bluuebunny/crossref_metadata_2025 huggingface dataset:
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Authors: Toivanen Kirsi , Kilpinen Sami , Ojala Kalle , Merikoski Nanna , Salmikangas Sami , Sampo Mika , Böhling Tom , Sihto Harri
Published: November 2023

Liposarcomas (LPSs) are a heterogeneous group of malignancies that arise from adipose tissue. Although LPSs are among the most common soft-tissue sarcoma subtypes, precision medicine treatments are not currently available. To discover LPS-subtype-specific therapy targets, we investigated RNA sequenced transcriptomes of 131 clinical LPS tissue samples and compared the data with a transcriptome database that contained 20,218 samples from 95 healthy tissues and 106 cancerous tissue types. The identified genes were referred to the NCATS BioPlanet library with Enrichr to analyze upregulated signaling pathways. PDE3A protein expression was investigated with immunohistochemistry in 181 LPS samples, and PDE3A and SLFN12 mRNA expression with RT-qPCR were investigated in 63 LPS samples. Immunoblotting and cell viability assays were used to study LPS cell lines and their sensitivity to PDE3A modulators. We identified 97, 247, and 37 subtype-specific, highly expressed genes in dedifferentiated, myxoid, and pleomorphic LPS subtypes, respectively. Signaling pathway analysis revealed a highly activated hedgehog signaling pathway in dedifferentiated LPS, phospholipase c mediated cascade and insulin signaling in myxoid LPS, and pathways associated with cell proliferation in pleomorphic LPS. We discovered a strong association between high PDE3A expression and myxoid LPS, particularly in high-grade tumors. Moreover, myxoid LPS samples showed elevated expression levels of SLFN12 mRNA. In addition, PDE3A- and SLFN12-coexpressing LPS cell lines SA4 and GOT3 were sensitive to PDE3A modulators. Our results indicate that PDE3A modulators are promising drugs to treat myxoid LPS. Further studies are required to develop these drugs for clinical use.
Genome-Wide Extrachromosomal Circular DNA Profiling of Paired Hepatocellular Carcinoma and Adjacent Liver Tissues
Authors: Ye Jianyu , Huang Peixin , Ma Kewei , Zhao Zixin , Hua Ting , Zai Wenjing , Chen Jieliang , Fu Xiutao
Published: November 2023

Hepatocellular carcinoma (HCC) develops through multiple mechanisms. While recent studies have shown the presence of extrachromosomal circular DNA (eccDNA) in most cancer types, the eccDNA expression pattern and its association with HCC remain obscure. We aimed to investigate this problem. The genome-wide eccDNA profiles of eight paired HCC and adjacent non-tumor tissue samples were comprehensively elucidated based on Circle-seq, and they were further cross-analyzed with the RNA sequencing data to determine the association between eccDNA expression and transcriptome dysregulation. A total of 60,423 unique eccDNA types were identified. Most of the detected eccDNAs were smaller than 1 kb, with a length up to 182,363 bp and a mean sizes of 674 bp (non-tumor) and 813 bp (tumor), showing a greater association with gene-rich rather than with gene-poor regions. Although there was no statistical difference in length and chromosome distribution, the eccDNA patterns between HCC and adjacent non-tumor tissues showed significant differences at both the chromosomal and single gene levels. Five of the eight HCC tissues showed significantly higher amounts of chromosome 22-derived eccDNA expression compared to the non-tumor tissue. Furthermore, two genes, SLC16A3 and BAIAP2L2, with a higher transcription level in tumor tissues, were related to eccDNAs exclusively detected in three HCC samples and were negatively associated with survival rates in HCC cohorts from public databases. These results indicate the existence and massive heterogeneity of eccDNAs in HCC and adjacent liver tissues, and suggest their potential association with dysregulated gene expression.
Dpep Inhibits Cancer Cell Growth and Survival via Shared and Context-Dependent Transcriptome Perturbations
Authors: Zhou Qing , Greene Lloyd A.
Published: November 2023

Dpep is a cell-penetrating peptide targeting transcription factors ATF5, CEBPB, and CEBPD, and that selectively promotes the apoptotic death of multiple tumor cell types in vitro and in vivo. As such, it is a potential therapeutic. To better understand its mechanism of action, we used PLATE-seq to compare the transcriptomes of six cancer cell lines of diverse origins before and after Dpep exposure. This revealed a context-dependent pattern of regulated genes that was unique to each line, but that exhibited a number of elements that were shared with other lines. This included the upregulation of pro-apoptotic genes and tumor suppressors as well as the enrichment of genes associated with responses to hypoxia and interferons. Downregulated transcripts included oncogenes and dependency genes, as well as enriched genes associated with different phases of the cell cycle and with DNA repair. In each case, such changes have the potential to lie upstream of apoptotic cell death. We also detected the regulation of unique as well as shared sets of transcription factors in each line, suggesting that Dpep may initiate a cascade of transcriptional responses that culminate in cancer cell death. Such death thus appears to reflect context-dependent, yet shared, disruption of multiple cellular pathways as well as of individual survival-relevant genes.
Intraductal Carcinoma of the Prostate: To Grade or Not to Grade
Authors: Surintrspanont Jerasit , Zhou Ming
Published: November 2023

