Life

13 pages, 610 KB

Open AccessArticle

Retrospective Analysis of Angiographic Radial Artery Spasm Predictors

by Adrian Sebastian Zus, Simina Crișan, Silvia Luca, Daniel Nișulescu, Mihaela-Daniela Valcovici, Oana Pătru, Mihai-Andrei Lazăr, Cristina Văcărescu, Dan Gaiță and Constantin-Tudor Luca

Life 2025, 15(11), 1759; https://doi.org/10.3390/life15111759 (registering DOI) - 16 Nov 2025

Abstract

Background: Radial artery spasm remains a frequent complication during transradial coronary and peripheral angiography. Despite its impact on procedural success and patient discomfort, consistent predictors remain elusive, as does a standard definition. Objectives: This study aimed to identify independent clinical, hemodynamic, and anatomical [...] Read more.

Background: Radial artery spasm remains a frequent complication during transradial coronary and peripheral angiography. Despite its impact on procedural success and patient discomfort, consistent predictors remain elusive, as does a standard definition. Objectives: This study aimed to identify independent clinical, hemodynamic, and anatomical predictors of radial artery spasm using data from a single-operator, real-world cohort of patients undergoing both elective and emergency procedures, utilizing an angiographic definition of radial artery spasm. Methods: A retrospective observational analysis was conducted on 96 patients with successful radial artery access. Radial artery spasm was objectively defined as >50% luminal narrowing on radial angiography. Patient demographics, procedural characteristics, comorbidities, and arterial parameters were analyzed. Univariate and multivariate logistic regression models were used to identify significant predictors. Results: Radial artery spasm occurred in 62.5% of patients. Univariate analysis identified lower height, weight, smaller radial artery diameter, higher pain scores, and lower diastolic blood pressure as associated with radial artery spasm. In multivariate analysis, only lower body weight (β = −0.043, p = 0.0307) and smaller radial artery diameter (β = −1.352, p = 0.0200) remained independent predictors. Age, sex, and most comorbidities, including diabetes, chronic kidney disease, and peripheral artery disease, showed no significant association. Clinically, these findings suggest that simple pre-procedural assessment of patient weight and radial artery diameter may help operators identify individuals at higher risk of radial spasm, allowing for tailored preventive strategies and potentially improving procedural comfort and success. Conclusions: Our findings suggest that low body weight and small radial artery diameter are significant independent predictors of angiographic radial artery spasm, highlighting the importance of anatomical considerations over demographic or clinical factors. Preprocedural assessment of radial artery size may enhance risk stratification and guide preventive strategies. Further multicenter validation is warranted. Incorporating routine evaluation of radial artery size and body habitus into pre-procedural assessment may help identify patients who could benefit from tailored preventive approaches—such as smaller sheath sizes, increased vasodilator use, or ultrasound-guided puncture—to optimize procedural success and patient comfort. Full article

(This article belongs to the Special Issue Management of Ischemia and Heart Failure—3rd Edition)

16 pages, 1370 KB

Open AccessArticle

Evaluation of Immune Response Dynamics: Analyzing the Parameters of Complete Blood Count (CBC) in Experimental Borreliosis

by Diana Mihaela Alexandru, Diana Larisa Ancuţa and Cristin Coman

Life 2025, 15(11), 1758; https://doi.org/10.3390/life15111758 (registering DOI) - 16 Nov 2025

Abstract

The spirochete Borrelia is responsible for Lyme disease, a multisystemic infection and growing public health concern. This study aimed to evaluate host response dynamics to Borrelia bavariensis by analyzing hematological parameters as potential immuno-inflammatory markers in a murine model. Forty C3He/HeNCrl mice were [...] Read more.

The spirochete Borrelia is responsible for Lyme disease, a multisystemic infection and growing public health concern. This study aimed to evaluate host response dynamics to Borrelia bavariensis by analyzing hematological parameters as potential immuno-inflammatory markers in a murine model. Forty C3He/HeNCrl mice were inoculated intradermally with B. bavariensis (5 × 10⁵ spirochetes/100 µL/mouse) and monitored for 90 days. Samples were collected at defined intervals for microbiological examination, hematology, and qPCR. Microbiological and qPCR testing revealed infection between days 7–21; results were negative on days 28–42. At later stages (days 60 and 90), Borrelia was only detectable by qPCR, highlighting differences in diagnostic sensitivity. Hematological analysis showed that the neutrophil-to-lymphocyte ratio (NLR) and systemic immuno-inflammatory index (SII) peaked on day 7 (p < 0.0001), followed by gradual normalization until day 35. These markers reflected the intensity of the inflammatory response and defined three distinct phases of host reaction. Overall, results demonstrate the complexity of immune responses in B. bavariensis infection and underscore the value of monitoring hematological indices for understanding host–pathogen interactions. This approach supports the potential use of simple blood markers in diagnostic strategies with translational relevance for clinical practice. Full article

(This article belongs to the Special Issue From Animal Models to Clinical Innovations: Translating Research into Medicine)

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17 pages, 1213 KB

Open AccessEssay

Spaceflight and Medical Microbiology: Possible Implications for Standard Infection Diagnostics and Therapy

by Alessa Lalinka Boschert, Stefan Leuko, Carolin Luisa Krämer, Katharina Siems, Yen-Tran Ly-Sauerbrey and Franca Arndt

Life 2025, 15(11), 1757; https://doi.org/10.3390/life15111757 (registering DOI) - 15 Nov 2025

Abstract

Infections pose a major risk during long-term human spaceflight missions. By applying standard procedures in medical microbiology to a hypothetical urinary tract infection during a Mars-bound flight, important practical aspects become apparent. From infection diagnostics to antimicrobial treatment during spaceflight, issues include technological [...] Read more.

