bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Subclass of Bi-Univalent Functions Defined by a Certain Integral Operator
Authors: Breaz Daniel , Orhan Halit , Cotîrlă Luminiţa-Ioana , Arıkan Hava
Published: February 2023

We introduce a comprehensive subfamily of analytic and bi-univalent functions in this study using Horadam polynomials and the q-analog of the Noor integral operator. We establish upper bounds for the absolute values of the second and the third coefficients and the Fekete–Szegö functional for the functions belonging to this family. Various observations of the results presented here are also discussed.
The Decomposability of Toroidal Graphs without Adjacent Triangles or Short Cycles
Authors: Lu Huajing , Li Fengwei
Published: February 2023

A graph G has a (d,h)-decomposition if there is a pair (D,F) such that F is a subgraph of G and D is an acyclic orientation of G−E(F), where the maximum degree of F is no more than h and the maximum out-degree of D is no more than d. This paper proves that toroidal graphs having no adjacent triangles are (3,1)-decomposable, and for {i,j}⊆{3,4,6}, toroidal graphs without i- and j-cycles are (2,1)-decomposable. As consequences of these results, toroidal graphs without adjacent triangles are 1-defective DP-4-colorable, and toroidal graphs without i- and j-cycles are 1-defective DP-3-colorable for {i,j}⊆{3,4,6}.
Effect of Initial Structure on Performance of High-Entropy Oxide Anodes for Li-Ion Batteries
Authors: Marques Otavio J. B. J. , Walter Michael D. , Timofeeva Elena V. , Segre Carlo U.
Published: February 2023

Two different high-entropy oxide materials were synthesized and studied as Li-ion battery anodes. The two materials have the same active metal constituents but different inactive elements which result in different initial crystalline structures: rock salt for (MgFeCoNiZn)O and spinel for (TiFeCoNiZn)3O4. Local structural studies of the metal elements in these two materials over extended electrochemical cycling reveal that the redox processes responsible for the electrode capacity are independent of the initial crystallographic structure and that the capacity is solely dependent on the initial random distribution of the metal atoms and the amount of active metals in the starting material.
Recent Progress in Biomass-Derived Carbon Materials for Li-Ion and Na-Ion Batteries—A Review
Authors: Molaiyan Palanivel , Dos Reis Glaydson Simões , Karuppiah Diwakar , Subramaniyam Chandrasekar M. , García-Alvarado Flaviano , Lassi Ulla
Published: February 2023

Batteries are the backbones of the sustainable energy transition for stationary off-grid, portable electronic devices, and plug-in electric vehicle applications. Both lithium-ion batteries (LIBs) and sodium-ion batteries (NIBs), most commonly rely on carbon-based anode materials and are usually derived from non-renewable sources such as fossil deposits. Biomass-derived carbon materials are extensively researched as efficient and sustainable anode candidates for LIBs and NIBs. The main purpose of this perspective is to brief the use of biomass residues for the preparation of carbon anodes for LIBs and NIBs annexed to the biomass-derived carbon physicochemical structures and their aligned electrochemical properties. In addition, an outlook and some challenges faced in this promising area of research is presented. This review enlightens the readers with valuable insights and a reasonable understanding of issues and challenges faced in the preparation, physicochemical properties, and application of biomass-derived carbon materials as anode candidates for LIBs and NIBs.
Carbon-Coated Si Nanoparticles Anchored on Three-Dimensional Carbon Nanotube Matrix for High-Energy Stable Lithium-Ion Batteries
Authors: Fang Hua , Liu Qingsong , Feng Xiaohua , Yan Ji , Wang Lixia , He Linghao , Zhang Linsen , Wang Guoqing
Published: February 2023

An easy and scalable synthetic route was proposed for synthesis of a high-energy stable anode material composed of carbon-coated Si nanoparticles (NPs, 80 nm) confined in a three-dimensional (3D) network-structured conductive carbon nanotube (CNT) matrix (Si/CNT@C). The Si/CNT@C composite was fabricated via in situ polymerization of resorcinol formaldehyde (RF) resin in the co-existence of Si NPs and CNTs, followed by carbonization at 700 °C. The RF resin-derived carbon shell (~10 nm) was wrapped on the Si NPs and CNTs surface, welding the Si NPs to the sidewall of the interconnected CNTs matrix to avoid Si NP agglomeration. The unique 3D architecture provides a highway for Li+ ion diffusion and electron transportation to allow the fast lithiation/delithiation of the Si NPs; buffers the volume fluctuation of Si NPs; and stabilizes solid–electrolyte interphase film. As expected, the obtained Si/CNT@C hybrid exhibited excellent lithium storage performances. An initial discharge capacity of 1925 mAh g−1 was achieved at 0.1 A g−1 and retained as 1106 mAh g−1 after 200 cycles at 0.1 A g−1. The reversible capacity was retained at 827 mAh g−1 when the current density was increased to 1 A g−1. The Si/CNT@C possessed a high Si content of 62.8 wt%, facilitating its commercial application. Accordingly, this work provides a promising exploration of Si-based anode materials for high-energy stable lithium-ion batteries.
Biofuel Cells and Biobatteries: Misconceptions, Opportunities, and Challenges
Authors: Choi Seokheun
Published: February 2023

