bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-substituted Tertiary Amine-chitosans as Promising Nanocarriers for siRNA Delivery
Authors: Martinez Júnior André Miguel , de Oliveira Vera Aparecida , Tiera Marcio José 
Published: January 2025

Introduction:
The clinical translation of chitosan-based formulations for siRNA delivery
has been partially limited by their poor stability/solubility at physiological conditions, although they
have good biocompatibility and cost-effectiveness.

Method:
In this study, the chitosan was O-substituted with diisopropylethylamine (DIPEA) groups,
which improved its solubility at pH 7.4 by increasing the degree of ionization and enhanced the
ability of chitosan to load siRNA at very low amine/phosphate (N/P) ratios. The O-DIPEAchitosan/
siRNA nanopolyplexes were self-assembled by complexation and presented positive Zeta
potentials (ζ = +8 to +10 mV), spherical-like morphology, 200-300 nm size, low polydispersity index
(PDI < 0.2), and were able to protect the siRNA from degradation by RNAse. Also, the resistance
to albumin-induced disassembly and aggregation revealed both good structural and colloidal
stabilities of the siRNA nanopolyplexes.

Result:
The nanopolyplexes displayed low cytotoxicities in RAW 264.7 macrophages and were
successfully uptaken by both macrophages and HeLa cells achieving internalization efficiency
similar to Lipofectamine. A positive correlation was observed between the physicochemical properties
of the siRNA nanocarrier and its transfection efficiency.

Conclusion:
A knockdown of about 60-70% of tumor necrosis factor alpha (TNFα) was reached
in lipopolysaccharide-stimulated macrophages treated with O-DIPEA-chitosan/siTNFα nanopolyplexes.
Overall, the results confirmed that O-DIPEA chitosans are promising carriers for
siRNA delivery.

conclusion:
Overall, the results confirmed that O-DIPEA chitosans are promising carriers for siRNA delivery.
Development, Optimization, and Evaluation of Rutin-Loaded Liposomes in the Management of Rheumatoid Arthritis
Authors: Nautiyal Gunjan , Sharma Shiv Kant , Kaushik Dhirender , Pandey Parijat 
Published: January 2025

Background:
Rheumatoid arthritis is a chronic autoimmune disease, progressively
distinctive via cartilage destruction, auto-antibody production, severe joint pain, and synovial
inflammation. Nanotechnology represents one of the utmost promising scientific technologies of the
21st century. Nanocarriers could be the key to unlocking its potential by encapsulating Rutin in targeted
drug delivery systems, potentially for targeted Rheumatoid arthritis therapy.

Objective:
The rationale of current research is to prepare liposomes loaded with a bioflavonoid drug
rutin for effective management of rheumatoid arthritis.

Materials and Methods:
This study investigated the formulation of rutin liposomes using the thinfilm
hydration technique, also known as the Bangham method. A Box-Behnken design was
employed to optimize the formulation parameters. The LP2 batch was then characterized for its mean
particle size, zeta potential, shape, diffraction pattern, and thermal properties. Finally, the in-vitro
anti-oxidant and anti-inflammatory potential of the rutin liposomes were evaluated using appropriate
assays.

Results:
Out of thirteen batches, LP2 was found to be an optimized batch with a mean particle size of
167.1 nm, zeta potential -13.50 mV, and entrapment efficiency of 61.22%. The above results showed
higher stability of rutin liposomes. Further characterization of LP2 for morphological assessment,
XRD analysis, and DSC revealed its spherical shape less than 1 μm, polycrystalline nature, and
thermographic peak at 139°C, respectively. Evaluation of the antioxidant properties and antiinflammatory
potential of LP2 revealed its maximum therapeutic potential in the reduction of
inflammation and protein denaturation when evaluated via in-vitro assays.

Conclusion:
Rutin liposomal formulation has tremendous potential for the management of
Rheumatoid arthritis due to its enhanced bioavailability, anti-oxidant, and anti-inflammatory
properties when compared to free rutin.
100 Years of Insulin: A Historical Perspective
Authors: Pinto Gabrielle Barbosa , Junior Ivaldo Itabaiana , Magalhães Jorge Lima , Antunes Adelaide Maria de Souza 
Published: January 2025

Background:
Diabetes mellitus, a metabolic disease characterized by high blood glucose
levels, has increased dramatically in recent years, prompting the need for more affordable
diagnoses and treatments.

Objective:
This study aimed to conduct a brief historical and theoretical review on the development
of insulin.

