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Future Pharmacol., Volume 5, Issue 2 (June 2025) – 10 articles

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13 pages, 587 KiB  
Article
Antimicrobial Activity of N-Methyl 4-Piperidone-Derived Monoketone Curcuminoids Against Cariogenic Bacteria
by Richard H. Lima, Yan R. Robles, Isabelle M. Oliva, Anna L. O. Santos, Júlia G. Teixeira, Maria A. S. C. Chellegatti, Niege A. J. C. Furtado, Carlos H. G. Martins, Viviani Nardini and Antônio E. M. Crotti
Future Pharmacol. 2025, 5(2), 23; https://doi.org/10.3390/futurepharmacol5020023 - 19 May 2025
Abstract
Background/Objectives: Dental caries and candidiasis are major health problems worldwide. Dental caries is caused by cariogenic bacteria, especially those belonging to the Streptococcus genus, whereas candidiasis is caused by Candida species. In this study, the antimicrobial activity of a series of synthetic N [...] Read more.
Background/Objectives: Dental caries and candidiasis are major health problems worldwide. Dental caries is caused by cariogenic bacteria, especially those belonging to the Streptococcus genus, whereas candidiasis is caused by Candida species. In this study, the antimicrobial activity of a series of synthetic N-methyl-4-piperidone-derived monoketone curcuminoids (MKCs) against Candida albicans, C. krusei, and a representative panel of cariogenic bacteria was assessed. Methods: Fifteen MKCs were synthesized using an environmentally friendly base-catalyzed Claisen–Schmidt condensation between an aromatic aldehyde (R-PhCHO) and N-methyl-4-piperidone ethanol using NaOH as the catalyst. These compounds were evaluated for their antibacterial activity against a representative panel of cariogenic bacteria, along with their antifungal activity against Candida krusei and C. albicans. The antimicrobial activity was determined based on the Minimum Inhibitory Concentration (MIC) values. Results: Most of the compounds were obtained in about 2 h in yields ranging from 40 to 70%. None of the compounds displayed antifungal activity, even at 100 μg/mL, the highest tested concentration. Similarly, none of the compounds were active against Enterococcus faecalis. On the other hand, compounds 1 (R = H), 10 (R = 3,4,5-OMe), and 13 (R = 3-F) displayed moderate activity against Streptococcus mutans (13), S. salivarus (1), L. paracasei (1 and 10), S. mitis (1, 10, and 13), S. sanguinis (1, 10, and 13), and S. sobrinus (13), with MIC values of 250 μg/mL and 500 μg/mL. The presence of the N-methyl-4-piperidone ring was found to boost the antibacterial activity as compared to the corresponding acetone-derived MKCs. Moreover, the antibacterial activity of compounds 10 and 13 was associated with the presence and position of the fluor atom and the methoxy groups at the aromatic ring. Conclusions: This study contributed to a better understanding of the antimicrobial activity of MKCs, whose data in the literature are still scarce. Full article
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17 pages, 3285 KiB  
Article
Effects of Polydatin on Pentylenetetrazol-Induced Seizures in Zebrafish Larvae
by Fernanda Barros de Miranda, Lucia Emanueli Schimith, Dennis Guilherme da Costa Silva, Camila de Oliveira Vian, Diele Bopsin da Luz, Rafael Felipe de Aguiar, Crístian Yan Montana da Rocha, Anna Maria Siebel, Jean Pierre Oses and Mariana Appel Hort
Future Pharmacol. 2025, 5(2), 22; https://doi.org/10.3390/futurepharmacol5020022 - 15 May 2025
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Abstract
Background/Objectives: Epilepsy is a common neurological condition characterized by the occurrence of a seizure. It affects around 50 million individuals worldwide, and despite the large quantity of anti-seizure medications available, 30% of epileptic patients still suffer from seizures. Therefore, it is necessary to [...] Read more.
