bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovative Therapies: A Major Breakthrough in Combating Multi-Drugresistant Bacterial Infections Using Mixture Design and Multi-Objective
Optimization with NSGA-II Algorithm
Authors: Adouane Meriem , Kadri Nabil , Benzitoune Nourelimane , Lakhdari Chafika , Djellal Samia , Ousmer Lilla , Tahraoui Hichem , Amrane Abdeltif , Remini Hocine , Dahmoune Farid , Madani Khodir 
Published: February 2025

Introduction/Objective:
The increasing resistance of pathogens to antibiotics poses a
major public health challenge. This study aims to develop an innovative approach to combat this
resistance by exploring synergies between standard antibiotics and marine metabolites.

Methods:
The methodology combines disk diffusion testing and mixture design to assess the antimicrobial
efficacy of the combinations.

Results:
The results demonstrate promising synergies between carotenoids, polyphenols, and alkaloids
with standard antibiotics, offering potential targeted use in the fight against clinical multidrug-
resistant bacteria. Specifically, Gram-negative bacteria (BGN) showed increased resistance
to antibiotics such as amoxicillin-clavulanic acid (AMC), ceftazidime, cefotaxime, tetracycline,
and cefazolin. These antibiotics, when combined with marine compounds, exhibited substantial
inhibitory effects against specific isolates, circumventing antibiotic resistance mechanisms. Similarly,
substantial synergies were observed in Gram-positive bacteria. Leveraging advanced algorithms
such as multi-objective optimization, notably the NSGA-II algorithm, we accurately predicted
minimum inhibitory concentrations (MICs) against clinically resistant bacterial isolates.
Optimal conditions against Escherichia coli, characterized by carotenoids = 0.6335, total polyphenols
= 0, indole alkaloids = 0.1723, and AMC = 0.1941, yielded a predicted MIC of 41.1126
mg/L, closely mirroring the experimental MIC of 41.66 ± 0.18 mg/L. Similarly, for Staphylococcus
aureus, optimal conditions produced a predicted MIC of 30.8304 mg/L, closely aligning with
the experimental MIC of 30.69 ± 1.80 mg/L.

Conclusion:
The consistent and reliable predictions for bacterial strains affirmed the robustness of
the applied methodology. These results not only pave the way for further exploration but also
offer valuable insights for optimizing pharmaceutical and medical interventions, presenting innovative
avenues for combating antibiotic-resistant bacterial infections.

conclusion:
The consistent and reliable MIC predictions for bacterial strains validate the robustness of the applied methodology. These findings provide a foundation for further research and potential pharmaceutical applications, offering innovative strategies to combat antibiotic-resistant bacterial infections.
Unveiling the Anticancer Potential of Phytocompounds: Pioneering Future Cancer Therapies
Authors: Chauhan Prashant , Pandey Pratibha , Ramniwas Seema , Verma Meenakshi , Ganeshan Subbulakshmi , Rajotiya Sumit , Devi Seema , Lakhanpal Sorabh , Kumar M Ravi , Pandey Shivam , Khan Fahad 
Published: February 2025

Abstract:
Cancer epidemiological studies highlight the critical need for identifying better treatment
options against cancer. Plants have been widely studied to obtain their efficacy as potent therapeutic
agents to treat several diseases, including cancer. Interestingly, some phytocompounds, such as
flavonoids, terpenoids, alkaloids, phenolics, and organosulphur compounds [OSCs], have been
demonstrating their potential role in combating several pathologies, including the second most devasting
disease, cancer, which contributes a significant portion of annual mortality cases. Several in
vitro, in vivo, and in silico investigations have recently established remarkable properties of phytocompounds
such as antioxidant effects, induction of apoptosis, inhibition of metastasis, autophagy
modulation, cell cycle regulation, and chemosensitization that lead to cancer suppression. This underscores
the great potential of phytocompounds to contribute as an effective anticancerous drug for
the prevention of cancer cases and advancement in cancer research. Therefore, comprehending the
complicated mechanism involved in the anticancerous effects of phytocompounds against several
carcinomas is crucial to establishing novel therapeutic strategies. Thus, this review tends to summarize
the involvement of the most promising classes of phytompounds in cancer management and
highlights several clinical trial data that demonstrate significant results in managing diverse carcinomas.
Identification of a Novel HIV-1 Recombinant Form Comprising CRF01_AE and Subtype C in Hebei Province, China
Authors: Guan Yapeng , Wang Jun , Lu Xinli 
Published: February 2025

Background:
Circulating recombinant form (CRF) 01_AE and subtype C are two
HIV-1 subtypes. In recent years, novel HIV-1 recombinant forms have become more and more
prevalent in China; however, new HIV-1 CRF01_AE/C recombinant forms are less prevalent
nationwide.