Methods:
Scientific and technological data have been retrieved and analyzed with a focus on the
development of the active pharmaceutical ingredient insulin and insulin-based medicines. Data
have been retrieved from the PubMed database available via the CAPES portal

Results:
Diabetes is one of the oldest diseases in the world. The year 2021 marked the 100th anniversary
of the discovery of insulin, which transformed diabetes from a fatal disease into a
chronic disease. The extraction and purification of insulin from bovine or porcine pancreases
from slaughterhouses has enabled the pharmaceutical industry to produce insulin on a large scale.
The introduction of insulin analogs in 1996 expanded the options. Currently, commercial insulin
consists of human insulin and/or human insulin analogs.

Conclusion:
The state-of-the-art and technological development of insulin over the last 100 years
has been presented in this work. The development of new pharmaceutical technologies has led to
the obtainment of improved versions of insulin, as well as the emergence of different types of insulin.
Alongside the innovations in the development of the active ingredient and related medicines,
new formulations, methods, and routes of administration have emerged based on the pharmacodynamic,
pharmacokinetic, and pharmacotechnical modulations of the drug.
Development of Benzimidazole Anticancer Leads for EGFR Inhibition by 3D-QSAR Based Virtual Screening, Molecular Docking, Molecular Simulation and Drug Likeness Study
Authors: Verma Ranjeeta , Verma Shweta , Abbas Nahid 
Published: January 2025

Background:
Breast cancer is the most common cancer in women. Tyrosine kinase inhibitors
were developed to treat breast cancer. EGFR/ErbB1 inhibition has proved to be a promising
target in breast carcinoma therapy. Drugs with benzimidazole nucleus have been approved by the
FDA for cancer treatment.

Objective:
To design and develop benzimidazole anticancer small molecules for EGFR inhibition for
the treatment of breast cancer.

Methods:
By 3D-QSAR-based virtual screening, molecular docking, molecular simulation and drug
likeness study.

Results:
In this research, a 3D-QSAR pharmacophore was generated with four salient features.
Namely H-bond acceptor (HBA), two ring aromatic (RA) and hydrophobic (HY) features. Its correlation-
coefficient (r) is 0.8412, RMSD of 0 .96 and with 32.84 bits cost difference value. With virtual
screening, 4 top hits were identified. Novel benzimidazole derivatives were designed (1a-ll) by using
the features of hit molecules and the pharmacophore. The novel designed small molecules that were
druggable as they passed the Lipinski and Veber rule. Novel ligands and EGFR protein interaction
were good. 1a and 1i were found to be the best-designed molecules. They had -8.6 Kcal/mol and -8.4
Kcal/mol docking interaction energy, respectively, whereas Compound 4 (reference) scored -7.4
Kcal/mol. Both these molecules were stable inside the binding pocket of the EGFR protein. The molecular
dynamic simulation study revealed that 1a attained equilibrium at 0.15nm.

Conclusion:
In silicon novel benzimidazole small molecules were designed and developed as EGFR
inhibitors to treat breast cancer.
Prevalence of the Utilization of Dietary Supplements Among Female Adults in ACCRA, Ghana
Authors: Miller Marian Esther 
Published: January 2025

Objective:
The utilization of dietary supplements has spiked in Sub-Saharan Africa despite
no statistical evidence of their safety and effectiveness in disease protection, prevention and
promotion. This study was conducted to investigate the prevalence rate of the utilization of dietary
supplements among female adults in Accra, Ghana.

Methods:
A cross-sectional study design was carried out with a sample size of 392 female adults
in Accra, Ghana. Participants completed a valid and reliable online questionnaire (Cronbach's alpha
= 0.776 and valid at 2-tailed significant value). Pie Chart and Chi-square analyses were used
to determine the significant difference between variables.

Results:
According to the study findings, 84% of female adults in Accra, Ghana, take some form
of dietary supplements. 91% of female adults between the ages of 21-40 years old in Accra, Ghana,
consume vitamins as a form of dietary supplement. In addition, there is a statistically significant
association between age and the utilization of dietary supplements. Younger female adults utilize
dietary supplements more than older female adults.

Conclusion:
Health promotion and education are needed to provide knowledge and awareness on
dietary supplements to ensure the safety and efficacy of dietary supplement consumption.
The Attitudes of Dentists towards Patient Care during COVID-19 Endemic: A Study in Indonesia
Authors: Laksmiastuti Sri Ratna , Wijaya Harryanto , Astoeti Tri Erri 
Published: January 2025

Background
Dentists are susceptible to COVID-19 transmission during patient care. Therefore, health protocols were recommended for dental practice during the COVID-19 pandemic. The pandemic restrictions have been lifted, yet the awareness of COVID-19 transmission in dental care is still necessary. However, it remains unclear whether or not the health protocol is still implemented by dentists.

