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Life, Volume 15, Issue 11 (November 2025) – 144 articles

Cover Story (view full-size image): Platelets, traditionally viewed as mediators of clot formation, are now recognized as key contributors to the development of atherosclerosis. Beyond their role in hemostasis, platelets actively release chemokines, interact with immune cells, promote endothelial dysfunction, and secrete extracellular vesicles that amplify vascular thrombo-inflammatory signaling. Through their involvement in plaque development, progression, and rupture, platelets have emerged as promising therapeutic targets. Advances such as nanoparticle drug delivery and selective inhibition of platelet-derived mediators offer increasing precision and efficiency while minimizing bleeding risks in patients with atherosclerosis. View this paper
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15 pages, 296 KB  
Review
Platelets in Dry Eye Disease: A Narrative Review of Biological Mechanisms and Therapeutic Applications Derived from Platelets
by Marco Zeppieri, Caterina Gagliano, Alessandro Avitabile, Antonino Maniaci, Francesco Cappellani, Riccardo Foti, Giosuè Giordano Incognito, Dalila Incognito and Roberta Foti
Life 2025, 15(11), 1785; https://doi.org/10.3390/life15111785 - 20 Nov 2025
Viewed by 500
Abstract
Background: Platelets have conventionally been viewed as cellular fragments crucial for hemostasis; nonetheless, their extensive secretome of cytokines and growth factors has been increasingly acknowledged as a significant regulator of inflammation and tissue healing at the ocular surface. Aims: The objective of this [...] Read more.
Background: Platelets have conventionally been viewed as cellular fragments crucial for hemostasis; nonetheless, their extensive secretome of cytokines and growth factors has been increasingly acknowledged as a significant regulator of inflammation and tissue healing at the ocular surface. Aims: The objective of this narrative review is to synthesize existing knowledge of platelet biology with new findings about the therapeutic use of platelet-derived products in dry eye disease (DED). Methods: A qualitative review of the PubMed, Scopus, and Web of Science databases up to June 2025 identified preclinical, translational, and clinical studies assessing platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), platelet lysate, and autologous serum tears for dry eye disease (DED) and associated ocular surface disorders. Results: Platelet-derived formulations have exhibited reliable immunomodulatory and regenerative effects by diminishing inflammatory signaling, lowering cytokine expression, and facilitating epithelial and neurotrophic restoration. Clinical investigations have indicated enhancements in tear film stability, corneal staining, and patient-reported symptoms, especially in cases of moderate-to-severe or refractory illness. Nonetheless, methodological diversity, inconsistent preparation techniques, and restricted sample sizes have impeded comparability among experiments. Conclusions: Platelet-derived treatments constitute a biologically viable and clinically promising strategy for the management of dry eye disease (DED). Future research must emphasize the standardization of preparation protocols, the identification of predictive biomarkers such as transforming growth factor-β1 (TGF-β1), nerve growth factor (NGF), and matrix metalloproteinase-9 (MMP-9), as well as the design of multicenter randomized controlled trials to guarantee reproducible, GMP-compliant clinical applications. Full article
(This article belongs to the Special Issue The Biology and Functions of Platelets: Emerging Challenges)
15 pages, 551 KB  
Systematic Review
The Impact of Sodium Glucose Co-Transporter 2 (SGLT-2) Inhibitors on Atherogenesis: A Systematic Review of Experimental and Clinical Evidence
by Filippo Luca Gurgoglione, Marco Covani, Laura Torlai Triglia, Giorgio Benatti, Davide Donelli, Michele Bianconcini, Emilia Solinas, Iacopo Tadonio, Andrea Denegri, Mattia De Gregorio, Gabriella Dallaglio, Alessandra Dei Cas, Riccardo C. Bonadonna, Luigi Vignali and Giampaolo Niccoli
Life 2025, 15(11), 1784; https://doi.org/10.3390/life15111784 - 20 Nov 2025
Viewed by 488
Abstract
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant benefits in cardiovascular outcomes trials, but their effect on atherosclerotic plaques remains unclear. This review aims to summarize the current evidence on the impact of SGLT2i on atherogenesis. Methods: A systematic search was conducted across [...] Read more.
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant benefits in cardiovascular outcomes trials, but their effect on atherosclerotic plaques remains unclear. This review aims to summarize the current evidence on the impact of SGLT2i on atherogenesis. Methods: A systematic search was conducted across PubMed, Embase, Scopus, Web of Science, and Google Scholar databases up to August 2025. Preclinical and clinical studies on the effect of SGLT2i on atherogenesis and atherosclerotic plaque extent and phenotype were included. Results: A total of 27 studies were included. Twenty-four studies examined in vitro and animal models of atherosclerosis exposed to SGLT2i, while three studies focused on the effects of SGLT2i on coronary plaques in patients with ischemic heart disease. SGLT2is modulate atherogenesis through multiple mechanisms: prevention and reversal of endothelial dysfunction, reduction in monocyte recruitment and promotion of anti-inflammatory macrophage polarization. Additionally, SGLT2is reduce inflammation and inhibit vascular calcification. Through these mechanisms, SGLT2is decrease plaque burden in both diabetic and non-diabetic atherosclerosis models. Furthermore, they reduce lipid content and macrophages accumulation while increasing fibrous cap thickness, thereby contributing to plaque stabilization. Conclusions: Preclinical and clinical evidence suggest that SGLT2is modulate every step of the atherogenic process, reduce atherosclerotic burden and promote coronary plaque stabilization. Full article
(This article belongs to the Section Medical Research)
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13 pages, 481 KB  
Article
Long-Term Study of the Changes in Symptoms and Signs of Dry Eye Disease in Participants Non-Adherent to Treatment
by Belen Sabucedo-Villamarin, Jacobo Garcia-Queiruga, Hugo Pena-Verdeal, María José Ginzo-Villamayor, Carlos Garcia-Resua, Maria J. Giraldez and Eva Yebra-Pimentel
Life 2025, 15(11), 1783; https://doi.org/10.3390/life15111783 - 20 Nov 2025
Viewed by 437
Abstract
Background: The purpose of this study was to assess differences in clinical symptoms and signs of DED in non-adherent to treatment patients to describe long-term disease progression. Methods: 120 patients previously diagnosed with Dry Eye Disease (DED) were contacted to undergo a second [...] Read more.
