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14 pages, 1266 KiB  
Systematic Review
Molecular Detection of Mycobacterium leprae and the Process of Infection and Illness in Contacts of Leprosy Patients: A Systematic Review
by Sarah Lamas Vidal, Lavínia Cássia Ferreira Batista, Daniele dos Santos Lages, Bruna Eduarda Bortolomai, Isabela de Caux Bueno, Eyleen Nabyla Alvarenga Niitsuma, Nathan Guilherme de Oliveira, Ida Maria Foschiani Dias Baptista and Francisco Carlos Félix Lana
Trop. Med. Infect. Dis. 2025, 10(2), 32; https://doi.org/10.3390/tropicalmed10020032 (registering DOI) - 23 Jan 2025
Abstract
Various techniques have been used for the molecular identification of Mycobacterium leprae (M. leprae). The aim of this review was to identify the relationship between the molecular presence of M. leprae and the process of infection and/or illness of contact of [...] Read more.
Various techniques have been used for the molecular identification of Mycobacterium leprae (M. leprae). The aim of this review was to identify the relationship between the molecular presence of M. leprae and the process of infection and/or illness of contact of leprosy cases. A systematic review was carried out by searching the Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane Library, Embase, Scopus, Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) databases in January 2024. The studies were selected by two pairs of reviewers. Observational cross-sectional, case–control and cohort studies were included. A descriptive synthesis of the results by category was carried out. A total of 443 studies were identified, and 36 were included in the review. Twelve molecular targets were tested to identify the presence of the bacillus. A relationship was established between the identification of M. leprae DNA and factors related to the index case, housing characteristics, living conditions, epidemiology and anti-PGL-1 serology. None of the studies identified evaluated the molecular viability of M. leprae among contacts. The detection of M. leprae DNA alone does not necessarily predict the development of infection or clinical illness among contacts. Full article
(This article belongs to the Special Issue Towards Zero Leprosy: Epidemiology and Prevention Strategy)
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<p>Flowchart of the pathogenesis of leprosy.</p>
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<p>PRISMA diagram: the process of selecting eligible studies for the systematic review.</p>
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24 pages, 971 KiB  
Review
Mechanisms, Biomarkers, and Treatment Approaches for Diabetic Kidney Disease: Current Insights and Future Perspectives
by Jean Paule Joumaa, Angela Raffoul, Charbel Sarkis, Elizabeth Chatrieh, Sally Zaidan, Philippe Attieh, Frederic Harb, Sami Azar and Hilda E. Ghadieh
J. Clin. Med. 2025, 14(3), 727; https://doi.org/10.3390/jcm14030727 - 23 Jan 2025
Viewed by 113
Abstract
Diabetic Kidney Disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Among individuals with type 1 diabetes mellitus (T1DM), 30–40% are at risk of developing DKD. This review focuses on the mechanistic processes, available and emerging biomarkers for diagnosing, monitoring, [...] Read more.
Diabetic Kidney Disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Among individuals with type 1 diabetes mellitus (T1DM), 30–40% are at risk of developing DKD. This review focuses on the mechanistic processes, available and emerging biomarkers for diagnosing, monitoring, and preventing DKD, as well as treatment options targeted at DKD patients. A literature search was conducted on PubMed and Scopus using specific keywords. Inclusion and exclusion criteria were applied to select the articles used for this review. The literature highlights various mechanisms involved in the progression of DKD to more severe stages. Additionally, several biomarkers have been identified, which aid in diagnosing and monitoring the disease. Furthermore, numerous treatment approaches are being explored to address the underlying causes of DKD. Advanced research is exploring new medications to aid in DKD remission; sodium-glucose cotransport (SGLT2) inhibitors and finerenone, in particular, are gaining attention for their novel renoprotective effects. DKD is a major complication of diabetes, marked by complex and multifactorial mechanisms. Thus, understanding these processes is essential for developing targeted therapies to potentially reverse DKD progression. Biomarkers show promise for early diagnosis and monitoring of disease progression, while current treatment strategies underscore the importance of a multifaceted approach. Full article
(This article belongs to the Section Nephrology & Urology)
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<p>Flow diagram illustrating the selection process of the included studies.</p>
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<p>Mechanisms Underlying DKD Induced by Hyperglycemia. Upward arrows indicate an increase, while downward arrows indicate a decrease. Created in <a href="https://BioRender.com" target="_blank">https://BioRender.com</a>.</p>
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15 pages, 1172 KiB  
Review
Microbiota Dysbiosis: A Key Modulator in Preeclampsia Pathogenesis and Its Therapeutic Potential
by Johnatan Torres-Torres, Jorge Alberto Basurto-Serrano, Zaira Alexi Camacho-Martinez, Francisco Rafael Guadarrama-Sanchez, Irma Eloisa Monroy-Muñoz, Javier Perez-Duran, Juan Mario Solis-Paredes, Raigam Martinez-Portilla, Salvador Espino-y-Sosa, Andrea Ramirez-Gonzalez, Rodrigo Guadarrama-Mora and Lourdes Rojas-Zepeda
Microorganisms 2025, 13(2), 245; https://doi.org/10.3390/microorganisms13020245 - 23 Jan 2025
Viewed by 88
Abstract
Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Emerging evidence implicates gut and vaginal microbiota dysbiosis in preeclampsia pathogenesis through its roles in immune regulation, inflammation, and placental function. This review explores the mechanisms linking microbiota alterations to [...] Read more.
Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Emerging evidence implicates gut and vaginal microbiota dysbiosis in preeclampsia pathogenesis through its roles in immune regulation, inflammation, and placental function. This review explores the mechanisms linking microbiota alterations to preeclampsia and evaluates the therapeutic potential of microbiota-targeted interventions. A systematic search using MeSH terms related to “preeclampsia”, “microbiota”, and “dysbiosis” identified studies on microbiota and preeclampsia pathophysiology. Data extraction focused on microbial alterations and mechanistic insights. Gut dysbiosis, characterized by reduced beneficial bacteria and short-chain fatty acid production, weakens the intestinal barrier, exacerbates systemic inflammation, and impairs placental development. Vaginal dysbiosis, marked by reduced Lactobacillus species, promotes local inflammation, increasing placental dysfunction risk. Therapeutic strategies, including probiotics, prebiotics, and dietary modifications, show promise in restoring microbial balance and mitigating preeclampsia risk. Microbiota dysbiosis significantly contributes to preeclampsia pathogenesis through inflammation, endothelial dysfunction, and placental impairment. Interventions targeting microbial balance, such as probiotics and dietary modifications, show promise for prevention, but further research and large-scale trials are essential to validate their efficacy and safety. Full article
(This article belongs to the Section Medical Microbiology)
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<p>The role of gut microbiota in preeclampsia pathogenesis. A healthy lifestyle, including exercise and a balanced diet, promotes microbial diversity and the production of short-chain fatty acids (SCFAs), which maintain the intestinal barrier and modulate inflammation. In contrast, intestinal dysbiosis leads to reduced SCFA production and increased intestinal permeability, allowing lipopolysaccharides (LPS) to enter the circulation. LPS triggers systemic inflammation by promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which contribute to endothelial dysfunction. The dysfunctional endothelium, coupled with elevated anti-angiogenic factors such as soluble Fms-like tyrosine kinase-1 (sFlt-1), impairs placental vascular remodeling and promotes hypoxia, perpetuating the cycle of inflammation and preeclampsia pathophysiology.</p>
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<p>Mechanistic role of vaginal microbiota in preeclampsia development.</p>
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22 pages, 2275 KiB  
Systematic Review
Systematic Literature Review of Simulation-Based Learning for Developing Teacher SEL
by Ronen Kasperski, Orna Levin and Merav Esther Hemi
Educ. Sci. 2025, 15(2), 129; https://doi.org/10.3390/educsci15020129 - 23 Jan 2025
Viewed by 120
Abstract
This systematic literature review provides a comprehensive analysis of simulation-based learning methods aimed at enhancing teachers’ social–emotional learning (SEL). The study follows PRISMA guidelines, focusing on peer-reviewed journal articles published in English between 2010 and 2023. Four academic databases—APA Psych, ERIC, Scopus, and [...] Read more.
This systematic literature review provides a comprehensive analysis of simulation-based learning methods aimed at enhancing teachers’ social–emotional learning (SEL). The study follows PRISMA guidelines, focusing on peer-reviewed journal articles published in English between 2010 and 2023. Four academic databases—APA Psych, ERIC, Scopus, and Web of Science—were searched, resulting in 68 articles that met stringent inclusion criteria after thorough screening and validation. Findings indicate inconsistencies in terminology and the categorisation of simulation types across studies, highlighting the need for standardised definitions. Findings identify specific simulation types that prioritise SEL development, offering valuable insights into their effective implementation. The theoretical contribution of this systematic literature review lies in proposing a clear typology of simulations, distinguishing between various simulation types and their roles in advancing SEL in teacher training and professional development. In light of the findings, we suggest that, to optimise the use of simulations and enhance their effectiveness in developing SEL competencies within teacher education programs, educators and researchers should adopt a more comprehensive approach to SEL-targeted simulations. Full article
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<p>Stages of the study selection process, following PRISMA (<a href="#B79-education-15-00129" class="html-bibr">Page et al., 2021</a>).</p>
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<p>Geographic distribution of studies by country.</p>
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<p>The number of studies on teachers’ SEL simulations.</p>
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<p>Types of simulation arranged by level of immersion, from low (<b>left</b> side) to high (<b>right</b> side).</p>
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<p>SEL competencies in the social awareness and relationship clusters.</p>
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<p>Proportional distribution of SEL competencies across different simulation types. Note: S-Awa—self-awareness; S-Man—self-management; Social A—social awareness; Relations—relationship skills; Ethics—Ethical Decision Making.</p>
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20 pages, 2992 KiB  
Review
Evaluating the Efficacy of Repurposed Antiretrovirals in Hepatitis B Virus Treatment: A Narrative Review of the Pros and Cons
by Samuel Chima Ugbaja, Simon Achi Omerigwe, Saziso Malusi Zephirinus Ndlovu, Mlungisi Ngcobo and Nceba Gqaleni
Int. J. Mol. Sci. 2025, 26(3), 925; https://doi.org/10.3390/ijms26030925 (registering DOI) - 23 Jan 2025
Viewed by 230
Abstract
Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) continue to be global public health issues. Globally, about 39.9 million persons live with HIV in 2023, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2024 Fact Sheet. Consequently, the World Health [...] Read more.
Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) continue to be global public health issues. Globally, about 39.9 million persons live with HIV in 2023, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2024 Fact Sheet. Consequently, the World Health Organisation (WHO) reported that about 1.5 million new cases of HBV occur, with approximately 820 thousand mortalities yearly. Conversely, the lower percentage of HBV (30%) cases that receive a diagnosis is a setback in achieving the WHO 2030 target for zero HBV globally. This has necessitated a public health concern to repurpose antiretroviral (ARV) drugs for the treatment of HBV diseases. This review provides an introductory background, including the pros and cons of repurposing antiretrovirals (ARVs) for HBV treatment. We examine the similarities in replication mechanisms between HIV and HBV. We further investigate some clinical studies and trials of co-infected and mono-infected patients with HIV–HBV. The topical keywords including repurposing ARV drugs, repurposing antiretroviral therapy, Hepatitis B drugs, HBV therapy, title, and abstracts are searched in PubMed, Web of Science, and Google Scholar. The advanced search includes the search period 2014–2024, full text, clinical trials, randomized control trials, and review. The search results filtered from 361 to 51 relevant articles. The investigations revealed that HIV and HBV replicate via a common route known as ‘reverse transcription’. Clinical trial results indicate that an early initiation of ARVs, particularly with tenofovir disoproxil fumarate (TDF) as part of a regimen, significantly reduced the HBV viral load in co-infected patients. In mono-infected HBV, timely and correct precise medication is essential for HBV viral load reduction. Therefore, genetic profiling is pivotal for successful ARV drug repurposing in HBV treatment. Pharmacogenetics enables the prediction of the right dosages, specific individual responses, and reactions. This study uniquely explores the intersection of pharmacogenetics and drug repurposing for optimized HBV therapy. Additional in vivo, clinical trials, and in silico research are important for validation of the potency, optimum dosage, and safety of repurposed antiretrovirals in HBV therapy. Furthermore, a prioritization of research collaborations comprising of regulators and funders to foster clinically adopting and incorporating repurposed ARVs for HBV therapy is recommended. Full article
(This article belongs to the Section Molecular Microbiology)
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<p>HIV replication cycle highlighting the key stages targeted by antiretrovirals for HIV treatment, redrawn with a bio-render as adapted from source [<a href="#B32-ijms-26-00925" class="html-bibr">32</a>].</p>
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<p>HBV replication cycle highlighting the key stages targeted by the antiretrovirals repurposed for HBV treatment, redrawn with a bio-render as adapted from source [<a href="#B33-ijms-26-00925" class="html-bibr">33</a>].</p>
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17 pages, 1411 KiB  
Review
Exploring the Role of Non-Structural Carbohydrates (NSCs) Under Abiotic Stresses on Woody Plants: A Comprehensive Review
by Ayesha Fazal Nawaz, Sara Gargiulo, Alessandro Pichierri and Valentino Casolo
Plants 2025, 14(3), 328; https://doi.org/10.3390/plants14030328 - 22 Jan 2025
Viewed by 307
Abstract
Global climate change has increased the severity and frequency of abiotic stresses, posing significant challenges to the survival and growth of woody plants. Non-structural carbohydrates (NSCs), including starch and sugars, play a vital role in enabling plants to withstand these stresses, helping to [...] Read more.