Background/Objectives: Epilepsy is a common neurological condition characterized by the occurrence of a seizure. It affects around 50 million individuals worldwide, and despite the large quantity of anti-seizure medications available, 30% of epileptic patients still suffer from seizures. Therefore, it is necessary to find new therapeutic options. Interestingly, polydatin has shown promising effects on epilepsy treatment due to its antioxidant and anti-inflammatory properties. Thus, this study aimed to evaluate the effects of polydatin (200, 300, and 400 µM) on a pentylenetetrazol (PTZ)-induced seizure model in wild-type zebrafish (Danio rerio) larvae. Methods: Seizure-like behavior, cell death, reactive species (RS) production, and lipid peroxidation were analyzed. Results: Pre-treatment with polydatin at 200 and 300 µM did not have a significant impact on seizure occurrence and the behavior of animals exposed to PTZ. Diazepam decreased seizure occurrence and increased the latency to achieve each seizure stage. Exposure to PTZ increased the swimming activity, and this effect was suppressed by diazepam but not by polydatin. PTZ exposure increased the RS production, which was significantly attenuated by polydatin at 400 µM and DMSO. Cell death and lipid peroxidation were not changed when compared to the experimental groups. Conclusions: Only the experimental positive control (diazepam) showed anti-seizure effects. Therefore, we failed to observe any anti-seizure effects of polydatin using a zebrafish experimental model. However, we cannot rule out its effects in other experimental models and different treatment protocols. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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23 pages, 7785 KiB  
Systematic Review
Harnessing the Power of Natural Terpenoid Compounds Against Esophageal Squamous Cell Carcinoma: A Systematic Review
by Eugene Jamot Ndebia and Gabriel Tchuente Kamsu
Future Pharmacol. 2025, 5(2), 21; https://doi.org/10.3390/futurepharmacol5020021 - 6 May 2025
Viewed by 176
Abstract
Background/Objectives: Limitations of conventional treatments for esophageal cancer, which include poor solubility, drug resistance, and undesirable side effects, make it imperative to explore new therapeutic approaches to slow the progression of this disease. This study aims to assess the potential of terpene compounds [...] Read more.
Background/Objectives: Limitations of conventional treatments for esophageal cancer, which include poor solubility, drug resistance, and undesirable side effects, make it imperative to explore new therapeutic approaches to slow the progression of this disease. This study aims to assess the potential of terpene compounds as anti-cancer agents for esophageal squamous cell carcinoma (ESCC). Methods: This work was carried out following the PRISMA 2020 guidelines to ensure rigorous methodology. Results: A systematic analysis of 34 compounds revealed various mechanisms of action, such as induction of oxidative stress and modulation of apoptotic pathways. The results also show that several compounds, including (1Z,3R,4S,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene, dehydrocostus lactone, (3R,4S)-3,4,6,7-tetrachloro-3,7-dimethyl-octene-1-ene, acetyl-macrocalin B, jesridonin, longikaurin A, sphaerococcenol A, DS2, rabdocoestin B, ingenol C, ingenol-3,20-dibenzonate, JDA-202, xerophilusin B, betulinic acid, euphol, and (20S) ginsenoside Rh2, with IC50s below 10 µM, show promising efficacy both in vitro and in vivo, sometimes surpassing certain conventional treatments. Conclusions: However, despite these encouraging prospects, limitations remain, notably a lack of in vivo data and clearly defined mechanisms of action for certain compounds. These challenges require further research to validate their safety and efficacy, facilitating their development as viable therapeutic options for ESCC. Full article
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20 pages, 871 KiB  
Review
Can Drug-Induced Yawning Serve as a Biomarker for Drug Safety and Effectiveness?
by Mohammad Rokan Ali, Khaled Alzaeem, Mostafa Bejermie, Cole Ngwachi Mangong Fofang, Siamand Mohamad and Parisa Gazerani
Future Pharmacol. 2025, 5(2), 20; https://doi.org/10.3390/futurepharmacol5020020 - 29 Apr 2025
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Abstract
Background/Objectives: Yawning, a common physiological behavior, has emerged as a potential biomarker for drug responsiveness and side effects. This scoping review synthesizes current evidence on drug-induced yawning (DIY), focusing on its neurobiological mechanisms and clinical implications. Methods: A scoping review (INPLASY [...] Read more.