Background: The purpose of this study was to assess differences in clinical symptoms and signs of DED in non-adherent to treatment patients to describe long-term disease progression. Methods: 120 patients previously diagnosed with Dry Eye Disease (DED) were contacted to undergo a second eye examination. The final included participants were classified into three groups based on when the second examination was scheduled: 4 years (Group 1; n = 33), 6 years (Group 2; n = 18) or 8 years (Group 3; n = 37) since the diagnostic visit. All included participants were classified as ‘non-adherent to DED treatment’, defined as patients who reported not following their prescribed DED therapy. In both examinations, Ocular Surface Disease Index (OSDI) questionnaire, tear film osmolarity, inter-eye osmolarity (osmolarity |OD-OS|), Fluorescein Break-Up Time (FBUT), Maximum Blink Interval (MBI) and corneal staining were evaluated. Results: OSDI score improved after 4 years of DED diagnosis (Group 1, mean difference close to 12 points, p < 0.001) and after 8 years (Group 3, mean difference of 9 points, p < 0.001), but remained stable after 6 years (Group 2, p = 0.328). Osmolarity worsened only after 6 years of DED diagnosis (Group 2, mean difference of 13.2 mOsm/L, p = 0.011), while osmolarity |OD–OS| showed no change (all p ≥ 0.231). FBUT values were stable across all groups (all p ≥ 0.265). MBI increased after 4 and 8 years of DED diagnosis (Groups 1 and 3, p ≤ 0.003), but not after 6 years (Group 2, p = 0.391). Corneal staining worsened after 8 years of DED diagnosis (Group 3, 0.55 points, p = 0.011), with no changes at 4 or 6 years (Groups 1 and 2, both p ≥ 0.318). Conclusions: In non-adherent DED patients, osmolarity |OD-OS| and tear film stability remain stable during the natural course of the disease, while ocular surface damage increases. However, the subjective symptomatology and the nociceptive blink reflex due to ocular discomfort decreased since the diagnostic visit. Full article
(This article belongs to the Section Physiology and Pathology)
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11 pages, 706 KB  
Article
Contrasting Effects of Larval Escitalopram and Serotonin-Synthesis Inhibitor on Adult Phototaxis in Drosophila w1118
by Indrikis Krams, Vadims Kolbjonoks, Sergejs Popovs, Māris Munkevics, Ronalds Krams, Giedrius Trakimas, Markus J. Rantala, Jorge Contreras-Garduño, Priit Jõers, Colton B. Adams and Tatjana Krama
Life 2025, 15(11), 1782; https://doi.org/10.3390/life15111782 - 20 Nov 2025
Viewed by 630
Abstract
Phototaxis, the movement toward or away from light, is a fundamental behavior with ecological and evolutionary relevance. In Drosophila melanogaster, phototactic choice shows individual variability and has been linked to serotonergic signaling. Using a high-throughput FlyVac assay to test single flies in [...] Read more.
Phototaxis, the movement toward or away from light, is a fundamental behavior with ecological and evolutionary relevance. In Drosophila melanogaster, phototactic choice shows individual variability and has been linked to serotonergic signaling. Using a high-throughput FlyVac assay to test single flies in parallel, we reared w1118 flies on (1) standard food (Control), (2) aMW (a serotonin-synthesis inhibitor), (3) 5-HTP (a serotonin precursor), or (4) escitalopram (a selective serotonin reuptake inhibitor, SSRI). Light-choice probability (LCP) did not differ between Control and aMW. LCP was lower in 5-HTP and escitalopram than in Control and aMW, and lower with escitalopram than with 5-HTP. Between-fly variability (MADn) differed across treatments: escitalopram exhibited higher dispersion than Control and aMW, whereas 5-HTP did not differ reliably from Control. These findings support the hypothesis that serotonin modulates behavioral predictability and mean choice bias; variability effects were compound-specific (escitalopram modestly increased MADn, whereas 5-HTP did not differ from Control). Given the rising costs and ethical constraints of vertebrate models, our results highlight Drosophila and FlyVac as a powerful, cost-effective system for investigating SSRI effects on decision phenotypes. Full article
(This article belongs to the Section Animal Science)
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18 pages, 1054 KB  
Article
Vulvar Squamous Cell Carcinoma: A Retrospective Analysis of Epidemiologic Characteristics, HPV Status, and Surgical Outcomes in 35 Cases
by Daniela Marinescu, Laurențiu Augustus Barbu, Tiberiu Stefăniță Țenea Cojan, Ștefania Tudorache, Dominic Iliescu, Răzvan Alexandru Marinescu, Lucian George Zorilă and Valeriu Șurlin
Life 2025, 15(11), 1781; https://doi.org/10.3390/life15111781 - 20 Nov 2025
Viewed by 450
Abstract
Background: Vulvar squamous cell carcinoma (VSCC) is an uncommon yet increasingly relevant malignancy characterized by two distinct etiopathogenetic pathways: HPV-associated and HPV-independent. Data from Eastern Europe remain scarce, where demographic and diagnostic variability may influence disease presentation and outcomes. Purpose: This study aimed [...] Read more.
Background: Vulvar squamous cell carcinoma (VSCC) is an uncommon yet increasingly relevant malignancy characterized by two distinct etiopathogenetic pathways: HPV-associated and HPV-independent. Data from Eastern Europe remain scarce, where demographic and diagnostic variability may influence disease presentation and outcomes. Purpose: This study aimed to assess the epidemiologic characteristics, HPV status, surgical management, and postoperative morbidity of VSCC in a Romanian single-center cohort, providing real-world evidence from an underrepresented region. Methods: A retrospective analysis was conducted on all 35 consecutive patients with histologically confirmed vulvar squamous cell carcinoma (VSCC) diagnosed and treated between January 2017 and December 2024 at the Department of Obstetrics and Gynecology, County Emergency Clinical Hospital of Craiova, Romania. Demographic, histopathologic, and surgical data were reviewed. HPV genotyping was performed on formalin-fixed paraffin-embedded (FFPE) tissue using PCR-based methods. Results: HPV DNA was detected in 31.4% of cases, predominantly genotypes 16, 18, and 33. HPV-positive patients were significantly younger than HPV-negative ones (median 58 vs. 72.5 years, p < 0.001), supporting the dual-pathway model of carcinogenesis. Early postoperative complications occurred in 65.7% of patients and late morbidity in 71.4%, secondary lymphedema. Surgical radicality was not significantly associated with early complications or length of hospitalization. Conclusions: This study highlights the epidemiologic and surgical patterns of VSCC in an Eastern European population, showing that conservative surgical strategies can maintain oncologic safety while reducing morbidity. These findings emphasize the need for standardized HPV testing, optimized perioperative care, and improved surveillance programs to enhance outcomes and survivorship. Full article
(This article belongs to the Special Issue Cancer Epidemiology)
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18 pages, 5551 KB  
Article
Isolation and Characterization of Integrin α9 Positive Extracellular Vesicles Derived from Human Corneoscleral Rings
by Hung-Yin Lai, Ming-Chieh Hsieh, Hao-Hsiang Wu, Chien-Wei Lee, Shih-Hua Liu, Hsing-Yu Lin, Yi-Wen Chen, Chun-Chi Chiang, Yi-Ching Hsieh, Ying-Hsuen Wu, You-Ling Li, Hsiao-Fan Tung, Jennifer Hui-Chun Ho and Yi-Yu Tsai
Life 2025, 15(11), 1780; https://doi.org/10.3390/life15111780 - 20 Nov 2025
Viewed by 376
Abstract
Corneoscleral-ring-derived extracellular vesicles represent a potential therapeutic strategy for promoting in vitro corneal wound healing. In this study, we successfully isolated and characterized extracellular vesicles from human corneolimbal tissue obtained from 42 donors, with a mean age of 51.62 ± 15.56 years. Donor-related [...] Read more.
