bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances and Challenges in Molecular Docking Applied to Neglected Tropical Diseases
Authors: de Angelo Rafaela Molina , Nascimento Lucas Alex , Encide João Pedro Portilho , Barbosa Henrique , Ghilardi Lago João Henrique , da Silva Emery Flávio , Honorio Kathia Maria 
Published: January 2025

Abstract:
The discovery of new drugs for neglected tropical diseases (NTDs) is challenging
due to the complexity of parasite-host interactions, causing resistance and the
scarcity of financial resources. However, computational techniques, particularly molecular
docking, have made significant advancements. This approach allows for the virtual
screening of large compound libraries against specific molecular targets in parasites, efficiently
cost-effectively identifying potential drug candidates. On the other hand, reverse
docking seeks biological targets that can interact with specific substances of interest, integrating
structural data from parasitic proteins with chemical information. Integrating
computational approaches with experimental data drives the discovery of new therapeutic
targets and the optimization of candidate compounds. In addition, artificial intelligence
and molecular docking offer an innovative approach, enhancing prediction accuracy
and driving advancements in discovering new treatments for NTDs. Thus, the primary
focus of this review is to present the relevance, evolution, and prospects of the use
of molecular docking techniques in the discovery and design of drug candidates for neglected
diseases, despite advancements, challenges persist, including the need for increased
investment in research and development, validation of predictive results, and collaboration
among institutions. In this study, we aim to address the significant advancements
in molecular docking and how this technique, along with modern medicinal chemistry
tools, has been relevant in discovering and designing drug candidates for neglected
diseases.
The COX-2 Inhibitor Celecoxib Sensitizes Nasopharyngeal Carcinoma Cells to Ferroptosis
Authors: Li Dawei , Guo Shuang , Wang Kunrong , Liu Zhaoqi , Yu Taixin , Zhang Yingqiu 
Published: January 2025

Background::
Nasopharyngeal cancer [NPC] is prevalent in Southeast Asia and North Africa, and is generally associated with limited treatment options and poor patient prognosis.

Objective::
Ferroptosis is a recently observed cell death modality and has been shown to link to the efficacy of different anti-cancer treatments, thus offering opportunities for the develop-ment of novel therapies. This study aims to investigate the potentiating effects of COX-2 in-hibitors on ferroptosis in nasopharyngeal cancer.

Methods::
The inhibitory effects of COX-2 inhibitors celecoxib and rofecoxib on nasopharyn-geal cancer cells were assessed with MTT, colony formation, sphere formation, Transwell, and wound healing assays. The status of COX-2 with celecoxib and rofecoxib treatment was investigated by Western blotting and immunofluorescence experiments. Ferroptosis was in-duced with the GPX4 inhibitor RSL3 with or without COX-2 inhibition and was monitored by fluorescence microscopy. Transcriptomic profiling was conducted with 5-8F cells treated with DMSO as control or celecoxib, and ferroptosis-related candidates were validated by RT-PCR analysis.

Results::
Celecoxib and rofecoxib effectively inhibited the growth and migration of nasopha-ryngeal cancer cells. Both inhibitors evidently sensitized nasopharyngeal cancer cells to fer-roptosis induction by RSL3, with celecoxib outperforming rofecoxib. Celecoxib treatment re-sulted in significantly differentially expressed genes in 5-8F cells, among which CHAC1 was validated as a ferroptosis-related target.

Conclusion::
The COX-2 inhibitor celecoxib effectively sensitized nasopharyngeal cancer cells to ferroptosis induction.
GeneXpert MTB/RIF Ultra in Pediatric Tuberculosis: How Disease Characteristics Modify Test Performances
Authors: Pace Domenico , Pellegrino Roberta , Dalpiaz Irene , Renni Marco , Galli Luisa , Chiappini Elena 
Published: January 2025

Introduction:
The diagnosis of pediatric tuberculosis (TB) is challenging, due to the
lower sensitivity of microbiological tests, such as culture and microscopy, compared to their performance
in adult cases. Guidelines have introduced molecular tests, including GeneXpert MTB/
RIF and GeneXpert MTB/RIF Ultra. These tests use a real-time polymerase chain reaction
method and provide information on M. tuberculosis detection and drug-resistance-associated mutations
in less than 2 hours. This retrospective single-center study aimed to evaluate the accuracy of
GeneXpert and GeneXpert Ultra for the diagnosis of pediatric TB.