Objective:
Our research study aimed to investigate new recombinant forms between different
HIV-1 subtypes and evaluate their transmission risk among men who have sex with men (MSM)
in Hebei, China.

Method:
The near full-length genome (NFLG) of HIV-1 was identified using the analyses of the
phylogenetic tree and gene breakpoints.

Results:
In the present work, we have reported a novel HIV-1 recombinant form composed of
CRF01_AE and subtype C. The NFLG of this CRF01_AE/C form contained eight gene subregions,
with four subtype C gene segments inserted into the CRF01_AE backbone, consisting of I
CRF01_AE (790–1,171 nt), Ⅱ subtype C (1,172–1,840 nt), Ⅲ CRF01_AE (1,841–5,089 nt), Ⅳ
subtype C (5,090–5,666 nt), Ⅴ CRF01_AE (5,667–6,317 nt), Ⅵ subtype C (6,318–8,586 nt), Ⅶ
CRF01_AE (8,587–9,246 nt), and Ⅷ subtype C (9,247–9,409 nt). This new recombinant form
was named CRF140_0107.

Conclusion:
The study suggested that it is important to monitor HIV-1 diversity to reduce HIV-
1 transmission in China.
The Conjugation of Chlorambucil with 4-Phenylbutanoic Acid and Valproic Acid respectively for Enhancing Anti-tumor Activity
Authors: Dai Yi , Zhang Yang , Wang Xiangxiang , Zhang Yupei , Bai Juan 
Published: February 2025

Background:
Nitrogen mustards exert their anticancer activity by alkylating DNA. However, except for alkylating DNA, nitrogen mustards may alkylate other bio-molecules to cause off-target effects due to their highly active functional groups. So, more exposure of DNA from chromosomes can facilitate the binding of nitrogen mustards to DNA to present stronger anticancer activity, simultaneously avoiding more side effects.

Objective:
To design and synthesize the 4-phenylbutanoic acid-chlorambucil conjugates and valproic acid-chlorambucil conjugates. Upon cellular internalization, the two conju-gates can more strongly damage the DNA of cancer cells due to the more exposure of cel-lular DNA caused by 4-phenylbutanoic acid or valproic acid.

Methods:
To validate this hypothesis, we designed and synthesized two hybrids of chlo-rambucil with 4-phenylbutanoic acid and valproic acid, denoted as compound 2a and compound 2b respectively. The antitumor activity of the aforementioned hybrids was evaluated by the MTT method, mitochondrial membrane potential analysis, apoptosis as-say, DNA damage assay, and scratch assay respectively.

Results:
Compound 2a and compound 2b were synthesized via esterification. The results of bioactivity evaluation showed compound 2a and compound 2b had stronger cytotoxici-ty against breast cancer MDA-MB-231 cells and MCF-7 cells than chlorambucil. More importantly, toward triple negative breast cancer MDA-MB-231 cells, compound 2a ex-hibited significantly greater cytotoxicity compared to both compound 2b and chlorambu-cil. Further studies were conducted on MDA-MB-231 cells, showing that compound 2a could more strongly decrease the mitochondrial membrane potential, induce cell apopto-sis, and damage cellular DNA compared to compound 2b and chlorambucil. Interestingly, in combating the migration of MDA-MB-231 cells, the results exhibited that compound 2b had a much stronger anti-migratory effect than compound 2a, inconsistent with the aforementioned in vitro cytotoxicity.

Conclusion:
These findings demonstrate that the combination of nitrogen mustards with histone deacetylase inhibitors is an effective strategy to exert synergistic anti-tumor ef-fects.
Design, Synthesis, and Biological Evaluation of Some Novel o-aminophenol Derivatives
Authors: Nguyen Dat Van , Tran Ly Duou , Vu Phuong Ngoc Uyen , Meervelt Luc Van , Nguyen Mai Ngoc Thi , Ngo Anh Lan , Duong Hoan Quoc 
Published: February 2025

Background:
o-Aminophenol derivatives are of particular interest for their di-verse biological activities and potential therapeutic applications. Such as, antioxidant, an-tibacterial, and cytotoxic activities.

Objective:
This study aimed to design and synthesize a series of novel o-aminophenol de-rivatives through an efficient multi-step process, characterize them using modern spectro-scopic techniques, and evaluate their antimicrobial, antioxidant, and cytotoxic activities.