Infections pose a major risk during long-term human spaceflight missions. By applying standard procedures in medical microbiology to a hypothetical urinary tract infection during a Mars-bound flight, important practical aspects become apparent. From infection diagnostics to antimicrobial treatment during spaceflight, issues include technological constraints, the lack of breakpoints, and epidemiological data. A potential solution is a combination of data acquisition, artificial intelligence, individualized medicine, novel diagnostic tools, and antimicrobial strategies. This work takes an exploratory approach to highlight challenges and potential directions in developing diagnostic strategies for long-term space missions. Full article

(This article belongs to the Section Microbiology)

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14 pages, 726 KB

Open AccessBrief Report

Guiding Antibiotic Therapy with Machine Learning: Real-World Applications of a CDSS in Bacteremia Management

by Juan Carlos Gómez de la Torre, Ari Frenkel, Carlos Chavez-Lencinas, Alicia Rendon, Yoshie Higuchi, Jose M. Vela-Ruiz, Jacob Calpey, Ryan Beaton, Isaac Elijah, Inbal Shachar, Everett Kim, Sofia Valencia Osorio, Jason James Lee, Gabrielle Grogan, Jessica Siegel, Stephanie Allman and Miguel Hueda-Zavaleta

Life 2025, 15(11), 1756; https://doi.org/10.3390/life15111756 (registering DOI) - 15 Nov 2025

Abstract

Bacteremia is a life-threatening condition contributing significantly to sepsis-related mortality worldwide. With delayed appropriate antibiotic therapy, mortality increases by 20% regardless of antimicrobial resistance. This study evaluated the perceived clinical utility of Artificial Intelligence (AI)-powered Clinical Decision Support Systems (CDSSs) (OneChoice and OneChoice [...] Read more.

Bacteremia is a life-threatening condition contributing significantly to sepsis-related mortality worldwide. With delayed appropriate antibiotic therapy, mortality increases by 20% regardless of antimicrobial resistance. This study evaluated the perceived clinical utility of Artificial Intelligence (AI)-powered Clinical Decision Support Systems (CDSSs) (OneChoice and OneChoice Fusion) among specialist physicians managing bacteremia cases. A cross-sectional survey was conducted with 65 unique specialist physicians from multiple medical specialties who were presented with clinical vignettes describing patients with bacteremia and 90 corresponding AI-CDSS recommendations. Participants assessed the perceived helpfulness of AI decision-making, the impact of AI recommendations on their own clinical judgment, and the concordance between AI recommendations and their own clinical judgment, as well as the validity of changing therapy based on CDSS recommendations. The study encompassed a diverse range of bacterial pathogens, with Escherichia coli representing 38.7% of the isolates and 30% being extended-spectrum β-lactamase (ESBL) producers. Findings show that 97.8% [(95% CI: 92.2–99.7%)] of physicians reported that AI facilitated decision-making and substantial concordance (87.8% [95% CI: 79.2–93.7%; Cohen’s κ = 0.76]) between AI recommendations and physicians’ therapeutic recommendations. Stratification by pathogen revealed the highest concordance for Escherichia coli bacteremia (96.6%, 28/29 cases). Implementation analysis revealed a meaningful clinical impact, with 68.9% [(95% CI: 58.3–78.2%)] of cases resulting in AI-guided treatment modifications. These findings indicate that AI-powered CDSSs effectively bridge critical gaps in infectious disease expertise and antimicrobial stewardship, providing clinicians with evidence-based therapeutic recommendations that can be integrated into routine practice to optimize antibiotic selection, particularly in settings with limited access to infectious disease specialists. For optimal clinical integration, we recommend that clinicians utilize AI-CDSS recommendations as an adjunct to clinical judgment rather than a replacement, particularly in complex cases involving immunocompromised hosts or polymicrobial infections. Future research should prioritize prospective clinical trials that evaluate direct patient outcomes to establish evidence of broader clinical effectiveness and applicability across diverse healthcare settings. Full article

(This article belongs to the Special Issue Bacterial Antibiotic Resistance: From Mechanisms to Strategies for Restoring Antibiotic Efficacy)

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16 pages, 5443 KB

Open AccessArticle

Effects of Surface Treatments on Innovative Additively Manufactured Scaffolds: Implications for Biocompatibility in Bone Tissue Engineering

by Qun Zhao, Florian Fischer, Maximilian Voshage, Lucas Jauer, Alexander Kopp, Maximilian Praster, Rald Victor Maria Groven, Johannes Henrich Schleifenbaum, Jörg Eschweiler, Philipp Kobbe, Eva Miriam Buhl, Frank Hildebrand, Elizabeth R. Balmayor and Johannes Greven

Life 2025, 15(11), 1755; https://doi.org/10.3390/life15111755 (registering DOI) - 15 Nov 2025

Abstract

Purpose: The increasing demand for alternatives to autologous and resorbable bone grafts in the treatment of bone defects is driving research efforts. This study aims to evaluate the effects of different surface treatments on zinc-1%-magnesium (Zn-1Mg) alloy scaffolds on chondrocytes and osteoblasts, [...] Read more.

