bluuebunny/crossref_metadata_2025 huggingface dataset:
A eficiência das Capitanias Fluviais da Marinha do Brasil, sob a ótica de Custos, baseada na Análise Envoltória de Dados
Authors: Oliveira da Silva Johnny , Moreira Pessanha José Francisco , Dos Santos Alves Francisco Jose , Carvalho de Mello Luiz Sergio
Published: January 2025

Este estudo mensurou e analisou a eficiência das Capitanias Fluviais da Marinha do Brasil, no exercício de suas atividades de segurança do tráfego aquaviário, no período de 2021 a 2023. Trata-se de uma pesquisa descritiva, de natureza quantitativa, com a aplicação de um modelo de análise envoltória de dados, baseado nas folgas e orientado aos insumos. Para tal, foram utilizados, como insumos, os dados de custos e valores líquidos dos ativos imobilizados relacionados à atividade operacional de segurança do tráfego aquaviário, além dos custos associados à manutenção e ao funcionamento da infraestrutura das unidades. Como produtos, foram consideradas a quantidade de inspeções e vistorias navais realizadas e a extensão da área sob jurisdição de cada organização. Verificou-se que, no geral, as Capitanias Fluviais obtiveram índice de eficiência médio de 0,8890, no período. Três unidades foram eficientes nos três anos, sendo apontadas como benchmarking para as demais. Também, foram demonstradas as folgas nos insumos, que geraram as ineficiências das unidades, e os valores ideais de cada elemento de custo para que elas alcancem a fronteira de eficiência, mantendo o nível de produtos. Os resultados alcançados mostram-se úteis como parâmetros de alocação de recursos, bem como para o possível estabelecimento de metas de redução de custos anuais dessas organizações. Portanto, mensurar e avaliar a eficiência de organizações públicas, sob a ótica de custos, revela-se um indicador significativo para os gestores dessas unidades orientarem a administração dos limitados recursos postos sob suas responsabilidades. Academicamente, a pesquisa contribui ao adicionar à literatura um estudo sobre a eficiência de organizações militares, sobretudo no desenvolvimento de atividades de segurança do tráfego aquaviário. Do ponto de vista prático, esta pesquisa pode contribuir para aprimoramento da gestão de custos da Marinha do Brasil, o qual é um objetivo estratégico naval constante no Plano Estratégico da Força.
A CLINICAL STUDY OF VASCULAR ANOMALIES AND THEIR MANAGEMENT IN A TERTIARY CARE CENTER IN TELANGANA
Authors: Lakshmi Palukuri , Sai Rekha Sree , Sankar Swathi , Kishore P. Ashwin , Nannam Rishitha , Ahlad Sreedharala
Published: January 2025

Aim & Objectives Of The Study Aim Of The Study: The aim of this study is to analyze the various modalities of treatment for vascular anomalies and their response at a Tertiary care centre in Telangana.

Objectives Of The Study: 1. To study the incidence of various vascular anomalies. 2. To study the demographic features of various vascular anomalies. 3. To study the various modalities of treatment used at Tertiary care center 4. To study the complications.

Need For The Study: Vascular anomalies signify a deviation from normal vasculature. Their morbidity can range from mild discoloration of skin to massive involvement leading to functional compromise ?These anomalies include a group of disorders which are difficult to classify as well as to treat. ?They are commonly misdiagnosed and hence mistreated. Hence, correct diagnosis which is of paramount importance for the proper management of vascular anomalies is done by proper history and clinical examination and proper investigations like color Doppler study and if needed Angiogram. ?These lesions can cause cosmetic deformities of the head and neck and can interfere with the normal function in these areas. ?Hence, early diagnosis with clinical evaluation and investigations like Color doppler study and if needed angiogram and treatment needs to be done to avoid dangerous complications associated with these lesions such as bleeding, cosmetic deformity, airway obstruction which might even cause death of the individual.

Materials & Methods Study Design: Retroprospective clinical study Ã‚ Study subjects: Ã‚ All patients admitted in the Department of Plastic and Reconstructive surgery with vascular anomalies within the stipulated time period of 48 months ( 2 years retrospective and 2 years prospective from February 2021 to March 2025) are included in the study Sample size: All patients with vascular anomalies attending the OPD of Department of Ã‚ Plastic and Reconstructive Surgery within the stipulated time period is included in the study with minimum sample size taken as 20 Ã‚ Inclusion Criteria: All patients with vascular anomalies admitted in the Department of Burns Plastic And Reconstructive Surgery willing to participate are included in the study.

Exclusion criteria:Ã‚ 1. Patients not willing to participate in the study. 2. Patients who are unfit for anesthesia. 3. Patients with CNS AV malformation Period of study: 48 Months (2 years Retrospective and 2 years Prospective).