Methods:
A series of novel derivatives of o-aminophenol have been successfully synthe-sized with very high efficiency through a simple six-step process using readily available chemicals and straightforward reactions. The structures of all products were accurately de-termined using modern spectroscopic methods such as 1D and 2D NMR, as well as IR, MS spectroscopy, and X-ray methods. The antimicrobial activities of eight o-nitrophenol derivatives were assessed against Gram (-) and Gram (+) bacteria as well as fungi. In comparison, antioxidant activities were tested for two o-nitrophenol and 11 o-aminophenol derivatives using SC50 and EC50 assays. Cytotoxicity was evaluated on KB, HepG2, A549, and MCF7 cancer cell lines.

Results:
Six synthesized compounds 5b, 5c, 5g, 6b, 6c, 6g exhibited unusual doublet sig-nals in the H8 region of the 1H NMR spectrum, attributed to atropisomer formation. Eight o-nitrophenol derivatives demonstrated weak antimicrobial activity, with MIC values ranging from 100 to 200 μg/mL. Compound 5g showed activity against all tested bacterial and fungal strains. In antioxidant testing, eight o-aminophenol derivatives 6a, 6b, 6c, 6e, 6f, 6h, 6i, and 12b displayed excellent activity, with SC50 values between 18.95 and 34.26 μg/mL, approaching ascorbic acid's SC50 value of 12.60 μg/mL. Three derivatives 6d, 6g, and 12a showed superior antioxidant activity with EC50 values between 4.00 and 11.25 μg/mL, surpassing quercetin's standard of 9.8 μg/mL. Cytotoxicity assays revealed that o-aminophenol derivatives 6b, 6c, 6f, 6i, and 12b exhibited moderate inhibitory effects on KB cell lines with IC50 values from 32 to 74.94 μg/mL. Compound 6i demonstrated mod-erate cytotoxic activity against HepG2, A549, and MCF7 cell lines, with IC50 values of 29.46, 71.29, and 80.02 μg/mL, respectively.

Conclusion:
Design, synthesis, antimicrobial activity, DPPH Radical Scavenging, Cyto-toxic activity, Evaluation of H8 signal anomalies in certain compounds, and Single crystal X-ray diffraction analysis.
A Convenient one-pot Approach to the Synthesis of Novel Benzimidazole-Indole Molecular Hybrids as Benzazacamalexin Related Analogues
Authors: Stremski Yordan , Bachvarova Maria , Kirkova Desislava , Milinova Elena , Statkova-Abeghe Stela 
Published: February 2025

Background:
New benzazacamalexin-related analogues are synthesized in an easily accessible one-pot approach. The method is based on the reaction of indoles with in situ formed electrophilic N-alkoxycarbonylbenzimidazolium reagents. For the first time, their application for N-alkylation of the indole nitrogen atom is announced toward novel tris-heterocyclic hybrids. The structure of newly obtained products was spectrally charac-terized by 1D and 2D-NMR, FTIR and HRMS spectral data. The current scientific re-search is based on the application of a convenient and efficient route for the preparation of various benzimidazoles. This approach is both straightforward and economical, utilizing readily accessible and affordable reagents leading to target compounds.

Objective:
The synthesis of novel benzimidazole-indole molecular hybrids as benzazaca-malexin related analogues

Methods:
A suitable in situ method has been successfully applied, using an α-amidoalkylation reaction of indoles with N,N-diacyliminium reagents derived from ben-zimidazoles and alkyl chloroformates.

Results:
The reactions led to the obtaining of ten novel compounds (5a-e, 6a-e), including bromine and iodine-containing benzo-analogues on a gram-scale scope and yields ranging from 82% to 99%. For the first time the synthesis of indole tris-heterocycles (7a, b) through the reaction of N-alkylation of the indole nitrogen atom is announced giving an-other potential synthetic application of the N,N-dialkoxycarbonyl-5,6-dimethylbenzimidazolium adducts.

Conclusion:
The structure of the newly synthesized products is spectrally analysed and proved.
In silico Identification and Computational Screening of Potential AFP Inhibitors Against Liver Cancer
Authors: Waseem Hassan Bin , Shakeel Muhammad , Hassan Faiz-ul , Yaqoob Asma , Iqbal Azhar , Khalid Amina , Akram Hafiza Nisha , Dilbar Noshaba , Qamar Saad , Tahir Rana Adnan , Sehgal Sheikh Arslan 
Published: February 2025

Introduction:
Liver cancer is considered one of the most common types of cancer and a
major cause of ephemerality worldwide having a higher prevalence rate in Asia and sub-Saharan
Africa. The alpha-fetoprotein (AFP) is a serum glycoprotein that belongs to a class of oncodevelopmental
proteins and is also involved in tumor formation.