Biofuel cells have been in the spotlight for the past century because of their potential and promise as a unique platform for sustainable energy harvesting from the human body and the environment. Because biofuel cells are typically developed in a small platform serving as a primary battery with limited fuel or as a rechargeable battery with repeated refueling, they have been interchangeably named biobatteries. Despite continuous advancements and creative proof-of-concept, however, the technique has been mired in its infancy for the past 100 years, which has provoked increasing doubts about its commercial viability. Low performance, instability, difficulties in operation, and unreliable and inconsistent power generation question the sustainable development of biofuel cells. However, the advancement in bioelectrocatalysis revolutionizes the electricity-producing capability of biofuel cells, promising an attractive, practical technique for specific applications. This perspective article will identify the misconceptions about biofuel cells that have led us in the wrong development direction and revisit their potential applications that can be realizable soon. Then, it will discuss the critical challenges that need to be immediately addressed for the commercialization of the selected applications. Finally, potential solutions will be provided. The article is intended to inspire the community so that fruitful commercial products can be developed soon.
Effects of Pulsed Radiofrequency Source on Cardiac Ablation
Authors: Iasiello Marcello , Andreozzi Assunta , Bianco Nicola , Vafai Kambiz
Published: February 2023

Heart arrhythmia is caused by abnormal electrical conduction through the myocardium, which in some cases, can be treated with heat. One of the challenges is to reduce temperature peaks—by still guaranteeing an efficient treatment where desired—to avoid any healthy tissue damage or any electrical issues within the device employed. A solution might be employing pulsed heat, in which thermal dose is given to the tissue with a variation in time. In this work, pulsed heat is used to modulate induced temperature fields during radiofrequency cardiac ablation. A three-dimensional model of the myocardium, catheter and blood flow is developed. Porous media, heat conduction and Navier–Stokes equations are, respectively, employed for each of the investigated domains. For the electric field, solved via Laplace equation, it is assumed that the electrode is at a fixed voltage. Pulsed heating effects are considered with a cosine time-variable pulsed function for the fixed voltage by constraining the product between this variable and time. Different dimensionless frequencies are considered and applied for different blood flow velocity and sustained voltages. Results are presented for different pulsed conditions to establish if a reasonable ablation zone, known from the obtained temperature profiles, can be obtained without any undesired temperature peaks.
Traditional Wild Food Plants Gathered by Ethnic Groups Living in Semi-Arid Region of Punjab, Pakistan
Authors: Waheed Muhammad , Haq Shiekh Marifatul , Arshad Fahim , Bussmann Rainer W. , Pieroni Andrea , Mahmoud Eman A. , Casini Ryan , Yessoufou Kowiyou , Elansary Hosam O.
Published: February 2023

Wild edible food plants (WFPs) are valuable resources in the traditional food systems of many local cultures worldwide, particularly in underdeveloped regions. Understanding patterns of food preferences requires conducting cross-cultural food studies among various ethnic groups in a specific area. In this context, the current study aimed to record WFP use among five ethnic groups in Punjab, Pakistan, by interviewing 175 informants selected through snowball sampling. The indicator food species for different ethnic groups were calculated using indicator analysis based on the percentage of citations. A total of 71 wild food plants (WFPs) belonging to 57 genera and 27 families were observed in the study area. A high proportion of these wild food plants (WFPs) belonged to Fabaceae with eleven species (15%), followed by Moraceae with seven species (9%). Fruits were most widely used (43%), followed by leaves (19%), and shoots (16%). The majority (35 species, 49%) of plants of WFPs were eaten as cooked vegetables. A cross-cultural comparison revealed that four species overlapped among five ethnic groups (Arain, Jutt, Rajpot, Mewati, and Dogar). The Arain ethnic group gathered and consumed a remarkable number of wild plants (35 species), possibly due to a special connection with the general abundance of the local flora, and being close to nature by adopting professions more allied to WFPs in the study area. The analysis of indicator species revealed distinct significant indicator values (p ≤ 0.05) between the main food species among the various ethnic groups. Amaranthus viridis was a common indicator of food in all five ethnic groups, while Ziziphus nammularia was a common indicator food plant of the Mewati, Rajpot, and Jutt ethnic groups; these plants are important in local diets, especially during times of food scarcity brought on by disease or drought. In addition, the current study reports 20 WFPs that have been rarely documented as human food in Pakistan’s ethnobotanical literature. Future development plans should consider biocultural heritage and pay appropriate attention to local ecological knowledge, dynamics, and historical exchanges of traditional food systems.
The Anti-Epileptic Drugs Lamotrigine and Valproic Acid Reduce the Cardiac Sodium Current
Authors: Jia Lixia , Verkerk Arie O. , Tan Hanno L.
Published: February 2023