Global climate change has increased the severity and frequency of abiotic stresses, posing significant challenges to the survival and growth of woody plants. Non-structural carbohydrates (NSCs), including starch and sugars, play a vital role in enabling plants to withstand these stresses, helping to stabilize cellular functions by buffering plant energy demands and facilitating recovery on the alleviation of stress. Despite the recognized multiple functions of NSCs, the contrasting effects of multiple abiotic stresses on NSCs dynamics in woody plants remain poorly understood. This review aims to explore the current knowledge of the contrasting effects of abiotic stress conditions including drought, salinity, heat, water logging, and cold on NSCs dynamics. The roles of NSCs in regulating stress-resilience responses in woody plants are also discussed, along with the challenges in NSC measurement, and options for future research directions are explored. This review is based on comprehensive literature research across different search engines like Scopus, Web of Science, and Google Scholar (2000–2024) using targeted keywords. This study compiles the current research on NSCs functions and provides insights into the adaptive strategies of woody plants in response to changing climate conditions, providing groundwork for future research to improve stress tolerance in woody plants. Full article
(This article belongs to the Special Issue Carbon Management during Plant Acclimation to Abiotic Stresses)
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<p>Effects of abiotic stress on plant functions and implications of NSCs for stress tolerance. The changes in different physiological parameters in response to specific stress are indicated by arrows as upward red arrows representing increase and downward red arrows indicating decrease. Green arrows highlight the positive responses for the accumulation of stress-protective compounds.</p>
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<p>Variation in photosynthesis, starch, and glucose dynamics under different drought conditions. Pre-drought conditions show a normal photosynthesis rate with regular glucose concentration and starch accumulation. In mild drought conditions, the photosynthesis rate declines (downward red arrow), increasing starch degradation to maintain high glucose levels (upward red arrow) and lower the starch reserves (downward red arrow). Severe drought ceases photosynthesis (red cross), resulting in minimal glucose and starch levels (respective red arrows).</p>
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39 pages, 1094 KiB  
Systematic Review
Associations Between Dietary Factors and Breast Cancer Risk: A Systematic Review of Evidence from the MENA Region
by Najoua Lamchabbek, Chaimaa Elattabi, Abdellatif Bour, Bernadette Chimera, Saber Boutayeb, Lahcen Belyamani, Elodie Faure, Inge Huybrechts and Mohamed Khalis
Nutrients 2025, 17(3), 394; https://doi.org/10.3390/nu17030394 - 22 Jan 2025
Viewed by 385
Abstract
Background: The Middle East and North Africa (MENA) region is witnessing a continuous rise in the incidence of breast cancer (BC). This region is characterized by distinct cultural and lifestyle habits. Despite the importance of diet as a modifiable risk factor for BC, [...] Read more.
Background: The Middle East and North Africa (MENA) region is witnessing a continuous rise in the incidence of breast cancer (BC). This region is characterized by distinct cultural and lifestyle habits. Despite the importance of diet as a modifiable risk factor for BC, its role in the development of BC within the MENA context has not been extensively studied. This systematic review aims to identify and synthesize existing evidence regarding the effect of different dietary factors on BC risk among women from this region. Methods: We systematically reviewed the scientific literature for observational studies that examined the association between specific dietary factors and the risk of BC in MENA, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Our comprehensive search included databases such as PubMed, Web of Science, ScienceDirect, and Scopus, identified a total of 18,085 records, of which 65 met our inclusion criteria and were assessed for quality using the National Institute of Health Quality Assessment Tool. Results: The findings of the 65 included studies were categorized into food groups, nutrients, and dietary patterns. Studies in the MENA region have consistently shown that the consumption of fruit and vegetables, fish and seafood, and black tea are associated with a reduced BC risk. In contrast, the intake of milk and white bread is linked to an increased risk. Specific dietary patterns such as the Mediterranean diet, a healthy plant-based diet, dietary antioxidant index, and overall healthy dietary patterns have shown a negative association with BC risk. Conversely, the dietary insulin index and load, dietary glycemic index, dietary inflammatory index, and unhealthy dietary patterns are associated with an increased risk of BC. For the remaining dietary factors, research was too limited or inconsistent to draw conclusions. Conclusions: Our findings highlight the significant role of dietary factors in modulating BC risk among women in the MENA region, an area that faces a notable gap in research on this topic. Further studies are essential to deepen our understanding and develop targeted dietary recommendations for BC prevention in this population. Full article
(This article belongs to the Special Issue Nutrition and Non-Communicable Disease Prevention or Improvement)
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<p>A flow chart illustrating the selection process for studies included in the study.</p>
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20 pages, 4780 KiB  
Article
Large-Space Laser Tracking Attitude Combination Measurement Using Backpropagation Algorithm Based on Neighborhood Search
by Ziyue Zhao, Zhi Xiong, Zhengnan Guo, Hao Zhang, Xiangyu Li, Zhongsheng Zhai and Weihu Zhou
Appl. Sci. 2025, 15(3), 1083; https://doi.org/10.3390/app15031083 - 22 Jan 2025
Viewed by 286
Abstract
Large-space high-precision attitude dynamic measurement technology has urgent application needs in large equipment manufacturing fields, such as aerospace, rail transportation, automobiles, and ships. In this paper, taking laser tracking equipment as the base station, a backpropagation algorithm based on neighborhood search is proposed, [...] Read more.