Intraductal carcinoma of the prostate (IDC-P) is a distinct tumor type characterized by an expansile growth of atypical glandular epithelial cells within pre-existing prostate glands and ducts and has significant implications on clinical outcomes and patient management. There is an agreement that isolated IDC-P should not be graded, and IDC-P should be reported with a comment on its clinical significance. However, whether IDC-P should be factored into Grade Group (GG) in the presence of concurrent prostate cancer (PCa) has been debated vigorously. The contradicting opinions were promulgated when the Genitourinary Pathology Society (GUPS) and the International Society of Urological Pathologists (ISUP) published their recommendations for this issue. When IDC-P is present with PCa, the ISUP recommends incorporating it in the GG for the entire case, whereas the GUPS recommends excluding it from the final GG. Consequently, pathologists and clinicians are faced with the conundrum of conflicting recommendations. In this review article, the authors evaluate the magnitude of discrepant GG between the two grading methods, explore the rationales behind the differing views of the two urological societies, present the current reporting practices for IDC-P, and propose a provisional and pragmatic guide to alleviate the dilemma of which recommendation to follow.
Rapid Detection of Plasmodium vivax by the Hematology Analyzer for Population Screening
Authors: Khodaiji Shanaz , Sehgal Kunal , Sethi Monisha , Mansukhani Dia
Published: November 2023

In India, where malaria is endemic, the prompt and accurate detection of infections is crucial for disease management and vector control. Our study aimed to evaluate the “iRBC” flag, a novel parameter developed for routine hematology analyzers, for its sensitivity and specificity in detecting Plasmodium vivax (P. vivax) infections. We used residual blood samples from patients with suspected malaria and compared the iRBC flag results with microscopy, which serves as the gold standard. Additionally, we compared the results with rapid immuno-chromatographic tests (RDTs) commonly used in the field. Our study included 575 samples, of which 187 were positive for P. vivax. The iRBC flag demonstrated a high sensitivity of 88.7% and 86.1% on the XN and XN-L hematology analyzers, respectively, and a clinical specificity of 100% on both analyzers. Furthermore, the scattergram derived from each positive dataset exhibited distinct patterns, which facilitated rapid confirmation by laboratory specialists. Notably, the iRBC flag remained effective even in the presence of interfering conditions. Overall, our results indicate that the iRBC flag is a reliable and rapid screening tool for identifying P. vivax in routine blood testing. Our findings have significant implications for malaria detection and control in endemic regions like India.
Detonation in van der Waals Gas
Authors: Avramenko Andriy A. , Shevchuk Igor V. , Kovetskaya Margarita M. , Kovetska Yulia Y.
Published: November 2023

Solving problems of detonation control is associated with obtaining detailed information about the gas dynamics accompanying the detonation process. This paper focuses on the dynamics of real gas flow through a plane detonation wave. The influence of real gas parameters on the Chapman–Jouguet detonation process has been studied. The process is described using the Rankine–Hugoniot system of equations. To model the thermodynamic properties of a real gas, the van der Waals equation of state is used. Equations are obtained to determine the ratio of speeds and pressures during the passage of a wave. The influence of van der Waals parameters on changes in the parameters of the detonation process was elucidated. An increase in parameter A slows down the increase in pressure in the detonation wave, and an increase in parameter B enhances it. Differences in the speed of combustion products for ideal and real gases are shown. For an ideal gas, combustion products flow from the detonation front at a critical (sonic) speed. For a van der Waals gas, the speed of combustion products may be greater than the critical one. Moreover, both factors, additional pressure (A) and additional volume (B), lead to acceleration of combustion products. Effects of heat release on the process parameters were elucidated.
Comment on Redmayne, M.; Maisch, D.R. ICNIRP Guidelines’ Exposure Assessment Method for 5G Millimetre Wave Radiation May Trigger Adverse Effects. Int. J. Environ. Res. Public Health 2023, 20, 5267
Authors: Foster Kenneth R. , Balzano Quirino
Published: November 2023

This article discusses the contention in the commented-upon paper that Brillouin precursors generated by 5G New Radio (5G NR) and other cellular systems are a possible cause of tissue damage at deeper layers of tissue than the power penetration depth of the carrier frequency. The original theory for Brillouin precursors from pulsed radiofrequency signals (RF-EMF) and speculation about their possible health effects dates back to the 1990’s and was based on studies of the propagation of very short (nanosecond) ultrawide-bandwidth RF pulses through water. This assumption is not correct for cellular telephone signals due to their narrow bandwidth. The commented-on paper provides no alternative rationale as to why Brillouin effects should cause tissue damage from RF-EMF radiation from cellular and other communications systems. Other inaccuracies in this paper concerning thermal responses of tissue to RF-EMF are also noted.
Provider- and System-Level Barriers and Facilitators to Colonoscopy and Multi-Target Stool DNA for Colorectal Cancer Screening in Rural/Remote Alaska Native Communities
Authors: Redwood Diana , Toffolon Melissa , Flanagan Christie , Kisiel John , Kaur Judith Salmon , Jeffries Lauren , Zenku Manusake , Lent Jennifer , Bachtold Joseph
Published: November 2023