Corneoscleral-ring-derived extracellular vesicles represent a potential therapeutic strategy for promoting in vitro corneal wound healing. In this study, we successfully isolated and characterized extracellular vesicles from human corneolimbal tissue obtained from 42 donors, with a mean age of 51.62 ± 15.56 years. Donor-related factors such as age, corneal endothelial cell density, and underlying systemic conditions did not confound extracellular vesicle size and concentration with mean peak size of 99.52 ± 13.00 nm by nanoparticle tracking analysis. Western blotting analysis revealed positive Alix, stable expression of CD9 and CD81, and variable expression of CD63. Limbal stem cell (LSC)-associated markers, i.e., ABCG2, p63, Notch-1, and Integrin α9 were positively detected in the isolated extracellular vesicles. Notably, Integrin α9 showed stable and relatively strong expression in all samples serving a specific marker of LSC-derived extracellular vesicles. Functional assays demonstrated that LSC-derived extracellular vesicles exhibited better wound healing potency compared to extracellular vesicles derived from mesenchymal stem cells (MSCs). These findings suggest that corneoscleral-ring-derived extracellular vesicles express distinct LSC markers, including Integrin α9, and hold significant potential for application in corneal wound healing and ocular surface regeneration. Full article
(This article belongs to the Special Issue Vision Science and Optometry: 2nd Edition)
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20 pages, 885 KB  
Article
Response of Wheat and Sugar Beet to Different Mineral–Organic Fertilization in a Long-Term Experiment
by Przemysław Barłóg, Lukáš Hlisnikovský, Remigiusz Łukowiak, Ladislav Menšík and Eva Kunzová
Life 2025, 15(11), 1779; https://doi.org/10.3390/life15111779 - 20 Nov 2025
Viewed by 357
Abstract
The effect of cyclic pig slurry (PS) application in long-term crop rotations with alfalfa is poorly recognized, particularly with regard to nitrogen use efficiency (NUE) in crops requiring relatively high nitrogen (N) inputs. A long-term field experiment was established in Prague-Ruzyně, Czechia, in [...] Read more.
The effect of cyclic pig slurry (PS) application in long-term crop rotations with alfalfa is poorly recognized, particularly with regard to nitrogen use efficiency (NUE) in crops requiring relatively high nitrogen (N) inputs. A long-term field experiment was established in Prague-Ruzyně, Czechia, in 1955. The experiment evaluated the effects of eight fertilization combinations, involving PS application and various N, phosphorus (P) and potassium (K) rates (N0P0K0; N1P1K1; N3P2K2; and N4P2K2). The effect of fertilization was evaluated in a 9-year crop rotation, in which PS was applied only three times under root crops. Long-term different mineral fertilization treatments and the application of PS significantly affected the yield of the tested crops: winter wheat and sugar beet. The highest wheat yield (8.34 t ha−1) was observed in the PS+N3P2K2 treatment, while the highest beet yield (86.1 t ha−1) was recorded in the PS+N4P2K2 treatment. The differences compared with the absolute control (N0P0K0) were 62.3% and 40.5%, respectively. However, statistically significant differences between treatments with different NPK rates were recorded only in plots without PS. With increasing NPK fertilizer rates, the uptake of macronutrients by plants also increased. The only exception was calcium in sugar beet in PS plots. The total N accumulation in plants was proportionally related to the total N input to the soil–plant system (Nin). For winter wheat, this trend was beneficial, as it resulted in higher protein yield, whereas in beet, the sugar yield did not increase significantly when Nin exceeded 250 kg N ha−1. The obtained results indicate that, in the soil conditions of this experiment, N rates should be primarily balanced with appropriate rates of phosphorus. Full article
(This article belongs to the Special Issue Cereal Production Systems: Climate-Fertilizer-Crop Yield Dynamics)
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11 pages, 469 KB  
Article
Objective Analysis of Reading Ability Using an Eye Tracker in Intermittent Exotropia
by Dong Hyun Kim, Jeong-Min Hwang and Hee Kyung Yang
Life 2025, 15(11), 1778; https://doi.org/10.3390/life15111778 - 20 Nov 2025
Viewed by 420
Abstract
Background/Objectives: This study’s objective was to analyze the reading ability in patients with intermittent exotropia using an eye tracker and determine how the clinical characteristics of intermittent exotropia may affect reading ability. Methods: We compared the reading speed (LPS; letters per [...] Read more.
Background/Objectives: This study’s objective was to analyze the reading ability in patients with intermittent exotropia using an eye tracker and determine how the clinical characteristics of intermittent exotropia may affect reading ability. Methods: We compared the reading speed (LPS; letters per second) of 25 intermittent exotropia patients to 25 age-matched normal controls who were 13 years old or older with best-corrected visual acuities of ≥20/25. Correlations between reading ability and clinical characteristics of intermittent exotropia were evaluated. Results: Reading speed was significantly slower in the intermittent exotropia group (6.1 ± 0.81 LPS) than in the control group (6.8 ± 1.11 LPS, p = 0.014). The Newcastle control scores, Mayo Clinic office-based scale and the patients’ deviation angle were not significantly related to reading speed (p = 0.132, 0.197, and 0.807, respectively). Fixation disparity score measured with an eye tracker during the reading task showed a statistically significant negative correlation with reading speed (Spearman’s rank correlation coefficient = −0.458, p = 0.028). Conclusions: Reading speed was slower in patients with intermittent exotropia compared to age-matched controls without strabismus. Only objective fusional control scores measured with an eye tracker showed significant correlation with the reading speed. Full article
(This article belongs to the Section Physiology and Pathology)
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16 pages, 311 KB  
Article
Laser Hemorrhoidoplasty: Postoperative Outcomes and Predictive Factors for Pain, Bleeding, and Recovery
by Laurențiu Augustus Barbu, Nicolae-Dragoș Mărgăritescu, Liliana Cercelaru, Tiberiu Stefăniță Țenea Cojan, Mădălina Costinela Stănică, Irina Enăchescu, Ana-Maria Țenea Cojan, Valentina Căluianu, Gabriel Florin Răzvan Mogoș and Liviu Vasile
Life 2025, 15(11), 1777; https://doi.org/10.3390/life15111777 - 19 Nov 2025
Viewed by 547
Abstract
Background: Laser hemorrhoidoplasty (LHP) is a minimally invasive alternative to excisional hemorrhoidectomy, with promising short-term outcomes. However, predictors of postoperative pain, bleeding, and recovery remain insufficiently characterized. Methods: We conducted a prospective study including 140 patients with Goligher grade I–IV hemorrhoidal disease (January [...] Read more.