Place of study: Osmania General Hospital, Hyderabad.
Examining air pollution dynamics in Ploiesti: a focus on vehicular emissions
Authors:   National Research and Development Institute for Industrial Ecology ECOIND Bucharest, Gavrila Georgeta-Olguta , Parvulescu Oana Cristina ,   National University of Science and Technology Politehnica Buchares, Constantin Cristian ,   National Research and Development Institute for Industrial Ecology ECOIND Bucharest, Danciulescu Valeriu ,   National Research and Development Institute for Industrial Ecology ECOIND Bucharest, Calinescu Simona Mariana ,   National Research and Development Institute for Industrial Ecology ECOIND Bucharest, Tanase Gheorghita ,   National Research and Development Institute for Industrial Ecology ECOIND Bucharest, Stancu Valentin ,   National Research and Development Institute for Industrial Ecology ECOIND Bucharest
Published: January 2025

This paper presented the topic of urban air pollution in Ploiesti Municipality, located 60 km north of Bucharest. The study analyzes the seasonal variations in 2023 of air pollutants such as nitrogen dioxide (NO2), sulphur dioxide (SO2) and particulate matter (PM10), the impact of road traffic on air quality, as well as the monitoring measures according to the in force environmental legislation. For the air quality assessment two types of data were collected: data from the National Air Quality Monitoring Station (AQMS) of Ploiesti for the winter ÷ summer period and data obtained from field measurements carried out in November. The location of the sampling points took into account several factors such as: pollution source (road traffic, industry), measured meteorological parameters (temperature, humidity, atmospheric pressure, wind speed and direction). The experimental data were analyzed using Principal Component Analysis (PCA), and were also compared with AQMS values. The comparisons between measured and AQMS data showed significantly higher concentrations for the samples (P1, P2, P3), which could indicate the presence of local sources of SO2 emissions or conditions favoring the accumulation of this pollutant. The PCA indicate that the higher concentrations of pollutants seemed to be associated with cooler temperatures and reduced solar radiation, suggesting a significant impact of meteorological conditions on the distribution of pollutants.
Ginsenoside Rg3 in Cancer Research: Current Trends and Future Prospects - A Review
Authors: Tanko Auwal Ibrahim , Hosawi Salman , Moglad Ehssan , Afzal Muhammad , Ghaboura Nehmat , Alzareaa Sami I. , Osman Ahmed , Nadeem Muhammad Shahid , Kazmi Imran
Published: January 2025

Cancer is one of the most devastating illnesses in the world, impacting millions
of individuals every year. Despite various therapies, the final effect is unsatisfactory.
Chemotherapy currently dominates as the primary option of treatment. However, its
severe adverse effects, limited efficacy, and resistance to drugs undermine its potential.
Growing evidence suggests that ginsenoside Rg3, a natural compound obtained from the
ginseng plant (Panax ginseng), holds significant promise in cancer therapy. Its proposed
mechanisms primarily involve the enhancement of immunity, retardation of cancer cellular
proliferation and metastasis, triggering apoptosis, angiogenesis, epigenetic modification,
and Regulation of transition of epithelial mesenchyma (EMT) and miRNAs/lncRNA.
Furthermore, Rg3-ginsenoside potentiates the effectiveness of conventional treatments
of cancer and reduces the adverse effects through synergistic interactions.
Ginsenoside Rg3's present status in cancer research is thoroughly reviewed in this article,
shedding light on its intricate mechanisms and potential to revolutionize cancer therapy
through combinatorial and nano-based targeted therapy.
Current Perspectives of Diabetic Dyslipidemia and Treatment Modalities
Authors: AKKUS Gamze
Published: January 2025

Introduction:

Diabetes mellitus is associated with an increased risk of
atherosclerosis related to dyslipidemia. Although the terms hyperlipidemia and Diabetes
Mellitus [DM] or diabetic dyslipidemia are interrelated to each other, these two conditions
have some differences.

Aim:

This study aimed to highlight possible mechanisms of hyperlipidemia and/or dyslipidemia
in diabetic patients, which can be treated with available and newer hypolipidemic
drugs. We also re-checked current specific guidelines and their recommendations
on the management of patients with diabetic dyslipidemia.

Method:

Comprehensive search of peer-reviewed journals was performed based on a
wide range of keywords, including diabetes mellitus, dyslipidemia, hyperlipidemia, insulin
resistance, free-fatty acids, cardiovascular disease, SCORE-2 calculation, statins,
PCSK-9 inhibitors, and fibrates.

Discussion:

Diabetic patients with dyslipidemia, including decreased HDL cholesterol,
a predominance of small dense LDL particles, and increased triglyceride levels, are
more prone to suffering from micro and macrovascular complications regardless of plasma
fasting glucose levels. Recent guidelines suggested using the validated scoring system
called SCORE2-Diabetes. Moderate to high dosages of statins, aiming for LDL
cholesterol reduction, is still the cornerstone in the management of diabetic patients with
dyslipidemia. Nowadays, other recommended non-statin drugs, including proprotein convertase
subtilisin/kexin type 9 [PCSK9] inhibitors or other novel therapeutic agents
[bempedoic acid, inclisiran], are particularly important and given place in recently published
guidelines.

Conclusion:

The risk of developing atherosclerotic cardiovascular diseases in people
with DM is relatively higher than in patients’ without DM. Optimal management of
lipid parameters and achieving desired target values in lipid parameters are still a challenging
issue for clinicians.
Recent Advances in the Synthetic Utility of ortho-Quinone Methides for Cyclization Reactions: A Versatile Skeleton
Authors: Hou Qinggao , Liu Xianping , Chen Liyong , Cao Renfeng , Yue Sitong , Zhu Longzhi , Xiong Biquan
Published: January 2025

