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25 pages, 9050 KiB  
Article
Field Blast Tests and Finite Element Analysis of A36 Steel Sheets Subjected to High Explosives
by Anselmo S. Augusto, Girum Urgessa, José A. F. F. Rocco, Fausto B. Mendonça and Koshun Iha
Eng 2025, 6(8), 187; https://doi.org/10.3390/eng6080187 - 5 Aug 2025
Abstract
Blast mitigation of structures is an important research topic due to increasing intentional and accidental human-induced threats and hazards. This research area is essential to building capabilities in sustaining structural protection, site planning, protective design efficiency, occupant safety, and response and recovery plans. [...] Read more.
Blast mitigation of structures is an important research topic due to increasing intentional and accidental human-induced threats and hazards. This research area is essential to building capabilities in sustaining structural protection, site planning, protective design efficiency, occupant safety, and response and recovery plans. This paper investigates experimental tests and finite element analysis (FEM) of thin A36 steel sheets subjected to blast. Six field blast tests were performed at standoff distances of 300 mm and 500 mm. The explosive charges comprised 334 g of bare Composition B, and the steel sheets were 2 mm thick. The experimental results, derived from the analysis of high-speed camera recordings of the blast events, were compared with FEM simulations conducted using Abaqus®/Explicit version 6.10. Three constitutive material models were considered in these simulations. First, the FEM simulation results were compared with experimental results. It was shown that the FEM analysis provided reliable results and was proven to be robust and cost-effective. Second, an extensive set of 460 additional numerical simulations was carried out as a parametric study involving varying standoff distances and steel sheet thicknesses. The results and methodologies presented in this paper offer valuable and original insights for engineers and researchers aiming to predict damage to steel structures during real detonation events and to design blast-resistant structures. Full article
(This article belongs to the Special Issue Interdisciplinary Insights in Engineering Research)
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14 pages, 1282 KiB  
Systematic Review
Actinic Cheilitis: A Systematic Review and Meta-Analysis of Interventions, Treatment Outcomes, and Adverse Events
by Matthäus Al-Fartwsi, Anne Petzold, Theresa Steeb, Lina Amin Djawher, Anja Wessely, Anett Leppert, Carola Berking and Markus V. Heppt
Biomedicines 2025, 13(8), 1896; https://doi.org/10.3390/biomedicines13081896 - 4 Aug 2025
Abstract
Introduction: Actinic cheilitis (AC) is a common precancerous condition affecting the lips, primarily caused by prolonged ultraviolet radiation exposure. Various treatment options are available. However, the optimal treatment approach remains a subject of debate. Objective: To summarize and compare practice-relevant interventions for AC. [...] Read more.
Introduction: Actinic cheilitis (AC) is a common precancerous condition affecting the lips, primarily caused by prolonged ultraviolet radiation exposure. Various treatment options are available. However, the optimal treatment approach remains a subject of debate. Objective: To summarize and compare practice-relevant interventions for AC. Materials and Methods: A pre-defined protocol was registered in PROSPERO (CRD42021225182). Systematic searches in Medline, Embase, and Central, along with manual trial register searches, identified studies reporting participant clearance rates (PCR) or recurrence rates (PRR). Quality assessment for randomized controlled trials (RCTs) was conducted using the Cochrane Risk of Bias tool 2. Uncontrolled studies were evaluated using the tool developed by the National Heart, Lung, and Blood Institute. The generalized linear mixed model was used to pool proportions for uncontrolled studies. A pairwise meta-analysis for RCTs was applied, using the odds ratio (OR) as the effect estimate and the GRADE approach to evaluate the quality of the evidence. Adverse events were analyzed qualitatively. Results: A comprehensive