Background: Laser hemorrhoidoplasty (LHP) is a minimally invasive alternative to excisional hemorrhoidectomy, with promising short-term outcomes. However, predictors of postoperative pain, bleeding, and recovery remain insufficiently characterized. Methods: We conducted a prospective study including 140 patients with Goligher grade I–IV hemorrhoidal disease (January 2020–December 2024) at Independența Vita Plus Hospital, Craiova. All patients received preoperative diosmin and topical ointments. Procedures were performed under spinal anesthesia using a standardized 1470 nm diode laser technique. Outcomes included postoperative pain (VAS), bleeding, early and late complications, recovery time, HDSS change, and quality of life assessed with a simple 0–10 numerical scale used in routine clinical practice (not a validated QoL instrument). Results: Mean operative time was 17.9 ± 4.8 min, with minimal blood loss. Postoperative bleeding occurred in 28.6% and was mild. Early complications increased with disease stage: 10% (II), 53% (III), 68% (IV) (p < 0.001). VAS pain decreased from 2.1 on day 1 to 0.3 on day 7 (p < 0.0001). Median recovery time was 3 days, longer in advanced stages. HDSS improved from 10.3 ± 2.5 preoperatively to 1.7 ± 1.1 at 3 months (p < 0.0001). QoL numerical scores also improved significantly at 3 months. Goligher grade independently predicted late bleeding (OR 70.2), high pain (OR 4.9), and prolonged recovery (OR 8.6). No recurrences were observed at 12 months. Conclusions: LHP provides low postoperative pain, minimal bleeding, rapid recovery, and significant symptom and QoL improvement. Disease severity strongly predicts outcomes and should guide perioperative planning. Full article
20 pages, 962 KB  
Review
Interplay Among Synaptic Glutamate Release and Excitotoxicity: Neuronal Damage and Graphene-Based Materials Related Protection
by Giada Cellot and Laura Ballerini
Life 2025, 15(11), 1776; https://doi.org/10.3390/life15111776 - 19 Nov 2025
Viewed by 720
Abstract
Glutamate-related excitotoxicity represents a fundamental pathological process underlying both acute and chronic disorders of the central nervous system. Excessive stimulation of ionotropic and metabotropic glutamate receptors induces ionic dysregulation, mitochondrial dysfunction, and oxidative stress, which can activate necrotic and apoptotic pathways, processes further [...] Read more.
Glutamate-related excitotoxicity represents a fundamental pathological process underlying both acute and chronic disorders of the central nervous system. Excessive stimulation of ionotropic and metabotropic glutamate receptors induces ionic dysregulation, mitochondrial dysfunction, and oxidative stress, which can activate necrotic and apoptotic pathways, processes further amplified by defective glutamate clearance and astrocytic impairment. These mechanisms are recognized as key contributors to neuronal damage in ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, identifying excitotoxicity as a convergent hallmark of neurodegeneration. Despite considerable progress in elucidating its molecular mechanisms, clinical translation of excitotoxicity-targeted interventions remains limited, largely due to the difficulty of selectively attenuating pathological glutamatergic activity while preserving physiological neurotransmission. Recent advances in nanotechnology, particularly the development of graphene-based materials (GBMs), have offered innovative approaches for neuroprotection. Owing to their unique physicochemical properties and compatibility with neural tissue, GBMs have been investigated as platforms for neural interfacing, regenerative scaffolds, drug delivery platforms, and direct modulators of glutamatergic transmission. In particular, small graphene oxide nanosheets exhibit the capacity to downregulate glutamate release and confer anti-inflammatory and neuroprotective effects. These findings suggest that GBMs may represent a promising class of neuromodulatory tools for mitigating excitotoxic injury, warranting further preclinical and translational investigations. Full article
(This article belongs to the Special Issue Ion Channels and Neurological Disease: 2nd Edition)
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26 pages, 713 KB  
Review
The Social Relevance of Numbers: Insights from Animal Studies
by Matteo Macchinizzi, Arianna Felisatti and Rosa Rugani
Life 2025, 15(11), 1775; https://doi.org/10.3390/life15111775 - 19 Nov 2025
Viewed by 656
Abstract
Number processing offers significant adaptive advantages, enabling animals to navigate their environment and maximize survival outcomes. Extensive evidence across species demonstrates that numerical cognition is a ubiquitous cognitive trait that enhances fitness by supporting critical behaviors such as foraging, hunting, and intergroup conflict. [...] Read more.
Number processing offers significant adaptive advantages, enabling animals to navigate their environment and maximize survival outcomes. Extensive evidence across species demonstrates that numerical cognition is a ubiquitous cognitive trait that enhances fitness by supporting critical behaviors such as foraging, hunting, and intergroup conflict. In this review, we examine the evolutionary and developmental roots of numerical cognition, focusing on its functional role in social contexts. First, we report research findings on the use of numerical information in various social behaviors among a wide range of animals. Then, we discuss how selective pressures arising from social complexity, like group size, hierarchical structure, and cooperation, contribute to the refinement of numerical abilities during social interactions. Finally, we explore how early social deprivation during ontogeny may shape the development of numerical cognition. We present a novel and integrative perspective on the evolutionary and developmental link between numerical skills and social life. Full article
(This article belongs to the Section Animal Science)
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25 pages, 1112 KB  
Article
Influence of Atmospheric Pollutants on Allergic Sensitization to Cupressaceae, Olea, and Platanus Pollen in the Community of Madrid (2017–2021)
by Javier Chico-Fernández, Angélica Feliu Vila, Beatriz Rodríguez-Jiménez, Teresa Valbuena Garrido and Esperanza Ayuga-Téllez
Life 2025, 15(11), 1774; https://doi.org/10.3390/life15111774 - 19 Nov 2025
Viewed by 424
Abstract
Tree pollen is the most abundant in the Community of Madrid (CAM), and specifically, pollen types from Olea, Cupressaceae, and Platanus are the most allergenic, after Gramineae, in this Spanish region. Air pollutants are one of the most significant stress factors for [...] Read more.
Tree pollen is the most abundant in the Community of Madrid (CAM), and specifically, pollen types from Olea, Cupressaceae, and Platanus are the most allergenic, after Gramineae, in this Spanish region. Air pollutants are one of the most significant stress factors for wind-pollinated vegetation, especially in urban areas, and can cause alterations in the immune system and the consequent triggering of type I hypersensitivity reactions mediated by immunoglobulin E (IgE). This study analyses the allergic sensitization caused by the interrelation of O3, NO2, and PM10 pollutants with the tree pollen types Olea, Cupressaceae, and Platanus in the period 2017–2021. To this end, general linear models were calculated using the Statgraphics Centurion 19 tool. The data collected came from the Air Quality Networks of the CAM and Madrid City Council, the CAM Palynological Network, and the Allergy Services of the reference hospitals in the five study areas. This research confirms a statistically significant correlation between allergic sensitivity to pollen types and their concentrations in the air, and those of atmospheric pollutants, in the different areas and years studied. These pollen and pollutant concentrations in the atmosphere of the CAM jointly influence the prevalence of allergic sensitisation, as is evident in all the models calculated. Full article
(This article belongs to the Section Epidemiology)
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13 pages, 692 KB  
Article
Association Between Birth Outcomes and Gestational Weight Gain Among Forcibly Displaced Rohingya and Nearby Host Community, in Cox’s Bazar, Bangladesh
by Shakil Ahamed, Elisa Ugarte, Mahbub Elahi, Eamam Hossain, Sajjadur Rahman, Kazi Istiaque Sanin, Abir Dutta, Goutam Kumar Dutta, Alice J. Wuermli and Fahmida Tofail
Life 2025, 15(11), 1773; https://doi.org/10.3390/life15111773 - 19 Nov 2025
Viewed by 383
Abstract
Gestational weight gain (GWG) is a critical determinant of maternal and neonatal health, yet its patterns and consequences in displaced populations remain understudied. This study examined the association between GWG and birth outcomes among Forcibly Displaced Rohingya (FDR) women in Cox’s Bazar, Bangladesh. [...] Read more.
