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18 pages, 1188 KiB  
Review
Functional and Neuroplastic Effects of Cross-Education in Anterior Cruciate Ligament Rehabilitation: A Scoping Review with Bibliometric Analysis
by Jorge M. Vélez-Gutiérrez, Andrés Rojas-Jaramillo, Juan D. Ascuntar-Viteri, Juan D. Quintero, Francisco García-Muro San José, Bruno Bazuelo-Ruiz, Roberto Cannataro and Diego A. Bonilla
Appl. Sci. 2025, 15(15), 8641; https://doi.org/10.3390/app15158641 (registering DOI) - 4 Aug 2025
Abstract
Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional [...] Read more.
Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional and neuroplastic effects of CE rehabilitation post-ACLR. Following PRISMA-ScR and JBI guidelines, PubMed, Scopus, Web of Science, and PEDro were searched up to February 2025. A bibliometric analysis was also conducted to report keyword co-occurrence and identify trends in this line of research. Of 333 screened references, 14 studies (price index: 43% and low-to-moderate risk of bias) involving 721 participants (aged 17–45 years) met inclusion criteria. CE protocols (6–12 weeks; 2–5 sessions/week) incorporating isometric, concentric, and eccentric exercises demonstrated strength gains (10–31%) and strength preservation, alongside improved limb symmetry (5–14%) and dynamic balance (7–18%). There is growing interest in neuroplasticity and corticospinal excitability, although neuroplastic changes were assessed heterogeneously across studies. Findings support CE as a feasible and low-cost strategy to complement early-stage ACLR rehabilitation, especially when direct loading of the affected limb is limited. Standardized protocols for clinical intervention and neurophysiological assessment are needed. Full article
(This article belongs to the Special Issue Novel Approaches of Physical Therapy-Based Rehabilitation)
13 pages, 1412 KiB  
Article
Person-to-Person Transmission During a Norovirus Outbreak in a Korean Kindergarten: A Retrospective Cohort Study
by Yongho Park, Hyelim Jang, Jieun Jang and Ji-Hyuk Park
Children 2025, 12(8), 1027; https://doi.org/10.3390/children12081027 - 4 Aug 2025
Abstract
Objectives: Norovirus outbreaks occur in densely populated environments, such as long-term care facilities, hospitals, and schools. On 22 October 2022, an outbreak of acute gastroenteritis was reported at a kindergarten in Korea. An epidemiologic investigation was conducted to identify the source of the [...] Read more.
Objectives: Norovirus outbreaks occur in densely populated environments, such as long-term care facilities, hospitals, and schools. On 22 October 2022, an outbreak of acute gastroenteritis was reported at a kindergarten in Korea. An epidemiologic investigation was conducted to identify the source of the infection and prevent further spread. Methods: Rectal swab and environmental samples were collected for bacterial and viral testing. A retrospective cohort study was conducted among 114 kindergarteners at the kindergarten. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to assess associations of contact with the primary case, as well as food and water consumption. Results: Of the kindergarteners, 28 out of 114 (24.6%) met the case definition. The primary case occurred on 19 October, and subsequent cases began on 21 October. Sharing the same four-year-old class as the primary case (RR, 2.56; 95% CI, 1.35–4.87), being in the same regular class (RR, 2.37; 95% CI, 1.27–4.41), being on the same floor during after-school class (RR, 3.49; 95% CI, 1.74–7.00), and attending the same English class (RR, 1.98; 95% CI, 1.05–3.72) were statistically significant. Consumption of drinking water on the third floor and fourth floor on 20 October had significantly higher and lower RRs, respectively. Norovirus was detected in 9 out of 18 rectal swab samples (50.0%). Conclusions: This norovirus outbreak at the kindergarten was presumed to have been caused by person-to-person transmission from the primary case. Isolation and restriction of symptomatic children in kindergartens should be thoroughly implemented. Additionally, enhanced surveillance among family members of affected individuals is necessary to prevent further outbreaks. Full article
(This article belongs to the Section Pediatric Infectious Diseases)
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42 pages, 1407 KiB  
Review
Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes
by Charles F. Manful, Eric Fordjour, Dasinaa Subramaniam, Albert A. Sey, Lord Abbey and Raymond Thomas
Int. J. Mol. Sci. 2025, 26(15), 7520; https://doi.org/10.3390/ijms26157520 (registering DOI) - 4 Aug 2025
Abstract
Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. [...] Read more.
Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. Oxidative/nitrosative stress is a pathological state, resulting from the overproduction of reactive species exceeding the antioxidant capacity of the body, which is implicated in several chronic human diseases. Antioxidant therapies aimed at restoring redox balance and preventing oxidative/nitrosative stress have demonstrated efficacy in preclinical models. However, their clinical applications have met with inconsistent success owing to efficacy, safety, and bioavailability concerns. This summative review analyzes the role of reactive species in human pathophysiology, the mechanisms of action of antioxidant protection, and the challenges that hinder their translation into effective clinical therapies in order to evaluate potential emerging strategies such as targeted delivery systems, precision medicine, and synergistic therapeutic approaches, among others, to overcome current limitations. By integrating recent advances, this review highlights the value of targeting reactive species in the prevention and management of chronic diseases. Full article
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23 pages, 470 KiB  
Systematic Review
Current Understanding and Future Research Direction for Estimating the Postmortem Interval: A Systematic Review
by Gabriela Strete, Andreea Sălcudean, Adina-Alexandra Cozma and Carmen-Corina Radu
Diagnostics 2025, 15(15), 1954; https://doi.org/10.3390/diagnostics15151954 - 4 Aug 2025
Abstract
Background: Accurate estimation of the postmortem interval (PMI) is critical in forensic death investigations. Traditional signs of death—algor mortis, livor mortis, and rigor mortis—are generally reliable only within the first two to three days after death, with their accuracy decreasing as decomposition [...] Read more.
Background: Accurate estimation of the postmortem interval (PMI) is critical in forensic death investigations. Traditional signs of death—algor mortis, livor mortis, and rigor mortis—are generally reliable only within the first two to three days after death, with their accuracy decreasing as decomposition progresses. This paper presents a systematic review conducted in accordance with PRISMA guidelines, aiming to evaluate and compare current methods for estimating the PMI. Specifically, the study identifies both traditional and modern techniques, analyzes their advantages, limitations, and applicable timeframes, critically synthesizes the literature, and highlights the importance of combining multiple approaches to improve accuracy. Methods: A systematic search was conducted in the PubMed, Scopus, and Web of Science databases, following the PRISMA guidelines. The review included original articles and reviews that evaluated PMI estimation methods (through thanatological signs, entomology, microbial succession, molecular, imaging, and omics approaches). Extracted data included study design, methodology, PMI range, and accuracy information. Out of the 1245 identified records, 50 studies met the inclusion criteria for qualitative synthesis. Results: Emerging methods, such as molecular markers, microbial succession, omics technologies, and advanced imaging show improved accuracy across extended postmortem intervals. RNA degradation methods demonstrated higher accuracy within the first 72 h, while entomology and microbial analysis are more applicable during intermediate and late decomposition stages. Although no single method is universally reliable, combining traditional and modern approaches tailored to case-specific factors improves overall PMI estimation accuracy. Conclusions: This study supports the use of an integrative, multidisciplinary, and evidence-based approach to improve time-since-death estimation. Such a strategy enhances forensic outcomes by enabling more precise PMI estimates in complex or delayed cases, increasing legal reliability, and supporting court-admissible expert testimony based on validated, multi-method protocols. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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19 pages, 554 KiB  
Systematic Review
Education, Neuroscience, and Technology: A Review of Applied Models
by Elena Granado De la Cruz, Francisco Javier Gago-Valiente, Óscar Gavín-Chocano and Eufrasio Pérez-Navío
Information 2025, 16(8), 664; https://doi.org/10.3390/info16080664 (registering DOI) - 4 Aug 2025
Abstract
Advances in neuroscience have improved the understanding of cognitive, emotional, and social processes involved in learning. Simultaneously, technologies such as artificial intelligence, augmented reality, and gamification are transforming educational practices. However, their integration into formal education remains limited and often misapplied. This study [...] Read more.
