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11 pages, 1752 KiB

Open AccessArticle

Echocardiographic Calcium Score of Aortic Valve Correlates with Coronary Artery Calcium Score in Heterozygous Familial Hypercholesterolemia

by Angelo Baldassare Cefalù, Emilio Nardi, Antonina Giammanco, Carola Maria Gagliardo, Carlo Maria Barbagallo, Ludovico La Grutta, Patrizia Toia, Federica Brucato, Chiara Scrimali, Teresa Maria Grazia Fasciana, Rossella Spina, Marina Lanza, Francesco Vitale, Davide Noto and Maurizio Averna

Life 2025, 15(3), 506; https://doi.org/10.3390/life15030506 - 20 Mar 2025

Viewed by 388

Abstract

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) are at a high risk of atherosclerotic cardiovascular disease. The coronary artery calcification (CAC) score by the Ct-scan Agatston calcium score (ACS) > 100 classifies FH at a higher risk. The echocardiographic calcium score (ECS) evaluates [...] Read more.

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) are at a high risk of atherosclerotic cardiovascular disease. The coronary artery calcification (CAC) score by the Ct-scan Agatston calcium score (ACS) > 100 classifies FH at a higher risk. The echocardiographic calcium score (ECS) evaluates aortic valve calcifications and is considered a good predictor of the atherosclerotic burden and cardiovascular outcome. Objective: To test the ECS as a predictor of ACS > 100 in a HeFH cohort. Methods: A coronary calcium CT scan with the calculation of ACS and an at rest-transthoracic echocardiogram with ECS evaluation were performed in 81 HeFH patients. Patients were divided into two groups according to the ACS: high-risk ACS patients (High-ACS) with Agatston value > 100 and low risk ACS patients (Low-ACS) with Agatston value ≤ 100. Patients were stratified according to ECS = 0 or ECS > 0. Results: High-ACS patients were older than Low-ACS patients; BMI, waist circumference, and blood systolic pressure were significantly higher (p < 0.001) in High-ACS patients. The ECS predicted an ACS > 100 with sensitivity = 0.84, specificity = 0.89, accuracy = 0.86, and precision = 0.76. Conclusions: The ECS could be a good surrogate of a coronary calcium CT scan for ACS evaluation in the specific subset of HeFH patients. Full article

(This article belongs to the Section Medical Research)

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8 pages, 3358 KiB

Open AccessCase Report

Therapeutic Challenges and Emerging Strategies for T674I and PTPN11 Mutations in a FIP1L1-PDGFRA-Positive Myeloproliferative Neoplasm: A Case Report

by Sıdıka Gülkan Özkan, Ali Kimiaei, Seyedehtina Safaei, Mutlu Karkucak, Mustafa Nuri Yenerel, Aslı Yüksel Öztürkmen, Burak Alp and Hasan Atilla Özkan

Life 2025, 15(3), 505; https://doi.org/10.3390/life15030505 - 20 Mar 2025

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Abstract

Myeloproliferative neoplasm (MPN) with eosinophilia associated with FIP1L1-PDGFRA is a rare eosinophilic disorder typically treated with imatinib. However, resistance due to the T674I mutation poses a significant challenge. This case presents the first reported instance of concurrent FIP1L1-PDGFRA T674I and PTPN11 (p.E76D) mutations [...] Read more.

Myeloproliferative neoplasm (MPN) with eosinophilia associated with FIP1L1-PDGFRA is a rare eosinophilic disorder typically treated with imatinib. However, resistance due to the T674I mutation poses a significant challenge. This case presents the first reported instance of concurrent FIP1L1-PDGFRA T674I and PTPN11 (p.E76D) mutations in a 38-year-old male patient with MPN and eosinophilia. The patient initially responded to imatinib but developed resistance after ten months, leading to severe spinal cord compression caused by granulocytic sarcoma. Despite undergoing radiotherapy, chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), the disease progressed. Although full donor chimerism was achieved post-transplant, the patient relapsed shortly afterward with eosinophilia, splenomegaly, and constitutional symptoms. Further treatments, including sorafenib and decitabine, failed to control the disease, and the patient ultimately died from multiorgan failure. This case illustrates the therapeutic challenges associated with FIP1L1-PDGFRA T674I-positive eosinophilic disorder, especially when compounded by the PTPN11 mutation. Resistance to standard treatments underscores the urgent need for novel therapies to manage this rare and aggressive disease. Full article

(This article belongs to the Section Medical Research)

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23 pages, 976 KiB

Open AccessReview

The Role of the Ubiquitin System in Eye Diseases

by Sandra Carolina Durán-Cristiano, Laura de Diego-García, Alba Martín-Gil and Gonzalo Carracedo

Life 2025, 15(3), 504; https://doi.org/10.3390/life15030504 - 20 Mar 2025

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Abstract

The ubiquitin–proteasome system (UPS) is a fundamental process that regulates various biological functions, including immune response, cell cycle, oxidative stress, migration, and cellular proliferation. This system is responsible for the degradation of proteins, while proteasomes play a significant role in mechanisms involved in [...] Read more.