Gestational weight gain (GWG) is a critical determinant of maternal and neonatal health, yet its patterns and consequences in displaced populations remain understudied. This study examined the association between GWG and birth outcomes among Forcibly Displaced Rohingya (FDR) women in Cox’s Bazar, Bangladesh. We conducted a longitudinal cohort study from October 2022 to October 2024, enrolling 2888 pregnant women at different stages of pregnancy. Among them, 301 were recruited in the first trimester and followed through the third trimester, with 231 neonatal outcomes recorded within 72 hours of delivery. Overall, 66.8% of women experienced inadequate GWG. Despite the high prevalence of inadequate GWG, mean birth weight (2.79 kg) and mean gestational age at delivery (38.6 weeks) were within favorable ranges. Inadequate GWG was more common in mothers aged 30–39 years (p = 0.061) but significantly less common in underweight mothers (p = 0.012). GWG was positively associated with neonatal birth weight, length, and weight–length ratio (WLR) Z score, but not with gestational age. After adjusting for confounding factors, inadequate GWG showed a significant independent association with lower birth length (p = 0.016). These findings highlight the need for targeted interventions in displaced populations. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
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11 pages, 2576 KB  
Article
Histological Analysis of Multiple Unilateral Testicular Tumors in Dogs
by Mirosław Kuberka, Przemysław Prządka and Stanisław Dzimira
Life 2025, 15(11), 1772; https://doi.org/10.3390/life15111772 - 19 Nov 2025
Viewed by 664
Abstract
Testicular tumors are, after skin tumors, the most common neoplasms in male dogs. Among all animals, these tumors occur most frequently within dogs. The etiology remains unclear, although the ectopic (non-scrotal) positioning of the testicles has an influence on tumor development. The most [...] Read more.
Testicular tumors are, after skin tumors, the most common neoplasms in male dogs. Among all animals, these tumors occur most frequently within dogs. The etiology remains unclear, although the ectopic (non-scrotal) positioning of the testicles has an influence on tumor development. The most common types of testicular tumors include seminomas, Sertoli cell tumors, and interstitial (Leydig) cell tumors. The aim of this study was a retrospective evaluation of preserved material. A total of 326 cases of testicular tumors in dogs, diagnosed between 2017 and 2024, were analyzed. A histological analysis of multiple unilateral testicular tumors was conducted, and the frequency of occurrence was determined. 27 instances (8.28%) of multiple tumors within the same testicle were identified. The most recurrent combination was seminoma and interstitial cell tumors—12 cases (44.44%), followed by Sertoli cell and Leydig cell tumors—6 cases (22.22%), and seminoma and Sertoli cell tumors—6 cases (22.22%). In three cases, the presence of three tumors within a single testicle was observed (11.11%). In one case, double tumors were found within both testicles. It was observed that malignant features, as in cases of single testicular tumors, are rare. Full article
(This article belongs to the Special Issue Animal Reproduction and Health)
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1 pages, 125 KB  
Correction
Correction: Almustanyir et al. Age-Related Effects on the Color Discrimination Threshold. Life 2025, 15, 1074
by Ali Almustanyir, Mohammed Alhazmi, Amal Aldarwesh, Meznah S. Almutairi, Mohammed Almahubi, Ansam Alateeq, Tahani Alqahtani, Muteb Alanazi, Sultan Alotaibi, Mansour Alghamdi, Essam Almutleb, Basal H. Altoaimi, Balsam Alabdulkader and Mosaad Alhassan
Life 2025, 15(11), 1771; https://doi.org/10.3390/life15111771 - 19 Nov 2025
Viewed by 188
Abstract
In the published publication [...] Full article
(This article belongs to the Special Issue Vision Science and Optometry: 2nd Edition)
19 pages, 4070 KB  
Article
Effects of Different Light Qualities on Proliferation and Physiological Characteristics of Aquilaria sinensis Tissue-Cultured Seedlings
by Le Feng, Chuqi Chen, Chongcheng Yang, Wei Li, Jiapeng Lai, Xiaoyun Min, Siting Gan, Runhua Yi, Chenjun Lin and Feng Feng
Life 2025, 15(11), 1770; https://doi.org/10.3390/life15111770 - 19 Nov 2025
Viewed by 292
Abstract
In this study, we applied eight different light quality treatments and investigated their effects on the proliferation and physiological characteristics of Aquilaria sinensis group-cultivated seedlings in order to screen the best light quality for optimizing group-cultivation fast multiplication technology. The results showed that [...] Read more.
In this study, we applied eight different light quality treatments and investigated their effects on the proliferation and physiological characteristics of Aquilaria sinensis group-cultivated seedlings in order to screen the best light quality for optimizing group-cultivation fast multiplication technology. The results showed that the highest multiplication rates were obtained with blue light and red light, which were significantly higher than those of white light. Blue light was the most effective in promoting the synthesis of photosynthetic pigments, while red light and blue violet light were favorable for the accumulation of soluble sugars. Correlation analysis showed that the multiplication rate was significantly and positively correlated with plant height, chlorophyll b, total chlorophyll, and soluble sugar content. The comprehensive evaluation indicated that blue light, blue-violet light, and red light was most suitable for fostering proliferation of, and physiological status improvement in, group-cultivated A. sinensis seedlings, with their superior performance likely attributable to the combined effects of specific spectral properties and appropriate photosynthetic photon flux density (PPFD) levels. The results of this study provide technical support for light environment regulation for the efficient and rapid propagation of group-cultured A. sinensis seedlings. Full article
(This article belongs to the Special Issue Physiological Responses of Plants Under Abiotic Stresses)
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20 pages, 2385 KB  
Article
Network Analysis of Predicted Therapeutic Symptoms in National Health Insurance Herbal Prescriptions
by Seokwoo Jang, Ahyoug Lee and Changwon Kho
Life 2025, 15(11), 1769; https://doi.org/10.3390/life15111769 - 18 Nov 2025
Viewed by 346
Abstract
Background: National Health Insurance Herbal prescriptions (NHPs) are widely used; however, their multi-component composition complicates mechanistic interpretation and impedes the development of evidence-based approaches in traditional medicine and healthcare policy. In this study, we applied a systems biology approach to link molecular mechanisms [...] Read more.