Advances in neuroscience have improved the understanding of cognitive, emotional, and social processes involved in learning. Simultaneously, technologies such as artificial intelligence, augmented reality, and gamification are transforming educational practices. However, their integration into formal education remains limited and often misapplied. This study aims to evaluate the impact of technology-supported neuroeducational models on student learning and well-being. A systematic review was conducted using PubMed, the Web of Science, ScienceDirect, and LILACS, including open-access studies published between 2020 and 2025. Selection and methodological assessment followed PRISMA 2020 guidelines. Out of 386 identified articles, 22 met the inclusion criteria. Most studies showed that neuroeducational interventions incorporating interactive and adaptive technologies enhanced academic performance, intrinsic motivation, emotional self-regulation, and psychological well-being in various educational contexts. Technology-supported neuroeducational models are effective in fostering both cognitive and emotional development. The findings support integrating neuroscience and educational technology into teaching practices and teacher training, promoting personalized, inclusive, and evidence-based education. Full article
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13 pages, 1635 KiB  
Article
Mechanical Performance of Sustainable Asphalt Mixtures Incorporating RAP and Panasqueira Mine Waste
by Hernan Patricio Moyano Ayala and Marisa Sofia Fernandes Dinis de Almeida
Constr. Mater. 2025, 5(3), 52; https://doi.org/10.3390/constrmater5030052 (registering DOI) - 4 Aug 2025
Abstract
The increasing demand for sustainable practices in road construction has prompted the search for environmentally friendly and cost-effective materials. This study explores the incorporation of reclaimed asphalt pavement (RAP) and Panasqueira mine waste (greywacke aggregates) as full replacements for virgin aggregates in hot [...] Read more.
The increasing demand for sustainable practices in road construction has prompted the search for environmentally friendly and cost-effective materials. This study explores the incorporation of reclaimed asphalt pavement (RAP) and Panasqueira mine waste (greywacke aggregates) as full replacements for virgin aggregates in hot mix asphalt (HMA), aligning with the objectives of UN Sustainable Development Goal 9. Three asphalt mixtures were prepared: a reference mixture (MR) with granite aggregates, and two modified mixtures (M15 and M20) with 15% and 20% RAP, respectively. All mixtures were evaluated through Marshall stability, stiffness modulus, water sensitivity, and wheel tracking tests. The results demonstrated that mixtures containing RAP and mine waste met Portuguese specifications for surface courses. Specifically, the M20 mixture showed the highest stiffness modulus, improved moisture resistance, and the best performance against permanent deformation. These improvements are attributed to the presence of stiff aged binder in RAP and the mechanical characteristics of the greywacke aggregates. Overall, the findings confirm that the combined use of RAP and mining waste provides a technically viable and sustainable alternative for asphalt pavement construction, contributing to resource efficiency and circular economy goals. Full article
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15 pages, 966 KiB  
Article
Long-Term Follow-Up of Left Atrial Appendage Exclusion: Results of the V-CLIP Multi-Center Post-Market Study
by Elias Zias, Katherine G. Phillips, Marc Gerdisch, Scott Johnson, Ahmed El-Eshmawi, Kenneth Saum, Michael Moront, Michael Kasten, Chanderdeep Singh, Gautam Bhatia, Hiroo Takayama and Ralph Damiano
J. Clin. Med. 2025, 14(15), 5473; https://doi.org/10.3390/jcm14155473 (registering DOI) - 4 Aug 2025
Abstract
Background: Cardiac surgery patients with pre- or post-operative atrial fibrillation are at an increased risk for thromboembolic stroke, often due left atrial appendage (LAA) thrombus. Surgical LAA exclusion (LAAE) can be performed and must be complete to avoid increased thrombus formation. Methods [...] Read more.
