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23 pages, 683 KiB  
Review
Endometriosis and Nutrition: Therapeutic Perspectives
by Francesco Giuseppe Martire, Eugenia Costantini, Claudia d’Abate, Giovanni Capria, Emilio Piccione and Angela Andreoli
J. Clin. Med. 2025, 14(11), 3987; https://doi.org/10.3390/jcm14113987 (registering DOI) - 5 Jun 2025
Abstract
Endometriosis is a chronic, hormone-dependent disorder characterized by an inflammatory response. The disease affects approximately 10% of the general female population, with prevalence rates reaching 30–40% in women with dysmenorrhea and 50–60% in those experiencing infertility. In addition to pelvic pain and reproductive [...] Read more.
Endometriosis is a chronic, hormone-dependent disorder characterized by an inflammatory response. The disease affects approximately 10% of the general female population, with prevalence rates reaching 30–40% in women with dysmenorrhea and 50–60% in those experiencing infertility. In addition to pelvic pain and reproductive issues, gastrointestinal symptoms, such as acute abdominal pain, constipation, diarrhea, or alternating bowel habits, are frequently reported and can be highly disabling. Emerging evidence indicates that dietary patterns may modulate the inflammatory environment associated with endometriosis, potentially influencing symptom severity by affecting oxidative stress, estrogen metabolism, and levels of sex hormone-binding globulin (SHBG). Diets rich in antioxidants, polyunsaturated fatty acids (PUFAs), and vitamins D, C, and E—alongside the avoidance of processed foods, red meat, and animal fats—may offer beneficial effects. This narrative review explores the relationship between nutrition and endometriosis, emphasizing the therapeutic potential of dietary interventions as a complementary strategy. Notably, dietary approaches may serve not only to alleviate pain and improve fertility outcomes but also to reduce lesion growth and recurrence, particularly in patients seeking pregnancy or those unable to undergo hormonal therapy due to contraindications. Furthermore, nutritional strategies may enhance postoperative recovery and act as a viable first-line therapy when conventional treatments are not applicable. A total of 250 studies were initially identified through PubMed and Scopus. After removing duplicates and non-relevant articles, 174 were included in this review. Our findings underscore the urgent need for further studies to develop evidence-based, personalized nutritional interventions for managing endometriosis-related symptoms. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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25 pages, 4654 KiB  
Article
The Impacts of Heatwaves on Population Distribution in the Subtropical City: A Case Study of Nanchang, China
by Zixun Chen and Zongcai Wei
Land 2025, 14(6), 1209; https://doi.org/10.3390/land14061209 (registering DOI) - 5 Jun 2025
Abstract
Global warming has intensified the frequency and intensity of heatwaves, particularly in urban areas, significantly affecting residents’ daily activities. Extant studies have mainly concentrated on the relationship between socio-economic attributes and the impacts of heatwaves on urban populations. However, the relationship between the [...] Read more.
Global warming has intensified the frequency and intensity of heatwaves, particularly in urban areas, significantly affecting residents’ daily activities. Extant studies have mainly concentrated on the relationship between socio-economic attributes and the impacts of heatwaves on urban populations. However, the relationship between the built environment and the impacts of heatwaves on urban population distribution has not received much attention. Furthermore, most studies have overlooked the temporal heterogeneity in heatwave impacts on population activities and distribution. Therefore, taking the central urban area of Nanchang as the case, this study investigated the impacts of heatwaves on population distribution and their temporal heterogeneity. Moreover, it identified the nonlinear relationships between built environment factors and population changes during heatwaves by using the XGBoost model and SHAP method. The results revealed that heatwaves exerted the largest impacts on population distribution during weekend nights, followed by weekend daytime and weekday nighttime, with the least impacts observed during weekday daytime. Furthermore, location and transportation factors significantly affected population changes during heatwaves across most time periods, with their influences being associated with policy factors such as the high-temperature leave policy for workers in industrial zones located in urban fringe areas and the cooling zone establishment policy for citizens in subway stations. Moreover, land use and building form factors exhibited significant temporal heterogeneity in their impacts on population changes during heatwaves. This temporal heterogeneity was fundamentally driven by individuals’ heat adaptation behaviors, the spatiotemporal patterns of their daily activities, and the diurnal variations in the built environment’s influence on local thermal environment. These findings provide valuable insights to proactively alleviate the adverse impacts of heatwaves. Full article
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12 pages, 622 KiB  
Review
Is African Swine Fever Driven by Flying Hematophagous Insects?