inclusion of 36 studies facilitated an evaluation of 614 participants for PCR, and 430 patients for PRR. Diclofenac showed the lowest PCR (0.53, 95% confidence interval (CI) [0.41; 0.66]), while CO2 laser showed the highest PCR (0.97, 95% CI [0.90; 0.99]). For PRR, Er:YAG laser showed the highest rates (0.14, 95% CI [0.08; 0.21]), and imiquimod the lowest (0.00, 95% CI [0.00; 0.06]). In a pairwise meta-analysis, the OR indicated a lower recurrence rate for Er:YAG ablative fractional laser (AFL)-primed methyl-aminolevulinate photodynamic therapy (MAL-PDT) (Er:YAG AFL-PDT) compared to methyl-aminolevulinate photodynamic therapy (MAL-PDT) alone (OR = 0.22, 95% CI [0.06; 0.82]). The CO2 laser showed fewer local side effects than the Er:YAG laser, while PDTs caused more skin reactions. Due to qualitative data, comparability was limited, highlighting the need for individualized treatment. Conclusions: This study provides a complete and up-to-date evidence synthesis of practice-relevant interventions for AC, identifying the CO2 laser as the most effective treatment and regarding PCR and imiquimod as most effective concerning PRR. Full article
(This article belongs to the Special Issue Skin Diseases and Cell Therapy)
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28 pages, 6624 KiB  
Article
YoloMal-XAI: Interpretable Android Malware Classification Using RGB Images and YOLO11
by Chaymae El Youssofi and Khalid Chougdali
J. Cybersecur. Priv. 2025, 5(3), 52; https://doi.org/10.3390/jcp5030052 - 1 Aug 2025
Viewed by 226
Abstract
As Android malware grows increasingly sophisticated, traditional detection methods struggle to keep pace, creating an urgent need for robust, interpretable, and real-time solutions to safeguard mobile ecosystems. This study introduces YoloMal-XAI, a novel deep learning framework that transforms Android application files into RGB [...] Read more.
As Android malware grows increasingly sophisticated, traditional detection methods struggle to keep pace, creating an urgent need for robust, interpretable, and real-time solutions to safeguard mobile ecosystems. This study introduces YoloMal-XAI, a novel deep learning framework that transforms Android application files into RGB image representations by mapping DEX (Dalvik Executable), Manifest.xml, and Resources.arsc files to distinct color channels. Evaluated on the CICMalDroid2020 dataset using YOLO11 pretrained classification models, YoloMal-XAI achieves 99.87% accuracy in binary classification and 99.56% in multi-class classification (Adware, Banking, Riskware, SMS, and Benign). Compared to ResNet-50, GoogLeNet, and MobileNetV2, YOLO11 offers competitive accuracy with at least 7× faster training over 100 epochs. Against YOLOv8, YOLO11 achieves comparable or superior accuracy while reducing training time by up to 3.5×. Cross-corpus validation using Drebin and CICAndMal2017 further confirms the model’s generalization capability on previously unseen malware. An ablation study highlights the value of integrating DEX, Manifest, and Resources components, with the full RGB configuration consistently delivering the best performance. Explainable AI (XAI) techniques—Grad-CAM, Grad-CAM++, Eigen-CAM, and HiRes-CAM—are employed to interpret model decisions, revealing the DEX segment as the most influential component. These results establish YoloMal-XAI as a scalable, efficient, and interpretable framework for Android malware detection, with strong potential for future deployment on resource-constrained mobile devices. Full article
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9 pages, 650 KiB  
Case Report
Beyond the Fever: A Serial Report on Moderate to Severe Murine Typhus Cases and Diagnostic Hurdles in Indonesia
by Velma Herwanto, Sandra Utami Widiastuti, Gunawan and Khie Chen Lie
Trop. Med. Infect. Dis. 2025, 10(8), 204; https://doi.org/10.3390/tropicalmed10080204 - 23 Jul 2025
Viewed by 238
Abstract
(1) Background: Murine typhus, caused by Rickettsia typhi, is a neglected rickettsial disease and an underdiagnosed cause of acute febrile illness (AFI), particularly in endemic regions such as Indonesia. (2) Case description: We report a case series of four patients presenting with [...] Read more.