The Alaska Tribal Health System is working to increase colorectal cancer (CRC) screening among Alaska Native people, who experience the highest CRC rates in the world. This study examined CRC screening provider- and system-level barriers and facilitators from the perspective of healthcare providers serving Alaska Native people in rural/remote communities. A total of 28 provider (physicians, advanced practice, and Community Health Aides/Practitioners) interviews were held from 1 February to 30 November 2021. Colonoscopy provider-level barrier themes included time, competing priorities, and staffing, while system-level barriers included travel costs, weather, and the COVID-19 pandemic. Multi-target stool DNA (mt-sDNA) barrier themes included test viability and unfamiliarity, and previous stool tests experiences. For both tests, limited medical record reminders was a major barrier. Facilitator themes for both tests included community outreach, cultural competency and patient navigation, and clinic/system improvements. In-depth interviews with tribal health providers showed that adding mt-sDNA testing may help address system-level colonoscopy barriers such as waitlists and travel costs, but other barriers remain. Further research is needed into patient barriers and facilitators, as well as the effectiveness of integrating mt-sDNA into a geographically dispersed tribal health system to reduce cancer disparities and build equity in CRC prevention among Alaska Native people.
“It Is Scary, but Then I Just Do It Anyway”: Children’s Experiences and Concerns about Risk and Challenge during Loose Parts Play
Authors: van Rooijen Martin , De Martelaer Kristine , Lensvelt-Mulders Gerty , van der Poel Lisette , Cotterink Mieke
Published: November 2023

Children’s risky play opportunities depend on supervising adults’ attitudes and the play environment. The possibilities to engage in risk-taking outdoor play for children have seriously decreased over the last few decades, due to safety concerns and adults’ preoccupation with protection. In response to this shift, research has increasingly focused on influencing factors on professional attitudes toward risk-taking in children’s play. However, children’s perspective on risky play is underrepresented in the recent literature. This study generates awareness of children’s risky play preferences and interests to help professional caretakers hone their facilitating role. We explored children’s notions of risk and challenge in play during a loose parts intervention stimulating risky play and facilitated by after-school childcare practitioners. A thematic analysis examined observations, informal conversations, and roundtable talks with children about their risky play experiences. Children describe their risk-taking in play as experimental and daring. The findings report on children’s general views on risky play, their play experiences with loose parts, their real-life risky play experiences, and their opinions on the role of practitioners. By relating the results to risky play research and self-determination theory, this study offers insight into children’s innate needs. Taking risks on their own terms gives children a sense of self-confidence and mastery, and forces them into new relationships with other children and guiding adults. Consequently, children fulfill the three universal needs of self-determination theory: autonomy, competence, and relatedness.
NeuroActivityToolkit—Toolbox for Quantitative Analysis of Miniature Fluorescent Microscopy Data
Authors: Gerasimov Evgenii , Mitenev Alexander , Pchitskaya Ekaterina , Chukanov Viacheslav , Bezprozvanny Ilya
Published: November 2023

The visualization of neuronal activity in vivo is an urgent task in modern neuroscience. It allows neurobiologists to obtain a large amount of information about neuronal network architecture and connections between neurons. The miniscope technique might help to determine changes that occurred in the network due to external stimuli and various conditions: processes of learning, stress, epileptic seizures and neurodegenerative diseases. Furthermore, using the miniscope method, functional changes in the early stages of such disorders could be detected. The miniscope has become a modern approach for recording hundreds to thousands of neurons simultaneously in a certain brain area of a freely behaving animal. Nevertheless, the analysis and interpretation of the large recorded data is still a nontrivial task. There are a few well-working algorithms for miniscope data preprocessing and calcium trace extraction. However, software for further high-level quantitative analysis of neuronal calcium signals is not publicly available. NeuroActivityToolkit is a toolbox that provides diverse statistical metrics calculation, reflecting the neuronal network properties such as the number of neuronal activations per minute, amount of simultaneously co-active neurons, etc. In addition, the module for analyzing neuronal pairwise correlations is implemented. Moreover, one can visualize and characterize neuronal network states and detect changes in 2D coordinates using PCA analysis. This toolbox, which is deposited in a public software repository, is accompanied by a detailed tutorial and is highly valuable for the statistical interpretation of miniscope data in a wide range of experimental tasks.
Optimized Design of the Carrier Structure of an Autonomous Glide Marine Seismometer
Authors: Li Kun , Zhu Xinke , Qin Huawei , Hou Fei
Published: November 2023

Mobile Earthquake Recording in Marine Areas by Independent Divers (MERMAID) provides a possibility for long-term and large-scale observation of natural seismic P waves, but it does not have mobility and can only drift with ocean currents, resulting in observation equipment locations that are too sparse or too dense, both of which are not suitable for network observation. Therefore, this paper developed a new type of Autonomous Glide Marine Seismometer (AGMS) with mobility and the ability to adjust the observation position. The AGMS adopts a flying saucer shape, which has better hydrodynamic characteristics and better motion stability. This paper focused on the material, shape, and structure of the pressure-resistant shell for the selection of design and strength checking research. Using the finite element analysis method and introducing the initial defect, the results showed that the yield strength of the pressure-resistant shell decreases with the initial defect value. The calculation results were compared and analyzed with the relevant theoretical formulas and specification calculation results, and all the results met the design requirements. The results of this design could also provide reference for the design of related deep-sea pressure chambers.
An Innovative Framework for Quality Assurance in Logistics Packaging
Authors: Matyi Henriett , Tamás Péter
Published: November 2023