by Marek Walczak, Maciej Frant, Krzesimir Szymankiewicz, Małgorzata Juszkiewicz, Katarzyna Podgórska and Marcin Smreczak
Pathogens 2025, 14(6), 563; https://doi.org/10.3390/pathogens14060563 (registering DOI) - 5 Jun 2025
Abstract
African swine fever (ASF) has become one of the most economically important diseases affecting swine and has a significant negative impact on the global pork production sector. In Europe, the main reservoir of the disease is the wild boar population, which poses a [...] Read more.
African swine fever (ASF) has become one of the most economically important diseases affecting swine and has a significant negative impact on the global pork production sector. In Europe, the main reservoir of the disease is the wild boar population, which poses a risk of transmitting the disease to pig farms. To date, no safe and effective vaccine is available on the market. Therefore, biosecurity measures and early recognition of the disease play a key role in preventing and combating ASF. In recent years, numerous insights into the nature of the virus have emerged; however, several knowledge gaps still need to be addressed. One of these gaps is an accurate understanding of all possible pathways through which the virus can reach a pig farm. Interrupting these pathways would significantly reduce the risk of disease outbreaks. Despite a general understanding of disease transmission, ASF can still affect farms with well-established high biosecurity measures. This article highlights the potential for mechanical transmission of ASF by flying hematophagous insects, considering several factors, including current knowledge of the putative role of insects in ASF transmission, insects’ abilities to transmit the virus, ASFV properties, the uncertainties regarding the effectiveness of indirect transmission, and the seasonality of disease outbreaks on domestic pig farms. Full article
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10 pages, 290 KiB  
Article
The Associations of Serum Folate Forms with Metabolic Dysfunction-Associated Fatty Liver Disease and Liver Fibrosis: A Nationwide Cross-Sectional Study
by Hai Zhao, Wei Fan, Yan Yan, Yuxing Liu and Xuejun Kang
Metabolites 2025, 15(6), 370; https://doi.org/10.3390/metabo15060370 (registering DOI) - 5 Jun 2025
Abstract
Background: Accumulating evidence indicates a link between folate and metabolic dysfunction-associated fatty liver disease (MAFLD). Objectives: The aim of this study was to ascertain whether different serum folate forms are associated with newly defined MAFLD as well as liver fibrosis in [...] Read more.