Background: Cardiac surgery patients with pre- or post-operative atrial fibrillation are at an increased risk for thromboembolic stroke, often due left atrial appendage (LAA) thrombus. Surgical LAA exclusion (LAAE) can be performed and must be complete to avoid increased thrombus formation. Methods: This prospective, multi-center, post-market study (NCT05101993) evaluated the long-term safety and performance of the epicardial V-shape AtriClip device. Patients ≥18 years who had received V-shape AtriClip devices during non-emergent cardiac surgery consented to a prospective 12-month follow-up visit and LAA imaging. The primary performance was LAAE without residual left atrium-LAA communication, assessed by imaging at the last follow-up visit. The primary safety was device- or implant procedure-related serious adverse events (SAEs) (death, major bleeding, surgical site infection, pericardial effusion requiring intervention, myocardial infarction) within 30 days. Results: Of 155 patients from 11 U.S. centers, 151 patients had evaluable imaging. Complete LAAE was obtained in all patients. Primary performance in the intent-to-treat population was met, with 97% (95% CI 93.52%, 99.29%; p = 0.0001) complete LAAE. Primary safety was met, with 100% (95% CI 97.75%, 100%; p < 0.0001) of patients free from pre-defined SAEs within 30 days. One device-related SAE was reported, which resolved intraprocedurally. Conclusions: AtriClip V-Clip showed safe and successful LAAE through 12 months of follow-up. Full article
(This article belongs to the Special Issue Cardiac Surgery: Clinical Advances)
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12 pages, 1178 KiB  
Systematic Review
Exploring the Preventive Effects of Omega-3 Polyunsaturated Fatty Acids Supplementation on Global Cognition: A Systematic Review and Meta-Analysis of Cognitively Unimpaired Older Adults
by Roberta Mulargia, Federica Ribaldi, Sophie Mutel, Ozge Sayin, Giorgi Khachvani, Gabriele Volpara, Giulia Remoli, Umberto Nencha, Stefano Gianonni-Luza, Stefano Cappa, Giovanni B. Frisoni and Augusto J. Mendes
Clin. Transl. Neurosci. 2025, 9(3), 34; https://doi.org/10.3390/ctn9030034 - 4 Aug 2025
Abstract
Dementia prevention is a global public health priority, and lifestyle interventions, including nutrition, have gained interest for their potential to maintain cognitive health. Among nutritional interventions, omega-3 polyunsaturated fatty acids (n-3 FA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been widely [...] Read more.
Dementia prevention is a global public health priority, and lifestyle interventions, including nutrition, have gained interest for their potential to maintain cognitive health. Among nutritional interventions, omega-3 polyunsaturated fatty acids (n-3 FA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been widely studied for their potential to support cognitive health. This systematic review evaluated whether n-3 FA supplementation improves global cognition in cognitively unimpaired older adults. Nineteen randomized controlled trials (RCTs) met inclusion criteria, of which five reported significant improvements in global cognition. A random-effects meta-analysis of 11 placebo-controlled RCTs showed no significant effect (SMD = −0.02, 95% CI: −0.07 to 0.04). Heterogeneity in supplement type, dosage, duration, and outcome measures may have contributed to inconsistent findings and limited comparability. Furthermore, methodological quality of the trials was generally low. While current evidence does not demonstrate a significant effect of n-3 FA supplementation on global cognition, future research should prioritize well-powered, longer-duration RCTs that incorporate biomarker monitoring and more appropriate doses. Clarifying the role of n-3 FA in cognitive aging remains essential for informing nutrition-based dementia prevention strategies. Full article
(This article belongs to the Special Issue Brain Health)
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14 pages, 3361 KiB  
Article
Bacteremia Caused by a Putative Novel Species in the Genus Erwinia: A Case Report and Genomic Analysis
by Jiwoo Lee, Taek Soo Kim, Hyunwoong Park and Jae Hyeon Park
Life 2025, 15(8), 1227; https://doi.org/10.3390/life15081227 - 3 Aug 2025
Abstract
We report a case of catheter-associated bloodstream infection caused by a putative novel species in the genus Erwinia, identified using whole-genome sequencing (WGS). A female adolescent receiving long-term home parenteral nutrition via a central venous catheter (CVC) presented with a fever. Gram-negative [...] Read more.