The ubiquitin–proteasome system (UPS) is a fundamental process that regulates various biological functions, including immune response, cell cycle, oxidative stress, migration, and cellular proliferation. This system is responsible for the degradation of proteins, while proteasomes play a significant role in mechanisms involved in health and human diseases. The participation of the UPS in immune response is particularly relevant, leading to the involvement of immunoproteasomes. This specialized proteasome is involved in the processing and presentation of antigenic peptides, making it crucial for proper immune function. Moreover, the impact of the UPS is considered essential in understanding several diseases, such as neurodegenerative disorders, infections, and vascular diseases. The dysregulation of the UPS may contribute to the pathogenesis of these conditions, highlighting its importance as a potential therapeutic target. Interestingly, the UPS is also related to ocular structures, playing a role in visual perception and ocular homeostasis. This involvement in the regulation of various ocular processes suggests its potential impact on both anterior and posterior eye pathologies. This review aims to discuss the general considerations of the UPS and provide information about its participation in anterior and posterior eye pathologies. By understanding its role in ocular health and disease, researchers and clinicians may explore novel therapeutic strategies targeting the UPS for the treatment of various eye conditions. In conclusion, the UPS is a crucial player in biological processes, with far-reaching implications in health and disease, including the anterior and posterior segments of the eye. Further research in this field may lead to the development of innovative therapies and a better understanding of the complex mechanisms underlying various eye disorders. Full article

(This article belongs to the Special Issue Eye Diseases: Diagnosis and Treatment, 2nd Edition)

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27 pages, 540 KiB

Open AccessReview

Efficacy of Neurorehabilitation Approaches in Traumatic Brain Injury Patients: A Comprehensive Review

by Diana Andrei, Alexandra Laura Mederle, Laura Andreea Ghenciu, Claudia Borza and Alexandra Corina Faur

Life 2025, 15(3), 503; https://doi.org/10.3390/life15030503 - 20 Mar 2025

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Abstract

Traumatic brain injury (TBI) represents a significant public health issue, causing long-term disabilities and imposing considerable socioeconomic and healthcare challenges. While advancements in acute care have improved survival rates, the demand for effective neurorehabilitation is increasing. This narrative review explores the evidence on [...] Read more.

Traumatic brain injury (TBI) represents a significant public health issue, causing long-term disabilities and imposing considerable socioeconomic and healthcare challenges. While advancements in acute care have improved survival rates, the demand for effective neurorehabilitation is increasing. This narrative review explores the evidence on neurorehabilitation strategies for TBI, focusing on interventions targeting cognitive, motor, and psychological recovery. A total of 32 studies were included and categorized into six approaches: non-invasive brain stimulation, virtual reality (VR), computer-based training, telerehabilitation, robot-assisted therapy (RAT), and mixed approaches. Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), showed variable effectiveness in improving cognitive outcomes. VR-based therapies enhanced attention and executive functions, while RAT, such as Lokomat and exoskeletons, improved gait symmetry and functional mobility. Computer-assisted programs demonstrated benefits in rehabilitating social cognition and executive functions. Telerehabilitation and telephone-based treatments provided short-term gains but lacked sustained effects. Overall, cognitive improvements were better described and represented, while several motor improvements lacked consistency. Despite the promising results, significant gaps remain, including heterogeneity in methodologies, small sample sizes, and limited long-term outcome data. Full article

(This article belongs to the Special Issue Neurological Diseases: Prevention, Diagnostics, Treatment and Rehabilitation)

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26 pages, 6539 KiB

Open AccessArticle

Genetic and Epigenetic Changes in Arabidopsis thaliana Exposed to Ultraviolet-C Radiation Stress for 25 Generations

by Andres Lopez Virgen, Narendra Singh Yadav, Boseon Byeon, Yaroslav Ilnytskyy and Igor Kovalchuk

Life 2025, 15(3), 502; https://doi.org/10.3390/life15030502 - 20 Mar 2025

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Abstract

Continuous exposure to stress contributes to species diversity and drives microevolutionary processes. It is still unclear, however, whether epigenetic changes, in the form of epimutations such as, for example, differential DNA methylation, are the pre-requisite to speciation events. We hypothesized that continuous stress [...] Read more.

