , Huang Yaxuan , Jiang Dewen , Jin Xiaojie , Wu Mingkai , Luo Jianjun , Zhang Yonghao 
Published: February 2025

Background:
PARP1 (poly ADP-ribose polymerase 1, also known as ADPRT1) plays a
significant role in DNA repair and has become an attractive target for treating PARP1-related diseases,
such as cancer.

Objective:
This study aimed to discover inhibitors targeting PARP1 from the phytochemicals of
Huangbai (Phellodendron chinense Schneid.), Baixianpi (Dictamnus dasycarpus Turcz.), and
Shechuangzi (Cnidium monnieri (L.) Spreng.).

Methods:
The chemical compositions of Huangbai, Baixianpi, and Shechuangzi were extracted
from the HERB database. Next, a combination of molecular docking and PARP1 enzyme assay was
used to identify PARP1 inhibitors from these chemical components. Finally, molecular dynamics
simulation and binding free energy calculation were used to explore the detailed interaction mode
of these inhibitors with PARP1.

Results:
A total of 507 chemical constituents of Huangbai, Baixianpi, and Shechuangzi were collected
from the HERB database. Four potential PARP1 inhibitors were screened based on molecular
docking and PARP1 enzyme assay. Demethyleneberberine exhibited strong PARP1 inhibitory
activity with an IC50 value of 2.0 ± 0.8 μM. The IC50 values of the inhibitory activities of 8-hydroxy
dictanmnine, meranzin hydrate, and osthol on PARP1 ranged from 44 μM to 76 μM. Molecular
dynamics simulation and binding free energy calculation suggested that the nonpolar interaction
energies of HIS862, GLY863, TYR889, TYR896, PHE897, and TYR907 played a primary role in
the binding of inhibitors to PARP1.

Conclusion:
Integrating molecular simulation and bioactivity testing was found to be an effective
approach for the rapid discovery of targeted PARP1 inhibitors. Demethyleneberberine demonstrated
strong PRAP1 inhibitory activity and has a good prospect for development.
ICPi-Induced Graves' Disease with Pre-existing Autoimmune Thyroid Disorders: A Case Report and Literature Review
Authors: Wang Xinpan , Chen Doudou , Shi Yun , Yang Tao , Zheng Xuqin 
Published: February 2025

Background:
Immune Checkpoint Inhibitor (ICPi) therapy has revolutionized cancer
treatment but can lead to immune-related adverse events (irAE), including thyroid dysfunction.
The impact of ICPi on patients with pre-existing autoimmune thyroid diseases (PATD), particularly
the development of Graves' disease, remains poorly understood.

Case Description:
We provide the first complete case of Graves' disease with ICPi therapy in a patient
who already had Hashimoto's thyroiditis.. The patient, a 52-year-old male, was diagnosed
with lung adenocarcinoma and received Atezolizumab. Clinical evaluation revealed hyperthyroidism,
confirmed by elevated thyroid hormones and autoantibodies (TRAb and TSAb). The patient
was managed with methimazole and demonstrated a transient hyperthyroid phase followed
by persistent hypothyroidism. Only 16 confirmed cases of Graves' disease induced by ICPi were
reported. We conducted a review to investigate the clinical characteristics, risk factors, and prognosis
trends associated with ICPi-induced Graves disease in PTAD patients. Additionally, changes
in thyroid function and autoantibodies during and after ICPi treatment are examined.

Conclusion:
This case underscores the importance of monitoring thyroid function and autoantibodies
in patients with PATD undergoing ICPi therapy. The findings suggest distinct differences
in the humoral immune response between ICPi-induced and spontaneous Graves' disease, necessitating
further research into autoantibody dynamics and their relationship with cellular immunity in
these patients.
Refractive Index Sensor Using Photonic Serial Loop Structures
Authors: El-Aouni Mimoun , Ben-Ali Youssef , Rahou Zakarea , Driss Bria 
Published: February 2025

Introduction:
This work presents a theoretical and numerical approach to the design of a
highly sensitive refractive index sensor operating in the visible spectrum. The proposed sensor features
a simple configuration utilizing serial loop structures that can support defect modes within the
photonic bandgap.

Methods:
These defect modes arise from the introduction of geometric and material imperfections
at the loop level of the structure. By employing continuous medium interface response theory, we
calculate the Green function for composite systems, enabling the determination of dispersion relations
and transmission rates.

Results:
Numerical simulations indicate that the sensor achieves a remarkable sensitivity of S
=1090 nm/RIU and a detection limit DL = 7.10-3 RIU. The quality factor Q of the sensor demonstrates
distinct characteristics, exhibiting a high sensitivity to minute variations in refractive index.