Background: Accumulating evidence indicates a link between folate and metabolic dysfunction-associated fatty liver disease (MAFLD). Objectives: The aim of this study was to ascertain whether different serum folate forms are associated with newly defined MAFLD as well as liver fibrosis in the US general population. Methods: This cross-sectional study used data from the 2017–2020 (March) cycle and 2017–2018 cycle of the National Health and Nutrition Examination Survey (NHANES) in the US. Hepatic steatosis and fibrosis were evaluated by transient elastography, which employed controlled attenuation parameters and liver stiffness measurements as assessment indicators. Results: 7447 eligible individuals were included. The estimated prevalence of MAFLD and liver fibrosis was 51.6% (95% confidence interval [CI]: 50.4–52.7%) and 10.0% (95% CI: 9.3–10.7%). After adjusting for confounding factors, for every 1 nmol/L increase in serum 5-methyltetrahydrofolate (5-mTHF), the risk of developing liver fibrosis decreased by 1% (95% CI: 1–2%, p < 0.001), and the risk of developing MAFLD decreased by 1% (95% CI: 0–2%, p = 0.005). There were also significant differences in indicators such as alanine aminotransferase (ALT), gamma-glutamyl transaminase (GGT), and C-reactive protein (CRP) between the MAFLD group and the non-MAFLD group (all p values < 0.001). Conclusions: This study suggests the prevalence of MAFLD and liver fibrosis decreased significantly with the increase in serum 5-mTHF concentration. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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13 pages, 851 KiB  
Article
Antiplatelet Treatment Strategy in MINOCA Patients: Predictors of Decision Making in Clinical Practice and Prognostic Implications
by Emmanouil Mantzouranis, Ioannis Leontsinis, Panayotis K. Vlachakis, Constantinos Mihas, Panagiotis Iliakis, Eirini Dri, Athanasios Sakalidis, Stergios Soulaidopoulos, Christos Fragoulis, Anastasios Milkas, Eleftherios Tsiamis, Dimitrios Tsiachris, Kyriakos Dimitriadis and Konstantinos Tsioufis
J. Clin. Med. 2025, 14(11), 3984; https://doi.org/10.3390/jcm14113984 (registering DOI) - 5 Jun 2025
Abstract
Background/Objectives: Large clinical trials have established the optimal antiplatelet strategy in the wide spectrum of coronary artery disease. However, data are scarce regarding MINOCA and the aim of our study is to present data from the current clinical practice. Methods: A total [...] Read more.
Background/Objectives: Large clinical trials have established the optimal antiplatelet strategy in the wide spectrum of coronary artery disease. However, data are scarce regarding MINOCA and the aim of our study is to present data from the current clinical practice. Methods: A total of 151 patients were included in this study after exclusion of 27 patients with myocarditis and other diagnoses. A cardiac magnetic resonance (CMR) performed at 123/151 patients demonstrated an ischemic pattern of late gadolinium enhancement (LGE) confirming the diagnosis of true acute myocardial infarction (AMI) in 42 cases (28%). Based on multimodality imaging and clinical judgement, Takotsubo syndrome (TTS) was diagnosed in 55 patients (36%), whereas CMR failed to reveal abnormal findings in 54 cases (36%), categorized as MINOCA of unknown origin. Results: Regarding antithrombotic prescriptions at discharge, 38% of patients received dual antiplatelet (DAPT) or dual antithrombotic therapy (DAT, 1 antiplatelet plus 1 anticoagulant), 49.7% received single antiplatelet (SAPT) or anticoagulant, and 12% received no antithrombotic treatment. Univariate analysis showed that the likelihood of prescribing DAPT or DAT was associated with left ventricular ejection fraction (LVEF) (r = 0.202, p = 0.013), atherosclerotic lesions on coronary angiography (r = 0.303, p < 0.001), prior use of anticoagulants (r = −0.258, p = 0.001), and marginally with the INTERTAK score (r = −0.198, p = 0.044). A multivariable model, adjusted for age, LVEF, ECG abnormalities, and history of anticoagulant use, confirmed the independent association between angiographic evidence of atherosclerosis and the decision for DAPT/DAT (OR: 0.334, 95% CI: 0.307–0.813, p < 0.001). However, the initial treatment decision did not seem to impact 2-year prognosis in our population. Conclusions: Our study results reveal that decision making in the antithrombotic strategy for MINOCA patients poses a challenge in clinical practice. More robust data are required for definite conclusions on the prognostic implications. Full article
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11 pages, 1115 KiB  
Article
Monitoring Multiple Sexually Transmitted Pathogens Through Wastewater Surveillance
by Balghsim Alshehri, Olivia N. Birch and Justin C. Greaves
Pathogens 2025, 14(6), 562; https://doi.org/10.3390/pathogens14060562 (registering DOI) - 5 Jun 2025
Abstract
Wastewater-based epidemiology (WBE) offers a promising tool for sexually transmitted infection (STI) surveillance, especially in settings where underdiagnosis or social stigma complicates conventional reporting. To assess its utility, we conducted a year-long study examining six STIs, Chlamydia trachomatis, Treponema pallidum, Neisseria [...] Read more.