In the past decade, the field of ortho-quinone methides (o-QMs) has witnessed remarkable advancements,
underscoring their pivotal role as synthetic intermediates in organic chemistry. These electrically neutral
species, distinguished by a cyclohexadiene moiety conjugated with a carbonyl and an exo-methylene group,
possess an aromatic zwitterionic resonance structure. This unique framework endows them with a pronounced
electrophilicity, particularly at the 1,4-positions. The rich chemistry of o-QMs encompasses three principal
reaction modalities: 1,4-conjugated addition, [4 + X] cycloaddition (X = 1, 2, 3, etc.), and oxa-6π-
electrocyclization pathways. Specifically, the synthesis of chromane derivatives is achieved through [4 + 2]
cycloaddition and subsequent oxa-6π-electrocyclization, whereas benzofuran derivatives are accessed via the [4
+ 1] cycloaddition route. This review provides a systematic summary of the latest advancements in cycloaddition
reactions involving ortho-quinone methides and their derivatives. It offers an in-depth analysis of the substrate
diversity and potential reaction mechanisms underlying these transformations. The cycloaddition reactions
presented herein are uniformly characterized as ionic systems, with the tautomerization between the oxygen
anion generated subsequent to the deprotonation of o-QMs and the resulting carbonyl group identified as a pivotal
step for reaction activation. Moreover, we have expanded on the discussion to include a detailed examination
of drug intermediate compounds derived from o-QMs. These skeletal derivatives are highlighted for their
growing utility in the realm of drug design and synthesis, effectively bridging the divide between foundational
research and pharmaceutical applications. We aspire to stimulate the evolution and innovation of synthetic
methodologies that leverage o-QMs as scaffolds. By in-depth investigation of the o-QMs-mediated cyclization
reactions, we aim to offer theoretical insights that will guide the synthesis of intricate (chiral) cyclic compounds,
thereby enhancing the practical application of o-QMs in both chemical research and medical development.
Mechanism Study on the Regulation of Th1/Th2 in the Treatment of Idiopathic Membranous Nephropathy by Shengyang Yiwei Decoction
Authors: Wu Yuan , Zhang Xue-Qin , An Heng-Tong , Wang Shuai-Jie , Zhao Ya-Yun , Chen Zhi-Qiang
Published: January 2025

Background:

Shengyang Yiwei Decoction showed efficacy in idiopathic membranous
nephropathy treatment, and this study aimed to assess the underlying molecular mechanisms.

Methods:

Rats with passive Heymann nephritis were divided into the model group, the Shengyang
Yiwei Decoction group, the JAK2 inhibitor group, and the STAT3 inhibitor group. Healthy
rats served as the normal control. 24-hour urinary protein excretion, IgG deposition, renal histopathology,
the expression levels of synaptopodin, nephrin, podocalyxin, interferon-γ, interleukin-
4, T-box expressed in T cells, GATA binding protein-3, and relevant pathway proteins were
measured.

Results:

Within the model group, a notable elevation in the 24-h urinary protein level was observed,
accompanied by evident IgG deposition, increased glomerular volume, eosinophilic deposits,
diminished expression of podocyte marker proteins, and a discernible imbalance in
Th1/Th2 cellular immunity. Conversely, in Shengyang Yiwei Decoction and both inhibitor
groups, enhancements were observed across the aforementioned indexes.

Conclusion:

Shengyang Yiwei Decoction may reduce glomerular podocyte injury through the
suppression of the JAK2/STAT3 signaling pathway and modulation of the Th1/Th2 immune balance.
The Anaphylactic and Anti-allergenic Properties of Shuanghuanglian: A Review
Authors: Jiang Xin , Li Ji , Yao Xiaohui , Ding Hao
Published: January 2025

Shuanghuanglian (SHL) and its primary constituents have demonstrated protective effects
against allergenic diseases. This review examines the anaphylactic and anti-allergenic activities
of SHL and its constituents. We also discuss potential avenues for future research, particularly
regarding the expansion of the clinical applications of SHL formulations (oral or nebulized)
for the treatment of allergenic disorders.
For this review, we searched the PubMed, Web of Science, and China National Knowledge Infrastructure
databases for relevant publications. Additionally, details of the essential active components
and target genes of SHL were obtained from the Traditional Chinese Medicine Systems
Pharmacology database (TCMSP), and information on allergy-related genes was collected from
the GeneCards and Online Mendelian Inheritance in Man(OMIM) databases. Lists of both the
SHL target and disease-related genes were imported into the ‘Draw Venn Diagram’ tool on the
website (http://bioinformatics.psb.ugen /web tools/Venn/). A protein–protein interaction network
for SHL and disease targets was constructed with reference to the Search Tool for the Retrieval
of Interacting Genes/Proteins (STRING) database, and the potential pathways were identified
based on Kyoto Encyclopaedia of Genes and Genome enrichment analyses.
The allergenic reactions induced by SHL injection (intravenous) and its main constituents (intraperitoneal
or intravenous injection) have been verified in animal experiments. Furthermore, the
protective effects of SHL injection (intraperitoneal) and its individual Chinese herb components
(intragastric administration), namely, Flos Lonicerae, Radix Scutellariae, and Fructus Forsythiae,
as well as their main constituents (intraperitoneal or intragastric administration), have been
verified in asthma, rhinitis, atopic dermatitis, and both IgE- and non-IgE-mediated systemic allergic
responses. The network pharmacology analysis revealed that the therapeutic effects of
SHL might be primarily mediated through the regulation of the IL-17 and TNF-α signalling
pathways and Th17 cell differentiation.
Accumulated research data provide a theoretical basis for the clinical application of SHL (via extravascular
routes) in the treatment of allergenic diseases.
TSPOAP1-AS1: A Novel Biomarker for the Prognosis and Therapeutic Target in Cervical Cancer
Authors: Li Jinyuan , Ye Zhen , Gan Yuhong , Li Dongbing , Chen Yibiao
Published: January 2025

Background:

TSPOAP1 antisense RNA 1 (TSPOAP1-AS1) is a long non-coding RNA
(lncRNA) that has received widespread attention in oncology research in recent years. Its role and
mechanism in some cancers have gradually been revealed. However, it is not clear what role
TSPOAP1-AS1 plays in cervical cancer (CESC).