We report a case of catheter-associated bloodstream infection caused by a putative novel species in the genus Erwinia, identified using whole-genome sequencing (WGS). A female adolescent receiving long-term home parenteral nutrition via a central venous catheter (CVC) presented with a fever. Gram-negative rods were isolated from two CVC-derived blood culture sets, while peripheral cultures remained negative. Conventional identification methods, including VITEK 2, Phoenix M50, MALDI-TOF MS, and 16S rRNA and rpoB gene sequencing, failed to achieve species-level identification. WGS was performed on the isolate using Illumina MiSeq. Genomic analysis revealed a genome size of 5.39 Mb with 56.8% GC content and high assembly completeness. The highest average nucleotide identity (ANI) was 90.3% with Pantoea coffeiphila, and ≤85% with known Erwinia species, suggesting that it represents a distinct taxon. Phylogenetic analyses placed the isolate within the Erwinia clade but separate from any known species. Antimicrobial susceptibility testing showed broad susceptibility. This case highlights the utility of WGS for the identification of rare or novel organisms not captured by conventional methods and expands the clinical spectrum of Erwinia species. While the criteria for species delineation were met, the phenotypic characterization remains insufficient to formally propose a new species. Full article
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25 pages, 34850 KiB  
Article
New Belgrade’s Thermal Mosaic: Investigating Climate Performance in Urban Heritage Blocks Beyond Coverage Ratios
by Saja Kosanović, Đurica Marković and Marija Stamenković
Atmosphere 2025, 16(8), 935; https://doi.org/10.3390/atmos16080935 (registering DOI) - 3 Aug 2025
Abstract
This study investigated the nuanced influence of urban morphology on the thermal performance of nine mass housing blocks (21–26, 28–30) in New Belgrade’s Central Zone. These blocks, showcasing diverse structures, provided a robust basis for evaluating the design parameters. ENVI-met simulations were used [...] Read more.
This study investigated the nuanced influence of urban morphology on the thermal performance of nine mass housing blocks (21–26, 28–30) in New Belgrade’s Central Zone. These blocks, showcasing diverse structures, provided a robust basis for evaluating the design parameters. ENVI-met simulations were used to assess two scenarios: an “asphalt-only” environment, isolating the urban structure’s impact, and a “real-world” scenario, including green infrastructure (GI). Overall, the findings emphasize that while GI offers mitigation, the inherent urban built structure fundamentally determines thermal outcomes. An urban block’s thermal performance, it turns out, is a complex interplay between morphological factors and local climate. Crucially, simple metrics like Green Area Percentage (GAP) and Building Coverage Ratio (BCR) proved unreliable predictors of thermal performance. This highlights the critical need for urban planning regulations to evolve beyond basic surface indicators and embrace sophisticated, context-sensitive design principles for effective heat mitigation. Optimal performance arises from morphologies that actively manage heat accumulation and facilitate its dissipation, a characteristic exemplified by Block 22’s integrated design. However, even the best-performing Block 22 remains warmer compared to denser central areas, suggesting that urban densification can be a strategy for heat mitigation. Given New Belgrade’s blocks are protected heritage, targeted GI reinforcements remain the only viable approach for improving the outdoor thermal comfort. Full article
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18 pages, 881 KiB  
Systematic Review
Association of Single Nucleotide Polymorphisms in the Cyclooxygenase-2 (COX-2) Gene with Periodontal Disease—A Systematic Review with Meta-Analysis and Implications for Personalized Dentistry
by Vasiliki Savva, Ioannis Fragkioudakis and Dimitra Sakellari
J. Pers. Med. 2025, 15(8), 351; https://doi.org/10.3390/jpm15080351 (registering DOI) - 3 Aug 2025
Abstract
Background: Genetic polymorphisms in the cyclooxygenase-2 (COX-2) gene may contribute to individual susceptibility to periodontal disease. A meta-analysis assessed the association between three COX-2 single-nucleotide polymorphisms (SNPs) namely, −765 G/C (rs20417), −1195 G/A (rs689466), and 8473 T/C (rs5275), and the risk of CP. [...] Read more.