(1) Background: Murine typhus, caused by Rickettsia typhi, is a neglected rickettsial disease and an underdiagnosed cause of acute febrile illness (AFI), particularly in endemic regions such as Indonesia. (2) Case description: We report a case series of four patients presenting with AFI of less than seven days in duration. Three patients were admitted with moderate disease, while one presented with septic shock with the macrophage activation-like syndrome (MALS) phenotype. Common clinical features included myalgia and headache; additional symptoms included cough, sore throat, and abdominal pain. Laboratory findings revealed bicytopenia, elevated transaminases, and raised inflammatory and bacterial infection markers. Common tropical infections—dengue, typhoid fever, and leptospirosis—and other potential sources of infection were excluded early during hospitalization. Diagnosis was confirmed by nucleic acid amplification testing (NAAT), which detected R. typhi in all patients. Doxycycline was initiated following confirmation, leading to defervescence within 36–48 h. (3) Conclusions: Murine typhus remains an underrecognized cause of febrile illness in Indonesia. In the near future, the inclusion of rickettsial testing in the diagnostic protocol of AFI will be crucial, as it enables timely administration of effective, low-cost treatment. Full article
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14 pages, 857 KiB  
Article
Short-Term Intake of Euphorbia tirucalli Latex Modifies Kidney Function in Rats: Possible Role of Oxidative Stress and Inflammatory Response
by Edgar Hell Kampke, Maria Eduarda Souza Barroso, Leonardo da Silva Escouto, Luciana Polaco Covre, Ágata Lages Gava, Bianca Prandi Campagnaro, Ricardo Machado Kuster and Silvana Santos Meyrelles
Antioxidants 2025, 14(7), 856; https://doi.org/10.3390/antiox14070856 - 13 Jul 2025
Viewed by 416
Abstract
Medicinal plants have been traditionally used for generations, often without scientific validation. Euphorbia tirucalli (E. tirucalli), a plant native to Africa, is commonly employed in folk medicine for treating various ailments, including cancer. However, most studies involving this species are limited [...] Read more.
Medicinal plants have been traditionally used for generations, often without scientific validation. Euphorbia tirucalli (E. tirucalli), a plant native to Africa, is commonly employed in folk medicine for treating various ailments, including cancer. However, most studies involving this species are limited to in vitro models, and its systemic effects remain poorly understood. This study aimed to evaluate the impact of E. tirucalli latex on renal function in healthy Wistar rats. Animals were divided into two groups: a control group receiving water and a treated group receiving E. tirucalli latex (13.47 mg/kg) by gavage for 15 days. Renal function was assessed by measuring glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF), renal vascular resistance (RVR), and mean arterial pressure (MAP). Additionally, oxidative stress markers, reactive oxygen/nitrogen species, and inflammatory activity were analyzed in renal tissue. E. tirucalli significantly reduced GFR, RPF, and RBF, while increasing RVR and MAP. Renal tissue exhibited elevated levels of advanced oxidation protein products, myeloperoxidase, nitric oxide, and peroxynitrite/hydroxyl radicals. These findings indicate that E. tirucalli latex adversely affects renal hemodynamics and promotes oxidative and inflammatory damage, suggesting potential nephrotoxic effects, even in healthy subjects. Full article
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19 pages, 9587 KiB  
Article
Histological and Histochemical Analysis of Austrocedrus chilensis Trees Healthy and Infected with Phytophthora austrocedri
by Oscar Troncoso and Alina G. Greslebin
Forests 2025, 16(7), 1073; https://doi.org/10.3390/f16071073 - 27 Jun 2025
Viewed by 284
Abstract
The endemic Patagonian conifer, Austrocedrus chilensis, is threatened by the pathogen Phytophthora austrocedri. This study presents the first histological and histochemical analysis of A. chilensis affected by this pathogen. We examined the stem tissues of naturally infected adult trees (over 30 [...] Read more.
