bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Sclerosis in the Digital Health Age: Challenges and Opportunities - A Systematic Review
Authors: Specht Bernhard , Jager Hana , Garbaya Samaher , Pincherle Alessandro , Sarvari Peiman Alipour , Khadraoui Djamel , Schneider Reinhard , Chavarriaga Ricardo , Tayeb Zied 
Published: November 2023

Abstract
In recent times, we have unequivocally witnessed a push towards digitising the healthcare system. Topics such as remote patient monitoring (RPM), digital health, and their use to monitor neurological disease progression have gained momentum and popularity. Notwithstanding the considerable advances that have been made in adopting such technologies and using them in the context of mental health or even a few neurodegenerative disease monitoring, they have not been widely used in the context of remote management and treatment of multiple sclerosis MS. In the same vein, given that (MS) is a very individualized disease to manage, there are numerous challenges yet opportunities associated with using digital health technologies for remote MS monitoring. This paper reviews the different research work and clinical attempts performed over the last decade (both home & hospital-based monitoring) en route to using digital health for MS monitoring and management. Similarly, this systematic review discusses the main challenges and barriers to translating that research from clinics into homes and highlights the opportunities in that context. Throughout this extensive review, we shine a light on various monitoring methods that hold the potential to be measured in a home environment, including electroencephalography (EEG) and evoked potentials (e.g., motor evoked potential (MEP), somatosensory evoked potentials (SSEP), and visual evoked potential (VEP)), electromyography (EMG), inertial measurement unit (IMU), and speech analysis. Combining such digital biomarkers could pave the way for developing a more personalised treatment for MS patients, thereby stopping its progression and avoiding silent MS disability. Adopting digital health for remote monitoring and management could also chart a route ahead for a new era of personalised medicine for MS patients and potentially other brain disorder patients.
Leukemia Inhibitory Factor Protects against Degeneration of Cone
Photoreceptors Caused by RPE65 Deficiency
Authors: Dong Shuqian , Zhen Fangyuan , Zou Tongdan , Zhou Yongwei , Wu Jiahui , Wang Ting , Zhang Houbin 
Published: November 2023

Background::
Retinal pigment epithelium (RPE) 65 is a key enzyme in the visual
cycle involved in the regeneration of 11-cis-retinal. Mutations in the human RPE65
gene cause Leber’s congenital amaurosis (LCA), a severe form of an inherited retinal disorder.
Animal models carrying Rpe65 mutations develop early-onset retinal degeneration.
In particular, the cones degenerate faster than the rods. To date, gene therapy has
been used successfully to treat RPE65-associated retinal disorders. However, gene therapy
does not completely prevent progressive retinal degeneration in patients, possibly
due to the vulnerability of cones in these patients. In the present study, we tested
whether leukemia inhibitory factor (LIF), a trophic factor, protects cones in rd12 mice
harboring a nonsense mutation in Rpe65.

Methods::
LIF was administered to rd12 mice by intravitreal microinjection. Apoptosis
of retinal cells was analyzed by TUNEL assay. The degeneration of cone cells was evaluated
by immunostaining of retinal sections and retinal flat-mounts. Signaling proteins
regulated by LIF in the retinal and cultured cells were determined by immunoblotting.

Results::
Intravitreal administration of LIF activated the STAT3 signaling pathway, thereby
inhibiting photoreceptor apoptosis and preserving cones in rd12 mice. Niclosamide
(NCL), an inhibitor of STAT3 signaling, effectively blocked STAT3 signaling and autophagy
in cultured 661W cells treated with LIF. Co-administration of LIF with NCL to
rd12 mice abolished the protective effect of LIF, suggesting that STAT3 signaling and
autophagy mediate the protection.

Conclusion::
LIF is a potent factor that protects cones in rd12 mice. This finding implies
that LIF can be used in combination with gene therapy to achieve better therapeutic outcomes
for patients with RPE65-associated LCA.
The Role of Genistein and its Derivatives in Ovarian Cancer: New Perspectives for Molecular Mechanisms and Clinical Applications
Authors: Chaichian Shahla , Nikfar Banafsheh , Bidgoli Sepideh Arbabi , Moazzami Bahram 
Published: November 2023