Large-space high-precision attitude dynamic measurement technology has urgent application needs in large equipment manufacturing fields, such as aerospace, rail transportation, automobiles, and ships. In this paper, taking laser tracking equipment as the base station, a backpropagation algorithm based on neighborhood search is proposed, which is applied to the fusion of multi-source information for solving the dynamic attitude angle. This paper firstly established a mathematical model of laser tracking attitude dynamic measurement based on IMU and CCD multi-sensor, designed a 6-11-3 back propagation network structure and algorithm flow, and realized the prediction of attitude angle through model training. Secondly, the method based on neighborhood search realizes the determination of the optimal training target value of the model, of which the MSE has a 34% reduction compared to the IMU determination method. Finally, the experimental platform is set up with the precision rotary table as the motion carrier to verify the effectiveness of the research method in this paper. The experimental results show that with the neighborhood-based backpropagation algorithm, the measurement results have a higher data update rate and a certain inhibition effect on the error accumulation of IMU. The absolute value of the system angle error can be less than 0.4° within 8 m and 0–50°, with an angle update rate of 100 Hz. The research method in this paper can be applied to the dynamic measurement of laser tracking attitude angles, which provides a new reference for the angle measurement method based on the fusion of multi-source information. Full article
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<p>Composition of the laser tracking attitude dynamic measurement system.</p>
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<p>Fusion method of visual and inertial combined measurements.</p>
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<p>Training effect of different numbers of neurons.</p>
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<p>Backpropagation algorithm training structure model.</p>
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<p>Backpropagation-based network model training process flowchart.</p>
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<p>Regression function for the learning process.</p>
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<p>The smallest MSE for the learning process.</p>
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<p>Diagram error histogram for the learning process.</p>
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<p>Neighborhood search flowchart.</p>
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<p>Comparison of neighborhood search effects.</p>
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<p>Experimental verification platform of attitude dynamic measurement system based on rotary table.</p>
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<p>Comparison of fusion effect and single measurement unit results at 4 m.</p>
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<p>The comparative analysis between the results of IMU integrated solution and data fusion solution.</p>
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22 pages, 4507 KiB  
Article
Visual Target-Driven Robot Crowd Navigation with Limited FOV Using Self-Attention Enhanced Deep Reinforcement Learning
by Yinbei Li, Qingyang Lyu, Jiaqiang Yang, Yasir Salam and Baixiang Wang
Sensors 2025, 25(3), 639; https://doi.org/10.3390/s25030639 - 22 Jan 2025
Viewed by 260
Abstract
Navigating crowded environments poses significant challenges for mobile robots, particularly as traditional Simultaneous Localization and Mapping (SLAM)-based methods often struggle with dynamic and unpredictable settings. This paper proposes a visual target-driven navigation method using self-attention enhanced deep reinforcement learning (DRL) to overcome these [...] Read more.
Navigating crowded environments poses significant challenges for mobile robots, particularly as traditional Simultaneous Localization and Mapping (SLAM)-based methods often struggle with dynamic and unpredictable settings. This paper proposes a visual target-driven navigation method using self-attention enhanced deep reinforcement learning (DRL) to overcome these limitations. The navigation policy is developed based on the Twin-Delayed Deep Deterministic Policy Gradient (TD3) algorithm, enabling efficient obstacle avoidance and target pursuit. We utilize a single RGB-D camera with a limited field of view (FOV) for target detection and surrounding sensing, where environmental features are extracted from depth data via a convolutional neural network (CNN). A self-attention network (SAN) is employed to compensate for the limited FOV, enhancing the robot’s capability of searching for the target when it is temporarily lost. Experimental results show that our method achieves a higher success rate and shorter average target-reaching time in dynamic environments, while offering hardware simplicity, cost-effectiveness, and ease of deployment in real-world applications. Full article
(This article belongs to the Section Remote Sensors)
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<p>A scenario of a mobile robot navigating in a crowded environment toward a visual target.</p>
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<p>System architecture of the proposed visual target-driven robot navigation.</p>
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<p>Convolution neural network (CNN) to extract features from depth data.</p>
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<p>Self-attention network to process sequences of past target positions and actions.</p>
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<p>The collision risk penalty based on the ratio of the number of “dangerous-level” depth pixels to the number of “warning-level” depth pixels.</p>
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<p>Enhanced TD3 framework for visual target-driven robot crowd navigation with simultaneous CNN and SAN updates using critic loss.</p>
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<p>Simulation environment for training and testing. The arrows indicate obstacle movements.</p>
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<p>Trajectories of the robot navigating a 5 m × 5 m simulated space with eight moving cylindrical obstacles. (<b>a</b>–<b>e</b>) illustrate the robot’s trajectory in an environment where the obstacles move in a Brownian pattern, while (<b>a’</b>–<b>e’</b>) illustrate the robot’s trajectory in an environment where the obstacles move in a crossing pattern.</p>
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<p>Learning curves in the ablation study.</p>
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<p>Real robot experiment. (<b>a</b>) Real robot with RGBD camera. (<b>b</b>) Experiment environment.</p>
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<p>Real robot operating in three scenarios. The arrows in (<b>b</b>) and (<b>c</b>) indicate human movements.</p>
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19 pages, 4049 KiB  
Article
Improvement of Mutant Galactose-1-Phosphate Uridylyltransferase (GALT) Activity by FDA-Approved Pharmacochaperones: A Preliminary Study
by Bernardina Scafuri, Stefania Piscosquito, Giulia Giliberti, Angelo Facchiano, Jaden Miner, Bijina Balakrishnan, Kent Lai and Anna Marabotti
Int. J. Mol. Sci. 2025, 26(3), 888; https://doi.org/10.3390/ijms26030888 - 21 Jan 2025
Viewed by 298
Abstract
Classic galactosemia is a rare disease with long-term consequences that seriously affect the quality of life of patients. To date, various therapeutic approaches are being developed, but treatments that target the molecular defects in the mutant galactose-1-phosphate uridylyltransferase (GALT) gene are [...] Read more.