Background: As a result of the effort to satisfy unique customer needs, the complexity of production and service processes is constantly increasing. In this context, the requirements for packaging systems, essential for carrying out logistic tasks, are also diversifying, and various quality defects and problems are appearing more and more frequently. Methods: The research used an inductive method. While practical problems were being solved, the need for developing the concept of a packaging inspection framework arose, the lack of which was also supported by a systematic literature review. Results: During the concept’s development, packaging errors found in the literature were identified and methods for detection and solution were systematized. A general framework was developed to identify and eliminate these errors. The applicability of the developed method was demonstrated through a complex case study, and its accuracy was verified. Conclusions: This research is important because, instead of using “island” solutions, in the future, companies will have a general framework available to them for handling all packaging-related errors according to a predefined methodology. This can reduce the time required for problem-solving and increase efficiency, which is a significant competitive factor.
Mutual Coupling Reduction in Compact MIMO Antenna Operating on 28 GHz by Using Novel Decoupling Structure
Authors: Islam Tanvir , Alsaleem Fahd , Alsunaydih Fahad N. , Alhassoon Khaled
Published: November 2023

This article presents an antenna with compact and simple geometry and a low profile. Roger RT6002, with a 10 mm × 10 mm dimension, is utilized to engineer this work, offering a wideband and high gain. The antenna structure contains a patch of circular-shaped stubs and a circular stub and slot. These insertions are performed to improve the impedance bandwidth of the antenna. The antenna is investigated, and the results are analyzed in the commercially accessible electromagnetic (EM) software tool High Frequency Structure Simulator (HFSS). Afterwards, a two-port multiple–input–multiple–output (MIMO) antenna is engineered by orthogonalizing the second element to the first element. The antenna offers good value for mutual coupling of less than −20 dB. The decoupling structure or parasitic patch is placed between two MIMO elements for more refined mutual coupling of the proposed MIMO antenna. The resultant antenna offers mutual coupling of less than −32 dB. Moreover, other MIMO parameters like envelop correlation coefficient (ECC), mean effective gain (MEG), diversity gain (DG), and channel capacity loss (CCL) are also studied to recommend antennas for future applications. The hardware model is fabricated and tested to validate the results, which resembles software-generated results. Moreover, the comparison of outcomes and other important parameters is performed using published work. The outcome of this proposed work is performed using already published work. The outcomes and comparison make the presented design the best option for future 5G devices.
Design of Optoelectronic Tracking Platform Driven by Ultrasonic Motor with a Novel Limiter
Authors: Liang Yongjin , Pan Song , Chen Lei
Published: November 2023

A high-performance servo control system is the basis for realizing high-precision photoelectric tracking. With high position resolution and power-off self-locking, ultrasonic motors have a wide range of applications for high-precision positioning control. An optoelectronic tracking platform driven by two ultrasonic motors is proposed in this study. The shaft structure of the tracking platform is designed and modeled. The shaft structure is simplified, and a dynamic model is established to analyze the motion characteristics. The parameters of the limit mechanism are optimized based on the analysis. The shaft structure is built to verify the response characteristics of the tracking platform at different velocities. The results show that the proposed design can fully utilize the self-locking of ultrasonic motors for rapid automatic alignment of the axis system. The maximum response time is less than 55 ms. When the operating velocity is less than 70°/s, the positioning error is less than 0.055°, and the lower the speed, the smaller the positioning error.
Nanoparticles and Mesenchymal Stem Cell (MSC) Therapy for Cancer Treatment: Focus on Nanocarriers and a si-RNA CXCR4 Chemokine Blocker as Strategies for Tumor Eradication In Vitro and In Vivo
Authors: Merino José Joaquín , Cabaña-Muñoz María Eugenia
Published: November 2023

Mesenchymal stem cells (MSCs) have a high tropism for the hypoxic microenvironment of tumors. The combination of nanoparticles in MSCs decreases tumor growth in vitro as well as in rodent models of cancers in vivo. Covalent conjugation of nanoparticles with the surface of MSCs can significantly increase the drug load delivery in tumor sites. Nanoparticle-based anti-angiogenic systems (gold, silica and silicates, diamond, silver, and copper) prevented tumor growth in vitro. For example, glycolic acid polyconjugates enhance nanoparticle drug delivery and have been reported in human MSCs. Labeling with fluorescent particles (coumarin-6 dye) identified tumor cells using fluorescence emission in tissues; the conjugation of different types of nanoparticles in MSCs ensured success and feasibility by tracking the migration and its intratumor detection using non-invasive imaging techniques. However, the biosafety and efficacy; long-term stability of nanoparticles, and the capacity for drug release must be improved for clinical implementation. In fact, MSCs are vehicles for drug delivery with nanoparticles and also show low toxicity but inefficient accumulation in tumor sites by clearance of reticuloendothelial organs. To solve these problems, the internalization or conjugation of drug-loaded nanoparticles should be improved in MSCs. Finally, CXCR4 may prove to be a promising target for immunotherapy and cancer treatment since the delivery of siRNA to knock down this alpha chemokine receptor or CXCR4 antagonism has been shown to disrupt tumor–stromal interactions.
A Novel Carotenoid-Producing Bacterium, Paenibacillus aurantius sp. nov., Isolated from Korean Marine Environment
Authors: Hwang Chi Young , Seo Sung Man , Cho Eui-Sang , Nam Young-Do , Park So-Lim , Lim Seong-Il , Seo Myung-Ji
Published: November 2023