Continuous exposure to stress contributes to species diversity and drives microevolutionary processes. It is still unclear, however, whether epigenetic changes, in the form of epimutations such as, for example, differential DNA methylation, are the pre-requisite to speciation events. We hypothesized that continuous stress exposure would increase epigenetic diversity to a higher extent than genetic diversity. In this work, we have analyzed the effect of 25 consecutive generations of UV-C-stress exposure on the Arabidopsis thaliana genome and epigenome. We found no evidence of increased tolerance to UV-C in the progeny of UV-C-stressed plants (F25UV) as compared to the progeny of control plants (F25C). Genetic analysis showed an increased number of single nucleotide polymorphisms (SNPs) and deletions in F25UV plants. Most common SNPs were mutations in cytosines, C to T, C to A, and C to G. Analysis of cytosine methylation showed a significant increase in the percentage of methylated cytosines at CG context in F25UV as compared to F25C or F2C (parental control). The most significant differences between F25UV and either control group were observed in CHG and CHH contexts; the number of hypomethylated cytosines at CHH contexts was over 10 times higher in the F25UC group. F25UV plants clustered separately from other groups in both genomic and epigenomic analyses. GO term analysis of differentially methylated genes revealed enrichments in “DNA or RNA metabolism”, “response to stress”, “response to biotic and abiotic stimulus”, and “signal transduction”. Our work thus demonstrates that continuous exposure to UV-C increases genomic and epigenomic diversity in the progeny, with epigenetic changes occurring in many stress-responsive pathways. Full article

(This article belongs to the Special Issue Plant Functional Genomics and Breeding)

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21 pages, 336 KiB

Open AccessArticle

Seasonal Variability and Sex-Specific Accumulation of Trace Metals in Black Scorpionfish (Scorpaena porcus Linnaeus, 1758) from Izmir Bay (Aegean Sea), Türkiye: Implications for Human Health Risk Assessment

by Mine Percin Olgunoglu, Ilkan Ali Olgunoglu and Engin Artar

Life 2025, 15(3), 501; https://doi.org/10.3390/life15030501 - 20 Mar 2025

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Abstract

This study investigates seasonal and gender-related variations in some metal (Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn) accumulation in black scorpionfish (Scorpaena porcus) from Izmir Bay (Aegean Sea, Türkiye) and assesses the associated human health risks. Samples, [...] Read more.

This study investigates seasonal and gender-related variations in some metal (Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn) accumulation in black scorpionfish (Scorpaena porcus) from Izmir Bay (Aegean Sea, Türkiye) and assesses the associated human health risks. Samples, collected across four seasons from 2023 to 2024, were analyzed for element concentrations using inductively coupled plasma mass spectrometry (ICP-MS). Health risks were calculated using several models, including estimated weekly intake (EWI), target hazard quotient (THQ), total THQ (∑THQ), carcinogenic risk (CR), Se health benefit value (HBVSe), and the Metal Pollution Index (MPI). The results indicate that the consumption of black scorpionfish poses potential health risks, primarily due to the accumulation of manganese (Mn), lead (Pb), and mercury (Hg), which exceeded international permissible legal limits. Gender-based differences were observed, with males showing higher accumulation (p > 0.05); however, these differences were not statistically significant. In contrast, significant sex-based differences were identified specifically for cadmium (Cd), with concentrations exhibiting a statistically meaningful difference (p < 0.05). Seasonal variations were also apparent (p < 0.05). The carcinogenic risk (CR) analyses revealed that chromium (Cr) and nickel (Ni) levels surpassed carcinogenic risk thresholds. Furthermore, the MPI values provided additional insights into the overall metal pollution levels in the fish. These findings underscore the critical importance of monitoring metal pollution, revising fishery management strategies, and managing fish consumption to safeguard public health. Full article

(This article belongs to the Section Animal Science)

12 pages, 1471 KiB

Open AccessArticle

A Pilot Randomized Controlled Trial (RCT) Evaluating the Efficacy of an Exosome-Containing Plant Extract Formulation for Treating Male Alopecia

by Farahnaz Amini, Jing Ju Teh, Chung Keat Tan, Eugenie Sin Sing Tan and Edmond Siah Chye Ng

Life 2025, 15(3), 500; https://doi.org/10.3390/life15030500 - 20 Mar 2025

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Abstract

Background/Objectives: Hair loss affects self-esteem, confidence, and psychological well-being. Exosomes, as molecular carriers of growth factors and active compounds, offer a promising treatment. This study evaluates the efficacy of an exosome formulation containing extracts from two known hair-regenerating plants, Ecklonia cava and [...] Read more.