Objective:

In this study, bioinformatic analysis and experimental validation were carried out to investigate
the relationship between TSPOAP1-AS1 and CESC.

Methods:

The relationships between clinical characteristics in patients with CESC, TSPOAP1-AS1
expression, prognostic factors, regulation network, and immune infiltration of TSPOAP1-AS1 were
evaluated using statistics and The Cancer Genome Atlas database. Real-Time Quantitative Reverse
Transcription PCR was used to test TSPOAP1-AS1, miR-17-5p, and AGFG2 expression in CESC cell
lines.

Results:

CESC patients exhibited markedly reduced expression of TSPOAP1-AS1. There was a significant
correlation between low expression of TSPOAP1-AS1 in CESC patients and the clinical stage (p
< 0.05), weight (p < 0.05), and BMI (p < 0.05). Lower expression of TSPOAP1-AS1 in patients with
CESC was associated with poorer overall survival (OS) (p = 0.014) and disease-specific survival
(DSS) (p = 0.030). There was also an independent correlation between high expression of TSPOAP1-
AS1 (p = 0.036) and DSS in patients with CESC. TSPOAP1-AS1 was involved in the ribosome, oxidative
phosphorylation, antigen processing and presentation, cell adhesion molecules (CAMs), the
chemokine signaling pathway, neuroactive ligand-receptor interaction, and primary immunodeficiencies.
The infiltration of immune cells and the expression of TSPOAP1-AS1 were found to be correlated.
A ceRNA network of TSPOAP1-AS1/miR-17-5p/AGFG2 was constructed in CESC. In CESC, a
ceRNA network involving TSPOAP1-AS1/miR-17-5p/AGFG2 was successfully established. When
comparing CESC cell lines with HcerEpic, the expression of TSPOAP1-AS1 and AGFG2 decreased
significantly, and the expression of miR-17-5p increased significantly.

Conclusion:

In CESC patients, low expression of TSPOAP1-AS1 was associated with poor survival
and immune infiltration. It may be effective to use TSPOAP1-AS1 as a biomarker of prognosis and
therapeutic target in CESC.
COL1A1, COL1A2, CHN1, and FN1 Promote Tumorogenesis and Act as Markers of Diagnosis and Survival in Gastric Cancer Patients
Authors: Yichao Yan , Yongbai Li , Hailiang Liang , Dongbo Chen , Bo Li , Murshed Abduh
Published: January 2025

Objectives:

This study aimed to comprehensively investigate the molecular landscape
of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.

Methodology:

GSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB,
cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR,
and cell proliferation assay were employed in this study.

Results:

Analysis of the GSE79973 dataset identified 300 differentially expressed genes
(DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using
protein-protein interaction network analysis. Subsequent validation across The Cancer Genome
Atlas (TCGA) datasets confirmed their up-regulation in GC tissues compared to normal controls.
Promoter methylation analysis revealed decreased methylation levels of these hubs in GC
tissues, suggesting their potential role in tumorigenesis. Mutational analysis using cBioPortal
showcased frequent mutations in these genes, particularly FN1, further highlighting their significance
in GC pathogenesis. Survival analysis indicated their correlation with reduced overall
survival rates among GC patients, supported by the development of a robust prognostic model.
Prediction of hub-associated miRNAs and gene enrichment analysis provided insights into their
regulatory mechanisms and downstream pathways, implicating their involvement in extracellular
matrix remodeling and cell migration. Drug sensitivity analysis revealed correlations between
hub gene expression and drug response, while RT-qPCR validation confirmed their upregulation
in clinical GC samples. Finally, functional assays demonstrated the impact of FN1
knockdown on cellular proliferation, colony formation, and wound healing capacities.

Conclusion:

Overall, this study elucidates the crucial role of COL1A1, COL1A2, CHN1, and
FN1 in GC pathogenesis and underscores their potential as diagnostic markers and therapeutic
targets.
Bioactive Sulfonamides Derived from Amino Acids: Their Synthesis and Pharmacological Activities
Authors: Egbujor Melford Chuka , Tucci Paolo , Saso Luciano
Published: January 2025