Wastewater-based epidemiology (WBE) offers a promising tool for sexually transmitted infection (STI) surveillance, especially in settings where underdiagnosis or social stigma complicates conventional reporting. To assess its utility, we conducted a year-long study examining six STIs, Chlamydia trachomatis, Treponema pallidum, Neisseria gonorrhoeae, human immunodeficiency virus (HIV), hepatitis C virus (HCV), and herpes simplex virus (HSV), in weekly composite samples from the primary influent of a small-sized Midwestern wastewater treatment plant. Pathogen detection and quantification were performed via digital PCR. Among the tested targets, Gonorrhea, HIV, HCV, and HSV were detected at the highest frequencies, often in 40–50% of the samples, while Chlamydia and Syphilis appeared less frequently. Despite the variability in detection patterns, this study demonstrates that even infrequent signals can reveal community-level shedding of poorly reported or asymptomatic infections. Although month-to-month wastewater data were not strongly correlated with corresponding clinical records, which could potentially reflect delayed healthcare seeking and pathogen-specific shedding dynamics, the overall findings underscore WBE’s ability to complement existing surveillance by capturing infections outside traditional healthcare channels. These results not only advance our understanding of STI prevalence and population shedding but also highlight the practical benefits of WBE as an early warning and targeted intervention tool. Full article
(This article belongs to the Special Issue Wastewater Surveillance and Public Health Strategies)
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24 pages, 7044 KiB  
Article
Genomics and Transcriptomics of 3ANX (NX-2) and NX (NX-3) Producing Isolates of Fusarium graminearum
by Philip L. Walker, Sean Walkowiak, Srinivas Sura, E. RoTimi Ojo and Maria A. Henriquez
Toxins 2025, 17(6), 284; https://doi.org/10.3390/toxins17060284 (registering DOI) - 5 Jun 2025
Abstract
Fusarium head blight (FHB) is an important fungal disease caused by Fusarium graminearum and other Fusarium spp., resulting in significant yield losses across cereal grains. Recently identified F. graminearum isolates in Canada, capable of producing type A trichothecene mycotoxins 3ANX (NX-2, 7-α hydroxy,15-deacetylcalonectrin) [...] Read more.
Fusarium head blight (FHB) is an important fungal disease caused by Fusarium graminearum and other Fusarium spp., resulting in significant yield losses across cereal grains. Recently identified F. graminearum isolates in Canada, capable of producing type A trichothecene mycotoxins 3ANX (NX-2, 7-α hydroxy,15-deacetylcalonectrin) and NX (NX-3, 7-α hydroxy, 3,15-dideacetylcalonectrin), demonstrated high levels of genetic diversity. While recent studies have detected this genetic and chemical diversity, little is known of the underlying molecular mechanisms and processes influenced by these distinct chemotypes and regional populations. In the current study, we used an -omics approach coupled with high-resolution mass spectrometry to characterize twenty F. graminearum isolates collected from five distinct regions across Manitoba. These data identified regional F. graminearum populations within Manitoba that demonstrate distinct genomic variation and patterns of gene expression, particularly within pathogenicity-associated processes. Further, we identified genetic variation and differential expression between isolates showing high and low levels of pathogenicity, allowing for the identification of previously characterized and novel putative pathogenicity factors. Lastly, we detected the production of 3ANX and/or NX mycotoxins within the majority of our twenty characterized F. graminearum isolates, suggesting the 3ANX chemotype may be more prevalent than previously expected in Canada. Ultimately, these findings highlight the diversity of F. graminearum across Manitoba and, more importantly, uncover specific genomic regions and candidate pathogenicity factors influenced by this diversity. Full article
(This article belongs to the Section Mycotoxins)
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26 pages, 920 KiB  
Article
Urban Maturity Performance Measurement System Through Smart City Actions
by Elizeu de Albuquerque Jacques, Alvaro Neuenfeldt Júnior, Sabine De Paris, Ronier Gutierrez and Julio Siluk
Sustainability 2025, 17(11), 5199; https://doi.org/10.3390/su17115199 (registering DOI) - 5 Jun 2025
Abstract
The uncontrolled urbanization of Brazilian cities accentuates the imbalance between population demands and urban space planning. The integrated management of human and technological resources constitutes a fundamental governance strategy for the proposition of sustainable and effective responses to the challenges faced by cities. [...] Read more.