Methods:
In the current effort, a hybrid approach of virtual screening followed by pharmacophore
generation and molecular dynamic simulation analyses were performed. The screened top-ranked
10 docked compounds from the selected anti-cancer compound library were utilized to generate the
ligand-based pharmacophore. Virtual screening was performed two-dimensional similarity search
against the selected natural compound library based on their physicochemical properties. It was
observed that all the compounds from the anti-cancer compound library and natural compound
library showed similar binding resides.

Results:
Therefore, the top-ranked screened compounds that showed the least binding energy and
highest binding affinity against AFP, obtained through the anti-cancer drug library and natural
compound library were reported. The molecular docking analyses revealed that Leu-219, His-222,
Lys-242, Lys-246, His-316, Glu-318, Ala-366, Val-367, Gly-475, Ile-479, Ala-471, Asp-478 were
observed as potential residues for interaction.

Conclusion:
The observed results of virtual screening, molecular docking, and MD simulation
analyses entail noteworthy observations illustrating that NC002 was a potent inhibitor. The proposed
compound NC002 may have potential against liver cancer by targeting AFP based on MD
simulation analyses, PCA, and MM-GBSA.
The ER Stress-related Gene Prognostic Signature for Predicting Chemosensitivity and Prognosis in AML
Authors: Guo Jie , Peng Hongwei , Long Luyao , Sun Li , Yang Lin , Ren Simei 
Published: February 2025

Introduction:
Acute myeloid leukemia is characterized by high heterogeneity, and
the current European Leukemia Net (ELN) risk stratification system is not universally applicable
to all AML patients, requiring approximately three weeks for testing.

Aim:
This study aimed to develop an applicable prognostic tool capable of addressing the limitations
of current methods. We selected AML patients from the clinic and TCGA database to
explore the role of ER stress in response to chemotherapy.

Methods:
Patients from the TCGA database were employed as the training cohort, and two
GEO datasets were used as external validation cohorts. Univariate/multivariate COX and LASSO
regression were exemplified to establish the prognostic model. Kaplan-Meier and timedependent
ROC were used to assess and compare the efficiency of the model with ELN stratification
and other models. In the training cohort, we selected 5 ER stress-related genes to predict
chemosensitivity and establish the ERS-5 prognostic model.

Results:
The model successfully predicted the overall survival of patients (p < 0.0001, HR =
4.86 (2.79-8.44); AUC = 0.83). It was verified in validation cohorts and could further stratify
the risk of various AML subgroups. It also enhanced the ability of ELN to predict the response
of patients with AML to main chemotherapeutic drugs. Finally, an “ERS-5” risk score was constructed
by the nomogram based on the ERS-5 model and age.

Conclusion:
Consequently, in this study, the ERS-5 model was constructed, which allowed
more rapid (about 3 hours) and accurate risk stratification and complemented the ability of ELN
to assess chemosensitivity.
Evaluation of Safety and Efficacy of Cuprum metallicum in Zebrafish and
Mouse Models as a Potential Drug Candidate for the Management of
Seizures
Authors: Sharma Mahima , Saka Vara Prasad , Kumar Godlaveti Vijay Narasimha , Behera Sangita , Regar Rajkumar , Gupta Pankaj , Narula Ritika H 
Published: February 2025

Background:
In an alternative medicinal system, Cuprum metallicum (CM) is used for
the management of seizure-like conditions. However, there is a lack of scientific evidence regarding its effect.

Objective:
The present study aimed to evaluate the effect of CM against Pentylenetetrazoleinduced seizures in zebrafish and mice.

Methods:
Zebrafish were exposed to CM-6C, CM-30C, and valproic acid for 1 Hr then fish were
exposed to pentylenetetrazole to record seizure score and locomotor pattern using ANY maze video tracking software. Mice were pretreated with CM-6C, CM-30C, and valproic acid for 10 days.
After 30 min of the last dose, pentylenetetrazole was administered intraperitoneally. Observations
during the next 30 min were recorded to detect latency to first myoclonic jerk (FMJ), tonic-clonic
seizures, and the severity of seizure and survival protection after 24 Hrs.