Abstract:
Genistein (GEN) is a member of the polyphenol family, known chiefly for its
effects on metabolic diseases and gynecological disorders. GEN has anti-cancer properties
by inhibiting tumor proliferation, tumor metastasis, invasion, migration, and inducing
apoptosis. Ovarian cancer (OC) is ranked 7th among the most common gynecological
cancers. Despite its low incidence compared to other cancers, it is the first cause of
death among gynecologic malignancies. Surgery and chemotherapy are the main options
for treating this fatal cancer. Therefore, further investigations into GEN may aid in the
discovery of novel therapeutics for preventing and/or treating OC. In this review, we
aim to investigate the role of GEN in ovarian cancer. We investigate the anti-tumor effects
of GEN on OC cell lines, including inducing apoptosis, suppressing tumor growth,
and inhibiting metastasis. Also, we review the studies investigating GEN's roles as an adjuvant
in therapeutic regimens with other chemotherapeutic agents (e.g., cisplatin,
quercetin, and gemcitabine).
Analysis of the Growth and Development of Children Born with ICSI of Epididymal and Testicular Spermatozoa: A Propensity Matching Study
Authors: Yu Chunmei , Zhou Chao , Lin Feng , Zhang Wanchao , Wang Xiaoyu , Hu Lingmin , Lu Renjie 
Published: November 2023

Objective::The study aimed to evaluate whether singleton live births (at 0, 1, 6, 12, and 24 months) following intracytoplasmic sperm injection (ICSI) using sperm of different origins (ejaculated or non-ejaculated sperm) are associated with the growth and development of children born.Methods::This was a retrospective cohort study conducted at a single center from January 2016 to December 2019. Follow-up data of the children were obtained from the Jiangsu Province Maternal and Child database. A total of 350 singleton live births after fresh embryo transfer (ET) with ICSI were included. Based on the origin of the sperm, the patients were divided into two groups: the ejaculated group (n = 310) and the non-ejaculated group (n = 40). Propensity score matching was used to control for multiple baseline covariates, resulting in 80 singleton live births (ejaculated sperm) matched to 40 singleton live births (non-ejaculated). The non-ejaculated group was further divided into two subgroups: the PESA group (n = 23) and the TESA group (n = 17). The primary outcome of the study was the growth and development of children. Secondary outcomes included the 2PN rate, high-cleavage embryo rate, blastocyst formation rate, and others.Results::After matching parental age, BMI, occupation, and maternal serum AMH level, there was no significant difference found in the growth and development of children between the non-ejaculated and ejaculated group or the PESA group and TESA group, respectively. However, the 2PN rate and the blastocyst formation rate were higher in the ejaculated group compared to the non-ejaculated group (91.02 and 85.45, P = 0.002) and (67.37 and 56.06, P = 0.019), respectively. The high-quality cleavage embryo rate was also higher in the TESA group compared to the PESA group (85.06 and 65.63, P = 0.001).Conclusion::This study suggests that there are no significant differences in the growth and development of children born following ICSI using sperm of different origins (ejaculated or non-ejaculated). For nonobstructive azoospermia (OA) patients, sperm derived from the testis may be more effective than derived from the epididymis. However, due to the limited sample size of the non-ejaculated group in this study, further investigations with larger sample sizes are needed to validate these findings.
Pan-cancer Analysis Identifies AIMP2 as a Potential Biomarker for
Breast Cancer
Authors: Qiu Jie , Zhou Tao , Wang Danhong , Hong Weimin , Qian Da , Meng Xuli , Liu Xiaozhen 
Published: November 2023

Introduction:
Aminoacyl tRNA synthetase complex interacting with multifunctional
protein 2 (AIMP2) is a significant regulator of cell proliferation and apoptosis. Despite its abnormal
expression in various tumor types, the specific functions and effects of AIMP2 on tumor immune
cell infiltration, proliferation, and migration remain unclear.

Materials and Methods:
To assess AIMP2's role in tumor immunity, we conducted a pan-cancer
multi-database analysis using the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression
(GTEx), and Cancer Cell Lines Encyclopedia (CCLE) datasets, examining expression levels, prognosis,
tumor progression, and immune microenvironment. Additionally, we investigated AIMP2's
impact on breast cancer (BRCA) proliferation and migration using cell counting kit 8 (CCK-8) assay,
transwell assays, and western blot analysis.

Results:
Our findings revealed that AIMP2 was overexpressed in 24 tumor tissue types compared to
normal tissue and was associated with four tumor stages. Survival analysis indicated that AIMP2
expression was strongly correlated with overall survival (OS) in certain cancer patients, with high
AIMP2 expression linked to poorer prognosis in five cancer types.