Conclusion:
These results show that the structure we have designed is suitable for applications such
as biosensors, gas detectors and medical diagnostic devices.
Ameliorating Paraquat-Induced Nephrotoxicity in Rats: Protective Effects of Nanocurcumin on Renal Histology and Molecular Pathways
Authors: Moghaddam Davood Ahmadi , Rahimi Mehdi , Kheiripour Nejat , Sadeghian Zohre , Asl Sara Soleymani , Azizi Zahra , Ranjbar Akram 
Published: February 2025

Background:
Paraquat (PQ) is a common herbicide, and its mortality results from injury
to several organs, including the kidneys. Nanocurcumin and curcumin have anti-inflammatory and
anti-oxidative activities, but their involvement in PQ-induced kidney damage is unclear. Therefore,
the goal of our study was to compare nanocurcumin and curcumin in male rats whose kidneys were
damaged by PQ.

Method:
42 eight-week male albino Wistar rats were put into six groups at random as control, control
+ curcumin, control + nanocurcumin, PQ, PQ + curcumin, PQ + nanocurcumin for 7 days. The
kidney tissues and serum were collected at the end of this period. Total antioxidant capacity (TAC),
lipid peroxidation (LPO), total thiol Molecule (TTM), urea, creatinine, and blood urea nitrogen
(BUN) levels were assessed. The histopathological evaluation of kidney damage was performed at
the end of our study. Moreover, the gene expression was assessed by biochemical and Reverse transcription
polymerase chain reaction (RT-PCR) analysis.

Result:
Curcumin and nanocurcumin administration alleviated PQ-induced renal injury, as evidenced
by reduced serum creatinine and BUN levels. The levels of antioxidant markers, like TAC
and TTM, increased and decreased the levels of oxidative stress indexes like LPO. Furthermore, our
result shows up-regulating the expression of nuclear factor-like 2 (Nrf2), NAD (P) H: quinine oxidoreductase
1 (NQO1), Heme oxygenase 1 (HO-1), and down-regulating the expression of Kelchlike
ECH-associated protein 1 (Keap-1) in renal tissue.

Conclusion:
Niosomal curcumin was more advantageous than ordinary curcumin in lowering oxidative
stress and renal tissue damage induced by paraquat intoxication.
Tool Condition Monitoring Using Artificial Intelligence in Machining: An Application Directed towards Industry 4.0
Authors: Tamang Santosh Kumar , Teyi N. , Mishra Madhusudhan , T Mythili , R Thanigaivelan 
Published: February 2025

Introduction:
In response to the growing demand for machining process automation,
both academic and industry experts have prioritized real-time tool condition monitoring. However,
this approach has been difficult previously owing to several known and unknown machining parameters,
as well as difficult working circumstances, such as high temperatures and pressure. Inprocess
condition monitoring and real-time process optimization have become easier because of
developments in sensor and digital technologies. These processes are now very precise, reliable,
and efficient.

Method:
This paper presents a comprehensive solution for monitoring machining systems, introducing
an Artificial Intelligence (AI) and Machine Learning (ML) framework that leverages integrated
sensory data to detect and predict flaws and wear issues in cutting tools. In the present work,
the time series data from CNC motors (in the X, Y, and Z axes and the spindle) recorded during 18
machining tests at 100 ms sampling rate were used for training and testing the system. The experimental
data reported the tool condition, whether worn or unworn.

Results:
Data pre-processing involved importing essential libraries, converting non-numerical labels
to numerical ones, and removing irrelevant columns. With feed rate and clamp pressure specified,
a correlation heatmap indicated important features for tool condition prediction. Two classification
algorithms have been implemented, i.e., decision tree and logistic regression models. Further,
the adequacy of the models was compared based on tool condition prediction.

Conclusion:
Logistic regression demonstrated superior predictive performance compared to decision
tree, establishing it as the preferred model for this analysis. Model performance was evaluated
through training and testing with a 70/30 dataset split. Logistic regression effectively predicted tool
condition as either worn or unworn based on input parameters of feed rate and clamp pressure.
Therapeutic Potential of Mesenchymal Stem Cells or their Secretome in Diabetic Mice with or without Preconditioning Treatment
Authors: Desai Shivani M. , Bhonde Ramesh R. , Veeranjaneyulu Addepalli , Sanap Avinash , Jarare Surabhi , Satpute Snehal , Janjire Omkar , Soundankar Anusaya , Ahmed Niyaz , Abhale Krushna 
Published: February 2025

Background:
Type 1 diabetes mellitus (T1DM) is an autoimmune disease with difficult
management, affecting the quality of life. Stem cell therapy has been proven to have regenerative
ability. Using the existing stem cell therapy and modifying it, the current study aims to
evaluate the effect of umbilical cord-derived mesenchymal stem cells (UCMSC), condition media
(CM), and UCMSC and CM preconditioned with methotrexate, reservetrol, and vitamin D
for its ability to manage T1DM in Swiss albino mice.

Materials & Methods:
Disease condition was established in the animals by using a diabetesinducing
agent streptozotocin (STZ). Then the animals were grouped into normal control, disease
control, standard, and test groups; and the treatments were given accordingly. The total
study period for this experiment was 28 days. During this period, the animals were supervised
for blood glucose levels, food-water intake, and body weight twice a week. At the end of 28
days, the biochemical estimations for serum insulin level, C-peptide, pro-inflammatory cytokines,
and anti-inflammatory cytokines level were done. Also, histopathology of the pancreas
was performed.