The uncontrolled urbanization of Brazilian cities accentuates the imbalance between population demands and urban space planning. The integrated management of human and technological resources constitutes a fundamental governance strategy for the proposition of sustainable and effective responses to the challenges faced by cities. To generate references to public management, the objective of this research was to develop a management tool to verify the maturity level of Brazilian cities for smart city actions. A performance measurement system (PMS) organized smart city actions into 11 thematic areas, quantitatively measuring smart city actions in a down–top structure since the indicators and metrics are described in a standardized scale to obtain the general maturity index (GMI). The PMS was implemented in the city of Santa Maria/Brazil, where its GMI equal to 43.72% indicated a currently intermediate maturity level of smart city actions, mainly related to the low performance in the thematic areas of mobility, coexistence and reciprocity, and security and protection. To improve the current performance, five incremental actions were proposed, contemplating the key performance indicators “Public roads”, “Multipurpose lanes”, “Public accessibility”, “Accessibility signage”, and “Monitoring”, projecting a GMI equal to 49.75% and 55.78%, respectively, for an intermediate and an advanced maturity level scenario. Full article
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32 pages, 2378 KiB  
Review
Pyrolysis Process, Reactors, Products, and Applications: A Review
by Prakhar Talwar, Mariana Alzate Agudelo and Sonil Nanda
Energies 2025, 18(11), 2979; https://doi.org/10.3390/en18112979 (registering DOI) - 5 Jun 2025
Abstract
With the rapid growth of the global population, increasing per capita energy demands, and waste generation, the need for innovative strategies to mitigate greenhouse gas emissions and effective waste management has become paramount. Pyrolysis, a thermochemical conversion process, facilitates the transformation of diverse [...] Read more.
With the rapid growth of the global population, increasing per capita energy demands, and waste generation, the need for innovative strategies to mitigate greenhouse gas emissions and effective waste management has become paramount. Pyrolysis, a thermochemical conversion process, facilitates the transformation of diverse biomass feedstocks, including agricultural biomass, forestry waste, and other carbonaceous wastes, into valuable biofuels such as bio-oil, biochar, and producer gas. The article reviews the benefits of pyrolysis as an effective and scalable technique for biofuel production from waste biomass. The review describes the different types of pyrolysis processes, such as slow, intermediate, fast, and catalytic, focusing on the effects of process parameters like temperature, heating rate, and residence time on biofuel yields and properties. The review also highlights the configurations and operating principles of different reactors used for pyrolysis, such as fixed bed, fluidized bed, entrained flow, plasma system, and microwaves. The review examines the factors affecting reactor performance, including energy consumption and feedstock attributes while highlighting the necessity of optimizing these systems to improve sustainability and economic feasibility in pyrolysis processes. The diverse value-added applications of biochar, bio-oil, and producer gas obtained from biomass pyrolysis are also discussed. Full article
(This article belongs to the Collection Bio-Energy Reviews)
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22 pages, 3223 KiB  
Article
An EMG-Based GRU Model for Estimating Foot Pressure to Support Active Ankle Orthosis Development
by Praveen Nuwantha Gunaratne and Hiroki Tamura
Sensors 2025, 25(11), 3558; https://doi.org/10.3390/s25113558 (registering DOI) - 5 Jun 2025
Abstract
As populations age, particularly in countries like Japan, mobility impairments related to ankle joint dysfunction, such as foot drop, instability, and reduced gait adaptability, have become a significant concern. Active ankle–foot orthoses (AAFO) offer targeted support during walking; however, most existing systems rely [...] Read more.