Currently, the synthesis of bioactive sulfonamides using amino acid as a starting reagent
has become an area of research interest in organic chemistry. Over the years, an amine-sulfonyl chloride
reaction has been adopted as a common step in traditional sulfonamide synthetic methods.
However, recent developments have shown amino acids to be better precursors than amines in the
synthesis of sulfonamides. Although amines and amino acids have some structural similarities, using
amino acids rather than amines in the synthesis of sulfonamides minimizes several drawbacks.
Comparatively, amino acids are preferred to amines as starting reagents in sulfonamide synthesis
due to their biological relevance, chirality, stereochemistry, diversity of side chains, orthogonality in
functional group manipulation, the potential for peptide and protein synthesis, mild reaction conditions,
alignment with green chemistry principles, diverse synthetic applications, easy availability,
and economic viability. Amino acids, having the aforementioned properties, offer a versatile platform
for the synthesis of sulfonamides with tailored structures. The reaction mechanism of the synthesis
of amino acid-derived sulfonamides involves a nucleophilic attack by the amino group on the activated
sulfonyl species to produce a sulfonamide functional group. Amino acid-based sulfonamides
have numerous pharmacological activities, including antibacterial, antiviral, anticancer, antioxidant,
anti-inflammatory, anti-plasmodial, antimalarial, anti-trypanosomal, and insect growth regulatory
properties. This review discusses several synthetic processes, emphasizing established ways, cutting-
edge techniques, and novel approaches that emphasize the significance of amino acids in the
synthesis of sulfonamides. The structure-activity relationship of amino acid-derived sulfonamides
and their pharmacological activities are also highlighted.
Development of Lentiviral Packaging Cells and Scale Up of Production to Meet the Growing Demand in Cell and Gene Therapy
Authors: van Heuvel Yasemin , Stitz Jörn
Published: January 2025

Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools
in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety
of human target cells. LVVs, in contrast to RVVs, are capable of stably genetically modifying
non-proliferating target cells, making them the superior instrument in cell and gene therapy. To
date, the LVV manufacturing process employs human embryonic kidney cells (HEK293) and derivatives
thereof transiently transfected with multiple plasmids encoding the required viral vector
components. Alternatively, stable packaging cell lines were developed and engineered to express
all vector components in trans. Currently, these cells are mostly cultured in cell stacks, where they
grow adherently in 2D layers, limiting the scale-up of vector production. The production of viral
vectors using stable suspension cell lines enables larger-scale production and higher yields under
controlled conditions. Here, we review the improvements made to enhance vector safety and production
yield. Current advancements in the establishment of stable packaging cell lines enabling
inducible and constitutive LVV production are summarized and discussed. Manufacturing processes
for lentiviral vectors using bioreactors with perfusion systems are required to meet the growing
demand in cell and gene therapy and to reduce production and therapy costs.
Recent Developments in Oral Drug Delivery of Prokinetic Agents: Nanoparticles and Beyond
Authors: Dass Rameshwar , Bhatia Meenakshi , Rath Goutam , Dhingra Ashwani K.
Published: January 2025

Prokinetic agents are drugs used to enhance gastrointestinal motility and treat disorders
such as Gastroesophageal Reflux Disease (GERD) and gastroparesis. pH-dependent release systems
offer targeted drug delivery, allowing prokinetic agents to be released specifically in desired
regions of the gastrointestinal tract. This optimizes drug efficacy and minimizes systemic side effects.
Gastroretentive formulations enable sustained drug release, which is particularly beneficial
in conditions requiring prolonged gastric residence time, such as gastroparesis. Nanoparticles have
emerged as promising carriers for improving prokinetic agent delivery and enhancing drug stability,
solubility, and absorption. These nano-systems protect drugs from degradation, leading to improved
bioavailability and controlled drug release. Furthermore, incorporating mucoadhesive technologies
promotes prolonged drug-mucosa interactions, facilitating enhanced drug absorption and
reducing dosing frequency. These recent advancements have the potential to revolutionize the oral
drug delivery of prokinetic agents, offering improved therapeutic outcomes, enhanced patient compliance,
and reduced side effects. However, scalability, biocompatibility, and safety challenges
warrant further investigation and validation through preclinical and clinical studies. This review
highlights recent advances in oral drug delivery systems for prokinetic agents, focusing on innovative
approaches such as pH-dependent release, gastroretentive formulations, nanoparticles, and mucoadhesive
technologies. In conclusion, integrating advanced oral drug delivery systems for prokinetic
agents presents a promising avenue for managing gastrointestinal disorders. Continued research
and collaboration among academia, industry, and healthcare professionals are crucial to unlocking
the full potential of these innovations and ultimately translating them into clinically effective
treatments for patients.
Improvement in Compatibility and Drug Release Performance of Hot-Melt Pressure-Sensitive Adhesives by Physical Blending Technique
Authors: Yang Jiayi , Yin Shuo , Wu Tan , Zhang Yangyang , Zhu Chunyun , Feng Nianping , Guo Teng
Published: January 2025

Background:

Hot-melt Pressure-sensitive Adhesives (HMPSA) are eco-friendly pressuresensitive
adhesives, with the potential of being used as substrates for transdermal patches. However,
due to the low hydrophilicity of HMPSA, the application is limited in the field of Traditional Chinese
Medicine (TCM) plasters.

Methods:

Three modified HMPSA were prepared with acrylic resin EPO, acrylic resin RL100, and
Polyvinylpyrrolidone (PVP) as the modifying materials. The physical compatibility between HMPSA
and the modifying materials was investigated through in vitro release performance, viscosity, softening
point, cohesion, and fluidity, so as to determine the most effective modifying material. The impact
of the modified HMPSA on the release properties of different TCM ingredients was elucidated
by the performance of water absorption and contact angle behavior.