Conclusion:
Finally, siRNA-mediated AIMP2 knockdown inhibited BRCA cell proliferation and
migration in vitro. In conclusion, our pan-cancer analysis suggests that AIMP2 may play a crucial
role in tumor immunity and could serve as a potential prognostic marker, particularly in BRCA.
Design and Simulation of the Microcantilever Biosensor for MITF Antigen
and D5 Monoclonal Antibody Interaction Finite Element Analysis, and
Experimental
Authors: Akcali Pelin , Kelleci Kübra , Ozer Sevil 
Published: November 2023

Background:
Biosensors and MEMS have witnessed rapid development and enormous
interest over the past decades. Constant advancement in diagnostic, medical, and chemical applications
has been demonstrated in several platforms and tools. In this study, the analytical and FEA
of the microcantilever used in biomolecular analyses were compared with the experimental analysis
results.

Methods:
In this study, MITF antigen, which is a melanoma biomarker, and anti-MITF antibody
(D5) were selected as biomolecules. A MEMS-type microcantilever biosensor was designed by
functionalizing the AFM cantilever by utilizing the specific interaction dynamics and intermolecular
binding ability between both molecules. Surface functionalization of cantilever micro biosensors
was performed by using FEA. The stress that will occur as a result of the interactions between
the MITF-D5 has been determined from the deviation in the resonant frequency of the cantilever.

Results:
It has been found that the simulation results are supported by analytical calculations and
experimental results.

Conclusion:
The fact that the results of the simulation study overlap with the experimental and
mathematical results allows us to get much cheaper and faster answers compared to expensive and
time-consuming experimental approaches.
Research Mechanism and Progress of the Natural Compound Curcumin in
Treating Alzheimer´s Disease
Authors: Li Li , Wang Fan , Jia Xirong , Yao Luyang , Liu Yu 
Published: November 2023

Abstract:
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. AD
patients usually present symptoms, such as cognitive dysfunction, progressive memory loss, and
other manifestations. With the increasing number of AD cases worldwide, there is an urgent need to
develop effective drug treatments. Currently, drugs targeting AD symptoms may not change or prevent
the progression of the disease. Curcumin, a polyphenol extracted from the turmeric herb, has
been used for the treatment of AD. In this review, we summarized both cellular and animal studies
and described the mechanism of action of curcumin in altering the pathological features of AD.
Curcumin attenuates the formation of amyloid-β plaques and promotes its decomposition, reduces
the phosphorylation of tau, improves its clearance rate, and binds with copper to reduce cholesterol.
It changes the activity of microglia, suppresses acetylcholinesterase, regulates insulin signal transduction,
and exhibits antioxidant properties. Studies have found that curcumin can promote nerve
repair and has a significant effect on AD. However, the low bioavailability of curcumin may hinder
its use as a therapeutic agent. If this limitation can be overcome, curcumin may emerge as a promising
drug for the treatment of AD.
FIGNL1 Promotes Hepatocellular Carcinoma Formation via Remodeling
ECM-receptor Interaction Pathway Mediated by HMMR
Authors: Wang Jiabei , Sun Linmao , Liu Yao , Zhang Yunguang 
Published: November 2023

Background:
The development of novel biomarkers is crucial for the treatment of
HCC. In this study, we investigated a new molecular therapeutic target for HCC. Fidgetin-like 1
(FIGNL1) has been reported to play a vital role in lung adenocarcinoma. However, the potential
function of FIGNL1 in HCC is still unknown.

Objective:
This study aims to investigate the key regulatory mechanisms of FIGNL1 in the formation
of HCC.

Methods:
The regulatory effect of FIGNL1 on HCC was studied by lentivirus infection. In vitro,
the effects of FIGNL1 on the proliferation, migration and apoptosis of cells were investigated by
CCK8, colony formation assay, transwell and flow cytometry. Meanwhile, the regulation of FIGNL1
on HCC formation in vivo was studied by subcutaneous transplanted tumors. In addition, using
transcriptome sequencing technology, we further explored the specific molecular mechanism of
FIGNL1 regulating the formation of HCC.

Results:
Functionally, we demonstrated that FIGNL1 knockdown significantly inhibited HCC cell
proliferation, migration and promoted cell apoptosis in vitro. Similarly, the knockdown of FIGNL1
meaningfully weakened hepatocarcinogenesis in nude mice. Transcriptome sequencing revealed
that FIGNL1 affected the expression of genes involved in extracellular matrix-receptor
(ECM-receptor) interaction pathway, such as hyaluronan mediated motility receptor (HMMR).
Further validation found that overexpression of HMMR based on knockdown FIGNL1 can rescue
the expression abundance of related genes involved in the ECM-receptor interaction pathway.