Purpose: The increasing demand for alternatives to autologous and resorbable bone grafts in the treatment of bone defects is driving research efforts. This study aims to evaluate the effects of different surface treatments on zinc-1%-magnesium (Zn-1Mg) alloy scaffolds on chondrocytes and osteoblasts, focusing on cytotoxicity, biocompatibility, and cell proliferation. Methods: Zn-1Mg alloy disks were manufactured additively by the powder bed fusion of metals using a laser beam (PBF-LB/M) and underwent different distinct surface treatments, including as-built treatment, sandblasting, Zn-1Mg-blasting, and electropolishing, respectively. Chondrocytes and osteoblasts were cultured separately on these additively manufactured Zn-1Mg alloy disks for 3, 7, and 14 days to assess biocompatibility and cellular growth. Cell viability, cytotoxicity, and proliferation were analyzed using DAPI staining, live/dead staining, fluorescence microscopy, and flow cytometry. Additionally, cellular morphology was investigated using Phalloidin/DAPI staining and scanning electron microscopy (SEM). Zn-1Mg scaffolds were also manufactured and subjected to the same surface treatments. All aforementioned experiments were repeated using Zn-1Mg scaffolds with co-cultured osteoblasts and chondrocytes. Results: All samples, irrespective of the surface treatment, showed similar effects compared to the reference surfaces in terms of cell viability, cytotoxicity, and proliferation for both chondrocytes and osteoblasts. SEM analysis revealed comparable cellular morphology across all scaffolds, with cells observed attaching and growing on all scaffold surfaces. This indicates that all scaffolds independent of different surface treatments exhibit good biocompatibility. Conclusions: The findings indicate that Zn-1Mg alloy samples with different surface treatments exhibit no significant differences in cytocompatibility with chondrocytes and osteoblasts. Zn-1Mg alloy scaffolds, composed of 99% zinc and 1% magnesium, demonstrate biocompatibility, with cells attaching and growing on all scaffold surfaces. These results suggest that Zn-1Mg alloy scaffolds manufactured additively by PBF-LB/M hold promise for use in resorbable bone graft applications. Full article

(This article belongs to the Section Medical Research)

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15 pages, 2195 KB

Open AccessArticle

Effect of Buah Merah (Pandanus conoideus Lamk.) Extract Supplementation on the Density and Apoptosis of Photoreceptor and Retinal Ganglion Cells in a Diabetic Rat Model

by Andi Muhammad Ichsan, Susan Waterina Salle, Itzar Chaidir Islam, Subehan Lallo, Andi Alfian Zainuddin, Budu Mannyu and Habibah Setyawati Muhiddin

Life 2025, 15(11), 1754; https://doi.org/10.3390/life15111754 - 14 Nov 2025

Abstract

Diabetic retinopathy (DR) is a microvascular disorder of the retina due to diabetes mellitus (DM). Natural products are widely used to prevent and treat various diseases caused by DM. This study aims to evaluate the effect of buah merah (Pandanus conoideus Lamk.) [...] Read more.

Diabetic retinopathy (DR) is a microvascular disorder of the retina due to diabetes mellitus (DM). Natural products are widely used to prevent and treat various diseases caused by DM. This study aims to evaluate the effect of buah merah (Pandanus conoideus Lamk.) extract on retinal density and apoptosis in a diabetic rat model. A total of 30 male rats (Rattus norvegicus) weighing 120–150 g were induced with diabetes using alloxan and divided into five groups: group 1 (normal control), 2 (diabetic control), 3 (diabetes + 1 mL buah merah extract), 4 (1.5 mL), and 5 (2 mL). Buah merah extract, equivalent to 12 mg total carotenoids, 10 mg total tocopherols, 1.348 mg alpha-tocopherol, and 3.4 mg beta-carotene, was administered for 14 days. Retina was examined using hematoxylin and eosin (HE) staining for photoreceptor and retinal ganglion cell density, and immunohistochemistry (IHC) of Caspase-3 for apoptosis. The results showed that group 3 had photoreceptor and retinal ganglion cell densities close to normal, with photoreceptor density values of 722.52 ± 147.56 and ganglion 18.73 ± 5.61. The post hoc test confirmed a significant protective effect of buah merah extract in group 3 (p-value 0.014). However, buah merah extract was found to maintain photoreceptor and retinal ganglion cell density, but no significant inhibitory effect was observed on photoreceptor or retinal ganglion cell apoptosis. Further studies are needed to better understand the mechanism and potential therapeutic effect of buah merah extract. Full article

(This article belongs to the Collection Retinal Disease and Metabolism)

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19 pages, 3717 KB

Open AccessArticle

Using Radiomics and Explainable Ensemble Learning to Predict Radiation Pneumonitis and Survival in NSCLC Patients Post-VMAT

by Tsair-Fwu Lee, Lawrence Tsai, Po-Shun Tseng, Chia-Chi Hsu, Ling-Chuan Chang-Chien, Jun-Ping Shiau, Yang-Wei Hsieh, Shyh-An Yeh, Cheng-Shie Wuu, Yu-Wei Lin and Pei-Ju Chao

Life 2025, 15(11), 1753; https://doi.org/10.3390/life15111753 - 14 Nov 2025

Abstract

Purpose: This study aimed to develop a precise predictive model to assess the risk of radiation pneumonitis (RP) and three-year survival in patients with non-small cell lung cancer (NSCLC) following volumetric modulated arc therapy (VMAT). Radiomics features, ensemble stacking, and explainable artificial [...] Read more.