Results:

With the addition of the modifying materials, both the viscosity and the softening point of
HMPSA were improved, with the flowability reduced and the cohesion maintained. The morphological
and structural changes reflected the physical compatibility between HMPSA and the three modifying
materials. According to the results of in vitro release experiments, PVP effectively improved
the release performance of paeoniflorin, ephedrine hydrochloride, and cinnamaldehyde in HMPSA,
with no significant impact on the release performance of eugenol. The changes in the drug release
performance of HMPSA may be attributed to the improved hydrophilicity of HMPSA after physical
modification.

Conclusion:

The compatibility and the drug release performance of HMPSA were effectively enhanced
after the addition of the modifying materials by the physical blending technique. Among the
three modifying materials, PVP has been found to be an ideal modifying material for HMPSA in the
field of TCM plasters due to its effects on drug release performance.
Aryl Hydrocarbon Receptor Establishes a Delicate Balance between the Level of the Trace Amine Tryptamine and Monoamine Oxidase Activity in the Brain and Periphery in Health and Conditions such as Neurodegenerative, Neurodevelopmental, and Psychiatric Disorders
Authors: Kot Marta
Published: January 2025

The purpose of this review was to analyse the literature regarding the correlation between
the level of tryptamine, aryl hydrocarbon receptor (AHR) signalling pathway activation, and monoamine
oxidase (MAO)-A and MAO-B activity in health and conditions such as neurodegenerative,
neurodevelopmental, and psychiatric disorders. Tryptamine is generated through the decarboxylation
of tryptophan by aromatic amino acid decarboxylase (AADC) in the central nervous system (CNS),
peripheral nervous system (PNS), endocrine system, and gut bacteria. Organ-specific metabolism of
tryptamine, which is mediated by different MAO isoforms, causes this trace amine to have different
pharmacokinetics between the brain and periphery. Reactive oxygen species (ROS) generated by
MAO can influence miRNA-CYP enzyme regulatory network and affect mitochondrial function.
Tryptamine regulates AHR function by acting as an endogenous ligand for AHR, initiating AHR activation
and inhibiting the expression of the CYP1A1 and CYP1A2 genes. The dysregulation of
AHR signalling, triggered by endogenous tryptamine binding, can disrupt the regulation of prolactin
levels. Depending on the tryptamine concentration and context, tryptamine can be beneficial or
harmful. By acting as an agonist of inhibitory serotonin receptors and trace-amine associated receptor
1 (TAAR1) and an antagonist of excitatory serotonin receptors, it can engage in diverse physiological
interactions with serotonin. Increased tryptamine production is observed under hypoxic conditions
and is associated with hypoxia-inducible factor 1α (HIF-1α) activation, leading to AHR activation.
Dysregulation of the association between tryptamine levels, AHR signalling pathway activation,
and MAO activity are observed in Alzheimer’s disease (AD), Parkinson’s Disease (PD), Autism
Spectrum Disorder (ASD) and schizophrenia.
DABCO-Based Ionic Liquids: A Non-Conventional Catalyst for the Synthesis of N-Substituted 2-Nitrophenylamines
Authors: Ambika  , Singh Pradeep Pratap
Published: January 2025

Isoalloxazines are the essential cofactors of flavoproteins, which are responsible for the
different redox reactions in various biological processes. They can be efficiently synthesized using Nsubstituted
2-nitrophenylamines as a precursor. In the present communication, we report a simple and
efficient method for the synthesis of N-substituted 2-nitrophenylamines in DABCO-based ionic liquids.
The method offers the use of DABCO-based ionic liquids as non conventional catalysts, which
eliminates the use of any additional base with excellent yields in short reaction time, easy product
isolation, high purity, and recyclability.
Physically Crosslinked Polymeric Network for Controlled and Mucoadhesive Release of Miconazole for Topical Ocular Delivery
Authors: Farooq Umar , Rasul Akhtar , Mehmood Yasir , Shahid Hira , Bin Jardan Yousef A. , Ibenmoussa Samir , Bourhia Mohammed
Published: January 2025

Background:

Eudragit L100, filled with miconazole and gelatinous polymeric eye drops,
is designed to sustain the drug release and increase ocular effect.

Methods:

The solvent diffusion technique was used to obtain the polymeric solution. The formulations
developed were fully characterized and examined.

Results:

The optimized drug had a particle size of 71.15 2.3 nm, a zeta potential of approx. 2.57 to
0.76 mV, a polydispersity index of approx. 0.184 and a capture efficiency of 0.10% of 58.049. The
prepared efforts showed a fungicidal effect on Candidiasis albicans cultures.

Conclusion:

The polymeric solution containing the drug-filled with miconazole (MZ) showed an
abrupt release in the first hours, followed by the pattern of sustained drug release. A higher cumulative
corneal permeability was observed from MZ-containing polymeric solution, which prolonged
MZ release in goat eyes. Mucoadhesive liners containing miconazole-loaded Eudragit L100 polymeric
solution provide a promising approach to the ocular administration of miconazole (a fungicide)
for the treatment of ocular infections requiring long-term drug administration.
Machine-Learning Based Computed Tomography Radiomics Nomgram For Predicting Perineural Invasion In Gastric Cancer
Authors: Huang Pei , Li Sheng , Deng Zhikang , Hu Fangfang , Jin Di , Xiong Situ , Fan Bing
Published: January 2025

Objective:

The aim of this study was to develop and validate predictive models for perineural invasion (PNI) in gastric cancer (GC) using clinical factors and
radiomics features derived from contrast-enhanced computed tomography (CE-CT) scans and to compare the performance of these models.