As populations age, particularly in countries like Japan, mobility impairments related to ankle joint dysfunction, such as foot drop, instability, and reduced gait adaptability, have become a significant concern. Active ankle–foot orthoses (AAFO) offer targeted support during walking; however, most existing systems rely on rule-based or threshold-based control, which are often limited to sagittal plane movements and lacking adaptability to subject-specific gait variations. This study proposes an approach driven by neuromuscular activation using surface electromyography (EMG) and a Gated Recurrent Unit (GRU)-based deep learning model to predict plantar pressure distributions at the heel, midfoot, and toe regions during gait. EMG signals were collected from four key ankle muscles, and plantar pressures were recorded using a customized sandal-integrated force-sensitive resistor (FSR) system. The data underwent comprehensive preprocessing and segmentation using a sliding window method. Root mean square (RMS) values were extracted as the primary input feature due to their consistent performance in capturing muscle activation intensity. The GRU model successfully generalized across subjects, enabling the accurate real-time inference of critical gait events such as heel strike, mid-stance, and toe off. This biomechanical evaluation demonstrated strong signal compatibility, while also identifying individual variations in electromechanical delay (EMD). The proposed predictive framework offers a scalable and interpretable approach to improving real-time AAFO control by synchronizing assistance with user-specific gait dynamics. Full article
(This article belongs to the Special Issue Sensor-Based Human Activity Recognition)
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24 pages, 1699 KiB  
Review
Evaluating Project Selection Criteria for Transportation Improvement Plans (TIPs): A Study of Southeastern U.S. Metropolitan Planning Organizations
by Mahdi Baghersad, Virginia P. Sisiopiku and Avinash Unnikrishnan
Future Transp. 2025, 5(2), 72; https://doi.org/10.3390/futuretransp5020072 (registering DOI) - 5 Jun 2025
Abstract
Metropolitan Planning Organizations (MPOs) are required to prepare a Transportation Improvement Plan (TIP) that outlines a fiscal strategy over a four-year period in order to qualify for federal funding. However, the growing population and limited financial resources available often pose significant challenges for [...] Read more.
Metropolitan Planning Organizations (MPOs) are required to prepare a Transportation Improvement Plan (TIP) that outlines a fiscal strategy over a four-year period in order to qualify for federal funding. However, the growing population and limited financial resources available often pose significant challenges for transportation agencies in aligning their needs with available budgets. This article examines the project selection criteria used by 20 MPOs in the Southeastern United States to identify the best practices for prioritizing projects in TIPs. Using document analysis, this study categorizes the most commonly used criteria into nine broad groups: safety and security; environmental impacts; mobility, accessibility, and connectivity; preservation; environmental justice; equity; economic factors; alignment with other plans; and local support. Many of these categories are further divided into subcategories and metrics. Despite variations in criteria, weighting, scoring, and methodologies across these MPOs, the study identifies several shared factors that support effective decision-making in regional transportation planning. These findings can help transportation planners and policymakers refine their project prioritization strategies, promote consistency, and lead to improved decision-making frameworks for future TIP development. Full article
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13 pages, 631 KiB  
Article
How Do Fear-Avoidance and Catastrophizing Pain Beliefs Affect Functional Status and Disease Activity in Axial Spondyloarthritis?
by Carlos Fernández-Morales, María de los Ángeles Cardero-Durán, Manuel Albornoz-Cabello and Luis Espejo-Antúnez
Medicina 2025, 61(6), 1039; https://doi.org/10.3390/medicina61061039 (registering DOI) - 5 Jun 2025
Abstract
Background and Objectives: The objective of our study was to describe the biopsychosocial profile of individuals diagnosed with axial spondyloarthritis (AxSpA) and to analyze how their clinical characteristics interact with disease activity. Materials and Methods: An observational study was conducted, involving [...] Read more.