The endemic Patagonian conifer, Austrocedrus chilensis, is threatened by the pathogen Phytophthora austrocedri. This study presents the first histological and histochemical analysis of A. chilensis affected by this pathogen. We examined the stem tissues of naturally infected adult trees (over 30 years old) and artificially inoculated saplings (8–12 years old) to identify the pathogen’s colonization strategies and the tree’s histological responses. Using light and scanning electronic microscopy along with several histochemical techniques (Lugol, toluidine blue, vanillin-HCl, Phloroglucinol, Calcofluor white, and aniline blue), we found that P. austrocedri can grow in all active tissues, leading to cambium and parenchyma necrosis. The pathogen spreads through sieve cells and tracheids, moving to the adjacent cells via sieve plates and bordered pits and colonizing nearby parenchyma cells. We observed loss of starch in necrotic tissues. In contrast, starch accumulation and an increase in the number of polyphenolic cells occur in the healthy areas adjacent to the margins of the lesion, indicating a tree’s induced defense mechanisms. The tree’s responses include cambium reprogramming, which leads to the formation of traumatic resin ducts, alterations in cell shape and size, and the deposition of phenolic compounds. We analyze the tree responses and discuss their potential relationship with a methyl jasmonate-induced defense and a hypersensitive-like response. Full article
(This article belongs to the Section Forest Health)
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13 pages, 420 KiB  
Article
Improving Upper-Limb Recovery in Patients with Chronic Stroke Using an 8-Week Bilateral Arm-Training Device
by Thanyaporn Wongwatcharanon, Pinailug Tantilipikorn Earde, Bunyong Rungroungdouyboon and Patcharee Kooncumchoo
Life 2025, 15(7), 994; https://doi.org/10.3390/life15070994 - 22 Jun 2025
Viewed by 532
Abstract
Upper-limb impairments after stroke significantly affect patients’ quality of life and require effective rehabilitation strategies. Rehabilitation devices play a vital role in enhancing motor recovery. This study evaluated the efficacy of the Arm Booster, a bilateral arm-training device, in improving upper-limb impairment [...] Read more.
Upper-limb impairments after stroke significantly affect patients’ quality of life and require effective rehabilitation strategies. Rehabilitation devices play a vital role in enhancing motor recovery. This study evaluated the efficacy of the Arm Booster, a bilateral arm-training device, in improving upper-limb impairment in patients with chronic stroke. Eighteen participants were randomly assigned to two groups: a device group (n = 9), using the Arm Booster; and a conventional physiotherapy group (n = 9). Both groups performed six bilateral upper-limb exercises (32 repetitions each) three times per week for eight weeks. Participants were further classified into mild spasticity (n = 5) and moderate-to-severe spasticity (n = 4) subgroups. The primary outcome was motor impairment, assessed using the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE). Secondary outcomes included spasticity, measured by the Modified Ashworth Scale (MAS), and daily functional use of the arm, assessed with the Motor Activity Log (MAL). Both groups showed significant improvements in FMA-UE scores and overall arm movement. The conventional group demonstrated additional gains in hand and wrist function and coordination. Notably, in the moderate-to-severe spasticity subgroup, the device group exhibited improvements in upper-limb movement and a trend toward reduced spasticity. These findings suggest that the Arm Booster may support motor recovery, encourage the use of the affected arm, improve movement control, and provide an efficient means for patients to exercise more frequently on their own. Full article
(This article belongs to the Section Medical Research)
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15 pages, 972 KiB  
Article
Tracking Drug Resistance in Plasmodium falciparum: Genetic Diversity of Key Resistance Markers in Brazilian Malaria Hotspots
by Rebecca de Abreu-Fernandes, Lucas Tavares de Queiroz, Natália Ketrin Almeida-de-Oliveira, Aline Rosa de Lavigne Mello, Jacqueline de Aguiar Barros, Lilian Rose Pratt-Riccio, Gisely Cardoso de Melo, Patrícia Brasil, Cláudio Tadeu Daniel-Ribeiro, Didier Menard and Maria de Fátima Ferreira-da-Cruz
Int. J. Mol. Sci. 2025, 26(13), 5977; https://doi.org/10.3390/ijms26135977 - 21 Jun 2025
Viewed by 518
Abstract
Malaria remains a health problem, with Plasmodium falciparum accounting for 96% of cases in Africa and 15% in Brazil. The growing threat of drug resistance to artemisinin-based combination therapies (ACTs) jeopardizes progress toward elimination. This study examined P. falciparum samples collected from 141 [...] Read more.