Anti-epileptic drugs (AEDs) are associated with increased risk of sudden cardiac death. To establish whether gabapentin, lamotrigine, levetiracetam, pregabalin, and valproic acid reduce the Nav1.5 current, we conducted whole-cell patch-clamp studies to study the effects of the five AEDs on currents of human cardiac Nav1.5 channels stably expressed in HEK293 cells, and on action potential (AP) properties of freshly isolated rabbit ventricular cardiomyocytes. Lamotrigine and valproic acid exhibited inhibitory effects on the Nav1.5 current in a concentration-dependent manner with an IC50 of 142 ± 36 and 2022 ± 25 µM for lamotrigine and valproic acid, respectively. In addition, these drugs caused a hyperpolarizing shift of steady-state inactivation and a delay in recovery from inactivation. The changes on the Nav1.5 properties were reflected by a reduction in AP upstroke velocity (43.0 ± 6.8% (lamotrigine) and 23.7 ± 10.6% (valproic acid) at 1 Hz) and AP amplitude; in contrast, AP duration was not changed. Gabapentin, levetiracetam, and pregabalin had no effect on the Nav1.5 current. Lamotrigine and valproic acid reduce the Nav1.5 current density and affect its gating properties, resulting in a decrease of the AP upstroke velocity. Gabapentin, levetiracetam, and pregabalin have no effects on the Nav1.5 current.
CXCR2 Antagonist RIST4721 Acts as a Potent Chemotaxis Inhibitor of Mature Neutrophils Derived from Ex Vivo-Cultured Mouse Bone Marrow
Authors: Szymczak Klaudia , Pelletier Margery G. H. , Mackay James M. , Reid DeAnne , Gaines Peter C. W.
Published: February 2023

Neutrophils act as critical mediators of innate immunity, which depends on their rapid responses to chemokines followed by their migration towards sites of infection during chemotaxis. Chemokine receptors expressed on the surface of neutrophils mediate chemotaxis by activating contractile machinery as the cells escape from capillary beds and then attack pathogens. Neutrophils also contribute to inflammatory responses, which support pathogen destruction but can lead to acute and chronic inflammatory disorders. CXCR2, a G-protein-coupled chemokine receptor expressed on both myeloid and epithelial cells, is well-characterized for its capacities to bind multiple chemokines, including interleukin-8 and growth-related oncogene alpha in humans or keratinocyte chemokine (KC) in mice. Here we show that a small molecule CXCR2 antagonist termed RIST4721 can effectively inhibit KC-stimulated chemotaxis by neutrophils derived from ex vivo-cultured mouse bone marrow in a potent and dose-dependent manner. Antagonistic properties of RIST4721 are thoroughly characterized, including the maximal, half-maximal and minimum concentrations required to inhibit chemotaxis. Importantly, RIST4721-treated neutrophils exhibit robust phagocytosis and reactive oxygen species production, confirming drug specificity to chemotaxis inhibition. Together our data indicate that RIST4721 acts to inhibit inflammation mediated and potentiated by neutrophils and therefore promises to facilitate treatment of a host of inflammatory conditions.
Multidrug-Loaded Lipid Nanoemulsions for the Combinatorial Treatment of Cerebral Cavernous Malformation Disease
Authors: Perrelli Andrea , Bozza Annalisa , Ferraris Chiara , Osella Sara , Moglia Andrea , Mioletti Silvia , Battaglia Luigi , Retta Saverio Francesco
Published: February 2023

Cerebral cavernous malformation (CCM) or cavernoma is a major vascular disease of genetic origin, whose main phenotypes occur in the central nervous system, and is currently devoid of pharmacological therapeutic strategies. Cavernomas can remain asymptomatic during a lifetime or manifest with a wide range of symptoms, including recurrent headaches, seizures, strokes, and intracerebral hemorrhages. Loss-of-function mutations in KRIT1/CCM1 are responsible for more than 50% of all familial cases, and have been clearly shown to affect cellular junctions, redox homeostasis, inflammatory responses, and angiogenesis. In this study, we investigated the therapeutic effects of multidrug-loaded lipid nanoemulsions in rescuing the pathological phenotype of CCM disease. The pro-autophagic rapamycin, antioxidant avenanthramide, and antiangiogenic bevacizumab were loaded into nanoemulsions, with the aim of reducing the major molecular dysfunctions associated with cavernomas. Through Western blot analysis of biomarkers in an in vitro CCM model, we demonstrated that drug-loaded lipid nanoemulsions rescue antioxidant responses, reactivate autophagy, and reduce the effect of pro-angiogenic factors better than the free drugs. Our results show the importance of developing a combinatorial preventive and therapeutic approach to reduce the risk of lesion formation and inhibit or completely revert the multiple hallmarks that characterize the pathogenesis and progression of cavernomas.
A Systematic Review and Meta-Analysis on the Efficacy of Locally Delivered Adjunctive Curcumin (Curcuma longa L.) in the Treatment of Periodontitis
Authors: Wendorff-Tobolla Louisa M. , Wolgin Michael , Wagner Gernot , Klerings Irma , Dvornyk Anna , Kielbassa Andrej M.
Published: February 2023

This meta-analysis intended to assess evidence on the efficacy of locally delivered curcumin/turmeric as an adjunctive to scaling and root planing (SRP), on clinical attachment level (CAL) and probing pocket depth (PPD), compared to SRP alone or in combination with chlorhexidine (CHX). RCTs were identified from PubMed, Cochrane Library, BASE, LIVIVO, Dentistry Oral Sciences Source, MEDLINE Complete, Scopus, ClinicalTrials.gov, and eLibrary, until August 2022. The risk of bias (RoB) was assessed with the Cochrane Risk of Bias tool 2.0. A random-effects meta-analysis was performed by pooling mean differences with 95% confidence intervals. Out of 827 references yielded by the search, 23 trials meeting the eligibility criteria were included. The meta-analysis revealed that SRP and curcumin/turmeric application were statistically significantly different compared to SRP alone for CAL (−0.33 mm; p = 0.03; 95% CI −0.54 to −0.11; I2 = 62.3%), and for PPD (−0.47 mm; p = 0.024; 95% CI −0.88 to −0.06; I2 = 95.5%); however, this difference was considered clinically meaningless. No significant differences were obtained between patients treated with SRP and CHX, compared to SRP and curcumin/turmeric. The RoB assessment revealed numerous inaccuracies, thus raising concerns about previous overestimates of potential treatment effects.
The Fuzzy Border between the Functional and Dysfunctional Effects of Beta-Amyloid: A Synaptocentric View of Neuron–Glia Entanglement
Authors: Fagiani Francesca , Fulop Tamas , Govoni Stefano , Lanni Cristina
Published: February 2023