Background and Objectives: The objective of our study was to describe the biopsychosocial profile of individuals diagnosed with axial spondyloarthritis (AxSpA) and to analyze how their clinical characteristics interact with disease activity. Materials and Methods: An observational study was conducted, involving 28 participants diagnosed with AxSpA. We evaluated clinical outcomes (perceived pain, range of motion [RoM], pressure pain threshold [PPT], and proprioceptive acuity), psychosocial outcomes (the Pain Catastrophizing Scale [PCS], Tampa Scale of Kinesiophobia [TSK-11], and the Fear-Avoidance Beliefs Questionnaire [FABQ]), and AxSpA-specific indices (the Bath Ankylosing Spondylitis Metrology Index [BASMI], Bath Ankylosing Spondylitis Functional Index [BASFI], and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Data were analyzed using Spearman’s correlation coefficients and simple and multiple linear regression models. Results: Cervical and lumbar RoM values were reduced compared to established normative values for the general population. Significant associations were found between perceived pain, pain catastrophizing, and FABQ scores with both BASDAI and BASFI (p < 0.05). The interaction between perceived pain and pain catastrophizing (p < 0.001) accounted for 45.7% of the variance in BASDAI, while the interaction between perceived pain and FABQ (p < 0.001) explained 52.1% of the variance in BASDAI. Conclusions: The biopsychosocial profile of patients with AxSpA is characterized by moderate-intensity perceived pain and reduced cervical and lumbar mobility. The observed associations between BASDAI, pain catastrophizing, and fear-avoidance beliefs underscore the influence of psychosocial factors on disease progression. Full article
(This article belongs to the Section Psychiatry)
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16 pages, 1600 KiB  
Article
Leveraging Neural ODEs for Population Pharmacokinetics of Dalbavancin in Sparse Clinical Data
by Tommaso Giacometti, Ettore Rocchi, Pier Giorgio Cojutti, Federico Magnani, Daniel Remondini, Federico Pea and Gastone Castellani
Entropy 2025, 27(6), 602; https://doi.org/10.3390/e27060602 (registering DOI) - 5 Jun 2025
Abstract
This study investigates the use of Neural Ordinary Differential Equations (NODEs) as an alternative to traditional compartmental models and Nonlinear Mixed-Effects (NLME) models for drug concentration prediction in pharmacokinetics. Unlike standard models that rely on strong assumptions and often struggle with high-dimensional covariate [...] Read more.
This study investigates the use of Neural Ordinary Differential Equations (NODEs) as an alternative to traditional compartmental models and Nonlinear Mixed-Effects (NLME) models for drug concentration prediction in pharmacokinetics. Unlike standard models that rely on strong assumptions and often struggle with high-dimensional covariate relationships, NODEs offer a data-driven approach, learning differential equations directly from data while integrating covariates. To evaluate their performance, NODEs were applied to a real-world Dalbavancin pharmacokinetic dataset comprising 218 patients and compared against a two-compartment model and an NLME within a cross-validation framework, which ensures an evaluation of robustness. Given the challenge of limited data availability, a data augmentation strategy was employed to pre-train NODEs. Their predictive performance was assessed both with and without covariates, while model explainability was analyzed using Shapley additive explanations (SHAP) values. Results show that, in the absence of covariates, NODEs performed comparably to state-of-the-art NLME models. However, when covariates were incorporated, NODEs demonstrated superior predictive accuracy. SHAP analyses further revealed how NODEs leverage covariates in their predictions. These results establish NODEs as a promising alternative for pharmacokinetic modeling, particularly in capturing complex covariate interactions, even when dealing with sparse and small datasets, thus paving the way for improved drug concentration predictions and personalized treatment strategies in precision medicine. Full article
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20 pages, 285 KiB  
Review
Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis: A Review of Registry-Based Evidence
by Donatello Salvatore and Angela Pepe
J. Clin. Med. 2025, 14(11), 3978; https://doi.org/10.3390/jcm14113978 - 5 Jun 2025
Abstract
Fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRms) have significantly improved outcomes in people with cystic fibrosis (CF). Real-world evidence, particularly from national and international CF registries, is essential to assess their long-term effectiveness and safety. We reviewed published studies using registry data to [...] Read more.
Fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRms) have significantly improved outcomes in people with cystic fibrosis (CF). Real-world evidence, particularly from national and international CF registries, is essential to assess their long-term effectiveness and safety. We reviewed published studies using registry data to evaluate the impact of CFTRms on clinical outcomes in individuals with CF. A narrative review of studies published between 2015 and 2025 was conducted, focusing on registry-based evaluations of ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor. Primary outcomes included lung function, pulmonary exacerbations, nutritional status, and survival. Fifty-seven registry-based studies confirmed the benefits of CFTRms across diverse CF populations. Ivacaftor has demonstrated sustained improvements in forced expiratory volume in one second (FEV1), reduced exacerbations, and improved nutritional outcomes. Lumacaftor/ivacaftor and tezacaftor/ivacaftor have shown modest benefits, especially in homozygous F508del patients. The introduction of elexacaftor/tezacaftor/ivacaftor has led to unprecedented improvements in lung function and quality of life, along with a reduced need for lung transplantation. Methodological heterogeneity and incomplete data remain challenges. Registry data provide essential, complementary evidence to clinical trials and support the effectiveness of CFTRms in routine care. Continued efforts are needed to harmonize registry methodologies and outcome measures. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Diagnosis and Treatment)
17 pages, 2876 KiB  
Article
Genetic Analyses, BSA-Seq, and Transcriptome Analyses Reveal Candidate Genes Controlling Leaf Plastochron in Rapeseed (Brassica napus L.)
by Mengfan Qin, Xiang Liu, Jia Song, Feixue Zhao, Yiji Shi, Yu Xu, Zhiting Guo, Tianye Zhang, Jiapeng Wu, Jinxiong Wang, Wu Li, Keqi Li, Shimeng Li, Zhen Huang and Aixia Xu
Plants 2025, 14(11), 1719; https://doi.org/10.3390/plants14111719 - 5 Jun 2025
Abstract
The leaf plastochron serves as an indicator of the rate of leaf appearance, biomass accumulation, and branch number, while also impacting plant architecture and seed yield. However, research on the leaf plastochron of crops remains limited. In this study, 2116C exhibited a rapid [...] Read more.
The leaf plastochron serves as an indicator of the rate of leaf appearance, biomass accumulation, and branch number, while also impacting plant architecture and seed yield. However, research on the leaf plastochron of crops remains limited. In this study, 2116C exhibited a rapid leaf plastochron compared to ZH18 during both rosette and bud periods. There were significant positive correlations among the leaf plastochron and primary branch number of the F2 populations (r ranging from 0.395 to 0.635, p < 0.01). Genetic analyses over two years demonstrated that two equally dominant genes might govern the leaf plastochron. Through bulk segregant analysis sequencing (BSA-seq), three novel genomic intervals were identified on chromosomes A02 (9.04–9.48 Mb and 13.52–13.66 Mb) and A04 (19.84–20.14 Mb) of ZS11 and Darmor-bzh reference genomes. By gene functional annotations, single-nucleotide variation (SNV) analyses, transcriptome data from parents, genetic progeny, and natural accessions, we identified ten candidate genes within the intervals, including FLOWERING LOCUS T, RGL1, MYB-like, CYP96A8, BLH3, NIT2, ASK6, and three CLAVATA3/ESR (CLE)-related genes. These findings lay the molecular foundation for further exploration into the leaf plastochron and the implications in plastochron-related breeding in rapeseed. Full article
(This article belongs to the Special Issue Crop Functional Genomics and Biological Breeding—2nd Edition)
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