Malaria remains a health problem, with Plasmodium falciparum accounting for 96% of cases in Africa and 15% in Brazil. The growing threat of drug resistance to artemisinin-based combination therapies (ACTs) jeopardizes progress toward elimination. This study examined P. falciparum samples collected from 141 patients in Brazil (2013–2023) by PCR and DNA sequencing to identify single-nucleotide polymorphisms in the pfcrt, pfmdr1, and pfk13 genes. Half of the samples carried the SVMNTMCGI haplotype in pfcrt, and none of the samples showed C350R mutations. In pfmdr1, the NYCDY haplotype was dominant (70%), with low occurrences of N86Y (4%) and no Y184F polymorphisms. No mutations linked to artemisinin partial resistance were detected in pfk13. Only one Amazonas sample exhibited wild-type haplotypes across all genes. Genetic diversity was more pronounced in pfcrt than pfmdr1, reflecting selective drug pressure. Significant linkage disequilibrium (LD) was observed within pfcrt (C72S and K76T) and pfmdr1 (S1034C and N1042D), but not between the two genes. The absence of pfk13-resistant mutations and the low prevalence of key pfmdr1 markers support the efficacy of ACTs. The persistence of diverse haplotypes and intragenic LD reflects ongoing drug pressure, underscoring the need for continuous genetic surveillance to anticipate emerging resistance. Full article
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17 pages, 3588 KiB  
Article
Exploring Daptomycin Hypersensitivity in Enterococcus faecium: The Impact of LafB Mutation on Bacterial Virulence
by Pamela I. Huanambal Esquén, Diego A. Leonardo, Livia R. Manzine, Erick Suclupe Farro, Jessica K. Kajfasz, Suelen S. Mello, Mara C. L. Nogueira, João Renato Muniz, Alessandro S. Nascimento, Michael S. Gilmore, Jacqueline Abranches, José A. Lemos and Ilana L. B. C. Camargo
Int. J. Mol. Sci. 2025, 26(13), 5935; https://doi.org/10.3390/ijms26135935 - 20 Jun 2025
Viewed by 473
Abstract
Daptomycin (DAP) is a therapeutic option for vancomycin-resistant Enterococcus faecium (VRE) infections, but DAP resistance may occur during treatment. Previously, we identified a mutation within the E. faecium lafB gene that induces hypersusceptibility to DAP. The lafB gene encodes a glycosyltransferase involved in [...] Read more.
Daptomycin (DAP) is a therapeutic option for vancomycin-resistant Enterococcus faecium (VRE) infections, but DAP resistance may occur during treatment. Previously, we identified a mutation within the E. faecium lafB gene that induces hypersusceptibility to DAP. The lafB gene encodes a glycosyltransferase involved in lipoteichoic acid anchor synthesis, which makes it a promising target for enhancing DAP efficacy. In this study, we characterized E. faecium LafB protein (EfLafB) biophysical properties, used AlphaFold3 to predict LafB in silico three-dimensional structure, and determined lafB gene mutation’s role in virulence, comparing E. faecium HBSJRP18 (DAP-hypersusceptible) and a lafB revertant, HBSJRP18_2.7, and analyzing bacterial growth kinetics, biofilm formation ability, and virulence in a Galleria mellonella model. After gene cloning and expressing and purifying EfLafB, circular dichroism and SEC-MALS assays revealed its monomeric nature under in vitro conditions, with approximately a 40 kDa molecular mass and a melting temperature of 50 °C. In silico prediction indicated that LafB is an αβ-type protein with two domains conforming to the GT-4 family glycosyltransferases. These results are further supported by the highly conserved amino acids (E257, D91, R184, and K185), likely involved in UDP-Glc binding. The studied lafB gene mutation resulted in a significant decrease in bacterial growth and virulence in the invertebrate model. Full article
(This article belongs to the Special Issue Antibacterial Activity against Drug-Resistant Strains, 2nd Edition)
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15 pages, 2552 KiB  
Article
Detection of CADM1, MAL, and PAX1 Methylation by ddPCR for Triage of HPV-Positive Cervical Lesions
by Maria Anisimova, Mark Jain, Liya Shcherbakova, Liana Aminova, Andrey Bugerenko, Natalia Novitskaya, Larisa Samokhodskaya, Vladislav Kokarev, Victoria Inokenteva and Olga Panina
Biomedicines 2025, 13(6), 1450; https://doi.org/10.3390/biomedicines13061450 - 12 Jun 2025
Viewed by 628
Abstract
The aberrant DNA methylation of tumour suppressor genes, including CADM1, MAL, and PAX1, is implicated in cervical carcinogenesis. Objectives: This pilot study aimed to evaluate the methylation levels of these genes in HPV-positive women and assess their diagnostic performance for [...] Read more.