Purpose: This study aimed to develop a precise predictive model to assess the risk of radiation pneumonitis (RP) and three-year survival in patients with non-small cell lung cancer (NSCLC) following volumetric modulated arc therapy (VMAT). Radiomics features, ensemble stacking, and explainable artificial intelligence (XAI) were integrated to enhance predictive performance and clinical interpretability. Materials and Methods: A retrospective cohort of 221 NSCLC patients treated with VMAT at Kaohsiung Veterans General Hospital between 2013 and 2023 was analyzed, including 168 patients for RP prediction (47 with ≥grade 2 RP) and 118 patients for survival prediction (34 deaths). Clinical variables, dose–volume histogram (DVH) parameters, and radiomic features (original, Laplacian of Gaussian [LoG], and wavelet filtered) were extracted. ANOVA was used for initial feature reduction, followed by LASSO and Boruta-SHAP for feature selection, which formed 10 feature subsets. The data were divided at an 8:2 ratio into training and testing sets, with SMOTE balancing and 10-fold cross-validation for parameter optimization. Six models—logistic regression (LR), random forest (RF), support vector machine (SVM), k-nearest neighbors (KNN), XGBoost, and Ensemble Stacking—were evaluated in terms of the AUC, accuracy (ACC), negative predictive value (NPV), precision, and F1 score. SHAP analysis was applied to interpret feature contributions. Results: For RP prediction, the LASSO-selected radiomic subset (FR) combined with Ensemble Stacking achieved optimal performance (AUC 0.91, ACC 0.89), with SHAP identifying V40 Firstorder_Min as the most influential feature. For survival prediction, the FR subset yielded an AUC of 0.97, an ACC of 0.92, and an NPV of 1.00, with V10 Wavelet Firstorder_Min as the top contributor. The multimodal subset (FC+R) also performed strongly, achieving an AUC of 0.91 for RP and 0.96 for survival. Conclusions: This study demonstrated the superior performance of radiomics combined with Ensemble Stacking and XAI for the prediction of RP and survival following VMAT in patients with NSCLC. SHAP-based interpretation enhances transparency and clinical trust, offering a robust foundation for personalized radiotherapy and precision medicine. Full article

(This article belongs to the Special Issue Advancing Cancer Radiodiagnostics Through Artificial Intelligence: Techniques, Applications, and Challenges)

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16 pages, 1676 KB

Open AccessArticle

Eight Weeks of Aerobic Exercise Training Improves Fitness, Metabolic Health, Inflammation, and Intestinal Barrier Integrity in Overweight and Obese Women of Different Age Groups

by Tae-Hyung Lee, Hyung-Il Lee, Hee-Tae Roh and Su-Youn Cho

Life 2025, 15(11), 1752; https://doi.org/10.3390/life15111752 - 14 Nov 2025

Abstract

This study investigated the effects of eight weeks of aerobic exercise training on body composition, lipid profiles, organokines (leptin, irisin), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6]), and intestinal barrier permeability markers (zonulin, lipopolysaccharide-binding protein [LBP]) in overweight and obese women of [...] Read more.

This study investigated the effects of eight weeks of aerobic exercise training on body composition, lipid profiles, organokines (leptin, irisin), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6]), and intestinal barrier permeability markers (zonulin, lipopolysaccharide-binding protein [LBP]) in overweight and obese women of different age groups. We hypothesized that aerobic exercise would improve cardiorespiratory fitness, body composition, lipid metabolism, and reduce pro-inflammatory responses and intestinal permeability, and that these effects would differ between age groups. A total of 32 participants with a body mass index (BMI) ≥ 23 kg/m² were randomly assigned to one of four groups (n = 8 per group): young exercise (YE), young control (YC), middle-aged exercise (ME), and middle-aged control (MC). The intervention consisted of treadmill running for 50 min per session, four times per week, at an intensity corresponding to 65% of the target heart rate (THR), calculated using the Karvonen formula, for a duration of eight weeks. Body composition variables included body weight, BMI, body fat mass (BFM), percentage body fat (PBF), lean body mass (LBM), and maximal oxygen uptake (VO₂max). Blood samples were analyzed for lipid profiles (total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C]), organokines, inflammatory markers, and intestinal barrier integrity biomarkers. After the intervention, the YE and ME groups exhibited significant reductions (p < 0.05) in body weight, BMI, BFM, PBF, TC, TG, LDL-C, leptin, hs-CRP, IL-6, zonulin, and LBP. In contrast, LBM and VO₂max significantly increased (p < 0.05) in both exercise groups. No significant changes were observed in irisin concentrations or HDL-C levels (p > 0.05). These results suggest that aerobic exercise training, irrespective of age, is effective in improving cardiorespiratory fitness, body composition, and lipid metabolism, while simultaneously reducing systemic inflammation and is associated with favorable changes in circulating biomarkers of intestinal barrier function in overweight and obese women. Full article

(This article belongs to the Special Issue Explore Innovative Exercise-Based Interventions for Chronic Diseases)

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24 pages, 6387 KB

Open AccessReview

Zebrafish as an Integrative Model for Central Nervous System Research: Current Advances and Translational Perspectives

by Lidia Pansera, Kamel Mhalhel, Mauro Cavallaro, Marialuisa Aragona, Rosaria Laurà, Maria Levanti, Maria Cristina Guerrera, Francesco Abbate, Antonino Germanà and Giuseppe Montalbano

Life 2025, 15(11), 1751; https://doi.org/10.3390/life15111751 - 14 Nov 2025

Abstract

Central nervous system disorders represent a heterogeneous set of conditions triggered by genetic alterations, environmental exposures, infections, injuries, and even iatrogenic causes. These conditions impact a significant portion of the global population, posing serious concerns for public health. Even though progress has been [...] Read more.

Central nervous system disorders represent a heterogeneous set of conditions triggered by genetic alterations, environmental exposures, infections, injuries, and even iatrogenic causes. These conditions impact a significant portion of the global population, posing serious concerns for public health. Even though progress has been made in understanding and treating some of these disorders, many others remain poorly understood, with research still in their early stages. For that, adapted experimental models are essential for deciphering the physiopathology of disorders and developing future therapeutic strategies. Within this context, zebrafish (Danio rerio) has emerged as a valuable model for central nervous system disorders, thanks to its high genetic and neuroanatomical homology with humans, the conservation in different aspects of cellular architecture and blood–brain barrier, and the remarkable regenerative ability of the CNS. This review presents the state of the art on zebrafish models for central nervous system disorders, presenting their potential in comprehending the pathophysiological processes and screening therapeutics. Full article

(This article belongs to the Section Physiology and Pathology)

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10 pages, 6571 KB

Open AccessCase Report

Swinging Mass Through the Pulmonary Valve: A Rare Case of Right Ventricular Myxoma

by Cristiana Bustea, Andrei-Flavius Radu, Paula Bianca Maghiar, Roxana Brata and Elena Emilia Babes

Life 2025, 15(11), 1750; https://doi.org/10.3390/life15111750 - 14 Nov 2025

Abstract

Primary cardiac tumors are rare, with an estimated incidence of 0.001% to 0.3% in autopsy series. Most are benign, the most common being cardiac myxomas, which typically originate in the left atrium. Right ventricular myxoma is among the rarest primary cardiac tumors, and [...] Read more.