Classic galactosemia is a rare disease with long-term consequences that seriously affect the quality of life of patients. To date, various therapeutic approaches are being developed, but treatments that target the molecular defects in the mutant galactose-1-phosphate uridylyltransferase (GALT) gene are lacking. We conducted a computational search for putative pharmacochaperones by applying a drug repurposing strategy, and we found that one compound, already active as a pharmacochaperone in another pathology, doubled the enzymatic activity of the purified mutant enzyme in an in vitro test. Furthermore, an extensive computational search in a database of known active molecules found another compound able in its turn to improve in vitro enzymatic activity. Both compounds are predicted to interact with a cavity at the enzyme interface previously supposed to be an allosteric site for the GALT enzyme. In vitro tests confirmed also the reduced accumulation of galactose-1-phosphate (G1P) in fibroblasts of patients. Although these results must be considered preliminary, our findings pave the way for future research lines focused on the search for promising pharmacochaperones that can directly rescue the activity of the enzyme. Full article
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<p>The Leloir pathway for galactose metabolism. This biochemical pathway is composed of four steps, each involving a different enzyme. In the first step, β-D-galactose is converted to α-D-galactose by the enzyme galactose mutarotase (GALM). Then, α-D-galactose is converted to galactose-1-phosphate (G1P) by galactokinase 1 (GALK1). Galactose-1-phosphate uridyltransferase (GALT) transfers a uridine monophosphate group from uridine diphosphate (UDP)-glucose to galactose-1-phosphate to form UDP-galactose. Finally, UDP-galactose-4′-epimerase (GALE) interconverts UDP-galactose and UDP-glucose. The figures of the sugars have been downloaded from PubChem (<a href="https://pubchem.ncbi.nlm.nih.gov/" target="_blank">https://pubchem.ncbi.nlm.nih.gov/</a>) (accessed on 12 January 2025), whereas the figures of the enzymes have been downloaded from the Galactosemia Proteins Database (<a href="http://protein-variants.eu/galactosemia/" target="_blank">http://protein-variants.eu/galactosemia/</a>) (accessed on 12 January 2025) and rendered in cartoon mode with ChimeraX (<a href="https://www.rbvi.ucsf.edu/chimerax/" target="_blank">https://www.rbvi.ucsf.edu/chimerax/</a>) (accessed on 12 January 2025).</p>
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<p>Chemical structures of the drugs tested in this work. Panel (<b>a</b>): ambroxol; panel (<b>b</b>): pyrimethamine; panel (<b>c</b>): ciclopirox; panel (<b>d</b>): ombrabulin. The first three molecules (panels (<b>a</b>–<b>c</b>)) were selected from the literature, as described in <a href="#sec2dot1dot1-ijms-26-00888" class="html-sec">Section 2.1.1</a>, whereas ombrabulin was identified by a virtual screening procedure based on the pharmacophore derived from ciclopirox, as described in <a href="#sec2dot1dot2-ijms-26-00888" class="html-sec">Section 2.1.2</a>. These structures have been downloaded from PubChem (<a href="https://pubchem.ncbi.nlm.nih.gov/" target="_blank">https://pubchem.ncbi.nlm.nih.gov/</a>) (accessed on 12 January 2025).</p>
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<p>Interactions between wtGALT (<b>left</b> panels) with selected drugs, and between p.Gln188Arg enzyme (<b>right</b> panels) with selected drugs, identified by docking focused on the putative allosteric site (site X). All the docking simulations were made in the presence of both substrates in the active sites. Panels (<b>a</b>,<b>b</b>) show the docking of ambroxol in the box focused on site Xa (cyan) or Xb (blue); panels (<b>c</b>,<b>d</b>) show the docking of pyrimethamine in the box focused on site Xa (yellow) or Xb (orange); panels (<b>e</b>,<b>f</b>) show the docking of ciclopirox in the box focused on site Xa (pink) or Xb (magenta). The three drugs are represented in CPK mode. The substrates are represented in stick mode and colored black, the Zn ion as a sphere and colored grey. In contrast to ambroxol (panels (<b>a</b>,<b>b</b>)) and pyrimethamine (panels (<b>c</b>,<b>d</b>)), ciclopirox (panels (<b>e</b>,<b>f</b>)) identified only one conformation within the X site, thus showing a higher specificity of interaction with that site.</p>
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<p>Detailed interactions between ciclopirox and wtGALT or p.Gln188Arg enzymes identified by docking focused on the putative allosteric site (site X). In all cases, the pose with best energy is also representative of the most populated cluster. Panel (<b>a</b>): result of docking on site Xa on wtGALT. Panel (<b>b</b>): result of docking on site Xa on p.Gln188Arg. Panel (<b>c</b>): result of docking on site Xb on wtGALT; Panel (<b>d</b>): result of docking on site Xb on p.Gln188Arg. In all cases, the interactions of ciclopirox with the enzyme were the same, confirming that the molecule binds specifically to the enzyme pocket.</p>
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<p>Further identification of pharmacological hits specific to site X of wtGALT and p.Gln188Arg enzymes starting from ciclopirox. Pharmacophoric models (PM) were obtained for each best pose of the docking of ciclopirox with site Xa and Xb. For each of these starting poses, the PM with the highest selectivity was used to make the corresponding pharmacophore hit search in DrugBank. Only hits with a fitness score &gt; 3 (as recommended) were selected. Then, selection criteria were applied as described in the scheme, to identify the final 25 best hits.</p>
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<p>Detailed interactions between DB12882 (ombrabulin) and wtGALT or p.Gln188Arg enzymes identified by docking focused on the putative allosteric site (site X). Panel (<b>a</b>): result of docking on site Xa on wtGALT, pose with best energy. Panel (<b>b</b>): result of docking on site Xa on wtGALT, pose representative of the most populated cluster. Panel (<b>c</b>): result of docking on site Xb on wtGALT, pose with best energy. Panel (<b>d</b>): result of docking on site Xb on wtGALT, pose representing the most populated cluster. Panel (<b>e</b>): result of docking on site Xa on p.Gln188Arg, pose with best energy. Panel (<b>f</b>): result of docking on site Xa on p.Gln188Arg, pose representative of the most populated cluster. Panel (<b>g</b>): result of docking on site Xb on p.Gln188Arg, pose with best energy. Panel (<b>h</b>): result of docking on site Xb on p.Gln188Arg, pose representing the most populated cluster. The interactions between DB12882 (ombrabulin) and the putative allosteric site X involve most of the residues interacting with ciclopirox, thereby confirming the predicted ability of ombrabulin to interact with site X similarly to the parent compound ciclopirox, especially in the poses with the best energy.</p>
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<p>Effect of putative PCs on purified mutant GALT enzyme activity and galactose-1-phosphate (G1P) accumulation in patient fibroblasts. Panel (<b>a</b>): Purified mutant GALT enzyme activity was determined in the presence of different compounds. Enzyme activity is expressed as units/mg enzyme/minute. Error bars indicate mean activity ± standard deviation of the mean (n = 3 independent experiments). Panel (<b>b</b>): G1P levels detected in untreated wt, untreated patient, and patient fibroblasts treated with various compounds. Error bars represent mean G1P/protein concentrations ± standard deviation (n = 3 independent experiments. Statistical significance: * <span class="html-italic">p</span> &lt; 0.05, compared to untreated patient fibroblasts (Student’s <span class="html-italic">t</span>-test). ns: not significant.</p>
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9 pages, 704 KiB  
Proceeding Paper
Utilization of Ultrasonic-Assisted Extraction for Bioactive Compounds from Floral Sources
by Sepidar Seyyedi-Mansour, Pauline Donn, Maria Carpena, Franklin Chamorro, Paula Barciela, Ana Perez-Vazquez, Ana Olivia S. Jorge and Miguel A. Prieto
Biol. Life Sci. Forum 2024, 40(1), 15; https://doi.org/10.3390/blsf2024040015 - 21 Jan 2025
Viewed by 150
Abstract
This systematic review aims to evaluate the effectiveness of ultrasound-assisted extraction (UAE) for obtaining bioactive compounds from floral sources, emphasizing its potential application in the pharmaceutical and food industries. As a “green extraction” technique, UAE minimizes use of organic solvents, energy consumption, and [...] Read more.