Objectives
The present study aimed to assess the attitudes of dentists towards patient care after COVID-19 became pandemic.

Materials and Methods
A cross-sectional study was conducted among 302 general dentists and dental specialists in Indonesia. Data were collected using an online questionnaire through Google Forms. The questionnaire was reviewed by clinical experts. It consists of 15 statements assessing the attitudes of dentists towards patient care, along with descriptive statistics, followed by the Mann-Whitney U test or Kruskal-Wallis H test, Post hoc Dwass, Steel, Critchlow, and Fligner analysis when significant differences were observed in the bivariate analysis.

Results
Female dentists were more likely to show a positive attitude towards COVID-19 patients’ screening in clinical practice (p = 0.008). Different attitudes were also observed regarding the use of a negative-pressure room to prevent potentially contaminated air from entering the room and flowing outside (p = 0.012). Dental attitude in terms of COVID includes a) COVID-19 screening using rapid antigen test, especially for patients with COVID-19-like symptoms, b) the operator wearing PPE and washing hands properly according to the WHO’s six steps, and c) using negative pressure room since it is the best dental practice room type to prevent air contamination differed by geographical area (p = 0.001, p = 0.001, and p = 0.009) respectively.

Conclusion
A difference in the attitudes of dentists towards patient care was observed. The differences included COVID-19 patient screening before dental procedures, the use of negative-pressure rooms, and the implementation of dentists’ health protocol and personal protective equipment.
Starch-ZnCr/LDH Composite and ZnCr-LDH: Synthesis, Characterization, and Adsorption Efficiency to Remove Congo Red from Aqueous Solution
Authors: Adim Safaa , Eddahmi Mohammed , Khanchaoui Amal El , Boukontar Nezha , Mansori Mohamed , Essoumhi Abdellatif , Bouissane Latifa 
Published: January 2025

Background:
To bring new materials with high performance, a large number of composites,
among others, such as starch-laminated double hydroxides (starch/ZnCr-LDH), have been
produced, which have shown significant adsorption predisposition to remove heavy metals and
dyes. These LDHs display great adsorption potential due to their high anion exchange capacity,
large surface area, and good thermal stability.

Objective:
This study aimed to develop starch-ZnCr-hydroxide composite (S/ZnCr-LDH) as a new
material and investigate its performance in removing various anionic dyes compared to ZnCr-
LDH.

Methods:
The starch-ZnCr-laminated double hydroxides (S/ZnCr-LDH) and ZnCr-LDH composites were prepared by the co-precipitation method and their structures were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential thermogravimetric/ thermal analysis (TG/DTA) Scanning electron microscopy (SEM), and Energy Dispersive Xrays Spectroscopy (EDX).

Results:
The effects of different operating parameters, such as pH, initial CR concentration, contact
time, and adsorbent dose, on CR removal were studied. The results showed that the S/ZnCr-
LDH composite is more efficient for CR removal, reaching 99% at pH 3, while ZnCr-LDH presented
a removal efficiency of 90%. Isothermal data were processed according to the Langmuir,
Freundlich, and Temkin models. According to the results, Langmuir's isothermal model best
matched the experimental data, with a maximum adsorption capacity of 252. 92 and 236. 98 mg/g
for S/ZnCr-LDH and ZnCr-LDH, respectively. The adsorption kinetics corresponded to the PSO
model. CR dye molecules were adsorbed to different sites on the S/ZnCr-LDH composite based on
various interactions, such as electrostatic interactions, hydrogen bonds, and Van der Waals forces.

Conclusions:
S/ZnCr-LDH composite displays the highest capacity to remove CR dye molecules
compared to ZnCr-LDH.
Problematika Aturan Pemungutan Suara Ulang dalam Perselisihan Hasil Pemilu Presiden dan Wakil Presiden
Authors: M Rizqi  , Arysandi Didan Neofal 
Published: January 2025