Primary cardiac tumors are rare, with an estimated incidence of 0.001% to 0.3% in autopsy series. Most are benign, the most common being cardiac myxomas, which typically originate in the left atrium. Right ventricular myxoma is among the rarest primary cardiac tumors, and its true incidence is difficult to determine, as most data come from isolated case reports. This paper aims to report a case of right ventricular myxoma in a young woman with a history of childhood malignancy and to discuss the possible association between the two conditions. Echocardiography, thoracic computed tomography (CT), and pulmonary CT angiography were used to assess the presence, location, and size of the tumor. The definitive diagnosis was established by histopathological examination. A 34-year-old woman, with a past medical history of acute lymphoblastic leukemia (ALL) in childhood, presented with a dry cough and exertional dyspnea persisting for three weeks. Transthoracic echocardiography revealed a mass located in the right ventricular outflow tract (RVOT), attached near the tricuspid valve and intermittently prolapsing into the pulmonary trunk. CT imaging confirmed the presence of the tumor in the RVOT and the main pulmonary artery. Because of the high risk of massive pulmonary embolism, the patient underwent urgent surgical excision of the tumor. Histopathological analysis confirmed the diagnosis of cardiac myxoma. The postoperative recovery was uneventful, and the three-month follow-up showed no recurrence or signs of pulmonary embolism. The patient’s history of ALL raised the question of a possible association; however, a review of the literature revealed no previously reported link. In conclusion, right ventricular myxomas are extremely rare. The occurrence of cardiac myxoma in this patient following childhood ALL appears to be incidental. Further research is needed to determine whether ALL survivors have an increased predisposition to subsequent cardiac tumors. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: From Basic Research to Clinical Application—3rd Edition)

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14 pages, 752 KB

Open AccessReview

Protective Role of Lipid-Lowering Drugs in Breast Cancer: Effects on Cancer Incidence and Cardiotoxicity

by Alfredo Mauriello, Adriana Correra, Anna Chiara Maratea, Celeste Fonderico, Arianna Amata, Valeria Cetoretta, Vincenzo Russo and Antonello D’Andrea

Life 2025, 15(11), 1749; https://doi.org/10.3390/life15111749 - 14 Nov 2025

Abstract

The bidirectional link between cancer and cardiovascular disease presents a growing clinical challenge, often exacerbated by the cardiotoxic effects of many anti-cancer drugs. Simultaneously, the incidence of cardiovascular pathologies in cancer patients is on the rise. Recently, lipid-lowering drugs, particularly statins, have emerged [...] Read more.

The bidirectional link between cancer and cardiovascular disease presents a growing clinical challenge, often exacerbated by the cardiotoxic effects of many anti-cancer drugs. Simultaneously, the incidence of cardiovascular pathologies in cancer patients is on the rise. Recently, lipid-lowering drugs, particularly statins, have emerged not only as first-line cardiovascular drugs but also as potential agents with pleiotropic effects that could influence cancer progression and mitigate cardiotoxic side effects. We will analyze data from epidemiological studies, clinical trials, and laboratory research. This comprehensive review aims to examine and synthesize the current evidence regarding the use of lipid-lowering drugs in breast cancer patients, focusing on two main areas: their potential protective role in reducing the incidence of breast cancer and their impact on the prevention and management of treatment-induced cardiotoxicity. Full article

(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)

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20 pages, 2912 KB

Open AccessReview

Molecular Mechanisms of Wound Healing: The Role of Medicinal Plants

by Merlin Esad, Ivica Dimov, Mariya Choneva, Mihaela Popova, Vesela Kokova, Elisaveta Apostolova and Anelia Bivolarska

Life 2025, 15(11), 1748; https://doi.org/10.3390/life15111748 - 14 Nov 2025

Abstract

Wound healing is a tightly regulated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. When these phases are disrupted, wound repair can be delayed or become chronic. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, coordinate immune activation, cytokine expression, cell proliferation, [...] Read more.

Wound healing is a tightly regulated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. When these phases are disrupted, wound repair can be delayed or become chronic. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, coordinate immune activation, cytokine expression, cell proliferation, and tissue repair. Medicinal plants and their bioactive compounds, such as flavonoids, alkaloids, tannins, and other phytoconstituents, have demonstrated significant anti-inflammatory, antioxidant, and immunomodulatory effects that modulate these pathways. Tannins contribute to repair through neutralization of reactive oxygen species (ROS), activation of antioxidant enzymes, and metal-chelating activity. Alkaloids, including tetrandrine, oxymatrine, and berberine, inhibit NF-κB signaling, thereby reducing pro-inflammatory cytokines such as IL-1β and TNF-α. Flavonoids regulate inflammatory mediators and enzymes, including COX and phospholipase A2, while also protecting against oxidative stress and stimulating fibroblast and keratinocyte proliferation—key steps in tissue regeneration. Collectively, these compounds accelerate wound closure by reducing oxidative stress and promoting cellular proliferation and migration. Thus, medicinal plants represent promising complementary approaches to wound management. Future research should focus on developing advanced drug delivery systems to enhance the stability, bioavailability, and targeted action of plant-derived compounds. Localized and biomaterial-based strategies show promise for sustained release at the wound site, and further preclinical and clinical studies are required to ensure their safety, reproducibility, and efficacy. Full article