Background/Objectives: Yawning, a common physiological behavior, has emerged as a potential biomarker for drug responsiveness and side effects. This scoping review synthesizes current evidence on drug-induced yawning (DIY), focusing on its neurobiological mechanisms and clinical implications. Methods: A scoping review (INPLASY registration number: INPLASY202540048) was conducted using PubMed, Scopus, and Web of Science, including studies published in the past decade. The review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Handbook guidelines, ensuring systematic selection. Selected articles led to the analysis of 10 relevant studies encompassing 473 participants. Studies were evaluated for relevance to DIY, neurobiology, and clinical applications, with thematic analysis used to synthesize findings. Results: Four key themes emerged. (1) Yawning patterns: DIY involves frequent episodes (up to 80 yawns/day), varying by drug type and dosage. (2) Neurobiological mechanisms: Yawning is mediated by serotonin, dopamine, and oxytocin pathways, particularly via 5-HT2C and μ-opioid receptors. (3) Drug responsiveness: DIY is linked to SSRIs, opioids, and dopamine agonists. SSRIs induce yawning, while opioids suppress it, reflecting distinct neurochemical effects. (4) Clinical implications: Yawning may serve as a non-invasive biomarker for drug efficacy and side effects, particularly in opioid withdrawal and SSRI monitoring. Conclusions: DIY holds promise as a biomarker for drug safety and effectiveness, but research is limited by small sample sizes, methodological variability, and the absence of standardized yawning metrics. Future studies should establish consistent measures, account for interindividual variability, and evaluate DIY’s long-term clinical utility across diverse populations. Full article
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11 pages, 2399 KiB  
Article
An In Vitro Diacetylcurcumin Study for Periodontitis: A New Approach to Controlling Subgingival Biofilms
by Valdo Antonio Aires da Silva, Bruno Bueno-Silva, Luciene Cristina Figueiredo, Tatiane Tiemi Macedo, Lucas Daylor Aguiar da Silva, Helio Chagas Chaves de Oliveira Junior, Carlos Roberto Polaquini, Luís Octávio Regasini and Janaina de Cássia Orlandi Sardi
Future Pharmacol. 2025, 5(2), 19; https://doi.org/10.3390/futurepharmacol5020019 - 25 Apr 2025
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Abstract
Background: Periodontal disease (PD) is a chronic inflammatory condition associated with dysbiotic biofilm, leading to the destruction of bone and periodontal ligament. Scaling and root planing (SRP) is the gold-standard treatment for PD, but some patients may not respond adequately, necessitating adjunctive therapies. [...] Read more.
Background: Periodontal disease (PD) is a chronic inflammatory condition associated with dysbiotic biofilm, leading to the destruction of bone and periodontal ligament. Scaling and root planing (SRP) is the gold-standard treatment for PD, but some patients may not respond adequately, necessitating adjunctive therapies. This study investigated the antimicrobial activity of diacetylcurcumin (DAC), a modified curcumin, against multispecies subgingival biofilm associated with periodontitis. Methods: The biofilm, containing 40 bacterial species, was cultured for seven days in the Calgary apparatus. Treatments with DAC (200 μg/mL), 0.12% chlorhexidine (CHX), and a vehicle (control) were applied twice daily for 1 min, starting on the third day. On the seventh day, biofilms were analyzed for metabolic activity (MA) and bacterial counts via DNA-DNA hybridization. DAC toxicity was tested on Galleria mellonella larvae. Results: DAC reduced biofilm metabolic activity by 51%, while CHX achieved 88% reduction compared to the vehicle (p < 0.05). DAC also significantly decreased counts of key periodontal pathogens, including P. gingivalis, T. forsythia, P. intermedia, and A. actinomycetemcomitans (p < 0.05). At the tested concentration, DAC showed no toxicity in larvae. Conclusions: These findings suggest that DAC effectively reduces biofilm activity and periodontal pathogen counts, presenting a promising adjunctive therapy for PD. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2024)
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13 pages, 1428 KiB  
Review
Scientifically Supported Best Practices in Leachable Screening Studies for Pharmaceutical and Parenteral Drug Products
by Arvind Singh Gusain, Subhash Chandra, Isaac Moura Araújo, João Paulo Martins de Lima and Henrique Douglas Melo Coutinho
Future Pharmacol. 2025, 5(2), 18; https://doi.org/10.3390/futurepharmacol5020018 - 12 Apr 2025
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Abstract
Purpose: Pharmaceutical parenteral drug products (PDPs) and orally inhaled nasal drug products (OINDPs) are critical medications for patient care, for which the route of administration is intravenous or oral/nasal inhalation, and the drug products directly infuse into the bloodstream or lungs, but they [...] Read more.