The aberrant DNA methylation of tumour suppressor genes, including CADM1, MAL, and PAX1, is implicated in cervical carcinogenesis. Objectives: This pilot study aimed to evaluate the methylation levels of these genes in HPV-positive women and assess their diagnostic performance for detecting histologic high-grade squamous intraepithelial lesions (HSILs) and carcinoma. Methods: Cervical samples from 73 HPV-positive women were analyzed using droplet digital PCR (ddPCR) to quantify methylation levels of CADM1, MAL, and PAX1. The methylation levels were further compared across cytological and histological classifications. A control group of 26 HPV-negative women with negative cytology was also included. The diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, as well as sensitivity and specificity calculations for individual genes and gene panels. Results: MAL methylation was absent in NILM, LSIL, and HSIL samples but was significantly elevated in carcinoma. PAX1 methylation was observed in both high-grade and some low-grade lesions. CADM1 methylation remained low or undetectable in the NILM, LSIL, and HSIL groups, with a significant increase observed in carcinoma cases. The CADM1/MAL panel demonstrated the highest diagnostic accuracy, with an area under the curve (AUC) of 0.912, 70% sensitivity, and 100% specificity. ddPCR exhibited superior analytical sensitivity compared to real-time PCR. Conclusions: The CADM1/MAL methylation panel, assessed by ddPCR, may serve as a specific biomarker for the triage of HPV-positive women at risk of HSIL and carcinoma. However, this study’s limited sample size and single-centre design necessitate cautious interpretation. Further validation in larger, population-based cohorts is necessary to confirm its clinical utility. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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14 pages, 605 KiB  
Article
Women’s Empowerment and Gender-Related Factors Associated with Maternal Tetanus Protection in 39 Low- and Middle-Income Countries
by Katherine Kirkby, Luisa Arroyave, Franciele Hellwig, M. Carolina Danovaro-Holliday, Nasir Yusuf, Shirin Heidari, Stephanie Shendale, Aluísio J. D. Barros and Ahmad Reza Hosseinpoor
Vaccines 2025, 13(6), 610; https://doi.org/10.3390/vaccines13060610 - 6 Jun 2025
Viewed by 623
Abstract
Background: Tetanus is a vaccine-preventable disease, and therefore vaccination of women of reproductive age or during pregnancy is recommended alongside childhood tetanus vaccination. Gender-related factors related to social empowerment have been established as determinants of health service utilization; however, these social determinants have [...] Read more.
Background: Tetanus is a vaccine-preventable disease, and therefore vaccination of women of reproductive age or during pregnancy is recommended alongside childhood tetanus vaccination. Gender-related factors related to social empowerment have been established as determinants of health service utilization; however, these social determinants have not yet been explored directly with tetanus vaccination. In response, the aim of this study was to assess overall and country-specific gender-related barriers to maternal tetanus vaccine coverage. Methods: We used data from Demographic and Health Surveys (DHS) in 39 countries implemented between 2013 and 2022. Women’s empowerment was measured through three domains of the Survey-based Women’s emPowERment index (SWPER), as well as other gender-related variables. To assess the association between measures of women’s empowerment and gender-related factors and maternal tetanus immunization coverage, we used multilevel logistic models with pooled data from the 39 countries to analyze overall patterns, and we used multivariable logistic regression for each country-specific dataset to analyze country-level associations. Results: There were notable variations in the factors associated with tetanus vaccination across countries. Overall, we observed that higher levels of women’s empowerment, as measured through social independence and decision-making autonomy using the SWPER index, were associated with higher odds of maternal tetanus protection, with adjusted odds ratios of 1.23 (95%CI: 1.10–1.37) and 1.20 (95%CI: 1.02–1.40), respectively. However, women’s empowerment related to attitude to violence was not. Higher household wealth was also associated with higher odds of maternal tetanus protection overall. Conclusions: Women’s empowerment can improve the uptake of maternal tetanus vaccine. Addressing gender-related barriers may enhance vaccination coverage and contribute to the elimination of maternal and neonatal tetanus as a public health problem. However, these barriers vary from country to country, necessitating country-specific investigations to formulate tailored recommendations. Full article
(This article belongs to the Special Issue Inequality in Immunization 2025)
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15 pages, 1770 KiB  
Article
The Impact of a Manufacturing Process on the Stability of Microcrystalline Long-Acting Injections: A Case Study on Aripiprazole Monohydrate
by Tomasz Pietrzak, Ziemowit Szendzielorz, Joanna Borychowska, Tomasz Ratajczak and Marcin Kubisiak
Pharmaceutics 2025, 17(6), 735; https://doi.org/10.3390/pharmaceutics17060735 - 3 Jun 2025
Viewed by 554
Abstract
Background/Objectives: Long-acting injections (LAIs) are innovative drug delivery systems that improve patient compliance by maintaining therapeutic drug levels over extended periods. Micro- and nanosuspensions are commonly used in LAIs to enhance bioavailability, but their thermodynamic instability poses challenges, including particle aggregation and growth. [...] Read more.