Recent observations from clinical trials using monoclonal antibodies against Aβ seem to suggest that Aβ-targeting is modestly effective and not sufficiently based on an effective challenge of the role of Aβ from physiological to pathological. After an accelerated approval procedure for aducanumab, and more recently lecanemab, their efficacy and safety remain to be fully defined despite previous attempts with various monoclonal antibodies, and both academic institutions and pharmaceutical companies are actively searching for novel treatments. Aβ needs to be clarified further in a more complicated context, taking into account both its accumulation and its biological functions during the course of the disease. In this review, we discuss the border between activities affecting early, potentially reversible dysfunctions of the synapse and events trespassing the threshold of inflammatory, self-sustaining glial activation, leading to irreversible damage. We detail a clear understanding of the biological mechanisms underlying the derangement from function to dysfunction and the switch of the of Aβ role from physiological to pathological. A picture is emerging where the optimal therapeutic strategy against AD should involve a number of allied molecular processes, displaying efficacy not only in reducing the well-known AD pathogenesis players, such as Aβ or neuroinflammation, but also in preventing their adverse effects.
Real-Life Effectiveness of Mepolizumab in Refractory Chronic Rhinosinusitis with Nasal Polyps
Authors: Domínguez-Sosa María Sandra , Cabrera-Ramírez María Soledad , Marrero-Ramos Miriam del Carmen , Dávila-Quintana Delia , Cabrera-López Carlos , Carrillo-Díaz Teresa , del Rosario Jesús Javier Benítez
Published: February 2023

The aim of this study was to evaluate the efficacy of mepolizumab in patients affected by chronic rhinosinusitis with nasal polyps (CRSwNP) in real-life. A single-center retrospective observational study was conducted on severe CRSwNP patients treated with mepolizumab. Nasal endoscopic polyp score (NPS), visual analogue scale (VAS) symptom score, sinonasal outcome test (SNOT-22), asthma control test (ACT) score, fractional exhaled nitric oxide (FeNO), eosinophils blood cells and prednisone intake were assessed at baseline and after 6 months. A total of 55 patients were included; 49 patients (89%) presented with asthma; aspirin exacerbated respiratory disease (AERD) in 28 patients (51%). A statistically significant decrease in the SNOT-22 score was observed (median difference −63; 95% CI: −68; −58; p < 0.001) with median t0 76 and IQR (61;90) to t6 10 (5;15). A reduction in NPS, median t0 NPS 4; (IQR:4;6), median t6 NPS 1; (IQR:0;1) p < 0.001, was greater in patients with AERD. The median baseline VAS score was 6 (IQR:6;7) and the differences between t0 and t6 were statistically significant p < 0.001. Significant changes in blood eosinophils cells, median t0 500 cell/mcl (IQR:340;830), median t6 97 cell/mcl (IQR:60;160) p < 0.001, were greater in patients with AERD. Mepolizumab treatment effects have been demonstrated with significantly reduced symptoms, polyp scores, blood eosinophils and systemic corticosteroid use, resulting in an increased health-related quality of life in patients with severe CRSwNP, regardless of the presence or absence of asthma or AERD.
Nonenzymatic Electrochemical Glutamate Sensor Using Copper Oxide Nanomaterials and Multiwall Carbon Nanotubes
Authors: Ali Md Younus , Knight Dorian , Howlader Matiar M. R.
Published: February 2023

Glutamate is an important neurotransmitter due to its critical role in physiological and pathological processes. While enzymatic electrochemical sensors can selectively detect glutamate, enzymes cause instability of the sensors, thus necessitating the development of enzyme-free glutamate sensors. In this paper, we developed an ultrahigh sensitive nonenzymatic electrochemical glutamate sensor by synthesizing copper oxide (CuO) nanostructures and physically mixing them with multiwall carbon nanotubes (MWCNTs) onto a screen-printed carbon electrode. We comprehensively investigated the sensing mechanism of glutamate; the optimized sensor showed irreversible oxidation of glutamate involving one electron and one proton, and a linear response from 20 μM to 200 μM at pH 7. The limit of detection and sensitivity of the sensor were about 17.5 μM and 8500 μA·mM−1·cm−2, respectively. The enhanced sensing performance is attributed to the synergetic electrochemical activities of CuO nanostructures and MWCNTs. The sensor detected glutamate in whole blood and urine and had minimal interference with common interferents, suggesting its potential for healthcare applications.
A Magnetoelectrochemical Bioassay for Highly Sensitive Sensing of Point Mutations in Interleukin-6 Gene Using TMB as a Hybridization Intercalation Indicator
Authors: Baachaoui Sabrine , Mastouri Mohamed , Meftah Maroua , Yaacoubi-Loueslati Basma , Raouafi Noureddine
Published: February 2023