Methods:
This retrospective study was conducted on a total of 95 children diagnosed with probable
or confirmed TB disease (74 diagnosed with pulmonary TB, 21 with extrapulmonary TB),
who referred to the infectious disease unit at Meyer Children’s Hospital in Florence, Italy, and tested
with GeneXpert MTB/RIF or GeneXpert Ultra, from 2013 to 2023.

Results:
GeneXpert and GeneXpert Ultra demonstrated a detection rate of 0.357 (95% CI 0.180 to
0.535) and 0.537 (95% CI 0.417-0.657), respectively. No child was tested with both tests. Patients’
characteristics, including age and sex, did not significantly influence the test's performances.
Notably, GeneXpert Ultra had a significantly higher detection rate in children with extrapulmonary
TB (0.813, 95% CI 0.621 to 1.004) compared to that in children with pulmonary TB (p
= 0.020). Gastric aspirate was the most tested specimen. Specimens that did not require invasive
procedures for collection (including stool) yielded poor results. GeneXpert and GeneXpert Ultra
permitted rapid evaluation of genotypic drug-sensitivity testing (DST), even though limited to rifampicin
resistance, making necessary confirmation through phenotypic DST (performed on culture).

Conclusion:
The introduction of GeneXpert and GeneXpert Ultra improved TB diagnosis in children,
by providing microbiological information in a short time, complementing results from culture,
which remains the reference test in pediatric TB diagnosis.
The Intersection of Heart Failure and Iron Deficiency Anemia: Diagnostic and Therapeutic Approaches
Authors: Thammitage Maleesha BW , Moussa Naji , Rezvani Ali , Dhillon Damandeep Kaur , Gamarra Miryam Lisseth Obando , Singh Kanwaraj , Hawwa Abdul , Vincente Alejandra , Kaur Sehajpreet , Nemalapuri Kiranmayee Seshasai , Poonwassie Devika , Rai Manju 
Published: January 2025

Abstract:
Iron deficiency anemia (IDA) is highly prevalent among individuals with heart failure
(HF), impacting 40-70% of patients and serving as a significant prognostic indicator. Linked
with oxidative metabolism and myocardial cell damage, IDA exacerbates HF symptoms, including
reduced exercise capacity, diminished quality of life, and heightened cardiovascular morbidity.
This review explores the diagnosis, treatment, clinical outcomes, prognostic indicators,
and forthcoming challenges associated with IDA in HF patients. Crucially, addressing IDA in
HF is critical for enhancing prognosis, including clinical outcomes, quality of life, hospitalizations,
and survival rates. While oral iron therapy shows efficacy in reducing mortality and hospitalizations,
it falls short in improving exercise capacity and quality of life, often deterring patients
due to side effects. In contrast, intravenous (IV) iron therapy is highly effective in enhancing
hematological parameters, functional capacity, and reducing HF hospitalizations. Optimizing
IV iron dosing based on individual patient characteristics is essential for balancing treatment efficacy
and adverse effects. Emphasizing individualized approaches, with IV iron emerging as a
superior option, underscores the necessity for ongoing research to refine dosing strategies and
explore novel therapies. Compliance remains paramount for positive outcomes with IDA treatment,
with oral supplementation being cost-effective and easily accessible. However, parenteral
supplementation proves beneficial for patients intolerant to oral therapy. Addressing IDA
through tailored interventions, including oral or parenteral supplementation, is pivotal in averting
complications and improving outcomes in HF patients. This paper consolidates insights into
the diagnosis, treatment, impact, pathophysiology, clinical outcomes, research gaps, and future
directions concerning IDA in HF patients, drawing on extensive literature to offer a comprehensive
understanding of this critical issue.
Successful Use of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Hypertriglyceridemia-induced Acute Pancreatitis: A Case Report
Authors: qi Rundi , Liu Hailei , Li Xin , Chen Minglong 
Published: January 2025

Background:
Managing hypertriglyceridemia-induced acute pancreatitis (HTG-AP)
can be challenging, particularly due to the need for rapid triglyceride reduction to below
500mg/dL (5.645mmol/L).

Case Report:
This is a case describing a 39-year-old female patient who presented to the Emergency
Department with acute abdominal pain resulting from severe HTG-AP. However, under
conventional therapy with oral lipid-lowering drugs, the triglyceride levels remained uncontrolled.
Oral moderate-intensity statins could not only reduce low-density lipoprotein cholesterol
(LDLc) by 25%-50%. However, increasing the dose could not further reduce blood lipids while
increasing the risk of liver damage. After the administration of proprotein convertase subtilisin/
kexin type 9 inhibitor (PCSK9i), the triglyceride levels were well controlled with no additional
side effects, and the symptoms of the patients were completely relieved.