Background/Objectives: Long-acting injections (LAIs) are innovative drug delivery systems that improve patient compliance by maintaining therapeutic drug levels over extended periods. Micro- and nanosuspensions are commonly used in LAIs to enhance bioavailability, but their thermodynamic instability poses challenges, including particle aggregation and growth. This study aimed to evaluate the impact of two helping processes—vehicle thermal treatment and high-shear homogenization—on the stability and manufacturing efficiency of aripiprazole monohydrate (AM) suspensions. Methods: AM suspensions containing sodium carboxymethyl cellulose (CMCNa), mannitol and disodium phosphate in water for injections (WFIs) were prepared using a combination of thermal treatment of the vehicle solution, high-shear homogenization and bead milling. Four manufacturing variants were tested to assess the influence of these processes on particle size distribution (PSD), viscosity and stability during a 3-month accelerated stability study. Molecular weight changes in CMCNa from thermal treatment were analyzed using size exclusion chromatography with multiangle scattering (SEC-MALS), and PSD was measured using laser diffraction. Results: Thermal treatment of the vehicle solution had minimal impact on CMCNa molecular weight, preserving its functionality. High-shear homogenization during bead milling significantly reduced particle aggregation, resulting in improved PSD and reduced viscosity. Synergistic effects of the two helping processes used in one manufacturing process were observed, which led to superior stability and minimal changes in PSD and viscosity during storage. Batches without the helping processes exhibited increased particle size and viscosity over time, indicating reduced suspension stability. Conclusions: Incorporating vehicle thermal treatment and high-shear homogenization during bead milling enhances the stability and manufacturing efficiency of AM suspensions. These findings underscore the importance of optimizing laboratory-scale processes to ensure the quality and safety of pharmaceutical suspensions. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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10 pages, 1669 KiB  
Article
RNAi-Mediated Silencing of Chitin Synthase 1 (CHS1) Disrupts Molting and Growth in Monochamus alternatus
by Wanlin Ye, Tong Li, Mingqing Weng, Wenchi Guo, Feiyi Xin, Wei Yu, Songqing Wu and Yajie Guo
Forests 2025, 16(6), 922; https://doi.org/10.3390/f16060922 - 30 May 2025
Viewed by 433
Abstract
Chitin synthase (CHS) plays a key role in chitin synthesis. CHS1 is ubiquitous in insects, and some studies have found that the RNA interference with CHS1 can hinder three types of molting processes (larva–larva, larva–pupa and pupa–adult). In the present study, the CHS1 [...] Read more.
Chitin synthase (CHS) plays a key role in chitin synthesis. CHS1 is ubiquitous in insects, and some studies have found that the RNA interference with CHS1 can hinder three types of molting processes (larva–larva, larva–pupa and pupa–adult). In the present study, the CHS1 of Monochamus alternatus was identified and characterized by a bioinformatics analysis. The developmental stage-specific expression of the MalCHS1 (Monochamus alternatus CHS1) gene was obtained by a RT-qPCR, and the corresponding dsRNA was designed for functional verification. The RNA interference experiment was conducted using the microinjection method, and the injection site was selected from the abdominal segments of fifth-instar larvae. The results showed that after silencing the CHS1 gene, the larvae of M. alternatus showed morphological abnormalities, such as the softening of the body wall, a transparent abdomen and the swelling of somites, indicating that MalCHS1 mediates the molting, growth and development of M. alternatus. RNAi-mediated MalCHS1 gene silencing may become a promising new biological pesticide that can provide a new target gene for pest control. Full article
(This article belongs to the Section Forest Health)
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17 pages, 1946 KiB  
Article
Genomic and Fermentation Characterization of Kluyveromyces marxianus and Saccharomyces cerevisiae in Root Extract-Based Low-Alcohol Beverage
by Eun-Ju Lee, Seung-Hyun Choi, Min-Ju Seo, A-Reum Lee, Chan-Song Jang, Woong-Kwon Kwak, Jung-Ki Kwak, Jae-Ho Lee, Won-Joo Yoon and Seok-Min Yoon
Fermentation 2025, 11(6), 299; https://doi.org/10.3390/fermentation11060299 - 23 May 2025
Viewed by 892
Abstract
Fermentation is widely recognized for enhancing the sensory attributes and nutritional value in foods, with recent research focusing on non-alcoholic and root-based functional beverages. In this study, the genomic and fermentation characteristics of Kluyveromyces marxianus LRCC8279 (KM8279) and Saccharomyces cerevisiae LRCC8293 (SC8293) were [...] Read more.