Background: National Health Insurance Herbal prescriptions (NHPs) are widely used; however, their multi-component composition complicates mechanistic interpretation and impedes the development of evidence-based approaches in traditional medicine and healthcare policy. In this study, we applied a systems biology approach to link molecular mechanisms to clinical effects. Methods: From 56 NHPs, 13 with sufficient clinical evidence were selected. Multi-layer networks connecting herbs, ingredients, genes, and diseases were constructed using SymMap, with interactions filtered for oral bioavailability and statistical significance (false discovery rate < 0.05). Network-predicted diseases were validated against a clinically validated benchmark using permutation-based null model analysis, and gene set enrichment analysis (GSEA) was used to identify key molecular pathways. Results: Networks predicted an average of 1359 diseases per NHP, reflecting their polypharmacology. Importantly, the overall predicted disease sets for 10 of 13 NHPs showed statistically significant overlap with known clinical uses (p < 0.05, several with p < 0.001). GSEA indicated that NHPs commonly modulate three biological axes—hormone–metabolic regulation, neural signaling, and cell proliferation control. Conclusions: NHPs act as potential systemic homeostasis regulators. Our study introduces a computationally validated framework integrating network pharmacology with permutation-based statistical testing, providing a data-driven rationale for NHP use. These computational findings are exploratory and require future biological and clinical validation. Full article
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10 pages, 494 KB  
Article
Prognostic Impact of Interleukin-27 in Peripheral Artery Disease
by Nataša Kokalj and Borut Jug
Life 2025, 15(11), 1768; https://doi.org/10.3390/life15111768 - 18 Nov 2025
Viewed by 330
Abstract
Atherosclerosis is a progressive arterial disease characterized by chronic inflammation, with interleukin-27 (IL-27) implicated as both a pro- and anti-inflammatory cytokine. This prospective cohort study evaluated association of circulating IL-27 levels in peripheral artery disease patients undergoing elective endovascular revascularization, with major adverse [...] Read more.
Atherosclerosis is a progressive arterial disease characterized by chronic inflammation, with interleukin-27 (IL-27) implicated as both a pro- and anti-inflammatory cytokine. This prospective cohort study evaluated association of circulating IL-27 levels in peripheral artery disease patients undergoing elective endovascular revascularization, with major adverse cardiovascular events (MACE) and major adverse limb events (MALE) over a median follow-up of 311 days. Elevated IL-27 levels were significantly associated with increased risk of MACE and MALE in unadjusted analyses. After adjusting for established cardiovascular and PAD risk factors, IL-27 remained an independent predictor of MACE (HR 2.95; p = 0.039), but not MALE. These findings indicate that elevated IL-27 levels are associated with unfavourable long-term prognosis. Full article
(This article belongs to the Section Medical Research)
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13 pages, 1117 KB  
Case Report
Diagnostic Reassessment of a Historical Case of Atypical Heparin-Induced Thrombocytopenia: Between Spontaneous Heparin-Induced Thrombocytopenia and a Vaccine-Induced Immune Thrombotic Thrombocytopenia-Like Syndrome
by Jordan Wimmer, Solène Kirscher, Manon Dolt, Agathe Herb, Léa Pierre, Lélia Grunebaum, Olivier Feugeas, Laurent Sattler and Dominique Desprez
Life 2025, 15(11), 1767; https://doi.org/10.3390/life15111767 - 18 Nov 2025
Viewed by 328
Abstract
PF4-dependent disorders encompass a heterogeneous group of immune-mediated thrombotic syndromes, including heparin-induced thrombocytopenia (HIT), its autoimmune variants such as spontaneous HIT, and vaccine-induced immune thrombotic thrombocytopenia (VITT). The recent identification of VITT and VITT-like entities has significantly expanded the diagnostic spectrum, complicating the [...] Read more.
PF4-dependent disorders encompass a heterogeneous group of immune-mediated thrombotic syndromes, including heparin-induced thrombocytopenia (HIT), its autoimmune variants such as spontaneous HIT, and vaccine-induced immune thrombotic thrombocytopenia (VITT). The recent identification of VITT and VITT-like entities has significantly expanded the diagnostic spectrum, complicating the retrospective interpretation of cases that occurred before their formal recognition. We report the case of a young patient who initially presented with a clinical and biological presentation suggestive of atypical HIT, at a time when neither spontaneous HIT nor VITT were defined. The patient was re-evaluated during the COVID-19 vaccination campaign, prompting a reassessment of the initial diagnosis in light of current knowledge on PF4-related disorders, which continue to increase in both diversity and complexity. A critical review of clinical and laboratory findings now favors a diagnosis of VITT-like syndrome over spontaneous HIT, although confirmatory testing is no longer feasible given the time elapsed since the acute phase. This case highlights the importance of revisiting historical cases using updated diagnostic criteria to improve the identification and management of these emerging and underrecognized syndromes. Full article
(This article belongs to the Special Issue New Horizons: Autoimmune-Related Thrombosis)
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28 pages, 5624 KB  
Review
Human Responses to Magnetic and Hypomagnetic Fields: Available Evidence and Potential Risks for Deep Space Travel
by Rustem R. Kaspranski, Vladimir N. Binhi and Ivan V. Koshel
Life 2025, 15(11), 1766; https://doi.org/10.3390/life15111766 - 18 Nov 2025
Viewed by 990
Abstract
The growing body of biomedical research reveals that many biological processes are governed by quantum physical principles, including the effects of weak magnetic fields (MFs) at or below geomagnetic strength. Given that life evolved within the geomagnetic field, its significant decrease—the hypomagnetic field [...] Read more.
The growing body of biomedical research reveals that many biological processes are governed by quantum physical principles, including the effects of weak magnetic fields (MFs) at or below geomagnetic strength. Given that life evolved within the geomagnetic field, its significant decrease—the hypomagnetic field (hypoMF)—may disrupt fundamental biological processes. This is particularly relevant for interplanetary missions, where astronauts will encounter prolonged hypoMF conditions alongside other spaceflight stressors. This mini-review synthesizes current knowledge on hypoMF effects, comparing terrestrial and extraterrestrial MF conditions and evaluating evidence from human studies. The initial database search identified 645 records. After most were excluded for various reasons, only 44 publications on the effects of MFs on the entire human body were included in the review. An effect of the hypoMF was reported in 10 of these studies and was absent in 4. Despite some methodological limitations in the available research, the evidence suggests that the human body is not indifferent to hypoMF exposure. We also discuss leading mechanistic molecular hypotheses—particularly the radical pair mechanism. Finally, we identify urgent research priorities to elucidate hypoMF’s biological role and develop countermeasures for future deep space exploration. Addressing these gaps is essential for safeguarding astronaut health and advancing magnetobiology as a frontier discipline in biophysics. Full article
(This article belongs to the Section Astrobiology)
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20 pages, 5081 KB  
Review
Hybrid Open and Endovascular Repair in Pararenal Abdominal Aortic Pseudoaneurysm—Literature Review and Case Presentation
by Vlad Anton Iliescu, Reza Nayyerani, Catalina Andreea Parasca, Pavel Platon, Catalin Baston, Bianca Morosanu and Ovidiu Stiru
Life 2025, 15(11), 1765; https://doi.org/10.3390/life15111765 - 18 Nov 2025
Viewed by 351
Abstract
Pararenal abdominal aortic aneurysm/pseudoaneurysms (PAAA/PAAP) are rare, high-risk complex aortic lesions involving the renal arteries. Management includes open surgical repair (OSR), endovascular aortic repair (EVAR), or hybrid repair, each with specific advantages and limitations. A review of the literature was performed to assess [...] Read more.