Methods:

This study included 205 GC patients, who were randomly divided into a training set (n=143) and a validation set (n=62) in a 7:3 ratio. Optimal
radiomics features were selected using the least absolute shrinkage and selection operator (LASSO) algorithm. A radiomics model was constructed
utilizing the optimal among five machine learning filters, and a radiomics score (rad-score) was computed for each participant. A clinical model
was built based on clinical factors identified through multivariate logistic regression. Independent clinical factors were combined with the radscore
to create a combined radiomics nomogram. The discrimination ability of the models was evaluated by receiver operating characteristic
(ROC) curves and the DeLong test.

Results:

Independent predictive factors of the clinical model included tumor T stage, N stage, and tumor differentiation, with AUC values of 0.777 and
0.809 in the training and validation sets. The radiomics model was constructed using the support vector machine (SVM) classifier with the best
AUC (0.875 in the training set and 0.826 in the validation set). The combined radiomics nomogram, which combines independent clinical
predictors and the rad-score, demonstrated better predictive performance (AUC=0.889 in the training set; AUC=0.885 in the validation set).

Conclusion:

The nomogram integrating independent clinical predictors and CE-CT radiomics was constructed to predict PNI in GC. This model demonstrated
favorable performance and could potentially assist in prognosis evaluation and clinical decision-making for GC patients.
Identification of Natural Terpenoid Compounds as Potential Inhibitors of Nucleoprotein of Influenza A Virus using in silico Approach: ADMET,
Molecular Docking, and Molecular Dynamic Simulation
Authors: Hossain Md. Saddam , Ali Md Mosahaq , Raj Prithbay , Khondokar Md. Parvez , Haque S. M. Jahurul , Bin Jardan Yousef A. , Ibenmoussa Samir , Bourhia Mohammed
Published: January 2025

Background:

We continue to struggle with the prevention and treatment of the influenza
virus. The 2009 swine flu pandemic, caused by the H1N1 strain of influenza A, resulted in numerous
fatalities. The threat of influenza remains a significant concern for global health, and the development
of novel drugs targeting these viruses is highly desirable.

Objective:

The objective of this study is to explore the inhibitory potential of terpenoid compounds
against the Nucleoprotein (NP) of influenza A virus, which is a highly effective drug target due to
its ability to facilitate the transcription and replication of viral RNA.

Method:

In silico research was performed to identify potential inhibitors of NP. Molecular docking
studies were conducted to assess the binding of terpenoid compounds to the active site residues of
the target protein. The most promising hits were then subjected to molecular dynamics simulations
to examine the stability of the protein-ligand complexes. Additionally, ADMET (Absorption, Distribution,
Metabolism, Excretion, and Toxicity) studies and Lipinski's rule of five were employed to
evaluate the drug safety and druglikeness of the compounds.

Result:

Docking studies revealed that the terpenoid compounds bind strongly to the active site residues
of the NP protein. Molecular dynamics simulations demonstrated the stability of the proteinligand
complexes for the best-hit compounds. ADMET studies and Lipinski's filter indicated that
the compounds exhibit desirable drug safety and drug-likeness profiles.

Conclusion:

This work may contribute significantly to drug discovery and the development of
therapeutic agents against the influenza A virus. The identification of terpenoid compounds that
bind strongly to the NP protein and exhibit favorable drug-like properties through in silico studies
provides a promising foundation for further research and the development of potential inhibitors
targeting this critical viral protein.

conclusion:

This work may contribute significantly to drug discovery and the development of therapeutic agents against influenza A virus. The identification of terpenoid compounds that bind strongly to the NP protein and exhibit favorable drug-like properties through in silico studies provides a promising foundation for further research and development of potential inhibitors targeting this critical viral protein.
A Rare Case of Fatal Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome in a Patient with Rheumatoid Arthritis
Authors: Munshi Renuka , Sachdeo Praneet , Solanki Vikas
Published: January 2025

Introduction:

This case study presents a rare and fatal instance of Toxic Epidermal
Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome
in a 51-year-old male patient diagnosed with Rheumatoid Arthritis (RA).

Case Presentation:

The patient was initially treated with sulfasalazine, leflunomide, and hydroxychloroquine,
following which he developed a rash, fever, and loose stools. Drug allergy
was suspected, and the antirheumatic medications were withdrawn, following which, the patient
improved. A subsequent attempt was made to treat the RA with methotrexate, prednisolone, and
hydroxychloroquine, following which the rash returned along with an increase in severity, including
detachment of the epidermis and mucosa, and systemic involvement, both hepatic and
renal. The patient ultimately succumbed to multiple organ dysfunction syndrome and neutropenic
sepsis.

Conclusion:

This case highlights the possibility of DRESS syndrome and Stevens-Johnson Syndrome
(SJS)/TEN following treatment with anti-rheumatic medications. Evidence of this is rare,
with the exception of sulfasalazine. This case also considers that the signs of a moderately severe
adverse drug reaction could be the early warning signs of DRESS syndrome, which can be difficult
to manage and may turn to be fatal. Additionally, this case highlights the need for maintenance
of quality health records in low- and middle-income countries due to the failure to identify
hydroxychloroquine as a suspected drug inducing the initial adverse reaction that resulted in it
being prescribed again, leading to a fatal outcome.
Unravelling the Role of Tyrosine and Tyrosine Hydroxylase in Parkinson’s Disease: Exploring Nanoparticle-based Gene Therapies
Authors: Jujjavarapu Satya Eswari , Mishra Arnav
Published: January 2025