The novel bacterial strain MBLB1776T was isolated from marine mud in Uljin, the Republic of Korea. Cells were Gram-positive, spore-forming, non-motile, and non-flagellated rods. Growth was observed at a temperature range of 10–45 °C, pH range of 6.0–8.0, and NaCl concentrations of 0–4% (w/v). Phylogenetic analysis of the 16S rRNA gene sequence revealed that MBLB1776T belonged to the genus Paenibacillus and was closely related to Paenibacillus cavernae C4-5T (94.83% similarity). Anteiso-C15:0, iso-C16:0, C16:0, and iso-C15:0 were the predominant fatty acids. Menaquinone 7 was identified as the major isoprenoid quinone. The major polar lipids included diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. Its whole genome was 6.3 Mb in size, with a G+C content of 55.8 mol%. Average nucleotide identity and in silico DNA–DNA hybridization values were below the species delineation threshold. Gene function analysis revealed the presence of a complete C30 carotenoid biosynthetic pathway. Intriguingly, MBLB1776T harbored carotenoid pigments, imparting an orange color to whole cells. Based on this comprehensive polyphasic taxonomy, the MBLB1776T strain represents a novel species within the genus Paenibacillus, for which the name Paenibacillus aurantius sp. nov is proposed. The type strain was MBLB1776T (=KCTC 43279T = JCM 34220T). This is the first report of a carotenoid-producing Paenibacillus sp.
Changes in Skeletal Muscle Protein Metabolism Signaling Induced by Glutamine Supplementation and Exercise
Authors: Rodrigues Junior Carlos Flores , Murata Gilson Masahiro , Gerlinger-Romero Frederico , Nachbar Renato Tadeu , Marzuca-Nassr Gabriel Nasri , Gorjão Renata , Vitzel Kaio Fernando , Hirabara Sandro Massao , Pithon-Curi Tania Cristina , Curi Rui
Published: November 2023

Aim: To evaluate the effects of resistance exercise training (RET) and/or glutamine supplementation (GS) on signaling protein synthesis in adult rat skeletal muscles. Methods: The following groups were studied: (1) control, no exercise (C); (2) exercise, hypertrophy resistance exercise training protocol (T); (3) no exercise, supplemented with glutamine (G); and (4) exercise and supplemented with glutamine (GT). The rats performed hypertrophic training, climbing a vertical ladder with a height of 1.1 m at an 80° incline relative to the horizontal with extra weights tied to their tails. The RET was performed three days a week for five weeks. Each training session consisted of six ladder climbs. The extra weight load was progressively increased for each animal during each training session. The G groups received daily L-glutamine by gavage (one g per kilogram of body weight per day) for five weeks. The C group received the same volume of water during the same period. The rats were euthanized, and the extensor digitorum longus (EDL) muscles from both hind limbs were removed and immediately weighed. Glutamine and glutamate concentrations were measured, and histological, signaling protein contents, and mRNA expression analyses were performed. Results: Supplementation with free L-glutamine increased the glutamine concentration in the EDL muscle in the C group. The glutamate concentration was augmented in the EDL muscles from T rats. The EDL muscle mass did not change, but a significant rise was reported in the cross-sectional area (CSA) of the fibers in the three experimental groups. The levels of the phosphorylated proteins (pAkt/Akt, pp70S6K/p70S6K, p4E-BP1/4E-BP1, and pS6/S6 ratios) were significantly increased in EDL muscles of G rats, and the activation of p4E-BP1 was present in T rats. The fiber CSAs of the EDL muscles in T, G, and GT rats were increased compared to the C group. These changes were accompanied by a reduction in the 26 proteasome activity of EDL muscles from T rats. Conclusion: Five weeks of GS and/or RET induced muscle hypertrophy, as indicated by the increased CSAs of the EDL muscle fibers. The increase in CSA was mediated via the upregulated phosphorylation of Akt, 4E-BP1, p70S6k, and S6 in G animals and 4E-BP1 in T animals. In the EDL muscles from T animals, a decrease in proteasome activity, favoring a further increase in the CSA of the muscle fibers, was reported.
Pharmacokinetics in Pharmacometabolomics: Towards Personalized Medication
Authors: Jian Jingai , He Donglin , Gao Songyan , Tao Xia , Dong Xin
Published: November 2023