Pararenal abdominal aortic aneurysm/pseudoaneurysms (PAAA/PAAP) are rare, high-risk complex aortic lesions involving the renal arteries. Management includes open surgical repair (OSR), endovascular aortic repair (EVAR), or hybrid repair, each with specific advantages and limitations. A review of the literature was performed to assess treatment strategies and outcomes for PAAA and PAAP. A PubMed search using relevant MeSH terms identified 184 articles published in the last five years. After applying inclusion and exclusion criteria, 34 studies comprising 6460 patients with complex AAA/AAP were included for analysis. Treatment strategies were predominantly endovascular (79.4%), followed by open (5.8%) and hybrid approaches (2.9%) (11.7% have used EVAR or OSR in the same study). To emphasize difficulties in the management of this pathology, a case report of a large PAAP involving both renal arteries and occluded celiac trunk with retrograde flow from patent superior mesenteric artery (SMA) is presented. Given the complex anatomy and high surgical risk, hybrid treatment was chosen consisting of bilateral ilio-renal Dacron bypasses followed by ChEVAR (chimney stenting of the SMA), with favorable postoperative recovery. The management of PAAP requires an individualized, anatomy- and risk-adapted approach. Open surgical repair remains preferable for younger, low-risk patients for superior long-term durability, whereas endovascular repair offers lower perioperative morbidity in high-risk cohorts. Optimal outcomes are dependent on high-volume centers with multidisciplinary expertise. Full article
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24 pages, 1112 KB  
Review
The Vicious Circle of Metabolic Dysfunction-Associated Steatotic Liver Disease When Micronutrient Deficiency Drives Microbial Imbalance and Liver Injury
by Iulia Cristina Marginean, Sergiu Marian Cazacu, Mihaela Popescu, George Alexandru Iacob, Larisa Daniela Sandulescu, Sevastita Iordache, Cristina Maria Marginean and Cristin Constantin Vere
Life 2025, 15(11), 1764; https://doi.org/10.3390/life15111764 - 18 Nov 2025
Viewed by 466
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an escalating global health burden and a leading cause of chronic liver disease. Without intervention, MASLD can progress to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Although lifestyle modification is the cornerstone of management, specific dietary patterns [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an escalating global health burden and a leading cause of chronic liver disease. Without intervention, MASLD can progress to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Although lifestyle modification is the cornerstone of management, specific dietary patterns are a primary driver of its development. The progression of MASLD is closely linked to micronutrient status, as these nutrients are critical for key biological functions such as antioxidant defense and immune regulation. Micronutrient deficiencies—particularly in essential vitamins and minerals—have been widely studied as independent contributors to MASLD pathogenesis. Similarly, the role of the gut microbiota in disease development has gained attention. However, the interplay between micronutrient deficiencies and gut dysbiosis is often underestimated. Emerging evidence suggests that micronutrient depletion not only directly exacerbates MASLD but also alters gut microbial composition, perpetuating a cycle of metabolic and hepatic dysfunction. This review aims to highlight the bidirectional relationship between micronutrient deficiency and gut microbiome imbalance in MASLD. It explores how dysbiosis impairs the bioavailability of micronutrients, thereby reinforcing a vicious cycle of disease progression. Therefore, effective MASLD management should address both nutritional deficiencies and microbial imbalances. Interventions such as prebiotic and probiotic supplementation may help restore microbial equilibrium and improve micronutrient absorption. Looking forward, personalized therapeutic strategies that combine targeted microbiota modulation with micronutrient repletion may offer promising approaches to curb the rising global burden of MASLD. Full article
(This article belongs to the Section Medical Research)
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19 pages, 2014 KB  
Article
Therapeutic Impact of Vericiguat on Ventricular Remodeling in a Pressure-Overload Heart Failure Model
by Wen-Rui Hao, Chun-Chao Chen, Fu-An Li, Huan-Yuan Chen, Ju-Chi Liu, Tzu-Hurng Cheng and Jin-Jer Chen
Life 2025, 15(11), 1763; https://doi.org/10.3390/life15111763 - 18 Nov 2025
Viewed by 405
Abstract
Pressure-overload-induced heart failure is characterized by pathological ventricular remodeling, including hypertrophy and fibrosis, which compromise cardiac function and worsen outcomes. Vericiguat, a soluble guanylate cyclase (sGC) stimulator, has shown therapeutic promise in heart failure with reduced ejection fraction (HFrEF). This study evaluated its [...] Read more.
Pressure-overload-induced heart failure is characterized by pathological ventricular remodeling, including hypertrophy and fibrosis, which compromise cardiac function and worsen outcomes. Vericiguat, a soluble guanylate cyclase (sGC) stimulator, has shown therapeutic promise in heart failure with reduced ejection fraction (HFrEF). This study evaluated its antihypertrophic, antifibrotic, and metabolic effects in a murine pressure-overload model. Male C57BL/6 mice (~25 g) underwent transverse aortic constriction (TAC) and received oral Vericiguat (10 mg/kg/day) for 14 days. Cardiac hypertrophy was assessed by gross morphology and heart weight; fibrosis was quantified using Masson’s trichrome and Picrosirius red staining. Collagen deposition and wall stress indices were measured by image analysis. Proteomic profiling of fibroblast- and myocyte-enriched tissues identified differentially expressed proteins (DEPs) across metabolic, structural, mitochondrial, and signaling pathways. Vericiguat significantly reduced heart weight and attenuated TAC-induced hypertrophy. Histological staining revealed marked reductions in myocardial fibrosis and collagen accumulation in the Vericiguat-treated TAC group compared to untreated TAC controls. Quantitative analysis demonstrated improved wall stress indices. Proteomic data showed consistent modulation of DEPs, with restoration of mitochondrial and energy-regulating proteins suppressed by TAC, indicating enhanced bioenergetic support. Collectively, Vericiguat mitigates pressure-overload-induced remodeling through coordinated antihypertrophic, antifibrotic, and metabolic reprogramming mechanisms. These findings support its potential as a therapeutic strategy for heart failure and warrant further clinical investigation. Full article
(This article belongs to the Special Issue Advanced Heart Failure and Transplant Cardiology)
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16 pages, 1302 KB  
Article
Preoperative Risk Factors and Phenotypic Clustering in Periprosthetic Joint Infection: A Matched Case–Control Study
by Tarek Omar Pacha, Sophia K. Klett, Gabi von Lewinski, Maximilian Koblenzer, Hür Özbek, Jorge Mayor, Jan D. Clausen, Axel Gänsslen, Schayan Faraj Tabrizi, Stephan Sehmisch and Gökmen F. Aktas
Life 2025, 15(11), 1762; https://doi.org/10.3390/life15111762 - 17 Nov 2025
Viewed by 538
Abstract
Periprosthetic joint infection (PJI) remains one of the most serious complications after total joint arthroplasty. This retrospective 1:1 matched case–control study investigated preoperative predictors and patient phenotypes associated with PJI in 182 patients (91 cases, 91 controls) undergoing hip or knee arthroplasty between [...] Read more.