This systematic review aims to evaluate the effectiveness of ultrasound-assisted extraction (UAE) for obtaining bioactive compounds from floral sources, emphasizing its potential application in the pharmaceutical and food industries. As a “green extraction” technique, UAE minimizes use of organic solvents, energy consumption, and extraction time, making it a sustainable alternative to traditional extraction methods. On the other hand, flowers serve as a valuable reservoir of bioactive compounds. Appropriate experimental strategies are necessary to maximize the yield of bioactive compound recovery. The increasing use of floral sources in manufacturing dietary supplements and functional foods, coupled with rapid advancements in these sectors, indicates significant potential for the application of UAE. Its effectiveness is influenced by a multitude of factors, including operational variables and the matrix effect, both of which have the potential to impact the molecular structures of the specific compounds being targeted. In flowers, these compounds usually entail active secondary metabolites such as polyphenols. Hence, it is imperative to establish the optimal experimental parameters. A comprehensive literature review was conducted, covering studies from 2000 to 2024. Electronic databases including PubMed, ScienceDirect, Web of Science, and Scopus were searched for peer-reviewed articles using keywords such as “Ultrasound-assisted extraction”, “bioactive compounds”, “flowers”, and “extraction optimization”. Results indicate that UAE significantly enhances the yield of bioactive compounds, such as polyphenols, with extraction efficiencies reaching up to 95% under optimal conditions. The findings also highlight the importance of parameter optimization, as variations in solvent concentration and ultrasonic intensity can affect the structural integrity of extracted compounds. In conclusion, this communication has emphasized the significance of UAE technologies and presented recent research and updated data on their contribution to obtaining bioactive compounds from plant-based materials, particularly flowers. Full article
(This article belongs to the Proceedings of The 5th International Electronic Conference on Foods)
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<p>Ultrasound-assisted extraction of bioactive compounds from floral sources: mechanism and benefits. Created with canva.com.</p>
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21 pages, 1714 KiB  
Review
The Role of Osteoprotegerin in Breast Cancer: Genetic Variations, Tumorigenic Pathways, and Therapeutic Potential
by Janan Husain Radhi, Ahmed Mohsen Abbas El-Hagrasy, Sayed Husain Almosawi, Abdullatif Alhashel and Alexandra E. Butler
Cancers 2025, 17(3), 337; https://doi.org/10.3390/cancers17030337 - 21 Jan 2025
Viewed by 437
Abstract
Introduction: Osteoprotegerin (OPG), encoded by the TNFRSF11B gene, is linked to the development of breast cancer via several pathways, including interactions with the receptor activator of nuclear factor-κB (RANK) ligands, apoptosis-inducing proteins like TRAIL, and genetic variations such as single nucleotide polymorphisms (SNPs), [...] Read more.
Introduction: Osteoprotegerin (OPG), encoded by the TNFRSF11B gene, is linked to the development of breast cancer via several pathways, including interactions with the receptor activator of nuclear factor-κB (RANK) ligands, apoptosis-inducing proteins like TRAIL, and genetic variations such as single nucleotide polymorphisms (SNPs), directly altering gene expression. This review aims to investigate the role of OPG expression in breast cancer. Methods: A comprehensive literature search was conducted using PubMed Medline, Google Scholar, and ScienceDirect. Only full-text English publications from inception to September 2024 were included. Results: Studies have demonstrated that certain SNPs in the OPG gene, specifically rs3102735 and rs2073618, are linked to a higher risk of breast cancer development. Additionally, OPG’s function as a TRAIL decoy receptor may inhibit the death of cancer cells. Furthermore, OPG in the serum and its interactions with BRCA mutations are being investigated for their potential influence on breast cancer progression. Studies have found that OPG promotes tumorigenesis by enhancing cell proliferation, angiogenesis, and aneuploidy in normal mammary epithelial cells. Moreover, OPG mediates the tumor-promoting effects of interleukin-1 beta and may serve as a biomarker for breast cancer risk, particularly in BRCA1 mutation carriers, through its role in dysregulated RANK signaling. Lastly, the use of recombinant OPG in mouse models has been found to exert anti-tumor effects. Conclusions: In this review, the role of OPG in breast cancer is examined. OPG has a multifaceted role in breast cancer tumorigenesis and exerts its effects through genetic variations (SNPs), interactions with TNF-related apoptosis-inducing ligand (TRAIL), and the modulation of the pro-tumorigenic microenvironment effects of angiogenesis, cell survival, and metastasis. Additionally, OPG’s dual role as a tumor suppressor and promoter serves as a possible therapeutic target to enhance apoptosis, limit bone metastasis, and modulate the tumor microenvironment. Whilst much is now known, further studies are necessary to fully delineate the role of OPG. Full article
(This article belongs to the Section Cancer Pathophysiology)
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<p>Osteoprotegerin (OPG) structure. OPG contains amino-terminal signal peptides and cysteine-rich tumor necrosis factor receptor (TNFR)-like domains, which are the key binding forces to the receptor activator of nuclear factor-κB (RANK). Additionally, OPG includes two death domain homologous regions of which the functions are currently not understood. A heparin binding domain limits the half-life of this molecule and serves as a basis for dimer formation [<a href="#B5-cancers-17-00337" class="html-bibr">5</a>].</p>