Parkinson’s disease (PD) is a neurodegenerative disorder that results from the progressive
loss of neurons in the brain followed by symptoms such as slowness and rigidity in movement, sleep
disorders, dementia and many more. The different mechanisms due to which the neuronal degeneration
occurs have been discussed, such as mutation in PD related genes, formation of Lewy bodies,
oxidation of dopamine. This review discusses current surgical treatment and gene therapies with
novel developments proposed for PD. Gene therapy based on novel approaches will possess more
potential advantages over the conventional methods. Currently, gene therapy for such disorders is
still under the process of clinical trials and approval. The pathogenesis comes from the breakdown
of dopaminergic neurons within substantia nigra (SN) by the action of tyrosinase enzyme and subsequent
accumulation of α-synuclein within the neurons. These dopaminergic neurons are the main
source of dopamine, the decline of which is responsible for the symptoms. So, gene therapy can
possibly provide more stable supplementation and regulate the expression of tyrosinase enzyme,
providing better symptomatic relief and lesser side effects. Dopamine replacement therapy is a wellstudied
gene therapy method for PD. Another approach involves introducing functional genes for
enzymes such as tyrosine hydroxylase, cyclohydrolases, and decarboxylases with the help of engineered
vectors such as AAV and LV. Further, the potential application of nanoparticles in gene
therapy as an efficient gene delivery and imaging system has been discussed. Among these, lipidbased
nanoparticles such as PILs offer important benefits in terms of enhanced bioavailability, permeability
to the cells, and solubility. So, this review paper summarizes some of the advanced gene
therapy approaches for PD and the current status of clinical research in the development of gene
therapy using nanoparticles.
Classification, Synthesis, Isomerism, and Spectral Characterization of Schiff Bases
Authors: Moanta Anca
Published: January 2025

Schiff bases have been known for 160 years and there is a multitude of information
about them. This review focuses on their classification. The examples were classified based on the
number of azomethine groups (mono-, bis-, tris-, tetrakis-, oligo-, and polymer Schiff bases) and
the nature of their chain (cyclic and acyclic Schiff bases). Many imines are synthesized by condensing
carbonyl compounds with amines and the mechanism of this reaction has been described.
The main types of isomerism found at Schiff bases are geometric isomerism, atropizomerism, and
imine-enamine tautomerism. After obtaining them they can be spectrally characterized using FTIR,
UV-Vis, 1H NMR, 13C NNR, and mass spectrum and they were presented.
Advancements in Cancer Therapeutics: Emerging Agents and Combination Strategies in Drug Discovery
Authors: Hussain Afzal , Hussain Ashfaq
Published: January 2025

In the last few years, there have been significant advances in cancer agent research,
most of which entered clinical trials after succeeding in initial preclinical studies. Here, we discuss
successful accomplishments in the promising approaches of targeted therapies, immunotherapies,
and combination therapies. The development in these areas includes sotorasib - targeting
the mutation of KRAS for lung and pancreatic cancer and pembrolizumab - an immune
checkpoint inhibitor for melanoma therapy; the latter has been synergistic with chemotherapy. In
addition, exciting results emerge from trials with the DNA damage repair inhibitor olaparib in
BRCA-mutated cancers and the tyrosine kinase inhibitor osimertinib for EGFR-mutant lung cancer.
Bevacizumab continues to establish itself as an evolving therapy in colorectal cancer, and
niraparib enters Phase III in ovarian cancer. New combinations will include alpelisib and PD-1
inhibitors and nanoparticle-based Abraxane for triple-negative breast cancers leading toward
precision medicine. These would improve the survival rates and quality of life in patients with
advanced or refractory malignancies.
Usefulness of High-resolution Computed Tomography for Macrolide Therapy of Idiopathic Bronchiectasis
Authors: Saito Zenya , Yoshida Masahiro , Uchiyama Shota , Nishioka Saiko , Tamura Kentaro , Tamura Nobumasa
Published: January 2025

Background:

High-resolution computed tomography (HRCT) correlates with clinical symptoms, respiratory function, and quality of life in bronchiectasis.

Objective:

We aimed to investigate the relationship between macrolide and acute exacerbation (AE) in idiopathic bronchiectasis classified by the Bronchiectasis Radiologically Indexed CT Score (BRICS).

Methods:

We retrospectively reviewed the medical records of patients diagnosed with idiopathic bronchiectasis between April 2014 and December 2020 at a single hospital. Overall, 115 patients with idiopathic bronchiectasis were selected and divided into three groups, according to the BRICS. Each group was divided into subgroups with and without macrolide therapy, and the number of patients with AE in each group was retrospectively compared.

Results:

About 45, 48, and 22 patients were included in the mild, moderate, and severe groups, respectively. In the mild group, the subgroup with macrolide therapy had significantly fewer patients with single AE than those without macrolide (
P = 0.029). There was no significant difference in the moderate and severe groups (
P = 1.00 and 0.64, respectively). In the multiple AE, the subgroup with macrolide therapy had significantly fewer patients than those without macrolide therapy in the mild, moderate, and severe groups (
P = 0.024, 0.029, and 0.026, respectively).

Conclusion:

HRCT severity assessment might be useful in predicting treatment efficacy in patients with idiopathic bronchiectasis without previous AEs. Further large-scale clinical trials are required on the usefulness of HRCT in the future.