Background: Genetic polymorphisms in the cyclooxygenase-2 (COX-2) gene may contribute to individual susceptibility to periodontal disease. A meta-analysis assessed the association between three COX-2 single-nucleotide polymorphisms (SNPs) namely, −765 G/C (rs20417), −1195 G/A (rs689466), and 8473 T/C (rs5275), and the risk of CP. Methods: Following the PRISMA 2020 guidelines, we conducted a comprehensive search of five electronic databases and additional sources. The eligible studies were observational (case–control or cohort) with genotypic data comparing individuals with periodontal disease and periodontally healthy controls. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS), and the certainty of evidence was evaluated via the GRADE framework. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under dominant genetic models. Results: Seven studies (n = 1467 participants) met the inclusion criteria. No eligible studies evaluated the 8473 T/C SNP. The meta-analysis of the −765 G/C variant revealed a significant association with periodontal disease (OR = 1.61; 95% CI: 1.12–2.32, p = 0.03; I2 = 0%). For the −1195 G/A variant, the pooled OR was 1.86 (95% CI: 1.00–3.43, p = 0.05; I2 = 35%), suggesting a borderline significant association. The certainty of evidence was graded as moderate for −765 G/C and low for −1195 G/A. Conclusions: The COX-2 −765 G/C polymorphism is significantly associated with increased CP risk, while the −1195 G/A variant shows a potential, though less certain, link. Larger, high-quality studies using standardized classifications are needed to confirm these associations. Full article
(This article belongs to the Section Omics/Informatics)
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12 pages, 682 KiB  
Article
Structural Posterior Fossa Malformations: MR Imaging and Neurodevelopmental Outcome
by Jorden Halevy, Hadar Doitch Amdurski, Michal Gafner, Shalev Fried, Tomer Ziv-Baran and Eldad Katorza
Diagnostics 2025, 15(15), 1945; https://doi.org/10.3390/diagnostics15151945 - 3 Aug 2025
Abstract
Objectives: The increasing use of fetal MRI has increased the diagnosis of posterior fossa malformations, yet the long-term neurodevelopmental outcomes of affected fetuses remain unclear. This study aims to examine the long-term neurodevelopmental outcomes of fetuses with structural posterior fossa malformation diagnosed [...] Read more.