(This article belongs to the Section Pharmaceutical Science)

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18 pages, 883 KB

Open AccessArticle

The Prevalence and Predictors of Hypertension and Albuminuria in People with HIV (PWHIV)—Real-World Greek Data

by Vasileios Petrakis, Andreas G. Tsantes, Petros Rafailidis, Konstantia Kantartzi, Maria Panopoulou, Theocharis Konstantinidis, Nikoleta Babaka, Pelagia Kriki, Stylianos Panagoutsos, Dimitrios Papazoglou and Periklis Panagopoulos

Life 2025, 15(11), 1747; https://doi.org/10.3390/life15111747 - 13 Nov 2025

Abstract

Background: After the implementations of Highly Active Antiretroviral Therapy (HAART) HIV infection became a chronic condition and the clinical focus on non-AIDS-related comorbidities such as hypertension and chronic kidney disease has increased. This study aims to investigate the prevalence and independent predictors of [...] Read more.

Background: After the implementations of Highly Active Antiretroviral Therapy (HAART) HIV infection became a chronic condition and the clinical focus on non-AIDS-related comorbidities such as hypertension and chronic kidney disease has increased. This study aims to investigate the prevalence and independent predictors of hypertension and albuminuria in a cohort of people with HIV (PWHIV) with high rates of viral suppression. Methods: This is a cross-sectional study of 183 HAART-experienced PWHIV. Hypertension, defined as office systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg and albuminuria, was defined as a sex-based albumin–creatinine ratio (ACR) of >355 mg/g for females and >250 mg/g for males. Univariable and multivariable logistic regression was conducted to identify the association of hypertension and albuminuria with demographic, clinical, and HIV-specific factors. Results: The prevalence of hypertension was 43.9% (n = 74) and albuminuria was 22.4% (n = 41). In the multivariable analysis, factors independently associated with prevalence of HTN were older age, overweight/obesity, and diabetes mellitus. TDF-based ART was explored as a potential factor but did not reach statistical significance (aRR = 1.85, p = 0.065). For albuminuria, older age, diabetes mellitus, and duration of HAART (aRR = 1.03 per year) were revealed as independent predictors. Conclusions: The results of this study demonstrate that the development of hypertension is primarily driven by traditional metabolic risk factors. However, the progression to albuminuria appears to be influenced not only by these comorbidities but also by long-term HIV disease and HAART exposure. These findings underline the critical need for the screening and management of hypertension and other comorbidities to mitigate the risk of long-term cardiovascular and renal complications in this aging population of PWHIV. Full article

(This article belongs to the Special Issue Emerging Knowledge on Human Immunodeficiency Virus)

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19 pages, 8438 KB

Open AccessArticle

Looking at the Possibility of Using Mushroom Mycelium for Developing Leather-like Materials Aligned with Eco-Friendly and Sustainable Fashion Trends

by Worawoot Aiduang, Thanawin Patipattanakul, Yutthaphum Keduk, Apiwit Rattanapat, Phumin Phumila, Praween Jinanukul, Phongeun Sysouphanthong, Orlavanh Xayyavong, Kritsana Jatuwong and Saisamorn Lumyong

Life 2025, 15(11), 1746; https://doi.org/10.3390/life15111746 - 13 Nov 2025

Abstract

The growing demand for sustainable alternatives to animal and synthetic leathers has accelerated interest in mycelium-based materials as an eco-friendly solution for the fashion industry. This study explores the potential of mushroom mycelium to create leather-like materials that align with circular fashion principles. [...] Read more.

The growing demand for sustainable alternatives to animal and synthetic leathers has accelerated interest in mycelium-based materials as an eco-friendly solution for the fashion industry. This study explores the potential of mushroom mycelium to create leather-like materials that align with circular fashion principles. Five species of edible and medicinal mushrooms were cultivated on sawdust substrates and evaluated for their growth performance, physical properties, and suitability as leather substitutes. Growth analysis revealed distinct species-specific behaviors: Cubamyces flavidus and Lentinus squarrosulus exhibited rapid colonization, achieving full substrate coverage within five days and forming dense mycelial networks at 14 days. In contrast, despite growing more slowly, Sanghuangporus vaninii and Ganoderma gibbosum formed thicker, more compact mats that might be suitable for strong leather-like materials. Visual and structural assessments showed diverse textures, colors, and hyphal architectures resembling natural leather. Physical characterization revealed shrinkage ranging from 13.17% to 24.09%, higher than for cow tanned leather (>5%) and PU microfiber (0.1–1.2%), suggesting a need for stabilization treatments. Apparent densities ranged from 0.13 g/cm³ to 0.30 g/cm³, lower than those of cow leather (0.49 g/cm³) and PU leather (0.38 g/cm³), highlighting species-specific hyphal structures that influence flexibility, porosity, and strength. SEM imaging confirmed the presence of interwoven hyphal mats resembling the fibrous architecture of natural leather, with S. vaninii showing the most uniform and continuous structure. Water absorption was significantly higher in mycelium sheets, consistent with their microporous nature, though S. vaninii showed the lowest uptake, reflecting possible natural water absorption. Thermogravimetric analysis revealed three-stage degradation profiles, with S. vaninii and G. gibbosum retaining >35% mass at 400 °C, indicating strong thermal stability for processing techniques such as hot pressing and finishing. Overall, the results demonstrate mycelium-based leathers as a biodegradable, low-impact alternative that can replicate the visual and functional characteristics of traditional leather, with opportunities for further improvement in substrate optimization, eco-tanning, surface coating, and scalable production toward a sustainable fashion future. Full article

(This article belongs to the Special Issue Trends in Microbiology 2025)

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43 pages, 1749 KB

Open AccessHypothesis

The Origin of Life and Cellular Systems: A Continuum from Prebiotic Chemistry to Biodiversity

by Jaime Gómez-Márquez

Life 2025, 15(11), 1745; https://doi.org/10.3390/life15111745 - 13 Nov 2025

Abstract

The origin of life remains one of the most profound and enduring enigmas in the biological sciences. Despite substantial advances in prebiotic chemistry, fundamental uncertainties persist regarding the precise mechanisms that enabled the emergence of the first cellular entity and, subsequently, the foundational [...] Read more.