Conclusions:
In cases of unsatisfactory lipid control under conventional therapy, PCSK9i may
offer a viable option for managing HTG-AP.
Identification of a ceRNA Network Regulating Malignant Transformation of Isocitrate Dehydrogenase Mutant Astrocytoma: An Integrated Bioinformatics Study
Authors: Cui Yaqian , Zheng Hongquan , Zhou Zhengwei , Liu Suo , Shen Mingxue , Qiu Runze , Zhang Xiong , Li Yingbin , Fan Hongwei 
Published: January 2025

Introduction:
Astrocytoma is the most common glioma, accounting for about 65% of
glioblastoma. Its malignant transformation is also one of the important causes of patient mortality,
making it the most prevalent and difficult to treat in primary brain tumours. However, little is
known about the underlying mechanisms of this transformation.

Methods:
In this study, we established a ceRNA network to screen out the potential regulatory
pathways involved in the malignant transformation of IDH-mutant astrocytomas. Firstly, the Chinese
Glioma Genome Atlas (CGGA) was employed to compare the expression levels of the differential
expressed genes (DEGs) in astrocytomas. Then, the ceRNA-regulated network was constructed
based on the interaction of lncRNA-miRNA-mRNA. The Gene Ontology (GO) and the
Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the main functions of
the differentially expressed genes. COX regression analysis and log-rank test were combined to
screen the ceRNA network further. In addition, quantitative real-time PCR (qRT-PCR) was conducted
to identify the potential regulatory mechanisms of malignant transformation in IDH-mutant
astrocytoma. We constructed a ceRNA network with 34 lncRNAs, 29 miRNAs, and 71 mRNAs.

Results:
GO and KEGG analyses results suggested that DEGs were associated with tumor-associated
molecular functions and pathways. In addition, we screened two ceRNA regulatory networks
using Cox regression analysis and log-rank test. QRT-PCR assay identified the NAA11/hsa-
miR-142-3p/GS1-39E22.2 regulatory axis of the ceRNA network to be associated with the malignant
transformation of IDH-mutant astrocytoma.

Conclusion:
The discovery of this mechanism deepens our understanding of the molecular mechanisms
of malignant transformation in astrocytomas and provides new perspectives for exploring
glioma progression and targeted therapies.
Next Generation Diagnostics: Exploring the Potential of Microfluidic Devices
Authors: Dhiman Komal , Dhiman Tanuja , Som Shalini , Sharma Achla , Sharma Ankit , Kaundal Amit Kumar , Ankalgi Amardeep , Ashawat Mahendra Singh 
Published: January 2025

Abstract:
In recent years, microfluidics systems have emerged as powerful tools for biological analysis,
integrating entire analytics protocols into a single chip platform. This article aims to review
recent developments in microfluidics systems for diagnostics applications, focusing on genes, proteins,
and cells. By categorizing fluids- manipulating mechanisms and biological detection approaches,
the articles provide an in-depth discussion of microfluidics-based diagnostics systems, including
materials and manufacturing techniques. The integration of microfluidics systems with diagnostics
shows promise for the development of practical point- of-care devices. The identification and monitoring
of Variants of Concern (VOCs) and Variants of Interest (VOIs) by WHO have significant
implications for diagnostics, public health measures, and vaccine development. Continuous, sequencing
and adaptation of diagnostic tests are essential for managing the impact of variants on diagnostics
and public health measures while advancing vaccine research and development.
Adverse Events Associated with Antivirals for COVID-19: An Analysis
Based on FDA Adverse Event Reporting System (FAERS)
Authors: Mohamad Radzuan Muhammad Ikhwan Syahmi , Karuppannan Mahmathi 
Published: January 2025

Background:
The COVID-19 pandemic has called for the rapid development and use
of antiviral drugs to effectively control the disease. Nirmatrelvir/Ritonavir (Paxlovid), Molnupiravir, and Remdesivir have been pivotal in therapeutic approaches, although they raise concerns regarding adverse drug reactions (ADRs).