Background/Objectives: Hair loss affects self-esteem, confidence, and psychological well-being. Exosomes, as molecular carriers of growth factors and active compounds, offer a promising treatment. This study evaluates the efficacy of an exosome formulation containing extracts from two known hair-regenerating plants, Ecklonia cava and Thuja orientalis (ECPE), for male pattern alopecia. Methods: A randomized controlled trial included 20 male participants with Norwood grade 2–3 androgenetic alopecia who were randomly assigned into two groups, placebo (0.9% sodium chloride) and ECPE, administered bi-weekly across four sessions. Evaluations included hair density measurements, adverse effect tracking, and self-assessments. Results: Most participants (55%) were aged 18 to 35, with 75% reporting hair loss for over a year and 80% noting scalp thinning. The hair counts showed no significant change in the placebo group from baseline to week 16 (Wilcoxon signed-rank test: V = 13.5, p = 0.163), while a significant increase was observed in the ECPE group (V = 0, p = 0.002). Between-group analysis revealed a significant difference in the hair count changes (Wilcoxon rank-sum test: W = 86.5, p = 0.006) with a large effect size (Cliff’s Delta: & = 0.73, 95% CI: 0.41–0.89), with the ECPE group showing higher median hair growth (9.5, IQR = 16.88) compared to the placebo group (1.5, IQR = 3.00). A Bayesian ANCOVA, adjusted for covariates (the father’s scalp hair condition, baseline hair count, and Norwood classification), showed no significant effect of these factors on the outcomes. Conclusions: These findings suggest that ECPE significantly improves hair regrowth compared to the placebo, with no notable adverse effects. Full article

(This article belongs to the Special Issue Implications of Bioactive Compounds in Lifelong Disorders)

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17 pages, 1717 KiB

Open AccessArticle

Vestibulo-Ocular Reflex Function and Its Impact on Postural Stability and Quality of Life in Cochlear Implant Recipients: A Cross-Sectional Study

by Khalid A. Alahmari and Sarah Alshehri

Life 2025, 15(3), 499; https://doi.org/10.3390/life15030499 - 20 Mar 2025

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Abstract

Background/Objectives: Vestibulo-ocular reflex (VOR) function, measured by the video head impulse test (vHIT) gains, plays a crucial role in postural stability and quality of life. Cochlear implant recipients often experience vestibular dysfunction, but its relationship with balance and patient-reported outcomes remains underexplored. This [...] Read more.

Background/Objectives: Vestibulo-ocular reflex (VOR) function, measured by the video head impulse test (vHIT) gains, plays a crucial role in postural stability and quality of life. Cochlear implant recipients often experience vestibular dysfunction, but its relationship with balance and patient-reported outcomes remains underexplored. This study aimed to (1) evaluate the relationship between vHIT gains and postural stability in cochlear implant recipients; (2) assess the impact of vHIT gains on quality-of-life metrics; and (3) identify key predictors of postural stability, including vHIT gains and demographic/clinical characteristics. Methods: This cross-sectional study was conducted between August 2023 and February 2024 and included 46 participants that comprised cochlear implant recipients and age-matched normal hearers who underwent the vHIT for lateral, anterior, and posterior semicircular canal function. Postural stability was assessed using dynamic posturography, and quality of life was measured using the Short Form-36 (SF-36). Multiple linear regression and correlation analyses were performed. Results: The vHIT gains demonstrated significant positive correlations with postural stability, with the lateral canal showing the strongest association (r = 0.742, p = 0.001), followed by the posterior (r = 0.701, p = 0.003) and anterior canals (r = 0.684, p = 0.005). A multiple regression analysis identified the lateral canal as the most significant predictor of postural stability (β = 0.512, p = 0.001, adjusted R² = 0.47). Quality-of-life metrics were inversely correlated with the vHIT gains, particularly in the posterior canal (r = −0.712, p = 0.002), which explained 43–51% of the variance. Conclusions: This study highlighted the lateral semicircular canal as the primary determinant of postural stability in cochlear implant recipients, underscoring the importance of vestibular assessments in optimizing balance and functional outcomes. Full article