Purpose: Pharmaceutical parenteral drug products (PDPs) and orally inhaled nasal drug products (OINDPs) are critical medications for patient care, for which the route of administration is intravenous or oral/nasal inhalation, and the drug products directly infuse into the bloodstream or lungs, but they are categorized as high-risk for leachables. Method: These external foreign chemical substances (leachables) may adversely affect and alter patient safety. Results: These primary container closure systems and manufacturing process equipment mainly comprise rubber elastomers, polypropylene, resin, ink, adhesives, glass, or plastic material. To establish the ID of detected compounds and their quantity in the finished parenteral drug formulation and then to assess the formulation for toxicological safety, broad-scope non-specific analytical screening methods are required that are capable of screening out and quantifying the predicted/unpredicted leachable compounds at the levels that pose anticipated toxicological concerns for human patients. Before the selection of the final primary packaging system for the parenteral drug product, their extractable screening profile/knowledge is required to minimize leachable compounds in the finished drug product formulation and to develop and manufacture a safe product for human patients. The adverse effect or toxicity of leachables proportionally increases with an increase in the dose of the drug product or the duration of therapy because the volume of the drug product administered to a patient in a larger quantity is directly proportional to the concentration of the detected leachable. Conclusion: This document outlines the detailed process/scientific approach for conducting an organic leachable screening profile for parenteral drug products with respect to the chemical nature of leachables, i.e., polarity, propensity, volatility, and techniques. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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21 pages, 1245 KiB  
Review
Anticancer Efficacy of Decursin: A Comprehensive Review with Mechanistic Insights
by Tanzila Akter Eity, Md. Shimul Bhuia, Raihan Chowdhury, Md. Arman Ali, Mst Muslima Khatun, Salehin Sheikh, Md. Sakib Al Hasan, Rubel Hasan, Ivo Cavalcante Pita Neto, Isaac Moura Araújo, Henrique D. M. Coutinho and Muhammad Torequl Islam
Future Pharmacol. 2025, 5(2), 17; https://doi.org/10.3390/futurepharmacol5020017 - 10 Apr 2025
Viewed by 349
Abstract
Introduction: Decursin is a pyranocoumarin natural phytochemical found in the Angelica gigas Nakai herb, which shows various therapeutic properties and beneficial effects against various diseases. Objective: The aim of this study was to find the anticancer potential of decursin and its molecular mechanisms [...] Read more.