Objectives: The increasing use of fetal MRI has increased the diagnosis of posterior fossa malformations, yet the long-term neurodevelopmental outcomes of affected fetuses remain unclear. This study aims to examine the long-term neurodevelopmental outcomes of fetuses with structural posterior fossa malformation diagnosed on fetal MRI. Methods: A historical cohort study was conducted at a single tertiary referral center, including fetuses diagnosed with structural posterior fossa malformations and apparently healthy fetuses who underwent fetal brain MRI between 2011 and 2019. Maternal, pregnancy, and newborn characteristics were compared between groups, alongside long-term neurodevelopmental outcomes using the Vineland Adaptive Behavior Scales II (VABS-II) questionnaire. This included an extensive assessment of malformation types, additional structural, genetic, or neurodevelopmental anomalies, and outcomes. Results: A total of 126 fetuses met the inclusion criteria, of which 70 were apparently healthy fetuses, and 56 had structural posterior fossa malformations. Among the latter, 18 pregnancies were terminated, 4 resulted in neonatal death, and 11 were lost to follow-up. No significant differences were found in the overall neurodevelopmental outcomes between fetuses with structural posterior fossa malformation (93.4 ± 19.0) and apparently healthy fetuses (99.8 ± 13.8). Motor skills scores were lower among fetuses with structural posterior fossa malformations (87.7 ± 16.5 vs. 99.3 ± 17.2, p = 0.01) but remained within the normal range. Conclusion: Fetuses with structural posterior fossa malformations may exhibit normal long-term neurodevelopmental outcomes if no additional anomalies are detected during thorough prenatal screening that includes proper sonographic, biochemical and genetic screening, as well as fetal MRI. Further research with larger cohorts and longer-term assessments is recommended to validate these findings and support clinical decision-making. Full article
(This article belongs to the Special Issue Advances in Fetal Imaging)
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21 pages, 1677 KiB  
Systematic Review
Pharmacoeconomic Profiles of Advanced Therapy Medicinal Products in Rare Diseases: A Systematic Review
by Marianna Serino, Milana Krstin, Sara Mucherino, Enrica Menditto and Valentina Orlando
Healthcare 2025, 13(15), 1894; https://doi.org/10.3390/healthcare13151894 - 2 Aug 2025
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Abstract
Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic [...] Read more.
Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic review aims to analyze the cost-effectiveness and cost-utility profiles of the European Medicines Agency-authorized ATMPs for treating rare diseases. Methods: A systematic review was conducted following PRISMA guidelines. Studies were identified by searching PubMed, Embase, Web of Science, and ProQuest scientific databases. Economic evaluations reporting incremental cost-effectiveness/utility ratios (ICERs/ICURs) for ATMPs were included. Costs were standardized to 2023 Euros, and a cost-effectiveness plane was constructed to evaluate the results against willingness-to-pay (WTP) thresholds of EUR 50,000, EUR 100,000, and EUR 150,000 per QALY, as part of a sensitivity analysis. Results: A total of 61 studies met the inclusion criteria. ATMPs for rare blood diseases, such as tisagenlecleucel and axicabtagene ciloleucel, were found to be cost-effective in a majority of studies, with incremental QALYs ranging from 1.5 to 10 per patient over lifetime horizon. Tisagenlecleucel demonstrated a positive cost-effectiveness profile in the treatment of acute lymphoblastic leukemia (58%), while axicabtagene ciloleucel showed a positive profile in the treatment of diffuse large B-cell lymphoma (85%). Onasemnogene abeparvovec for spinal muscular atrophy (SMA) showed uncertain cost-effectiveness results, and voretigene neparvovec for retinal diseases was not cost-effective in 40% of studies, with incremental QALYs around 1.3 and high costs exceeding the WTP threshold set. Conclusions: ATMPs in treating rare diseases show promising economic potential, but cost-effectiveness varies across indications. Policymakers must balance innovation with system sustainability, using refined models and the long-term impact on patient outcomes. Full article
(This article belongs to the Special Issue Healthcare Economics, Management, and Innovation for Health Systems)
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12 pages, 284 KiB  
Communication
Raw Sheep Milk as a Reservoir of Multidrug-Resistant Staphylococcus aureus: Evidence from Traditional Farming Systems in Romania
by Răzvan-Dragoș Roșu, Adriana Morar, Alexandra Ban-Cucerzan, Mirela Imre, Sebastian Alexandru Popa, Răzvan-Tudor Pătrînjan, Alexandra Pocinoc and Kálmán Imre
Antibiotics 2025, 14(8), 787; https://doi.org/10.3390/antibiotics14080787 (registering DOI) - 2 Aug 2025
Viewed by 52
Abstract
Background/Objectives: Staphylococcus aureus is a major pathogen of concern in raw milk due to its potential to cause foodborne illness and its increasing antimicrobial resistance (AMR). In Romania, data on the occurrence and resistance patterns of S. aureus in raw sheep milk [...] Read more.