The origin of life remains one of the most profound and enduring enigmas in the biological sciences. Despite substantial advances in prebiotic chemistry, fundamental uncertainties persist regarding the precise mechanisms that enabled the emergence of the first cellular entity and, subsequently, the foundational branches of the tree of life. After examining the core principles that define living systems, we propose that life emerged as a novel property of a prebiotically assembled system—formed through the integration of distinct molecular worlds, defined as sets of structurally and functionally related molecular entities that interact via catalytic, autocatalytic, and/or self-assembly processes. This emergence established a permanent system–process duality, wherein the system’s organization and its dynamic processes became inseparable. Upon acquiring the capacity to replicate and mutate its genetic program, this primordial organism initiated the evolutionary process, ultimately driving the diversification of life under the influence of evolutionary forces and leading to the formation of ecosystems. The challenge of uncovering the origin of life and the emergence of biodiversity is not solely scientific, it requires the integration of empirical evidence, theoretical insight, and critical reflection. This work does not claim certainty but proposes a perspective on how life and biodiversity may have arisen on Earth. Ultimately, time and scientific inquiry will determine the validity of this view. Full article

(This article belongs to the Special Issue 2nd Edition—Featured Papers on the Origins of Life)

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21 pages, 707 KB

Open AccessArticle

Mitochondrial DNA Deletions and Plasma GDF-15 Protein Levels Are Linked to Hormonal Dysregulation and Multi-Organ Involvement in Female Reproductive Endocrine Disorders

by Vera Varhegyi, Barnabas Banfi, Domonkos Trager, Dora Gerszi, Eszter Maria Horvath, Miklos Sipos, Nandor Acs, Maria Judit Molnar, Szabolcs Varbiro and Aniko Gal

Life 2025, 15(11), 1744; https://doi.org/10.3390/life15111744 - 13 Nov 2025

Abstract

Mitochondrial dysfunction contributes to female reproductive endocrine disorders and is frequently associated with multisystem symptoms. Insulin resistance (IR) is a common metabolic disorder strongly linked to polycystic ovary syndrome (PCOS), while premature ovarian insufficiency (POI) also impairs fertility. Mitochondrial DNA (mtDNA) deletions and [...] Read more.

Mitochondrial dysfunction contributes to female reproductive endocrine disorders and is frequently associated with multisystem symptoms. Insulin resistance (IR) is a common metabolic disorder strongly linked to polycystic ovary syndrome (PCOS), while premature ovarian insufficiency (POI) also impairs fertility. Mitochondrial DNA (mtDNA) deletions and the stress-responsive cytokine growth differentiation factor 15 (GDF-15) have recently emerged as complementary biomarkers of mitochondrial impairment. In this retrospective observational study, we examined reproductive hormones, plasma GDF-15, mtDNA deletions, and clinical symptoms in insulin-resistant women, including those with PCOS or POI. Eighty-one patients were divided into three subgroups: IR-only (n = 49), IR-PCOS (n = 19), and IR-POI (n = 13). IR was defined based on elevated insulin levels during oral glucose tolerance testing (>10 mU/L at 0 min, >50 mU/L at 60 min, >30 mU/L at 120 min) according to national gynecological endocrinology guidelines, acknowledging that IR is not universally accepted as a distinct clinical entity. POI was defined as reduced ovarian reserve before age 40 with anti-Müllerian hormone (AMH) <1.0 ng/mL. Clinical symptoms were assessed using a questionnaire, medical record, and physical examination. MtDNA deletions were detected by long-range PCR, and GDF-15 was measured by ELISA. Free thyroxine (T4) emerged as an independent predictor of GDF-15, suggesting that thyroid function modulates mitochondrial stress signaling in insulin-resistant women. MtDNA deletions and/or elevated GDF-15 correlated with endocrine, gastrointestinal, and neuropsychiatric symptoms, and reduced AMH/FSH ratios indicated impaired ovarian function. Cross-sectional analysis further revealed lower AMH and AMH/FSH ratios in older women with mtDNA deletions, consistent with a trend toward accelerated reproductive aging. Overall, these findings support the role of GDF-15 and mtDNA deletions as complementary biomarkers of mitonuclear stress, with potential relevance for both systemic and reproductive health. Full article

(This article belongs to the Special Issue Obstetrics and Gynecology Medicine: From Bench to Bedside—2nd Edition)

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12 pages, 1840 KB

Open AccessArticle

Polarized Light Microscopy-Based Quantification of Scleral Collagen Fiber Bundle Remodeling in the Lens-Induced Myopia Mouse Model

by Yajing Yang, Shin-ichi Ikeda, Longdan Kang, Ziyan Ma, Kazuno Negishi, Kazuo Tsubota, Yohei Tomita, Kate Gettinger and Toshihide Kurihara

Life 2025, 15(11), 1743; https://doi.org/10.3390/life15111743 - 13 Nov 2025

Abstract

Scleral remodeling plays a crucial role in myopia development. Although ultrastructural collagen changes have been described, quantitative assessment at the fiber bundle level remains limited. This study quantitatively evaluated scleral collagen remodeling in a lens-induced myopia (LIM) mouse model using polarized light microscopy [...] Read more.