Introduction: Decursin is a pyranocoumarin natural phytochemical found in the Angelica gigas Nakai herb, which shows various therapeutic properties and beneficial effects against various diseases. Objective: The aim of this study was to find the anticancer potential of decursin and its molecular mechanisms involved with different anticancer effects. Methodology: All of the relevant data concerning this compound and cancer were collected using different scientific search engines, including PubMed, Scopus, Springer Link, Wiley Online, Web of Science, Scifinder, ScienceDirect, and Google Scholar. Results: This study found that decursin shows anticancer properties through various mechanisms, such as apoptosis, cell cycle arrest, inhibition of cell proliferation, autophagy, inhibition of angiogenesis, cytotoxicity, and the inhibition of invasion and migration against a number of cancers, including breast, bladder, lung, colon, skin, ovarian, prostate, pancreatic, and bone cancers. This study also discovered that decursin has the ability to affect several signaling pathways in the molecular anticancer mechanisms, such as the PI3K/AKT/mTOR, JAK/STAT, and MAPK signaling pathways. Findings also revealed that decursin expresses poor oral bioavailability. Conclusions: Based on the data analysis from this literature-based study, decursin has properties to be considered as a potential candidate in the treatment of cancer. However, more clinical research is suggested to establish proper efficacy, safety, and human dosage. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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15 pages, 1660 KiB  
Article
Antioxidant Activity and Anxiolytic Effect of Cnidoscolus quercifolius Pohl Stem Bark Extract in Zebrafish
by Joice Barbosa do Nascimento, Johnatan Wellisson da Silva Mendes, José Jonas Ferreira Viturino, Maria Inácio da Silva, Mariana Pereira da Silva, Débora Odília Duarte Leite, Emmanuel Silva Marinho, Jane Eire Silva Alencar de Menezes, Hélcio Silva dos Santos and José Galberto Martins da Costa
Future Pharmacol. 2025, 5(2), 16; https://doi.org/10.3390/futurepharmacol5020016 - 5 Apr 2025
Viewed by 240
Abstract
Background: Cnidoscolus quercifolius, popularly known as “favela”, is used in traditional medicine to treat various conditions, such as infections and inflammations. However, its therapeutic potentials remain underexplored in scientific research. The present study aimed to evaluate the anxiolytic effect, toxicity, and [...] Read more.
Background: Cnidoscolus quercifolius, popularly known as “favela”, is used in traditional medicine to treat various conditions, such as infections and inflammations. However, its therapeutic potentials remain underexplored in scientific research. The present study aimed to evaluate the anxiolytic effect, toxicity, and antioxidant activity of methanolic (EMCq) and ethyl acetate (EAECq) extracts of C. quercifolius bark, as well as determine their chemical composition by HPLC/DAD and their levels of phenolic compounds and flavonoids. Methods: Anxiolytic effect and acute toxicity tests were conducted using the zebrafish model, while antioxidant activity was assessed using the DPPH and ABTS+ methods. The chemical composition was obtained by HPLC/DAD, and phenolic compounds and flavonoids were quantified with the Folin–Ciocalteu reagents and the aluminum chloride colorimetric method, respectively. Results: Caffeic acid, p-coumaric acid, cinnamic acid, pinocembrin, and apigenin were identified and quantified. The results indicated that both extracts exhibited low antioxidant activity, possibly due to their low levels of phenols (0.187 and 0.293 mg GAE/g) and flavonoids (0.84 and 0.64 mg QE/g). However, the extracts did not show acute toxicity (>400 mg/kg) and reduced the locomotor activity of zebrafish at all the doses tested (40 to 400 mg/kg), while increasing the time the animals remained in the light zone, indicating an anxiolytic effect. Conclusions: These findings suggest for the first time that C. quercifolius has anxiolytic properties, warranting further investigation into specific bioactive compounds and their mechanisms of action. Future studies may explore molecular analysis techniques to identify the responsible compounds, as well as investigate safety and clinical efficacy in mammalian models. Full article
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11 pages, 2249 KiB  
Article
Synergistic Antinociceptive Effects of Ketorolac and Ascorbic Acid in a Formalin-Induced Pain Model
by Josué Vidal Espinosa-Juárez, Erika Florecita Hoover-Lazo, Sergio de Jesús Rubio-Trujillo, Citlaly Natali de la Torre-Sosa, Nereida Violeta Vega-Cabrera, Josselin Carolina Corzo-Gómez, Refugio Cruz-Trujillo and Osmar Antonio Jaramillo-Morales
Future Pharmacol. 2025, 5(2), 15; https://doi.org/10.3390/futurepharmacol5020015 - 4 Apr 2025
Viewed by 291
Abstract
Pain is a widespread global issue and one of the most common disabling conditions in daily life. A wide range of medications are available to reduce or eliminate pain, with nonsteroidal anti-inflammatory drugs (NSAIDs) being among those most commonly used. Additionally, new analgesic [...] Read more.