Point mutations are common in the human DNA genome and are closely related to higher susceptibility to cancer diseases. Therefore, suitable methods for their sensing are of general interest. In this work, we report on a magnetic electrochemical bioassay using DNA probes tethered to streptavidin magnetic beads (strep-MBs) to detect T > G single nucleotide polymorphism (SNP) within the inteleukin-6 (IL6) gene in human genomic DNA. In the presence of the target DNA fragment and tetramethylbenzidine (TMB), the electrochemical signal related to the oxidation of TMB is observed, which is much higher than the one obtained in the absence of the target. The key parameters affecting the analytical signal, such as the concentration of the biotinylated probe, its incubation time with strep-MBs, DNA hybridization time, and TMB loading, were optimized using the electrochemical signal intensity and signal-to-blank (S/B) ratio as selection criteria. Using spiked buffer solutions, the bioassay can detect the mutated allele in a wide range of concentrations (over six decades) with a low detection limit (7.3 fM). Furthermore, the bioassay displays a high specificity with high concentrations of the major allele (one mismatched), and two mismatched and non–complementary DNA. More importantly, the bioassay can detect the variation in scarcely diluted human DNA, collected from 23 donors, and can reliably distinguish between heterozygous (TG genotype) and homozygous (GG genotype) in respect to the control subjects (TT genotype), where the differences are statistically highly significant (p-value < 0.001). Thus, the bioassay is useful for cohort studies targeting one or more mutations in human DNA.
High-Precision Detection of Cellular Drug Response Based on SERS Spectrum and Multivariate Statistical Analysis
Authors: Wu Fengfang , Wu Zhiwei , Wang Xiaoyan , Liu Yunliang , Ye Qing
Published: February 2023

The rapid development of personalized medicine places high demands on the control of drug dose and cellular drug response to provide patients with better curative effects and low side effects. To solve the problem of low detection accuracies of the cell-counting kit-8 (CCK8) method, a detection method based on surface-enhanced Raman spectroscopy (SERS) of cell-secreted proteins was adopted to evaluate the concentration of the anticancer drug cisplatin and the cellular drug response of nasopharyngeal carcinoma. CNE1 and NP69 cell lines were used to evaluate cisplatin response. The results showed that the combination of the SERS spectrum with principal component analysis–linear discriminant analysis could detect the difference in the response of cisplatin with a concentration difference of 1 μg/mL, which considerably exceeded that of CCK8. In addition, the SERS spectral peak intensity of the cell-secreted proteins strongly correlated with the cisplatin concentration. Furthermore, the mass spectrum of the secreted proteins of the nasopharyngeal carcinoma cells was analyzed to verify the results obtained using the SERS spectrum. The results demonstrated that SERS of secreted proteins has great potential for high-precision detection of chemotherapeutic drug response.
In Vitro Anti-HIV-1 Activity of Chitosan Oligomers N-Conjugated with Asparagine and Glutamine
Authors: Karadeniz Fatih
Published: February 2023

Chitosan oligomers (COS) are polysaccharides obtained by the hydrolyzation of chitosan. They are water-soluble, biodegradable, and have a wide range of beneficial properties for human health. Studies have shown that COS and its derivatives possess antitumor, antibacterial, antifungal, and antiviral activities. The goal of the current study was to investigate the anti-human immunodeficiency virus-1 (HIV-1) potential of amino acid-conjugated COS compared to COS itself. The HIV-1 inhibitory effects of asparagine-conjugated (COS-N) and glutamine-conjugated (COS-Q) COS were evaluated by their ability to protect C8166 CD4+ human T cell lines from HIV-1 infection and infection-mediated death. The results show that the presence of COS-N and COS-Q was able to prevent cells from HIV-1-induced lysis. Additionally, p24 viral protein production was observed to be suppressed in COS conjugate-treated cells compared to COS-treated and untreated groups. However, the protective effect of COS conjugates diminished by delayed treatment indicated an early stage inhibitory effect. COS-N and COS-Q did not show any inhibitory effect on the activities of HIV-1 reverse transcriptase and protease enzyme. The results suggest that COS-N and COS-Q possess an HIV-1 entry inhibition activity compared to COS and further studies to develop different peptide and amino acid conjugates containing N and Q amino acids might yield more effective compounds to battle HIV-1 infection.
Integrative Analysis Reveals the Expression Pattern of SOX9 in Satellite Glial Cells after Sciatic Nerve Injury
Authors: Liu Kuangpin , Ma Wei , Yang Jinwei , Liu Wei , Zhang Sijia , Zhu Kewei , Liu Jie , Xiang Xianglin , Wang Guodong , Wu Hongjie , Guo Jianhui , Li Liyan
Published: February 2023