Indiscriminate drug administration may lead to drug therapy results with varying effects on patients, and the proposal of personalized medication can help patients to receive effective drug therapy. Conventional ways of personalized medication, such as pharmacogenomics and therapeutic drug monitoring (TDM), can only be implemented from a single perspective. The development of pharmacometabolomics provides a research method for the realization of precise drug administration, which integrates the environmental and genetic factors, and applies metabolomics technology to study how to predict different drug therapeutic responses of organisms based on baseline metabolic levels. The published research on pharmacometabolomics has achieved satisfactory results in predicting the pharmacokinetics, pharmacodynamics, and the discovery of biomarkers of drugs. Among them, the pharmacokinetics related to pharmacometabolomics are used to explore individual variability in drug metabolism from the level of metabolism of the drugs in vivo and the level of endogenous metabolite changes. By searching for relevant literature with the keyword “pharmacometabolomics” on the two major literature retrieval websites, PubMed and Web of Science, from 2006 to 2023, we reviewed articles in the field of pharmacometabolomics that incorporated pharmacokinetics into their research. This review explains the therapeutic effects of drugs on the body from the perspective of endogenous metabolites and pharmacokinetic principles, and reports the latest advances in pharmacometabolomics related to pharmacokinetics to provide research ideas and methods for advancing the implementation of personalized medication.
Targeted Delivery of 5-Fluorouracil and Sonidegib via Surface-Modified ZIF-8 MOFs for Effective Basal Cell Carcinoma Therapy
Authors: Padya Bharath Singh , Fernandes Gasper , Hegde Sumukha , Kulkarni Sanjay , Pandey Abhijeet , Deshpande Praful Balavant , Ahmad Sheikh F. , Upadhya Dinesh , Mutalik Srinivas
Published: November 2023

The therapeutic effectiveness of the most widely used anticancer drug 5-fluorouracil (5-FU) is constrained by its high metabolism, short half-life, and rapid drug resistance after chemotherapy. Although various nanodrug delivery systems have been reported for skin cancer therapy, their retention, penetration and targeting are still a matter of concern. Hence, in the current study, a topical gel formulation that contains a metal-organic framework (zeolitic imidazole framework; ZIF-8) loaded with 5-FU and a surface modified with sonidegib (SDG; acting as a therapeutic agent as well as a targeting ligand) (5-FU@ZIF-8 MOFs) is developed against DMBA-UV-induced BCC skin cancer in rats. The MOFs were prepared using one-pot synthesis followed by post drug loading and SDG conjugation. The optimized MOFs were incorporated into hyaluronic acid-hydroxypropyl methyl cellulose gel and further subjected to characterization. Enhanced skin deposition of the 5-FU@ZIF-8-SDG MOFs was observed using ex vivo skin permeation studies. Confocal laser microscopy studies showed that 5-FU@ZIF-8-SDG MOFs permeated the skin via the transfollicular pathway. The 5-FU@ZIF-8-SDG MOFs showed stronger cell growth inhibition in A431 cells and good biocompatibility with HaCaT cells. Histopathological studies showed that the efficacy of the optimized MOF gels improved as the epithelial cells manifested modest hyperplasia, nuclear pleomorphism, and dyskeratosis. Additionally, immunohistochemistry and protein expression studies demonstrated the improved effectiveness of the 5-FU@ZIF-8-SDG MOFs, which displayed a considerable reduction in the expression of Bcl-2 protein. Overall, the developed MOF gels showed good potential for the targeted delivery of multifunctional MOFs in topical formulations for treating BCC cancer.
RETRACTED: Wiesinger et al. An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis. Pharmaceutics 2023, 15, 1565
Authors: Wiesinger Anna-Maria , Bigger Brian , Giugliani Roberto , Lampe Christina , Scarpa Maurizio , Moser Tobias , Kampmann Christoph , Zimmermann Georg , Lagler Florian B.
Published: November 2023

The journal retracts the article, An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis [...]
Nafion-212 Membrane Solvated by Ethylene and Propylene Carbonates as Electrolyte for Lithium Metal Batteries
Authors: Voropaeva Daria , Novikova Svetlana , Stenina Irina , Yaroslavtsev Andrey
Published: November 2023

The use of cation-exchange membranes as electrolytes for lithium metal batteries can prevent the formation of lithium dendrites during extended cycling and guarantee safe battery operation. In our study, the Nafion-212 membrane in lithium form solvated by a mixture of ethylene carbonate and propylene carbonate (EC-PC) was used as an electrolyte in a lithium metal battery with the LiFePO4 cathode. The Nafion-212-EC-PC electrolyte is electrochemically stable up to 6 V, indicating its suitability for high-energy density batteries. It has an ionic conductivity of 1.9 × 10−4 S/cm at 25 °C and a high lithium transference number. The symmetric Li|Nafion-212-EC-PC|Li cell shows a very low overvoltage of ~0.3 V at a current density of ±0.1 mA/cm2. At 25 °C, the LiFePO4|Nafion-212-EC-PC|Li battery exhibits a capacity of 141, 136, 125, and 100 mAh/g at 0.1, 0.2, 0.5, and 1C rates, respectively. It maintains a capacity of 120 mAh/g at 0 °C and 0.1C with stable performance for 50 charge/discharge cycles. The mechanism of conductivity and capacity retention at low temperatures is discussed.
Recent Advancements in Mechanistic Studies of Palladium- and Nickel-Catalyzed Ethylene Copolymerization with Polar Monomers
Authors: Song Zhihui , Wang Shaochi , Gao Rong , Wang Ying , Gou Qingqiang , Zheng Gang , Feng Huasheng , Fan Guoqiang , Lai Jingjing
Published: November 2023