Pain is a widespread global issue and one of the most common disabling conditions in daily life. A wide range of medications are available to reduce or eliminate pain, with nonsteroidal anti-inflammatory drugs (NSAIDs) being among those most commonly used. Additionally, new analgesic approaches, such as antioxidants (Ascorbic Acid), have been explored for their potential to relieve acute pain after surgery, cancer-related pain, and chronic pain not related to cancer with fewer adverse effects. Furthermore, the use of pharmacological combinations is an alternative treatment strategy to obtain a higher efficacy using lower drug concentrations, at which side effects are minimal. Background/Objectives: The aim of this study was to evaluate the pharmacological synergism of ketorolac and ascorbic acid in an inflammatory pain model. Methods: The individual and combined effects of ketorolac and ascorbic acid were evaluated in a formalin-induced pain model in mice. Four experimental groups were established: control (vehicle), ketorolac (KET), ascorbic acid (AA), and combination (KET/AA). Results: The combination of ketorolac and ascorbic acid produced a greater antinociceptive effect compared to the vehicle and individual treatments in the formalin model. Notably, even the lowest dose of the combination (KET 6.26/AA 3.21 µg/paw) exhibited a stronger effect than the maximum doses of each individual treatment KET (100 µg/paw) and AA (100 µg/paw). The effective concentration that produced 30% of antinociception (EC30) for the tested treatments were determined, and an isobologram analysis confirmed the presence of a synergistic interaction in these combinations. Conclusions: These findings suggest that the combination of ketorolac and ascorbic acid produces a synergistic antinociceptive effect in the formalin-induced pain model. The enhanced efficacy of the combination indicates a potential therapeutic advantage in pain management by reducing the required dosage of each compound while maintaining or improving analgesic effects. Full article
(This article belongs to the Special Issue Novel Therapeutic Approach to Inflammation and Pain)
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13 pages, 1734 KiB  
Review
Trifluralin Toxicology Revisited: Microtubule Inhibition, Mitochondrial Damage, and Anti-Protozoan Potential
by Darío Lirussi
Future Pharmacol. 2025, 5(2), 14; https://doi.org/10.3390/futurepharmacol5020014 - 23 Mar 2025
Viewed by 316
Abstract
The aim of this review is to evaluate the therapeutic possibilities of trifluralin and other 2,6-dinitroaniline herbicides by assessing different aspects of trifluralin’s toxicology (including its mitochondrial toxicity), pharmacokinetics, and environmental fate. The particular features of TFL have triggered a wide range of [...] Read more.
The aim of this review is to evaluate the therapeutic possibilities of trifluralin and other 2,6-dinitroaniline herbicides by assessing different aspects of trifluralin’s toxicology (including its mitochondrial toxicity), pharmacokinetics, and environmental fate. The particular features of TFL have triggered a wide range of policies about its properties. Is has been banned in some countries and, at the same time, has been proposed as a drug for the cure of parasitic disease by some scientific research articles. The use of this pre-emergence herbicide to control broadleaf weeds and annual grasses is assumed to rely only on its microtubule depolarization or cytoskeleton disassembly abilities (on-target effect), a fact that justifies its inhibition of a wide range of microorganisms (mostly protozoans), sharing a relatively high degree of conservation in tubulin protein sequences with weeds and grasses. Recent studies have confirmed that TFL also affects mitochondrial function (off-target effect), a hypothesis previously suggested in earlier works. Here, we account for the main issues in TFL toxicology, other potential uses of the herbicide outside crops, and its feasibility for use as an antiprotozoal drug. Full article
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