Objective:
This study aimed to thoroughly assess the ADRs associated with these drugs by utilizing the Adverse Event Reporting System (FAERS) database of the Food and Drug Administration
(FDA)

Methods:
ADR reports for Paxlovid, Molnupiravir, and Remdesivir throughout the period of January 2022 to May 2023 were extracted and classified according to the severity, type of reaction,
and demographic variables. Reporting Odds Ratios (RORs) with 95% confidence intervals were
calculated to evaluate the relationship between antiviral medications and various ADRs.

Results:
The study established notable correlations between Paxlovid and the recurrence of the disease (40.08%) and dysgeusia (16.29%). Molnupiravir was linked to gastrointestinal (16.73%) and
skin reactions (9.47%), while Remdesivir had impairments in the liver (25.21%) and kidneys
(13.34%). ADRs were more commonly observed in female patients treated with Paxlovid
(57.95%) and Molnupiravir (49.40%), whereas Remdesivir ADRs were mostly reported in males
(58.56%). Paxlovid and Remdesivir ADRs were frequently reported in adults between the ages of
18 and 64 (46.01% and 45.01%), while Molnupiravir ADRs were more common in older individuals aged 65 to 85 (40.38%).

Conclusion:
This thorough assessment emphasizes the importance of careful surveillance and control of ADRs linked to COVID-19 antiviral therapies. It is essential to customize treatments by
considering specific patient histories, particularly for pre-existing diseases.
The Role of Glial Cells in Autism Spectrum Disorder: Molecular Mechanisms and Therapeutic Approaches
Authors: Inamdar Aparna , Gurupadayya Bannimath , Sharma Himanshu 
Published: January 2025

Abstract:
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by
social communication deficits and repetitive behaviors. Emerging evidence highlights the significant
role of glial cells, particularly astrocytes and microglia, in the pathophysiology of ASD. Glial cells
are crucial for maintaining homeostasis, modulating synaptic function, and responding to neural injury.
Dysregulation of glial cell functions, including altered cytokine production, impaired synaptic
pruning, and disrupted neuroinflammatory responses, has been implicated in ASD. Molecular
mechanisms underlying these disruptions involve aberrant signaling pathways, such as the mTOR
pathway, and epigenetic modifications, leading to altered gene expression profiles in glial cells.
Moreover, microglial activation and reactive astrocytosis contribute to an inflammatory environment
that exacerbates neural circuit abnormalities. Understanding these molecular mechanisms
opens avenues for therapeutic interventions. Current therapeutic approaches targeting glial cell dysfunction
include anti-inflammatory agents, modulators of synaptic function, and cell-based therapies.
Minocycline and ibudilast have shown potential for modulating microglial activity and reducing
neuroinflammation. Additionally, advancements in gene editing and stem cell therapy hold
promise for restoring normal glial function. This abstract underscores the importance of glial cells in
ASD. It highlights the need for further research to elucidate the complex interactions between glial
dysfunction and ASD pathogenesis, aiming to develop targeted therapies that can ameliorate the
clinical manifestations of ASD.
Association of Toll-like Receptor 4 Gene Polymorphisms with Diabetes Type 2 Patients in the Palestinian Population
Authors: Al-Razem Fawzi , B. Iqnaibi Enas , A. Abu Rmeileh Razan , I Ideis Lara 
Published: January 2025

Background:
Toll-like Receptor 4 (TLR4) plays critical roles in innate immunity and
several other pathological responses, including a possible role in the susceptibility to Type 2
Diabetes Mellitus (T2DM). Understanding the relationship between TLR4 polymorphism and
T2DM is necessary to evaluate the role of innate immunity in diabetes.

Aim:
This study was conducted to evaluate the potential association between three TLR4 SNPs
(SNP ID rs11536858, rs4986790, and rs1927914) and risk susceptibility to T2DM in a crosssection
of the Palestinian population.

Methods:
A total of 96 individuals including 50 T2DM patients participated in this study. The
data were analyzed according to the TLR4 allelic variation results. DNAs were extracted from
blood samples collected from the T2DM patients and their matched healthy controls and used to
evaluate possible associations between the TLR4 SNP variations and T2DM. The genotypes of
TLR4 polymorphisms were analyzed by the Polymerase Chain Reaction-Restriction Fragment
Length Polymorphism (PCR-RFLP).