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<p>The OPG/RANK/RANKL pathway. A schematic to illustrate the OPG/RANK/RANKL pathway, which regulates bone remodeling by balancing osteoclast activation. The receptor activator of nuclear factor-κB ligand (RANKL) binds to the receptor activator of nuclear factor-κB (RANK) on osteoclast precursors, initiating a signaling cascade (via TRAF6 and NF-κB) that promotes bone resorption and is also involved in cellular proliferation. Osteoprotegerin (OPG) acts as a decoy receptor, binding RANKL to inhibit its interaction with RANK and prevent excessive osteoclast activity. Dysregulation of this pathway contributes to tumorigenesis. On the left, OPG binds to TNF-related apoptosis-inducing ligand (TRAIL), preventing its interaction with death receptors (DR4 and DR5) on tumor cells. This neutralization inhibits TRAIL-induced apoptosis, allowing cancer cells to survive.</p>
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<p>Osteoprotegerin (OPG)-mediated mechanisms in cancer progression. OPG enhances proliferation and promotes aneuploidy by activating chromosomal instability pathways involving Aurora A, Bub1, and BubR1 kinases, resulting in genomic disruption. Moreover, OPG drives neoangiogenesis by enhancing endothelial cell survival and vascular network formation through paracrine signaling, and facilitating tumor growth and progression, which is further reinforced by OPG’s ability to stimulate endothelial cell survival and differentiation. Moreover, OPG serves as a decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which prevents apoptosis. OPG also mediates protease activity, including cathepsin D and matrix metalloproteinase-2 (MMP-2), to facilitate cancer invasion and metastasis. Furthermore, single nucleotide polymorphisms (SNPs) associated with OPG (e.g., <span class="html-italic">rs3102735, rs2073617, rs2073618, rs4845627</span>) may influence susceptibility to malignancy.</p>
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<p>The role of osteoprotegerin (OPG) in inducing aneuploidy in mammary epithelial cells. A schematic to portray how osteoprotegerin (OPG) leads to chromosomal instability in human mammary epithelial cells (HMECs). The left panel represents a typical HMEC with a diploid genome and stable chromosomes. The middle panel shows the changes in the chromosomal integrity after the secretion of OPG in the tumor microenvironment. OPG has been shown to upregulate aneuploidy-related kinases such as Aurora A kinase (IAK-1), Bub1 kinase, and BubR1 protein, which disrupt mitotic checkpoint integrity and genomic stability. These regulatory effects underscore OPG’s contribution to driving aneuploidy and tumorigenesis. The right panel illustrates an aneuploid HMEC with disorganized chromosomes, highlighting the role of OPG in promoting chromosomal instability and aneuploidy, a key feature in cancer progression.</p>
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15 pages, 943 KiB  
Systematic Review
Spinal Cord Stimulation for Refractory Angina Pectoris: Current Status and Future Perspectives, a Narrative Review
by Roberto Gazzeri, Jacopo Mosca, Felice Occhigrossi, Marco Mercieri, Marcelo Galarza and Matteo Luigi Giuseppe Leoni
J. Cardiovasc. Dev. Dis. 2025, 12(1), 33; https://doi.org/10.3390/jcdd12010033 - 20 Jan 2025
Viewed by 336
Abstract
Refractory angina pectoris (RAP) is a clinical syndrome characterized by persistent chest pain caused by myocardial ischemia that is unresponsive to optimal pharmacological therapy and revascularization procedures. Spinal cord stimulation (SCS) has emerged as a promising therapeutic option for managing RAP, offering significant [...] Read more.
Refractory angina pectoris (RAP) is a clinical syndrome characterized by persistent chest pain caused by myocardial ischemia that is unresponsive to optimal pharmacological therapy and revascularization procedures. Spinal cord stimulation (SCS) has emerged as a promising therapeutic option for managing RAP, offering significant symptom relief and improved quality of life. A systematic literature review was conducted to evaluate the clinical effectiveness, mechanisms of action, and safety profile of SCS in treating RAP. Comprehensive searches were performed in PubMed, Scopus, and Web of Science for studies published between 1990 and 2023. Of 328 articles identified, 6 met the inclusion and exclusion criteria for final analysis. The included studies consistently demonstrated that SCS significantly reduces the frequency of anginal episodes and nitroglycerin use while improving exercise capacity and quality of life. Proposed mechanisms include modulation of pain signals via the gate control theory, enhancement of autonomic balance, and redistribution of myocardial perfusion. Novel stimulation modalities, including high-frequency, Burst, and Differential Target Multiplexed (DTM), show potential advantages in enhancing patient comfort and clinical outcomes. Nevertheless, long-term studies are necessary to validate these findings and establish the comparative efficacy of these advanced technologies. SCS is a safe and effective therapy for patients with RAP who are unsuitable for surgical interventions. Innovations in neurostimulation, including closed-loop systems and personalized treatment strategies have the potential to further optimize outcomes. Rigorous clinical trials are needed to consolidate the role of SCS as a cornerstone therapy for the management of RAP. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
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<p>Flowchart of study selection process for SCS research.</p>
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<p>Mechanism of action of SCS in RAP.</p>
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17 pages, 2086 KiB  
Article
The Target-Defining Attributes Can Determine the Effects of Attentional Control Settings in Singleton Search Mode
by Ying Chen, Junzhe Wang, Zhiwei Miao, Yunpeng Jiang and Xia Wu
Behav. Sci. 2025, 15(1), 97; https://doi.org/10.3390/bs15010097 - 20 Jan 2025
Viewed by 321
Abstract
The attentional control settings (ACSs) can help us efficiently select targets in complex real-world environments. Previous research has shown that category-specific ACS demands more attentional resources than feature-specific ACS. However, comparing natural or alphanumeric categories with color features does not distinguish the effects [...] Read more.