Results:
The test groups showed a significant decline in the blood glucose level, an increase
in C-peptide level, and a decrease in pro-inflammatory cytokines as compared to the
disease group. A statistically significant change was not observed within the groups in
terms of serum insulin and anti-inflammatory cytokine levels. There were improvements
in diabetic symptoms in treatment groups, such as polyphagia, polydipsia, and weight
loss. Treatment groups also showed pancreatic regeneration, indicating improved insulin
secretion.

Conclusion:
In the present study, we concluded that UCMSC, CM, and UCMSC and CM
preconditioned with synthetic and natural immunosuppressants and immunomodulators have
the ability to regenerate damaged pancreatic beta cells and have an antidiabetic activity,
along with an immunomodulating effect. This therapy is a promising choice for future
research.
Effectiveness of Adaptation of a Resilience-Building Intervention Among Individuals With Adverse Childhood Experience: Protocol for a Randomized Controlled Trial
Authors: Kiat Jun , Ahmad Mahadir , Mei Hsien Chan Caryn , Zainalabidin Satirah , Ungar Michael , Subramaniam Ponnusamy 
Published: February 2025

Background
The impact of adverse childhood experiences (ACEs) has been the focus of most studies for the past decade. There is an indication that developing resilience can help youth overcome these ACEs.

Objective
This article presents a study protocol for a randomized controlled trial (RCT) to investigate the effects of a resilience-building intervention on psychological well-being, coping strategies, stress, quality of life, resilience, resource finding, and resilience among individuals affected with ACEs in Malaysia.

Methods
The is a 2-armed, single-blind, RCT, whereby 50 participants (25 in each group) with ACEs will be randomly assigned to intervention and control groups. The former will be exposed to a resilience-building program (R2), which entails a multisystemic approach to resilience and recognizes the importance of rugged qualities and access to resources among individuals affected with ACEs. The intervention will be delivered via internet-based by a facilitator and broadly divided into 5 sessions, focusing on self-exploration and social support, coping techniques and coping skills, resource finding, spirituality, and resilience building. Meanwhile, the control group participants will not receive any form of intervention. Saliva samples will also be collected from both groups and assessed for salivary cortisol levels. Outcome measures will be assessed during baseline and postintervention using validated instruments. Another follow-up measurement will be conducted 4 weeks later.

Results
The clinical trial has been registered with the Australia New Zealand Clinical Trials Registry. Ethical approval was obtained from the Research Ethics Board at the National University of Malaysia (UKM PPI/111/8/JEP-2021-894). A total of 28 participants have been recruited to the RCT Participant recruitment will be completed by January 2025. The final analysis will be conducted by March 2025.

Conclusions
This is among the first studies to provide evidence in the context of RCTs for resilience-building intervention that combines self-report and physiological measures (ie, saliva and heart blood pressure) among individuals with ACEs. The findings will assist relevant authorities in the health and policy sectors to develop effective strategies for addressing the negative impacts of ACEs on the vulnerable population in Malaysia.

Trial Registration
ACTRN12622000604707; https://www.anzctr.org.au/Trial/Result/DataSharingStatement.aspx?id=383614

International Registered Report Identifier (IRRID)
DERR1-10.2196/56826
Identifying Misinformation About Unproven Cancer Treatments on Social Media Using User-Friendly Linguistic Characteristics: Content Analysis
Authors: Fridman Ilona , Boyles Dahlia , Chheda Ria , Baldwin-SoRelle Carrie , Smith Angela B , Elston Lafata Jennifer 
Published: February 2025

Background
Health misinformation, prevalent in social media, poses a significant threat to individuals, particularly those dealing with serious illnesses such as cancer. The current recommendations for users on how to avoid cancer misinformation are challenging because they require users to have research skills.

Objective
This study addresses this problem by identifying user-friendly characteristics of misinformation that could be easily observed by users to help them flag misinformation on social media.

Methods
Using a structured review of the literature on algorithmic misinformation detection across political, social, and computer science, we assembled linguistic characteristics associated with misinformation. We then collected datasets by mining X (previously known as Twitter) posts using keywords related to unproven cancer therapies and cancer center usernames. This search, coupled with manual labeling, allowed us to create a dataset with misinformation and 2 control datasets. We used natural language processing to model linguistic characteristics within these datasets. Two experiments with 2 control datasets used predictive modeling and Lasso regression to evaluate the effectiveness of linguistic characteristics in identifying misinformation.

Results
User-friendly linguistic characteristics were extracted from 88 papers. The short-listed characteristics did not yield optimal results in the first experiment but predicted misinformation with an accuracy of 73% in the second experiment, in which posts with misinformation were compared with posts from health care systems. The linguistic characteristics that consistently negatively predicted misinformation included tentative language, location, URLs, and hashtags, while numbers, absolute language, and certainty expressions consistently predicted misinformation positively.

Conclusions
This analysis resulted in user-friendly recommendations, such as exercising caution when encountering social media posts featuring unwavering assurances or specific numbers lacking references. Future studies should test the efficacy of the recommendations among information users.