Background: Several complex cellular and gene regulatory processes are involved in peripheral nerve repair. This study uses bioinformatics to analyze the differentially expressed genes (DEGs) in the satellite glial cells of mice following sciatic nerve injury. Methods: R software screens differentially expressed genes, and the WebGestalt functional enrichment analysis tool conducts Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analysis. The Search Tool for the Retrieval of Interacting Genes/Proteins constructs protein interaction networks, and the cytoHubba plug-in in the Cytoscape software predicts core genes. Subsequently, the sciatic nerve injury model of mice was established and the dorsal root ganglion satellite glial cells were isolated and cultured. Satellite glial cells-related markers were verified by immunofluorescence staining. Real-time polymerase chain reaction assay and Western blotting assay were used to detect the mRNA and protein expression of Sox9 in satellite glial cells. Results: A total of 991 DEGs were screened, of which 383 were upregulated, and 508 were downregulated. The GO analysis revealed the processes of biosynthesis, negative regulation of cell development, PDZ domain binding, and other biological processes were enriched in DEGs. According to the KEGG pathway analysis, DEGs are primarily involved in steroid biosynthesis, hedgehog signaling pathway, terpenoid backbone biosynthesis, American lateral skeleton, and melanoma pathways. According to various cytoHubba algorithms, the common core genes in the protein–protein interaction network are Atf3, Mmp2, and Sox9. Among these, Sox9 was reported to be involved in the central nervous system and the generation and development of astrocytes and could mediate the transformation between neurogenic and glial cells. The experimental results showed that satellite glial cell marker GS were co-labeled with Sox9; stem cell characteristic markers Nestin and p75NTR were labeled satellite glial cells. The mRNA and protein expression of Sox9 in satellite glial cells were increased after sciatic nerve injury. Conclusions: In this study, bioinformatics was used to analyze the DEGs of satellite glial cells after sciatic nerve injury, and transcription factors related to satellite glial cells were screened, among which Sox9 may be associated with the fate of satellite glial cells.
Selective Stimulus Intensity during Hotspot Search Ensures Faster and More Accurate Preoperative Motor Mapping with nTMS
Authors: Sartori Luca , Caliri Samuel Luciano , Baro Valentina , Colasanti Roberto , Furlanis Giulia Melinda , D’Amico Alberto , De Nardi Gianluigi , Ferreri Florinda , Corbetta Maurizio , d’Avella Domenico , Denaro Luca , Landi Andrea
Published: February 2023

Introduction: Navigated transcranial magnetic stimulation (nTMS) has emerged as one of the most innovative techniques in neurosurgical practice. However, nTMS motor mapping involves rigorous steps, and the importance of an accurate execution method has not been emphasized enough. In particular, despite strict adherence to procedural protocols, we have observed high variability in map activation according to the choice of stimulation intensity (SI) right from the early stage of hotspot localization. We present a retrospective analysis of motor mappings performed between March 2020 and July 2022, where the SI was only chosen with rigorous care in the most recent ones, under the guide of an expert neurophysiologist. Materials and methods: In order to test the ability to reduce inaccurate responses and time expenditure using selective SI, data were collected from 16 patients who underwent mapping with the random method (group A) and 15 patients who underwent mapping with the proposed method (group B). The parameters considered were resting motor threshold (%), number of stimuli, number of valid motor evoked potentials (MEPs), number of valid MEPs considered true positives (TPs), number of valid MEPs considered false positives (FPs), ratio of true-positive MEPs to total stimuli, ratio of true-positive MEPs to valid MEPs, minimum amplitude, maximum amplitude and mapping time for each patient. Results: The analysis showed statistically significant reductions in total stimulus demand, procedural time and number of false-positive MEPs. Significant increases were observed in the number of true-positive MEPs, the ratio of true-positive MEPs to total stimuli and the ratio of true-positive MEPs to valid MEPs. In the subgroups analyzed, there were similar trends, in particular, an increase in true positives and a decrease in false-positive responses. Conclusions: The precise selection of SI during hotspot search in nTMS motor mapping could provide reliable cortical maps in short time and with low employment of resources. This method seems to ensure that a MEP really represents a functionally eloquent cortical point, making mapping more intuitive even in less experienced centers.
Self-Monitoring Intervention for Adolescents and Adults with Autism: A Research Review
Authors: Li Yi-Fan , Byrne Suzanne , Yan Wei , Ewoldt Kathy B.
Published: February 2023

The ability to work and function independently is one of the most important skills for the achievement of ideal post-school outcomes. The use of self-monitoring to improve independence and/or reduce undesirable behaviors is an imperative need for individuals with autism. The purpose of this literature review was to examine technology-based self-monitoring interventions for individuals with autism. We used a four-step literature search process to identify studies for review. Online databases, such as ERIC, were used to search for studies. Using four inclusion criteria and PRISMA guidelines for the selection and screening process, we identified 16 studies that met the inclusion criteria. We used coding to summarize the following information from the included studies: participants who met the inclusion criteria, primary dependent variable, primary intervention, and study design. The results of the review revealed three primary functions of technology performed in self-monitoring. The included studies targeted on-task behaviors, skill acquisition, and socially relevant behaviors as primary dependent variables. The findings of the review suggested that future research could use self-monitoring interventions to support an adult with autism in employment settings and that a self-monitoring intervention could be tailored by considering individual differences.
Risk Decision Making and Executive Function among Adolescents and Young Adults
Authors: Marquez-Ramos Francisco , Alarcon David , Amian Josue G. , Fernandez-Portero Cristina , Arenilla-Villalba Maria J. , Sanchez-Medina Jose
Published: February 2023