Fermentation is widely recognized for enhancing the sensory attributes and nutritional value in foods, with recent research focusing on non-alcoholic and root-based functional beverages. In this study, the genomic and fermentation characteristics of Kluyveromyces marxianus LRCC8279 (KM8279) and Saccharomyces cerevisiae LRCC8293 (SC8293) were analyzed, specifically for their application in root extract-based low-alcohol fermentations. Whole-genome sequencing revealed that both strains harbored key genes involved in glucose, fructose, and sucrose metabolism and genes implicated in ethanol production. Although SC8293 harbored maltose-metabolizing genes, including MAL13 and MAL31, these genes were absent in KM8279. This genetic difference was evident in the fermentation performance, manifesting as distinct variations in alcohol production depending on the carbohydrate source. A further investigation of fermentation conditions demonstrated that both strains maintained low alcohol levels and exhibited a consistent growth at 15–20 °C within 72 h. Fermentation using extracts from Pueraria lobata, Arctium lappa (AL), Zingiber officinale (ZO), and Platycodon grandifloras revealed that KM8279 markedly increased the production of volatile compounds, contributing to floral and fruity sensory attributes in ZO and AL, whereas SC8293 contributed to a more complex flavor profile in AL. Notably, KM8279-ZO and KM8279-AL fermentations maintained alcohol contents below 1%, indicating their potential application in non-alcoholic beverages. Future studies are needed to investigate the relationship between the key volatile compound production and associated genetic characteristics, along with sensory evaluations, to develop optimized flavor modulation strategies. Full article
(This article belongs to the Section Fermentation for Food and Beverages)
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18 pages, 5351 KiB  
Article
Fault Analysis and Protection Principle for the Distribution Networks Integrated with PV and BESS
by Jianan He, Lei Li, Jian Niu, Yabo Liang, Haitao Liu, Zhenxin Yang, Chao Li and Zhihui Zheng
Appl. Sci. 2025, 15(10), 5568; https://doi.org/10.3390/app15105568 - 16 May 2025
Viewed by 399
Abstract
With the rapid development of renewable energy technologies, large numbers of photovoltaic (PV) and battery energy storage systems (BESS) have been connected to distribution networks. However, both PV and the BESS are inverter interfaced power sources, which may cause the traditional protection relays [...] Read more.
With the rapid development of renewable energy technologies, large numbers of photovoltaic (PV) and battery energy storage systems (BESS) have been connected to distribution networks. However, both PV and the BESS are inverter interfaced power sources, which may cause the traditional protection relays to mis-operate or mal-operate. Moreover, according to the latest grid connection specifications, PV and BESS are required to absorb negative sequence current during asymmetric faults of distribution networks, indicating that they both must adopt new control strategies during the fault ride through period. In response to the above challenges, this work first studies the fault ride through control strategies of PV and BESS when different phase-to-phase faults occur according to the latest grid connection requirements. Second, it analyzes the negative sequence impedance characteristics of PV and BESS under asymmetric faults and quantitatively calculates its variation range. Third, during symmetric faults, the differences in fault current provided by PV and BESS and those provided by the large power grid are compared. Then, this work proposes a fault direction detection principle for the distribution network with PV and BESS. For asymmetric phase-to-phase faults, this principle detects the fault direction by using the negative sequence power angle; for symmetric faults, it detects the fault direction by using the reactive current and active current. Finally, simulation tests are carried out to verify the operation performance of the proposed principle. Full article
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