Scleral remodeling plays a crucial role in myopia development. Although ultrastructural collagen changes have been described, quantitative assessment at the fiber bundle level remains limited. This study quantitatively evaluated scleral collagen remodeling in a lens-induced myopia (LIM) mouse model using polarized light microscopy (PLM) combined with picrosirius red (PSR) staining. LIM was induced in C57BL/6J male mice by applying a monocular −30 D lens from postnatal week 3 to 6. Eyes wearing −30 D lenses showed myopic shifts in refraction (−8.42 ± 3.87 D vs. 4.42 ± 4.45 D; p = 0.002) and axial elongation (0.21 ± 0.04 mm vs. 0.18 ± 0.05 mm; p = 0.020) compared with contralateral controls. PLM revealed looser, more disorganized collagen bundles in myopic sclera. Quantitative analysis showed reduced bundle proportion (40.91 ± 6.58% vs. 48.36 ± 6.47%; p = 0.040) and mean size (147.11 ± 59.38 µm² vs. 281.45 ± 101.00 µm²; p = 0.002). These results indicate that myopia development involves structural remodeling of the sclera and that PLM with PSR staining provides a practical approach for quantitative wide-field evaluation of collagen architecture in experimental myopia. Full article

(This article belongs to the Special Issue Dive into Myopia)

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11 pages, 528 KB

Open AccessArticle

Disparities in Colorectal Cancer Mortality and Survival Trends Among Hispanics Living in Puerto Rico (2000–2021): A Comparison Between Early-Onset and Average-Onset Disease

by Camille Montalvo-Pacheco, Carlos R. Torres-Cintrón, Marilyn Moró-Carrión, Hilmaris Centeno-Girona, Luis D. Borrero-García and María González-Pons

Life 2025, 15(11), 1742; https://doi.org/10.3390/life15111742 - 13 Nov 2025

Abstract

Colorectal cancer (CRC) is the leading cause of cancer-related death in Puerto Rico, a U.S. territory with noted disparities in CRC incidence, particularly among those with early-onset disease (EOCRC). Although EOCRC incidence has been consistently increasing in the U.S. mainland, and a disparate [...] Read more.

Colorectal cancer (CRC) is the leading cause of cancer-related death in Puerto Rico, a U.S. territory with noted disparities in CRC incidence, particularly among those with early-onset disease (EOCRC). Although EOCRC incidence has been consistently increasing in the U.S. mainland, and a disparate burden has been reported among Hispanics, EOCRC mortality and survival are yet to be assessed among Hispanics living in Puerto Rico (PRH). In this study, we analyzed EOCRC mortality and survival trends in PRH and compared these to those of other U.S. populations. Mortality data were obtained from the Puerto Rico Central Cancer Registry and the Surveillance, Epidemiology, and End Results (SEER) program. Descriptive characteristics and temporal trends were derived via SEER*Stat software (version 9.0.42) and Joinpoint regression models, respectively. Relative survival was estimated using the Actuarial method and the Ederer II approach. Overall, CRC mortality trends showed a decline, but an increase in EOCRC mortality among Hispanics. PRH exhibited the lowest 5-year survival in regional cancers (54.10%), with NHB having the lowest survival among younger individuals. This study highlights significant disparities in EOCRC mortality trends and underscores an urgent need for targeted public health strategies and research efforts to address the disproportionate burden of EOCRC among PRH. Full article

(This article belongs to the Special Issue Cancer Epidemiology)

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13 pages, 1805 KB

Open AccessArticle

Ultrasound Evaluation of Plantar Fascia in Individuals with Charcot–Marie–Tooth Disease: An Exploratory Study

by Noemi Vallario, Antonella Vitale, Alessandra Zeni, Eleonora Di Ciesco, Eloisa Martire, Rossella Calciano, Letizia Tarallo, Gianpaolo Ronconi, Costanza Pazzaglia, Ilaria Paolasso and Augusto Fusco

Life 2025, 15(11), 1741; https://doi.org/10.3390/life15111741 - 12 Nov 2025

Abstract

Background: Charcot–Marie–Tooth disease (CMTd) is the most prevalent inherited peripheral neuropathy, often associated with foot deformities and gait and balance impairments. While the structural characteristics of the foot have been extensively investigated, limited data are available regarding the features of the plantar fascia [...] Read more.

Background: Charcot–Marie–Tooth disease (CMTd) is the most prevalent inherited peripheral neuropathy, often associated with foot deformities and gait and balance impairments. While the structural characteristics of the foot have been extensively investigated, limited data are available regarding the features of the plantar fascia in individuals with CMTd. Aim: To investigate the ultrasound (US) structural characteristics of the plantar fascia in subjects with CMTd and to explore their relations with disease severity and functional outcomes, encompassing lower extremity function, gait, and balance. Methods: A total of 26 individuals with confirmed CMTd underwent clinical and functional assessments. Bilateral ultrasound examination of the plantar fascia was performed to assess thickness, echogenicity, fibrillar pattern, and inflammatory signs (as assessed by US Power Doppler). Correlations between ultrasound findings, clinical data, and functional measures were also evaluated. Results: No pathological increase in plantar fascia thickness was observed, although a significant side-to-side difference was noted (p = 0.031) on ultrasound (US) imaging. No inflammatory signs were also detected. Significant associations were found between fascial alterations and age (p = 0.024), disease severity (CMTES, p = 0.014), and functional performance (10 MWT p = 0.017; SPPB p = 0.039). Conclusions: In individuals with CMT, plantar fascia abnormalities likely reflect chronic structural degeneration rather than acute inflammation. These changes are more evident with an increase in age, disease progression, and functional decline, suggesting the role of US imaging as a valuable tool for clinical and therapeutic strategies. Full article

(This article belongs to the Section Medical Research)

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