The dual theory establishes that the decision-making process relies on two different systems, the affective system and the executive function (EF), developed during adolescence. This study analyzes the relationship between the decision-making and EF processes in a group of early adolescents (mean age = 12.51 years, SD = 0.61), where more affective impulse processes are developed, and in young adults (mean age = 19.38 years, SD = 1.97), where cognitive control processes have already matured. For this purpose, 140 participants in Spain completed the Iowa Gambling Task (IGT) to measure their risky decisions and the Wisconsin Card Sorting Task (WCST) to measure their EF. Performance on the IGT improves over blocks; however, adolescents received lower mean scores than young adults. However, controlling for age, perseverative errors were negatively associated with the mean net score on the risky blocks of IGT; thus, those who committed more perseverative errors in the WCST were more likely to take cards from the disadvantageous decks on the last blocks of the IGT. The current study shows that adolescents and adults solve ambiguous decisions by trial and error; however, adolescents are more likely to make risky decisions without attending to the long-term consequences. Following the dual theory hypothesis, the maturation of EF with age partly accounts for this difference in risky decision-making between adolescents and adults.
E2 Partner Tunes the Ubiquitylation Specificity of Arkadia E3 Ubiquitin Ligase
Authors: Delegkou Georgia N. , Birkou Maria , Fragkaki Nefeli , Toro Tamara , Marousis Konstantinos D. , Episkopou Vasso , Spyroulias Georgios A.
Published: February 2023

Arkadia (RNF111) is a positive regulator of the TGF-β signaling that mediates the proteasome-dependent degradation of negative factors of the pathway. It is classified as an E3 ubiquitin ligase and a SUMO-targeted ubiquitin ligase (STUBL), implicated in various pathological conditions including cancer and fibrosis. The enzymatic (ligase) activity of Arkadia is located at its C-terminus and involves the RING domain. Notably, E3 ligases require E2 enzymes to perform ubiquitylation. However, little is known about the cooperation of Arkadia with various E2 enzymes and the type of ubiquitylation that they mediate. In the present work, we study the interaction of Arkadia with the E2 partners UbcH5B and UbcH13, as well as UbcH7. Through NMR spectroscopy, we found that the E2–Arkadia interaction surface is similar in all pairs examined. Nonetheless, the requirements and factors that determine an enzymatically active E2–Arkadia complex differ in each case. Furthermore, we revealed that the cooperation of Arkadia with different E2s results in either monoubiquitylation or polyubiquitin chain formation via K63, K48, or K11 linkages, which can determine the fate of the substrate and lead to distinct biological outcomes.
Practical Application of Circulating Tumor-Related DNA of Human Papillomavirus in Liquid Biopsy to Evaluate the Molecular Response in Patients with Oropharyngeal Cancer
Authors: Mazurek Agnieszka M. , Rutkowski Tomasz W.
Published: February 2023

Recent findings have shown that human papillomavirus (HPV) DNA is present in the blood as a tumor-specific biomarker (circulating tumor-related HPV; ctHPV) in patients with HPV-related oropharyngeal cancer (HPV-related OPC). The molecular response (MR) in patients with HPV-related OPC can be defined as the change in the number of ctHPV copies in relation to its initial quantity. The optimal model for assessing the MR using a liquid biopsy (LB) should be based on the E6/E7 sequences of the viral genome. MR assessment can help to evaluate the intensity of ongoing treatments in relation to the tumor response. The evaluation of the residual disease at the end of therapy may also be performed by MR assessment. If a partial MR (pMR) is found, caution is indicated and a subsequent LB should be considered, due to the likelihood of disease progression. Complete radiological and clinical responses together with a complete MR (cMR) convincingly indicate a low risk of treatment failure. Moreover, molecular recurrence (Mrec) during a follow-up, confirmed in two consecutive assays, even despite the lack of any other clinical or radiological symptoms of progression, indicates patients at high risk of disease recurrence. In conclusion, MR by ctHPV assessment may hasten the early detection of disease progression, at any stage of the management of the patient with HPV-related OPC.
Estimation of ALU Repetitive Elements in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer
Authors: Nair Madhumathy G. , Ramesh Rakesh S. , Naidu Chandrakala M. , Mavatkar Apoorva D. , V. P. Snijesh , Ramamurthy Vishakha , Somashekaraiah Vidya M. , C. E. Anupama , Raghunathan Kiruthiga , Panigrahi Anuradha , Das Manjula , Dhar Sujan K. , Prabhu Jyothi S.
Published: February 2023

Background: Liquid biopsy is widely recognized as an efficient diagnostic method in oncology for disease detection and monitoring. Though the examination of circulating tumor cells (CTC) is mostly implemented for the assessment of genomic aberrations, the need of complex methodologies for their detection has impeded its acceptance in low-resource settings. We evaluated cell-free DNA (cfDNA) as a liquid biopsy tool and investigated its utility in breast cancer patients. Methods: Total cell-free DNA was extracted from the plasma of breast cancer patients (n = 167) with a median follow-up of more than 5 years, at various stages of the disease. Quantitative PCR was performed to estimate the copy numbers of two fractions of ALU repetitive elements (ALU 115 and ALU 247), and DNA integrity (DI) was calculated as the ratio of ALU 247/115. Mutations in TP53 and PIK3CA in the cfDNA were estimated by next-gen sequencing (NGS) in a subset of samples. Associations of the levels of both the ALU fragments with various clinico-pathological factors and disease-free survival at various stages were examined. Nomogram models were constructed with clinical variables and ALU 247 levels to predict disease-free survival and the best performing model was evaluated by decision curve analysis. Results: DI and ALU 247 levels were significantly lower (p < 0.0001) in the post-operative plasma when compared to their pre-surgery levels. DI and ALU 247 were found to be significantly higher in patients with metastasis (p < 0.05). Patients with higher levels of ALU 247 in their post-operative plasma had significant poor disease-free survival (p = 0.005). Higher levels of ALU 247 in the circulation also correlated with low tumor-infiltrating lymphocytes (TIL) within their primary tumors in the ER-negative breast cancer subtype (p = 0.01). Cox proportional hazard analysis confirmed ALU 247 as an independent variable of disease-free survival both in univariate and multivariate analysis [HR 1.3 (95% CI 1.047 to 1.613, p = 0.017)]. The nomogram model showed that the addition of ALU 247 with other variables significantly improved (C-index 0.823) the predictive ability of the model. Conclusion: Our results confirm the utility of cfDNA as an evolving liquid biopsy tool for molecular analysis. Evaluation of larger fragments of cfDNA estimated through ALU 247 can provide vital information concurrent with the pathological process of disease evolution in breast cancer and warrants expansion to other cancer types.
Pixelated Microfluidics for Drug Screening on Tumour Spheroids and Ex Vivo Microdissected Tumour Explants
Authors: Dorrigiv Dina , Goyette Pierre-Alexandre , St-Georges-Robillard Amélie , Mes-Masson Anne-Marie , Gervais Thomas
Published: February 2023