Conclusion:
Our study revealed that FIGNL1 could modulate the ECM-receptor interaction pathway
through the regulation of HMMR, thus regulating the formation of HCC.
USP3 inhibition is Active Against Chemo-resistant Hepatocellular
Carcinoma Anchorage-independent Growth via Suppressing
Wnt/β-catenin
Authors: Xu Jianguo , Gui Ge Sang Wang , Yang Chao , Zhu Shuchen , Chen Zemin , Ma Suo Lang Bai , Yang Ci , Bu Ci Ren Luo , Zhu Ying , Xu Wen 
Published: November 2023

Background::
USPs are a family of enzymes that regulate protein
degradation, and their dysregulation has been implicated in the development and
progression of cancer.

Aims::
This study aimed to determine whether ubiquitin-specific proteases 3 (USP3)
could be a potential target for therapy in hepatocellular carcinoma (HCC), particularly in
resistant HCC. This study systematically investigated the role of USP3 in HCC, with a
focus on chemo-resistant HCC cells.

Methods::
The level of USP3 from clinical samples was measured using an ELISA assay.
Cell proliferation, apoptosis, migration, and anchorage-independent colony formation
assays were performed. Transfection was performed to knock down USP3 expression
and measure β-catenin activity, and real-time PCR was used to measure levels of MYC
and CYCLIN D1 genes.

Results::
USP3 protein was upregulated in HCC tissues, but its upregulation was not
associated with clinicopathology. USP3 knockdown had a similar inhibitory effect on
growth in both sensitive and resistant HCC cells, did not affect migration, and induced
apoptosis in sensitive but not resistant HCC cells. Furthermore, USP3 knockdown was
more effective in suppressing anchorage-independent colony formation in chemoresistant
HCC cells compared to their chemo-sensitive counterparts. Pearson
correlation coefficient analysis revealed a strong positive correlation between USP3
and CTNNB1, and consistently, USP3 knockdown reduced the levels and activities of
β-catenin in HCC cells. Using a Wnt activator (lithium) in rescue studies significantly
reversed the inhibitory effects of USP3 knockdown.

Conclusion::
The findings suggest that inhibiting USP3 is an effective strategy against
cancer stem cells and chemo-resistant HCC cells.
Tanshinone Alleviates UVA-induced Melanogenesis in Melanocytes via the Nrf2-regulated Antioxidant Defense Signaling Pathway
Authors: Chen Jiaoquan , Yin Zonghao , Yu Nanji , Ou Shanshan , Wang Xue , Li Huaping , Zhu Huilan 
Published: November 2023

Background:
As a complex of natural plant compounds, tanshinone is
renowned for its remarkable antioxidant properties. However, the potential impact of
tanshinone on melanocyte pigmentation regulation has yet to be elucidated. This study
aimed to explore the protective effects of tanshinone I (T-I) and dihydrotanshinone
(DHT) on melanogenesis by modulating nuclear factor E2-related factor 2 (Nrf2)
signaling and antioxidant defenses in human epidermal melanocyte (HEM) cells.

Methods:
HEM cells and Nrf2 knockdown HEM cells were subjected to ultraviolet A
(UVA) and treated with T-I and/or DHT. Then, the anti-melanogenic properties of T-I
and DHT were examined by assessing tyrosinase activity, melanogenesis-related
proteins, and melanin content in UVA-irradiated HEM cells. Furthermore, the
antioxidant activities of T-I and DHT were evaluated by assessing oxidant formation
and modulation of Nrf2-related antioxidant defenses, including reactive oxygen species
(ROS), glutathione (GSH) content, and the activity and expression of antioxidant
enzymes, such as catalase (CAT), heme oxygenase-1 (HO-1), and superoxide
dismutase (SOD).

Results:
Our findings revealed that T-I and DHT diminished melanogenesis in UVAirradiated
HEM cells, activated Nrf2-antioxidant response element signaling, and
enhanced antioxidant defenses in the irradiated cells. Furthermore, Nrf2 knockdown by
shRNA abolished the anti-melanogenesis effects of T-I and DHT on HEM cells against
oxidative damage.