Results:
PTZ exposure significantly decreased the latency from score-1 to score-5, which CM-6C
and 30C significantly increased. Furthermore, CM-6C and 30C normalized the locomotor activity
affected by PTZ exposure. Among the animals treated with the CM-6C and 30C, significantly increased latency to FMJ, tonic-clonic seizures, and survival protection compared to the PTZ group
of Cuprum met.

Conclusion:
The results of the study indicate that CM 6C and 30C have the potential to work
against seizures as they attenuated the PTZ-induced seizures in Zebrafish and BALB/c mice. It
could be presumed that CM-6C and 30C could be a beneficial alternative drug candidate for the
treatment of epilepsy
Advances in Neuromorphic Computing Devices: Insights on Both Conventional and Unconventional Architectures
Authors: Decastri Davide , Borghi Francesca 
Published: February 2025

Abstract:
Neuromorphic circuits and devices have been introduced in the last decades as elements
of a key strategy for developing of new paradigms of computation, inspired by the intent to mimic
elementary neuron structure and biological mechanisms, for the overcoming of energy and timeconsuming
bottlenecks achieved by digital computing (DC) technologies. Although the term “neuromorphic”
is in common use, its meaning is often misunderstood and indistinctly associated with
many different technologies, based on both conventional and unconventional electronic components
and architectures. Here an overview of the different technological strategies used for developing
neuromorphic computing systems is proposed, with an insight on the neuromorphic features they
implement and a special focus on the technological strategies and patents that exploit unconventional
computing paradigms.
Precision Formulation of Ocular Films for Eye Infections Using Innovative Quality by Design Optimization
Authors: Maddileti Repollu , Chinthaginjala Haranath 
Published: February 2025

Aim:
The current study focused on formulating ocular films embedded with levofloxacin for the treatment of conjunctivitis by employing the solvent-casting technique.

Methods:
These films were formulated with gelatin, Aloe barbadensis leaves mucilage (ABLM), and HPMC K4M to enhance the therapeutic effectiveness of levofloxacin. Various evaluations were carried out to confirm the quality and stability of the films, including as-sessments of thickness, weight uniformity, uniformity in LFX, % loss of moisture, and perme-ation. In vitro drug release studies were conducted to simulate ocular environments and ana-lyze the precise release of LFX.

Results:
The films exhibited uniform thickness (0.15–0.19 mm) and weight (61.85–65.54 mg) with a consistent film area (0.502 cm²). LFX content ranged from 85.66% to 97.03%, with T-6 being the most uniform. Moisture loss was found to be 7.98–9.55%, and absorption (highest in T-6, i.e., 18.05%) increased with gelatin. LFX permeation peaked at 97.03% (T-6) in 24-h dif-fusion studies. T-8 demonstrated exceptional mucoadhesion (>10 h), and ANOVA confirmed the important influence of gelatin, ABLM, and HPMC K4M on LFX content (F-value: 129.91, p=0.0010).

Conclusion:
The study concluded that combining ABLM with HPMC K4M enabled con-sistent, diffusion-controlled release of LFX, offering an effective and sustained formulation for treating conjunctivitis.
Knowledge, Attitudes, and Practice about Teeth Bleaching Among Subpopulation in Saudi Arabia: A Cross-sectional Study
Authors: Algharbi Muteb , Alenezi Yousef E , Alshammari Fahad F , Alkhalaf Salem A , Siddiqui Ammar A 
Published: February 2025

Background
One of the most popular cosmetic dental procedures is teeth whitening. The public's comprehension of its safety and appropriate use, however, is still lacking. The purpose of this study is to assess knowledge, attitudes, and practices about teeth whitening among the population in Saudi Arabia.

Methods
Using a validated questionnaire, 500 persons in Saudi Arabia participated in a cross-sectional survey. The survey evaluated participant knowledge, opinions, and teeth-whitening behaviors in addition to demographic information. SPSS was used to analyze the data, and a significance level of p < 0.05 was considered significant.

Results
Most participants (88%, n=440) understood that getting a dental consultation was necessary before getting teeth whitening. On the other hand, only 29.2% (n=146) thought the bleaching was safe, while 53.6% (n=268) were unsure. Better attitudes and understanding about teeth whitening were substantially correlated with higher educational attainment (p < 0.001). While most people knew that smoking causes tooth discoloration (94.8%, n=474), fewer people knew that other factors, such as too much fluoride, can also cause it (59%, n=295).

Conclusion
Most people in Saudi Arabia understand how important it is to get professional advice before bleaching their teeth. However, there are still false beliefs about its safety, especially among the less educated. It is advised to implement focused educational programs to raise public awareness and encourage safer teeth-whitening procedures.