Background/Objectives: Staphylococcus aureus is a major pathogen of concern in raw milk due to its potential to cause foodborne illness and its increasing antimicrobial resistance (AMR). In Romania, data on the occurrence and resistance patterns of S. aureus in raw sheep milk from traditional farming systems remain limited. This study investigated the presence and antimicrobial resistance of S. aureus in 106 raw sheep milk samples collected from traditional farms in the Banat region of western Romania. Methods: Coagulase-positive staphylococci (CPS) were enumerated using ISO 6888-1:2021 protocols. Isolates were identified at the species level using the Vitek 2 system and molecularly confirmed via PCR targeting the 16S rDNA and nuc genes. Methicillin resistance was assessed by detecting the mecA gene. Antimicrobial susceptibility was determined using the Vitek 2 AST-GP79 card. Results: CPS were detected in 69 samples, with S. aureus confirmed in 34.9%. The mecA gene was identified in 13.5% of S. aureus isolates, indicating the presence of methicillin-resistant S. aureus (MRSA). Resistance to at least two antimicrobials was observed in 97.3% of isolates, and 33 strains (89.2%) met the criteria for multidrug resistance (MDR). The most frequent MDR phenotype involved resistance to lincomycin, macrolides, β-lactams, tetracyclines, and aminoglycosides. Conclusions: The high prevalence of S. aureus, including MRSA and MDR strains, in raw sheep milk from traditional farms represents a potential public health risk, particularly in regions where unpasteurized dairy consumption persists. These findings underscore the need for enhanced hygiene practices, prudent antimicrobial use, and AMR monitoring in small-scale dairy systems. Full article
22 pages, 1529 KiB  
Article
Native Flora and Potential Natural Vegetation References for Effective Forest Restoration in Italian Urban Systems
by Carlo Blasi, Giulia Capotorti, Eva Del Vico, Sandro Bonacquisti and Laura Zavattero
Plants 2025, 14(15), 2396; https://doi.org/10.3390/plants14152396 - 2 Aug 2025
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Abstract
The ongoing decade of UN restoration matches with the European goal of bringing nature back into our lives, including in urban systems, and Nature Restoration Regulation. Within such a framework, this work is aimed at highlighting the ecological rationale and strategic value of [...] Read more.
The ongoing decade of UN restoration matches with the European goal of bringing nature back into our lives, including in urban systems, and Nature Restoration Regulation. Within such a framework, this work is aimed at highlighting the ecological rationale and strategic value of an NRRP measure devoted to forest restoration in Italian Metropolitan Cities, and at assessing respective preliminary results. Therefore, the measure’s overarching goal (not to create urban parks or gardens, but activate forest recovery), geographic extent and scope (over 4000 ha and more than 4 million planted trees and shrubs across the country), plantation model (mandatory use of native species consistent with local potential vegetation, density of 1000 seedlings per ha, use of at least four tree and four shrub species in each project, with a minimum proportion of 70% for trees, certified provenance for reproductive material), and compulsory management activities (maintenance and replacement of any dead plants for at least five years), are herein shown and explained under an ecological perspective. Current implementation outcomes were thus assessed in terms of coherence and expected biodiversity benefits, especially with respect to ecological and biogeographic consistency of planted forests, representativity in relation to national and European plant diversity, biogeographic interest and conservation concern of adopted plants, and potential contribution to the EU Habitats Directive. Compliance with international strategic goals and normative rules, along with recognizable advantages of the measure and limitations to be solved, are finally discussed. In conclusion, the forestation model proposed for the Italian Metropolitan Cities proved to be fully applicable in its ecological rationale, with expected benefits in terms of biodiversity support plainly met, and even exceeded, at the current stage of implementation, especially in terms of the contribution to protected habitats. These promising preliminary results allow the model to be recognized at the international level as a good practice that may help achieve protection targets and sustainable development goals within and beyond urban systems. Full article
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