The introduction of polar functional groups into polyolefin chain structures creates opportunities to enhance specific properties, such as adhesion, dyeability, printability, compatibility, thermal stability, and electrical conductivity, which widen the range of potential applications for these modified materials. Transition metal catalysts, especially late transition metals, have proven to be highly effective in copolymerization processes due to their reduced Lewis acidity and electrophilicity. However, when compared to the significant progress and summary of synthetic methods, there is a distinct lack of a comprehensive summary of mechanistic studies pertaining to the catalytic systems involved in ethylene copolymerization catalyzed by palladium and nickel catalysts. In this review, we have provided a comprehensive summary of the latest developments in mechanistic studies of ethylene copolymerization with polar monomers catalyzed by late-transition-metal complexes. Experimental and computational methods were employed to conduct a detailed investigation of these organic and organometallic systems. It is mainly focused on ligand substitution, changes in binding modes, ethylene/polar monomer insertion, chelate opening, and β-H elimination. Factors that control the catalytic activity, molecular weight, comonomer incorporation ratios, and branch content are analyzed, these include steric repulsions between ligands and monomers, electronic effects arising from both ligands and monomers, and so on.
Life Expectancy of Transformer Paper Insulation Retrofilled with Natural Ester in the Laboratory
Authors: Montero Andrés , García Belén , López Carlos
Published: November 2023

The use of alternative insulating liquids instead of mineral oil in transformers is spreading around the world due to their superior fire resistance. Furthermore, researchers have demonstrated that these oils increase the lifespan of the solid insulation of the transformers and, thus, the life expectancy of the equipment. Retrofilling of transformers with natural and synthetic esters allows companies to benefit from the properties of using these liquids without making an investment into new machinery. This paper investigated the ageing process of Kraft paper that was retrofilled with a natural ester in the laboratory. The Kraft paper samples were subjected to accelerated thermal ageing in an oven at 130 °C, and markers such as the degree of polymerisation and tensile strength were measured. The ageing tests comprised a first period, where the samples were immersed in mineral oil, followed by a replacement of the oil with a natural ester. As moisture is a determinant factor for paper ageing, two sets of samples with different moisture contents were tested. The results showed that the retrofilling of the transformers may slow down the degradation rate of the solid insulation despite the presence of remaining mineral oil adsorbed in the paper.
Environmental Potential of Carbonized MOF-5/PANI Composites for Pesticide, Dye, and Metal Cations—Can They Actually Retain Them All?
Authors: Jevremović Anka , Savić Marjetka , Janošević Ležaić Aleksandra , Krstić Jugoslav , Gavrilov Nemanja , Bajuk-Bogdanović Danica , Milojević-Rakić Maja , Ćirić-Marjanović Gordana
Published: November 2023

The environmental application of the carbonized composites of the Zn-containing metal-organic framework MOF-5 and polyaniline (PANI) in its emeraldine salt and base forms (C-(MOF-5/PANI)) was investigated for the first time. Textural properties and particle size distributions revealed that composites are dominantly mesoporous and nanoscale in nature, while Raman spectroscopy revealed the ZnO phase beneath the carbon matrix. Adsorption of pesticide, dye, and metal cation on C-(MOF-5/PANI) composites in aqueous solutions was evaluated and compared with the behavior of the precursor components, carbonized MOF-5 (cMOF), and carbonized PANIs. A lower MOF-5 content in the precursor, a higher specific surface area, and the pore volume of the composites led to improved adsorption performance for acetamiprid (124 mg/g) and Methylene Blue (135 mg/g). The presence of O/N functional groups in composites is essential for the adsorption of nitrogen-rich pollutants through hydrogen bonding with an estimated monolayer capacity twice as high as that of cMOF. The proton exchange accompanying Cd2+ retention was associated with the Zn/Cd ion exchange, and the highest capacity (9.8 mg/g) was observed for the composite synthesized from the precursor with a high MOF-5 content. The multifunctionality of composites was evidenced in mixtures of pollutants where noticeably better performance for Cd2+ removal was found for the composite compared to cMOF. Competitive binding between three pollutants favored the adsorption of pesticide and dye, thereby hindering to some extent the ion exchange necessary for the removal of metal cations. The results emphasize the importance of the PANI form and MOF-5/PANI weight ratio in precursors for the development of surface, porosity, and active sites in C-(MOF-5/PANI) composites, thus guiding their environmental efficiency. The study also demonstrated that C-(MOF-5/PANI) composites retained studied pollutants much better than carbonized precursor PANIs and showed comparable or better adsorption ability than cMOF.
EFP-Net: A Novel Building Change Detection Method Based on Efficient Feature Fusion and Foreground Perception
Authors: He Renjie , Li Wenyao , Mei Shaohui , Dai Yuchao , He Mingyi
Published: November 2023

Over the past decade, deep learning techniques have significantly advanced the field of building change detection in remote sensing imagery. However, existing deep learning-based approaches often encounter limitations in complex remote sensing scenarios, resulting in false detections and detail loss. This paper introduces EFP-Net, a novel building change detection approach that resolves the mentioned issues by utilizing effective feature fusion and foreground perception. EFP-Net comprises three main modules, the feature extraction module (FEM), the spatial–temporal correlation module (STCM), and the residual guidance module (RGM), which jointly enhance the fusion of bi-temporal features and hierarchical features. Specifically, the STCM utilizes the temporal change duality prior and multi-scale perception to augment the 3D convolution modeling capability for bi-temporal feature variations. Additionally, the RGM employs the higher-layer prediction map to guide shallow layer features, reducing the introduction of noise during the hierarchical feature fusion process. Furthermore, a dynamic Focal loss with foreground awareness is developed to mitigate the class imbalance problem. Extensive experiments on the widely adopted WHU-BCD, LEVIR-CD, and CDD datasets demonstrate that the proposed EFP-Net is capable of significantly improving accuracy in building change detection.
Spatial–Temporal Variation Characteristics and Driving Factors of Net Primary Production in the Yellow River Basin over Multiple Time Scales
Authors: Lin Ziqi , Liu Yangyang , Wen Zhongming , Chen Xu , Han Peidong , Zheng Cheng , Yao Hongbin , Wang Zijun , Shi Haijing
Published: November 2023