Permasalahan ketidakjelasan regulasi terkait pelaksanaan Pemungutan Suara Ulang (PSU) dalam Pemilihan Presiden dan Wakil Presiden menjadi tantangan penting dalam menjamin proses pemilu yang adil. Regulasi yang ada saat ini terutama Undang-Undang Nomor 7 Tahun 2017 tentang Pemilihan Umum dan PKPU Nomor 25 Tahun 2023 tentang Pemungutan dan Penghitungan Suara dalam Pemilihan Umum menunjukkan adanya perbedaan, sehingga menimbulkan ketidakpastian hukum ketika PSU melibatkan lebih dari dua pasangan calon. Penelitian ini bertujuan untuk menganalisis kesenjangan antara teori dan praktik dalam pelaksanaan PSU, terutama pada kasus yang memunculkan ketidakpastian hukum. Menggunakan metode yuridis normatif, penelitian ini mengkaji secara kritis undang-undang terkait, putusan pengadilan, dan studi doktrinal untuk mengidentifikasi area kunci yang memerlukan perbaikan regulasi. Hasil temuan menunjukkan bahwa kurangnya harmonisasi antar aturan menyebabkan kesulitan bagi otoritas pemilu dalam menyelenggarakan PSU. Selain itu, panduan yang kurang memadai serta ketiadaan pedoman teknis yang jelas menghambat pelaksanaan PSU, yang berpotensi merusak integritas pemilu. Studi ini menyimpulkan bahwa perubahan UU Pemilu merupakan kebutuhan mendesak agar PSU dapat dilaksanakan secara efektif dan efisien serta mengurangi potensi permasalahan hukum dalam pemilu yang akan datang.
EFFECTS OF TOCILIZUMAB AND SYSTEMIC CORTICOSTEROIDS IN PATIENTS WITH CARDIOVASCULAR DISEASE ON CLINICAL OUTCOMES IN COVID-19
Authors: Osmani Zudi , Paralija Belma , Baljić Rusmir 
Published: January 2025

Background: COVID-19 is a respiratory disease caused by a novel coronavirus, with a high mortality, especially in patients with underlying diseases. Patients with COVID-19 pneumonia may express an immune response such as cytokine storm or macrophage activation syndrome, which can lead to organ failure and death.Some studies suggest that corticosteroid and tocilizumab can improve the respiratory status and clinical outcome of patients with COVID-19 pneumonia.
Aim: The aim of the study was to determine the potential effect of the use of tocilizumab and corticosteroids in patients with concomitant cardiovascular diseases on the clinical course and outcome during COVID-19 infection.
Methods: We performed an observational retrospective study of adult patients admitted to “Travnik” and “Jajce” Hospital, Bosnia and Herzegovina, between 01.03.2020 and 01.12.2022 with confirmed COVID-19 and underlying cardiovascular disease (CVD).
Results: The majority of patients (110 or 60.4%) had previously reported cardiomyopathy, and other cardiovascular disease included earlier myocardial infarction, stroke, cardiac arrhythmias, cardiac surgery, compensated cardial disease, and acute myocardial infarction. Total of 159 (87.4%) patients received corticosteroids during treatment. Tocilizumab has been used in 16 patients; nine survived and seven died.
Conclusion: Even some studies proved that it might improve clinical presentation and prevent lethal outcomes; in our study there were no significant results to confirm this thesis.

Peer Review History:
Received 28 September 2024; Reviewed 15 November; Accepted 21 December; Available online 15 January 2025
Academic Editor: Dr. DANIYAN Oluwatoyin Michael, Obafemi Awolowo University, ILE-IFE, Nigeria, toyinpharm@gmail.com
Average Peer review marks at initial stage: 6.0/10
Average Peer review marks at publication stage: 7.5/10
DATA-DRIVEN OPTIMIZATION IN PHARMACY OPERATIONS: A PRESCRIPTION FOR ENHANCED PATIENT CARE
Authors: Muhammad Shahzad Aslam  
Published: January 2025

The convergence of patient care and business efficiency in community pharmacies through a Comprehensive Datafication Approach marks a transformative journey toward enhanced healthcare services and operational effectiveness. The aim of this study was to examine diverse perspectives on datafication, AI, and emerging technologies in healthcare, with a particular focus on optimizing community pharmacy operations. The implementation of a Comprehensive Datafication Approach in community pharmacies significantly impacts overall operational efficiency and patient care outcomes. The strict criterion mandates studies to report outcomes related to patient care, business efficiency, or operational metrics, ensuring selected literature aligns cohesively with research objectives, providing a robust basis for exploring dimensions associated with optimizing community pharmacy operations through datafication. Drawing from multiple studies, our exploration encompasses the challenges and potentials inherent in the integration of digital technologies. As we delve into the optimization of community pharmacy operations through AI, these diverse perspectives contribute to a nuanced understanding of the challenges and opportunities in data-driven healthcare transformation. The integration of AI necessitates ethical considerations, inclusive practices, and a balance between optimization goals and individual rights, ensuring a holistic approach to healthcare datafication.