Conclusion:
These results suggest that T-I and DHT inhibit UVA-induced
melanogenesis in HEM cells, possibly through redox mechanisms involving Nrf2
signaling activation and increased antioxidant defenses. This indicates that T-I and
DHT have potential as whitening agents in cosmetics and medical treatments for
hyperpigmentation disorders.
Mechanism of Action and Related Natural Regulators of Nrf2 in
Nonalcoholic Fatty Liver Disease
Authors: Yu Wenfei , Zhang Fengxia , Meng Decheng , Zhang Xin , Feng Yanan , Yin Guoliang , Liang Pengpeng , Chen Suwen , Liu Hongshuai 
Published: November 2023

Abstract:
With the acceleration of people's pace of life, non-alcoholic fatty liver disease (NAFLD)
has become the most common chronic liver disease in the world, which greatly threatens people's
health and safety. Therefore, there is still an urgent need for higher-quality research and treatment in
this area. Nuclear factor Red-2-related factor 2 (Nrf2), as a key transcription factor in the regulation
of oxidative stress, plays an important role in inducing the body's antioxidant response. Although
there are no approved drugs targeting Nrf2 to treat NAFLD so far, it is still of great significance to
target Nrf2 to alleviate NAFLD. In recent years, studies have reported that many natural products
treat NAFLD by acting on Nrf2 or Nrf2 pathways. This article reviews the role of Nrf2 in the pathogenesis
of NAFLD and summarizes the currently reported natural products targeting Nrf2 or Nrf2
pathway for the treatment of NAFLD, which provides new ideas for the development of new
NAFLD-related drugs.
Pan-Immune-Inflammatory Value Predicts the 3 Months Outcome in Acute Ischemic Stroke Patients after Intravenous Thrombolysis
Authors: Wang Shan , Zhang Lulu , Qi Huan , Zhang F Lulu , Fang Qi , Qiu Lanfeng 
Published: November 2023

Background and Purpose:
Immune and inflammatory response plays a central role in
the clinical outcomes of stroke. This study is aimed to explore the clinical significance of the
new inflammation index named pan-immune-inflammation value (PIV) in patients with acute
ischemic stroke (AIS) after intravenous thrombolysis therapy (IVT).

Methods:
Data were collected from 717 patients who received IVT at the First Affiliated Hospital
of Soochow University. Baseline data were collected before intravenous thrombolysis. Multivariate
logistic regression analysis was used to assess the association between PIV and 3 months
clinical outcome after intravenous thrombolysis. We also used receiver operating characteristic
(ROC) curves analysis to assess the discriminative ability of PIV, platelet to lymphocyte ratio
(PLR), neutrophil to lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) in
predicting 3 months poor outcome.

Results:
Of 717 patients, 182 (25.4%) patients had poor outcomes at 3 months. Patients with 3
months of poor outcome had significantly higher PIV levels compared to those with favorable
outcomes [316.32 (187.42-585.67) vs. 223.80 (131.76-394.97), p < 0.001)]. After adjusting for
potential confounders, the risk of 3 months of poor outcome was significantly higher among patients
whose PIV fell in the third quartile (244.21-434.49) and the fourth quartile (> 434.49) than
those in the first quartile (< 139.93) (OR = 1.905, 95% CI: 1.040-3.489; OR = 2.229, 95%CI:
1.229-4.044). The area under the ROC curve of PIV to predict 3 months of poor outcome was
0.607 (95%CI: 0.560-0.654; p < 0.001). The optimal cut-off values of PIV were 283.84 (59%
sensitivity and 62% specificity).

Conclusion:
The higher levels of PIV were independently associated with 3 months of poor outcomes
in AIS patients receiving IVT. PIV like other inflammatory factors (PLR, NLR, and SII),
can also predict adverse outcomes after IVT in AIS patients.
A Comprehensive Review of Systemic Targeted Therapies in Cancer Treatment
Authors: Sharma Amit , Jadhav Hemant R. , Rai Anubhav , Lakkaniga Naga Rajiv , Chandramoorthy Harish C. , Kamli Hossam Mohammed , Alshahrani Mohammad Y. , Rajagopalan Prasanna 
Published: November 2023

Abstract:
Cancer is one of the significant healthcare challenges in today’s world, even after
advancements in modern science, including oncology. The complex nature of the disease, which
involves multiple proteins and pathways, poses a substantial challenge in drug discovery. Several
therapeutic options have emerged in the last decade. Systemic cancer therapies began with the
advent of chemotherapy and were revolutionized with the development of targeted therapies.
The present review is a definite overview of the advances in various therapeutic options
for cancer, with a particular emphasis on targeted therapy using small molecules and biologicals.