The attentional control settings (ACSs) can help us efficiently select targets in complex real-world environments. Previous research has shown that category-specific ACS demands more attentional resources than feature-specific ACS. However, comparing natural or alphanumeric categories with color features does not distinguish the effects of processing hierarchy and target-defining properties. The present study employed a spatial cueing paradigm to better understand the effects of target-defining properties and search mode on attentional resources in visual search. The target was defined as a combination of shape feature (shape “X”) and color category (green in different shades), which generated shape-specific ACS (sACS) and color-specific ACS (cACS). The degrees of shape matching (SM), color matching (CM), and spatial validity between the cue and target were manipulated. Search modes were manipulated by changing the homogeneity of distractors in either shape or color dimensions. Results show a main effect of CM across all four experiments, indicating that category can tune on attentional capture consistently. Importantly, the analysis between four experiments found different interactions across experiments, suggesting that the singleton search mode can reduce the effects of ACS and increase the interactions with other factors. In conclusion, this study suggests that the effects of ACS on attentional capture are determined by both target-defining properties and search mode, rather than processing hierarchy. The results indicate that attentional processes are highly dynamic and context-dependent, requiring a flexible allocation of resources to effectively prioritize relevant information. Full article
(This article belongs to the Special Issue Attention-Aware Interaction in Augmented Reality)
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<p>(<b>A</b>) Schematic representation of the procedure. After the fixation, a cue screen appears with four levels of match to the defined properties of the target: S+C+, shape and color match; S+C−, shape match, color mismatch; S−C+, shape mismatch, color match; and S−C−, shape and color mismatch. After a 100 ms interval, a search screen appeared and participants were asked to report the orientation of the frame gap surrounding the “green X” in the search screen quickly and accurately, with a response window of 1000 ms. The location of the target could be consistent with the cue (valid cue) or inconsistent with the cue (invalid cue). Distractors other than the target were different colored and shaped stimuli. The location of the cue and the orientation of the frame gap were randomized. (<b>B</b>) Accuracy (%) (<span class="html-italic">M</span> ± <span class="html-italic">SD</span>) and (<b>C</b>) reaction times (ms) (<span class="html-italic">M</span> ± <span class="html-italic">SD</span>) of matching level (S+C+, S+C−, S−C+, and S−C−) and cue validity (valid, invalid) are found in Experiment 1.</p>
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<p>(<b>A</b>) The schematic representation of the procedure of Experiment 2. (<b>B</b>) Accuracy (%) (<span class="html-italic">M</span> ± <span class="html-italic">SD</span>) and (<b>C</b>) reaction times (ms) (<span class="html-italic">M</span> ± <span class="html-italic">SD</span>) of matching level (S+C+, S+C−, S−C+, and S−C−) and cue validity (valid, invalid) in Experiment 2.</p>
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<p>(<b>A</b>) The schematic representation of the procedure of Experiment 3. (<b>B</b>) Accuracy (%) (<span class="html-italic">M</span> ± <span class="html-italic">SD</span>) and (<b>C</b>) reaction times (ms) (<span class="html-italic">M</span> ± <span class="html-italic">SD</span>) of matching level (S+C+, S+C−, S−C+, and S−C−) and cue validity (valid, invalid) in Experiment 3.</p>
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<p>(<b>A</b>) The schematic representation of the procedure of Experiment 4. (<b>B</b>) Accuracy (%) (<span class="html-italic">M</span> ± <span class="html-italic">SD</span>) and (<b>C</b>) reaction times (ms) (<span class="html-italic">M</span> ± <span class="html-italic">SD</span>) of matching level (S+C+, S+C−, S−C+, and S−C−) and cue validity (valid, invalid) in Experiment 4.</p>
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<p>Heatmaps of <span class="html-italic">p</span>-values for the main effects of SM, CM, and validity, as well as their three-way interaction, across four experiments. (<b>A</b>) Accuracy (%) and (<b>B</b>) reaction times (ms). “V” represents validity and the symbol “×” represents interaction. SF: shape feature search mode; CF: color feature search mode; SS: shape singleton search mode; and CS: color singleton search mode.</p>
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25 pages, 3438 KiB  
Review
The Impact of Sustainability Certification Schemes and Labels on Greenhouse Gas Emissions: A Systematic Evidence Map
by William J. Harvey, Naomi Black, Salma Essaouabi, Leo Petrokofsky, Vidya Rangan, Matt Stancliffe Bird, Daniel Villar, Marxine Waite and Gillian Petrokofsky
Sustainability 2025, 17(2), 792; https://doi.org/10.3390/su17020792 - 20 Jan 2025
Viewed by 538
Abstract
This systematic map explores the role of sustainability certification schemes and labels in reducing greenhouse gas emissions across biobased value chains. With increasing global and EU interest in transitioning to a sustainable bioeconomy, these certification mechanisms are seen as critical tools for promoting [...] Read more.
This systematic map explores the role of sustainability certification schemes and labels in reducing greenhouse gas emissions across biobased value chains. With increasing global and EU interest in transitioning to a sustainable bioeconomy, these certification mechanisms are seen as critical tools for promoting low-emission practices. This review maps the available evidence regarding the effectiveness of certification schemes, examining sector-specific variations and identifying knowledge gaps. A comprehensive search strategy was employed across three major databases and grey literature sources, yielding 41 relevant articles. There are significant disparities in the evidence on the impact of sustainability certification schemes and labels on greenhouse gas (GHG) emissions across biobased sectors. Agriculture has the most data, but studies are heavily focused on organic systems, limiting broader conclusions. Most research is concentrated in Southeast Asia and Europe, reducing generalizability to other regions. Additionally, most studies focus on the production stage, leaving value chain phases like processing and disposal under-represented. Knowledge gaps exist across sectors, certification schemes, and life cycle stages, highlighting the need for further research. While some schemes incorporate GHG management tools, evidence on their effectiveness remains insufficient and context-dependent, warranting more robust, targeted research. Though this research looked at all biobased feedstocks, it did not review schemes and labels specifically targeting biofuels, which presents an avenue for future research. Full article
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<p>The conceptual framework for the systematic evidence map.</p>
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<p>Selection and screening of articles detailing inclusion and exclusion at each stage of filtering process.</p>
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<p>Accessibility of included articles through subscriptions services or open access.</p>
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<p>Location of studies included in evidence base.</p>
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<p>Number of articles of literature by date of publication of articles included in the evidence map by (i) individual year (bars) and (ii) cumulatively (line).</p>
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<p>Number of articles addressing greenhouse gas emissions across certification scheme/label (<span class="html-italic">n</span> ≥ 3) grouped by geographic region as defined by United Nations Statistical Division.</p>
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<p>Number of articles addressing greenhouse gas emissions across sectors grouped by geographic region as defined by United Nations Statistical Division.</p>
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<p>Number of articles addressing greenhouse gas emissions (<span class="html-italic">n</span> ≥ 3) across feedstock/product grouped by geographic region as defined by United Nations Statistical Division.</p>
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<p>Number of articles addressing greenhouse gas emissions across certification scheme/label grouped by geographic region as defined by United Nations Statistics Division.</p>
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<p>Number of articles addressing greenhouse gas emissions across certification scheme/label grouped by sector.</p>
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<p>The risk of bias in the evidence base.</p>
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