Vegetation net primary productivity (NPP) serves as a crucial and intuitive indicator for assessing ecosystem health. However, the nonlinear dynamics and influencing factors operating at various time scales are not yet fully understood. Here, the ensemble empirical mode decomposition (EEMD) method was used to analyze the spatiotemporal patterns of NPP and its association with hydrothermal factors and anthropogenic activities across different temporal scales for the Yellow River Basin (YRB) from 2000 to 2020. The results indicate that: (1) the annual average NPP was 236.37 g C/m2 in the YRB and increased at rates of 4.64 g C/m2/a1 (R2 = 0.86, p < 0.01) during 2000 to 2020. Spatially, nonlinear analysis indicates that 72.77% of the study area exhibits a predominantly increasing trend in NPP, while 25.17% exhibits a reversing trend. (2) On a 3-year time scale, warming has resulted in an increase in NPP in the majority of areas of the study area (69.49%). As the time scale widens, the response of vegetation to climate change becomes more prominent; especially under the long-term trend, the percentage areas of the correlation between vegetation and precipitation and temperature increased with significance, reaching 48.21% and 11.57%, respectively. (3) Through comprehensive time analysis and multivariate regression analysis, it was confirmed that both human activities and climate factors had comparable impacts on vegetation growth. Among different vegetation types, climate was still the main factor affecting grassland NPP, and only 15.74% of grassland was affected by human activities. For shrubland, forest, and farmland, human activity was a dominating factor for vegetation NPP change. There are still few studies on vegetation change using nonlinear methods in the Yellow River Basin, and most studies have not considered the effect of time scale on vegetation evolution. The findings highlight the significance of multi-time scale analysis in understanding the vegetation dynamics and providing scientific guidance for future vegetation restoration and conservation efforts.
Towards a Modular Pathological Tremor Simulation System Based on the Stewart Platform
Authors: Fajardo Jair , Melo Leonimer Flávio de
Published: November 2023

Wearable technologies have aided in reducing pathological tremor symptoms through non-intrusive solutions that aim to identify patterns in involuntary movements and suppress them using actuators positioned at specific joints. However, during the development of these devices, tests were primarily conducted on patients due to the difficulty of faithfully simulating tremors using simulation equipment. Based on studies characterizing tremors in Parkinson’s disease, the development of a robotic manipulator based on the Stewart platform was initiated, with the goal of satisfactorily simulating resting tremor movements in the hands. In this work, a simulator was implemented in a computational environment using the multibody dynamics method. The platform structure was designed in a virtual environment using SOLIDWORKS® v2017 software and later exported to Matlab® R17a software using the Simulink environment and Simscape multibody library. The workspace was evaluated, and the Kalman filter was used to merge acceleration and angular velocity data and convert them into data related to the inclination and rotation of real patients’ wrists, which were subsequently executed in the simulator. The results show a high correlation and low dispersion between real and simulated signals, demonstrating that the simulated mechanism has the capacity to represent Parkinson’s disease resting tremors in all wrist movements. The system could contribute to conducting tremor tests in suppression devices without the need for the presence of the patient and aid in comparing suppression techniques, benefiting the development of new wearable devices.
Assessment of Seabream Fisheries Stock of Oman Using the Monte Carlo Catch Maximum Sustainable Yield and the Bayesian Schaefer Model Methods
Authors: Al Alawi Yasmin , Dutta Sachinandan
Published: November 2023

The establishment of managerial approaches for the sustainable use of fishery resources depends on a critical understanding of the stock status. The Monte Carlo catch maximum sustainable yield (CMSY) method and a Bayesian state–space implementation of the Schaefer model (BSM) are recent, but widely used, stock assessment methods for data-limited situations. Here, CMSY and BSM were used to evaluate the state and exploitation level of the seabream population. Collections of catch and effort data from 1988 to 2021, pertaining to time series, were obtained from the Fishery Statistics Book published by the Ministry of Agriculture, Fisheries and Water Resources of Oman. The CMSY and BSM results were similar, indicating that the seabream stock of Oman was overfished, as B/BMSY = 0.96 (<1) and F/FMSY = 1.25 (>1). The probability that the stock was being overfished and undergoing overfishing in 2021 was 53%, while the probability that the stock was healthy (high biomass and low fishing pressure) was only 16.2%, when the target should be higher than 75%. The conclusions are of a preliminary nature owing to the utilization of comparatively new methodologies employed to generate them, which commonly validate the condition and utilization of the populations under investigation. Our research suggests that the seabream population in Oman is overfished, and reducing fishing activity is necessary to restore its abundance.