Results:
Three allelic variations were detected in the participating individuals. The distribution
of alleles between T2DM and healthy controls in the three SNPs did not show significant differences,
even though some variations tended to favor certain alleles. To look at potential associations
of TLR4 gene polymorphisms with the risk of T2DM development, we analyzed the allelic
variation in both T2DM patients and health controls. The rs4986790 TLR4 SNPs showed a significant
association with T2DM. There were 20% heterozygous alleles in T2DM patients compared
to 4.35% in healthy controls with Odds Ratio (OR) = 5.26 and 95% CI = 1.08, 25.6 (P =
0.0252), indicating the AG allele to be a risk factor. Both rs11536858 and rs1927914 alleles
demonstrated a potential association of their allelic variations as either a protective or a highrisk
factor.

Conclusion:
Our data have indicated that TLR4 rs4986790, rs1927914, and rs11536858 may
play a potential role in innate immunity and susceptibility risk to diabetes and can be potential
targets for therapeutic drugs.
Pathway Targeting and Mechanistic Elucidation of Phyto-compounds Relevant in Triple-negative Breast Cancer (TNBC)
Authors: Mir Wajahat Rashid , Bhat Basharat Ahmad , Sofi Shazia Shafi , Jan Nusrat , Jan Asma , Mir Manzoor Ahmad 
Published: January 2025

Abstract:
Of the several forms of breast cancer, triple-negative breast cancer (TNBC) is the most
aggressive, is not responsive to traditional human/hormonal epithelial growth factor receptor 2
(HER2)-targeted therapies because the corresponding receptor targets are absent, TNBC tends to be
more invasive in form, metastasis, have an early recurrence rate and develop medication resistance.
For TNBC, some of the most popular types of treatments are resection, chemotherapy, and radiation
therapy. Several studies are being carried out for the development of novel treatment approaches for
improved TNBC diagnosis. As our knowledge of the molecular mechanisms behind the development
of cancer has grown, a vast array of anticancer drugs has been developed. The use of chemically
produced pharmaceuticals has not significantly raised the overall survival rate over the previous few
decades. As such, novel approaches and cutting-edge chemopreventive medications are needed to
improve the efficacy of existing TNBC therapies. Naturally occurring compounds derived from
plants called phytochemicals are valuable resources for the development of novel medications for
TNBC treatment. These phytochemicals often function by modulating molecular pathways associated
with the onset and propagation of TNBC. Some of the specific methods include boosting antioxidant
status, deactivating carcinogens, stopping proliferation, inducing cell cycle arrest, promoting
apoptosis, and immune system modulation. This review's main goal is to give a summary of the active
components of natural products, together with details on their molecular targets, pharmacologic
action, and current level of understanding. Several natural compounds that particularly target the
pathways linked to TNBC in our study have been thoroughly described by us. We have done extensive
research on many natural substances that could lead to the discovery of new targets for TNBC
detection.
A Study on the Regulation of TRPM8 Signaling Pathway by Interior-warming Medicines in Traditional Chinese Medicine
Authors: Wei Yuanjun , Xiong Chengcheng , Zhan Yanran , Fu Jiangbo , Yang Chaoyan , Chen Yanfen 
Published: January 2025

Background:
Interior-warming medicines (Wēnlǐ herbs) have the effect of warming the
interior of the body and dispelling cold, and they are traditionally used for interior cold syndrome.
Currently, they are used for treating gastrointestinal disorders, rheumatoid arthritis, tumors, etc.
Transient receptor potential channel M8 (TRPM8) is a non-selective cation channel that can be activated
by low temperature and menthol. However, the mechanism of temperature regulation of interior-
warming medicines is not clear. This study designed an in vitro experiment on the TRPM8
signaling pathway using interior-warming medicines, aiming to investigate the relationship between
the hot property of interior-warming medicines and the regulatory effect of TRPM8.

Methods:
The breast cancer cell line 7 was cultured at different temperatures as a research model,
six kinds of interior-warming medicines were used, and medicated serums from rats were prepared
as test drugs. PCR and western blotting were carried out to investigate their effects on TRPM8
mRNA and protein expression. ELISA and flow cytometry were conducted to detect intracellular
cAMP and Ca2+ concentration.

Results:
Compared with the blank-containing serum group, interior-warming medicines had no
significant effect on the expression of TRPM8 at 37°C, while they could inhibit the expression of
TRPM8 at low temperatures (30°C). Moreover, the six herbs could increase intracellular cAMP
content and reduce Ca2+ concentration at different temperatures.

Conclusion:
The natural hot property of interior-warming medicines may be associated with the
regulation of the TRPM8 signaling pathway, causing Ca2+ influx blocking, which provides a deeper
experimental basis for their clinical application and new drug development.