Peer Review History:
Received 2 October 2024; Reviewed 17 November; Accepted 24 December; Available online 15 January 2025
Academic Editor: Dr. Emmanuel O. Olorunsola, Department of Pharmaceutics & Pharmaceutical Technology, University of Uyo, Nigeria, olorunsolaeo@yahoo.com
Average Peer review marks at initial stage: 6.5/10
Average Peer review marks at publication stage: 7.0/10
A RETROSPECTIVE INVESTIGATION OF BLOOD COAGULATIVE PARAMETERS PT, KPTT, PROTEIN C, AND ANTITHROMBON III IN 95 PATIENTS WITH LIVER DISEASE
Authors: George Zhu  , Broekmans AW  , Bertina RM  
Published: January 2025

Background: The liver is a crucial synthesis of blood coagulation factors and anticoagulative serine proteases such as protein C(PC) and antithrombin III (ATIII), which exerts a key role in the regulation of hemostatic balance. Activated protein C(APC) and protein S complex inactivate the activated factor Va and VIIIa, thus limiting Xa and thrombin formation. The excess protein S can drive cancer cellular proliferation and cell survival through oncogenic receptor Axl. In presence of heparin binding, antithrombin III (ATIII) and thrombin form an inactive complex in a 1:1 molar ratio. ATIII also inactivate factor IXa, Xa, XIa and XIIa at slow rate. In the setting of liver diseases, this reduced dysregulation can be attributed to decreased synthesis by the liver and increased consumption of coagulative factors and protein C and ATIII.
Methods: In current study, using routine detection for the blood coagulative parameters in 75 patients with liver diseases.
Results: The results showed that there exist one or three coagulative parameters PT, KPTT, and TT abnormal longer. Moreover, the abnormal intensity of coagulative parameters was associated to the severity of liver diseases. In our detection of 20 liver cirrhosis, the results showed significantly decreased plasma protein C antigen (PC:Ag 0.5501 vs 1.0578 µ/ml) and antithrombin III level (ATIII: Ag 21.8 vs 39.8 mg/dl, ATIII:C 40.25 vs 105.04%), respectively.
Conclusions: The measurement of multidispillary analyses of coagulative and anticoagulative system protein C and ATIII level are helpful to monitoring the liver diseases and might play a predictable marker.

Peer Review History:
Received 13 September 2024; Reviewed 20 November; Accepted 26 December; Available online 15 January 2025
Academic Editor: Dr. Marwa A. A. Fayed, University of Sadat City, Egypt, maafayed@gmail.com
Average Peer review marks at initial stage: 6.0/10
Average Peer review marks at publication stage: 7.0/10
GC-MS ANALYSIS OF ETHYL ACETATE FRACTIONS OF QUST AL HINDI (Saussurea lappa) ROOT
Authors: Sukmawati  , A. Muflihunna  
Published: January 2025

Background: Qutsh al Hindi (Saussurea lappa), commonly known as Indian wood, is a traditional medicine that had been used empirically as anti-inflammatory and pneumonia. Its potential as anti-inflammatory activity is proven by many researches in vitro and in vivo.
Aim and objective: This study aims to identifying active compounds from the ethyl acetate fraction of Qutsh al Hindi (S. lappa) using GC-MS.
Method: The extract was obtained by powder of S. lappa roots using maceration method and evaporated to obtained thick extract. Then, the isolate of extract would be fractionated using n-hexane and ethyl acetate. The compounds that carried out by fractionation would be identified using GC-MS.
Result: Based on this research, the analysis of S. lappa ethyl acetate fraction showed 119 compounds using GC-MS. Other supporting factors using Mass Chromatography. The result was one of target compound identified, i.e. β-cyclocostunolide, a derivate compound from costunolide that has an anti-inflammatory activity.
Conclusion: It can be concluded that a fraction of S. lappa roots ethyl acetate contain β-cyclocostunolide as anti-inflammatory compounds.

Peer Review History:
Received 11 September 2024; Reviewed 12 November; Accepted 25 December; Available online 15 January 2025
Academic Editor: Dr. Ahmad Najib, Universitas Muslim Indonesia, Indonesia, ahmad.najib@umi.ac.id
Average Peer review marks at initial stage: 5.5/10
Average Peer review marks at publication stage: 7.0/10