Anticancer drugs have the lowest success rate of approval in drug development programs. Thus, preclinical assays that closely predict the clinical responses to drugs are of utmost importance in both clinical oncology and pharmaceutical research. 3D tumour models preserve the tumoral architecture and are cost- and time-efficient. However, the short-term longevity, limited throughput, and limitations of live imaging of these models have so far driven researchers towards less realistic tumour models such as monolayer cell cultures. Here, we present an open-space microfluidic drug screening platform that enables the formation, culture, and multiplexed delivery of several reagents to various 3D tumour models, namely cancer cell line spheroids and ex vivo primary tumour fragments. Our platform utilizes a microfluidic pixelated chemical display that creates isolated adjacent flow sub-units of reagents, which we refer to as fluidic ‘pixels’, over tumour models in a contact-free fashion. Up to nine different treatment conditions can be tested over 144 samples in a single experiment. We provide a proof-of-concept application by staining fixed and live tumour models with multiple cellular dyes. Furthermore, we demonstrate that the response of the tumour models to biological stimuli can be assessed using the platform. Upscaling the microfluidic platform to larger areas can lead to higher throughputs, and thus will have a significant impact on developing treatments for cancer.
Metronomic Chemotherapy Based on Topotecan or Topotecan and Cyclophosphamide Combination (CyTo) in Advanced, Pretreated Ovarian Cancer
Authors: Wysocki Piotr J. , Łobacz Mateusz , Potocki Paweł , Kwinta Łukasz , Michałowska-Kaczmarczyk Anna , Słowik Agnieszka , Konopka Kamil , Buda-Nowak Anna
Published: February 2023

Patients with advanced ovarian cancer (OC) have a detrimental prognosis. The options for systemic treatment of advanced OC in later lines of treatment are limited by the availability of active therapies and their applicability to often fragile, exhausted patients with poor performance status. Metronomic chemotherapy (MC) is a concept of a continuous administration of cytotoxic drugs, which is characterized by multidirectional activity (anti-proliferative, anti-angiogenic, and anti-immunosuppressive) and low toxicity. We have performed a retrospective analysis of consecutive, advanced, chemo-refractory OC patients treated with MC based on single-agent topotecan (1 mg p.o. q2d) or on a topotecan (1 mg q2d) and cyclophosphamide (50 mg p.o. qd) combination (CyTo). Metronomic chemotherapy demonstrated promising activity, with 72% and 86% of patients achieving biochemical or objective disease control and 18% and 27% of patients achieving a biochemical or objective response, respectively. The median PFS in the whole population was 3.65 months, but the median PFS in patients with a biochemical response to MC (18.2% of patients) reached 10.7 months. The study also suggested that overweight or obese patients had significantly better outcomes on MC than patients with BMI <25 kg/m2. This article is the first report in the literature on metronomic chemotherapy based on a topotecan + cyclophosphamide combination (CyTo). The CyTo regimen demonstrated safety, clinical activity, and potential broad clinical applicability in advanced OC patients and will be evaluated in a forthcoming clinical trial.
Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy
Authors: Padinharayil Hafiza , Rai Vikrant , George Alex
Published: February 2023

Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells’ potential to produce ATP as energy, despite retaining the redox potential optimum, and allocating materials for biosynthetic activities that are crucial for cell growth, survival, and proliferation, are assisted by mitochondria. The polyclonal tumor cells with different metabolic profiles may add to carcinogenesis through inter-metabolic coupling. Cancer cells frequently possess alterations in the mitochondrial genome, although they do not hinder metabolism; alternatively, they change bioenergetics. This can further impart retrograde signaling, educate cell signaling, epigenetic modifications, chromatin structures, and transcription machinery, and ultimately satisfy cancer cellular and nuclear demands. To maximize the tumor microenvironment (TME), tumor cells remodel nearby stromal cells and extracellular matrix. These changes initiate polyclonality, which is crucial for growth, stress response, and metastasis. Here, we evaluate all the intrinsic and extrinsic pathways drawn by mitochondria in carcinogenesis, emphasizing the perspectives of mitochondrial metabolism in PDAC progression and treatment.