Periprosthetic joint infection (PJI) remains one of the most serious complications after total joint arthroplasty. This retrospective 1:1 matched case–control study investigated preoperative predictors and patient phenotypes associated with PJI in 182 patients (91 cases, 91 controls) undergoing hip or knee arthroplasty between 2013 and 2024. Variables with skewed distributions were log-transformed, and multivariable logistic regression with LASSO regularization identified independent risk factors. Unsupervised K-means clustering was applied to perioperative features to explore data-driven patient phenotypes. Preoperative anemia (OR 5.91, p = 0.026), higher ASA score (OR 1.77, p = 0.033), and surgical delay (OR 1.67, p = 0.024) independently predicted infection, while age and CRP showed non-significant trends. The resulting five-variable preoperative model achieved an AUC of 0.718 (optimism-corrected AUC of 0.661) for infection prediction. Clustering analysis revealed three phenotypes: anemia-dominated, elderly but short-procedure, and high surgery duration with significantly different infection rates (χ2 = 23.5, p < 0.001) but similar mortality (p = 0.068). This integrative approach combining regression-based prediction and phenotype discovery enables clinically interpretable, preoperatively applicable risk stratification. The findings identify anemia, comorbidity burden, and surgical delay as key modifiable targets for preventive optimization before arthroplasty. External validation and recalibration to population-level incidence are warranted before clinical implementation. Full article
(This article belongs to the Special Issue Advanced Machine Learning for Disease Prediction and Prevention)
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16 pages, 2789 KB  
Article
Study of the Physicochemical and Phytochemical Parameters Together with Antibacterial Properties of Conventionally and Organically Cultivated Spirulina (Arthrospira platensis) in Greece
by Maria-Athanasia Christodoulopoulou, Dimitrios G. Lazaridis, Maria Simoni, Eirini Intzirtzi, Vassilios K. Karabagias, Nikolaos D. Andritsos, Vassilios Triantafyllidis and Ioannis K. Karabagias
Life 2025, 15(11), 1761; https://doi.org/10.3390/life15111761 - 17 Nov 2025
Viewed by 481
Abstract
Given the limited data in the recent literature regarding spirulina cultivated in Greece, the present study aimed to investigate physicochemical parameters (pH, color), antioxidant activity, and phytochemical content (total phenolic content, quercetin, caffeic acid, C-phycocyanin) of spirulina (Arthrospira platensis) obtained through [...] Read more.
Given the limited data in the recent literature regarding spirulina cultivated in Greece, the present study aimed to investigate physicochemical parameters (pH, color), antioxidant activity, and phytochemical content (total phenolic content, quercetin, caffeic acid, C-phycocyanin) of spirulina (Arthrospira platensis) obtained through conventional and organic cultivation methods in different forms (disk-shaped tablets, powder, and flakes) and using different solvents [water and ethanol of grape origin (EEGO)]. Furthermore, the antimicrobial activity of spirulina against selected food pathogens, namely Salmonella Typhimurium, Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli O157:H7, was also investigated. Results showed that the form of spirulina and the solvent used significantly (p < 0.05) affected the physicochemical parameters, antioxidant activity, and phytochemical compounds. Spirulina had a neutral to alkaline pH (6.79 ± 0.02 to 8.24 ± 0.01) and a considerable number of pigments, including C-phycocyanin (0.07 ± 0.01 to 1.65 ± 0.01 mg/mL). The most pronounced effects were recorded in the case of antioxidant activity, where EEGO proved to be the best solvent for the extraction of compounds with antioxidant activity (44.37 ± 2.28% to 48.28 ± 0.39%) against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. In contrast, water proved to be the best solvent for the recovery of total phenolics (4.83 ± 0.55 mg/g DM to 17.07 ± 0.66 mg/g DM), primarily in spirulina powder. Regarding the antibacterial activity, spirulina, primarily in powder and tablet form (in both solvents), showed considerable inhibition zones against the studied food pathogens. The present study presents new knowledge concerning spirulina cultivated in Greece in terms of physicochemical parameters, antioxidant activity, phytochemical content, and antibacterial activity. Full article
(This article belongs to the Section Plant Science)
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15 pages, 2986 KB  
Article
A Feasible Method for Evaluating Post-Stroke Knee Spasticity: Pose-Estimation-Assisted Pendulum Test
by Yun-Chien Yeh, Ching-Shiou Tang, Quang Hung Ho, Cheng-Yu Tsai and Jiunn-Horng Kang
Life 2025, 15(11), 1760; https://doi.org/10.3390/life15111760 - 16 Nov 2025
Viewed by 412
Abstract
Purpose: Post-stroke spasticity (PSS) substantially affects functional recovery and quality of life in stroke survivors. However, the current clinical assessment methods exhibit certain subjectivity and equipment limitations. Human pose estimation presents a promising alternative for objective and user-friendly spasticity assessment. Materials and Methods: [...] Read more.
Purpose: Post-stroke spasticity (PSS) substantially affects functional recovery and quality of life in stroke survivors. However, the current clinical assessment methods exhibit certain subjectivity and equipment limitations. Human pose estimation presents a promising alternative for objective and user-friendly spasticity assessment. Materials and Methods: A total of 20 stroke survivors with PSS underwent pendulum tests with smartphones from multiple angles to quantitatively assess knee muscle spasticity. Pose estimation was conducted using the AlphaPose and STCFormer algorithms, with simultaneous measurements using an electronic goniometer as a reference. Three pendulum parameters were evaluated: normalized relaxation index (P1), first maximum of oscillation (P2), and relaxation index at half swing (P3). Bland–Altman analyses were used to analyze the consistency between pose estimation and electronic goniometer measurements. Intraclass correlation coefficient (ICC) and Spearman’s correlation analyses were conducted to evaluate agreement and reliability between electronic goniometer measurements and clinical evaluation. Results: P1 demonstrated the highest consistency between pose estimation and electronic goniometer measurements, with the highest ICC values (0.931 for AlphaPose and 0.911–0.94 for STCFormer). P1 and P3 differentiated between affected and unaffected limbs (p < 0.01) and demonstrated significant negative correlations with Modified Ashworth Scale scores, particularly for knee extensors (P1: ρ = −0.747 for AlphaPose and −0.781 for STCFormer; p < 0.01). P2 demonstrated low consistency and differential performance across all analyses. Conclusions: Video-based human pose estimation, particularly using P1, offers a reliable and objective method for evaluating PSS, demonstrating strong agreement with electronic goniometer measurements. This approach is clinically feasible for evaluating spasticity. Full article
(This article belongs to the Section Epidemiology)
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13 pages, 834 KB  
Article
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 - 16 Nov 2025
Viewed by 298
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)
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16 pages, 1370 KB  
Article
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 - 16 Nov 2025
Viewed by 412
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
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17 pages, 1213 KB  
Essay
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 - 15 Nov 2025
Viewed by 593
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  
Brief 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 - 15 Nov 2025
Viewed by 473
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
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