(This article belongs to the Special Issue New Trends in Otorhinolaryngology)

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12 pages, 476 KiB

Open AccessReview

New Perspectives on Lung Cancer Screening and Artificial Intelligence

by Leonardo Duranti, Luca Tavecchio, Luigi Rolli and Piergiorgio Solli

Life 2025, 15(3), 498; https://doi.org/10.3390/life15030498 - 19 Mar 2025

Viewed by 1119

Abstract

Lung cancer is the leading cause of cancer-related death worldwide, with 1.8 million deaths annually. Early detection is vital for improving patient outcomes; however, survival rates remain low due to late-stage diagnoses. Accumulating data supports the idea that screening methods are useful for [...] Read more.

Lung cancer is the leading cause of cancer-related death worldwide, with 1.8 million deaths annually. Early detection is vital for improving patient outcomes; however, survival rates remain low due to late-stage diagnoses. Accumulating data supports the idea that screening methods are useful for improving early diagnosis in high-risk patients. However, several barriers limit the application of lung cancer screening in real-world settings. The widespread diffusion of artificial intelligence (AI), radiomics, and machine learning has dramatically changed the current diagnostic landscape. This review explores the potential of AI and biomarker-driven methods, particularly liquid biopsy, in enhancing early lung cancer detection. We report the findings of major randomized controlled trials, cohort studies, and research on AI algorithms that use multi-modal imaging (e.g., CT and PET scans) and liquid biopsy to identify early molecular alterations. AI algorithms enhance diagnostic accuracy by automating image analysis and reducing inter-reader variability. Biomarker-driven methods identify molecular alterations in patients before imaging signs of cancer are evident. Both AI and liquid biopsy show the potential to improve sensitivity and specificity, enabling the detection of early-stage cancers that traditional methods, like low-dose CT (LDCT) scans, might miss. Integrating AI and biomarker-driven methods offers significant promise for transforming lung cancer screening. These technologies could enable earlier, more accurate detection, ultimately improving survival outcomes. AI-driven lung cancer screening can achieve over 90% sensitivity, compared to 70–80% with traditional methods, and can reduce false positives by up to 30%. AI also boosts specificity to 85–90%, with faster processing times (a few minutes vs. 30–60 min for radiologists). However, challenges remain in standardizing these approaches and integrating them into clinical practice. Ongoing research is essential to fully realize their clinical benefits and enhance timely interventions. Full article

(This article belongs to the Special Issue Innovations in Thoracic Surgery and Medicine: Advancements and Challenges)

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16 pages, 1231 KiB

Open AccessArticle

KIAA2022/NEXMIF c.1882C>T (p.Arg628*) Variant in a Romanian Patient with Neurodevelopmental Disorders and Epilepsy: A Case Report and Systematic Review

by Catalina Mihaela Anastasescu, Veronica Gheorman, Simona Viorica Godeanu, Adriana Cojocaru, Floris Petru Iliuta, Mioara Desdemona Stepan and Victor Gheorman

Life 2025, 15(3), 497; https://doi.org/10.3390/life15030497 - 19 Mar 2025

Viewed by 527

Abstract

Pathogenic variants in the NEXMIF gene are associated with a broad neurodevelopmental phenotype, including autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. However, the role of NEXMIF in specific epileptic syndromes remains insufficiently explored. We present the case of an 11.9-year-old Romanian [...] Read more.

Pathogenic variants in the NEXMIF gene are associated with a broad neurodevelopmental phenotype, including autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. However, the role of NEXMIF in specific epileptic syndromes remains insufficiently explored. We present the case of an 11.9-year-old Romanian girl diagnosed with ASD, attention-deficit/hyperactivity disorder (ADHD), mild ID, and Jeavons syndrome (generalized epilepsy characterized by eyelid myoclonia, absence seizures, and photosensitivity). Genetic testing identified a pathogenic NEXMIF variant: c.1882C>T (p.Arg628*), a pathogenic variant rarely reported in the literature, with only two documented cases to date. To better understand the genotype–phenotype correlation, we conducted a systematic review of NEXMIF-associated disorders and compared our findings with previously reported cases. Our analysis suggests that NEXMIF variants may contribute to a broader spectrum of epileptic syndromes, including photosensitive epilepsy such as Jeavons syndrome. This highlights the need for a greater awareness of atypical seizure presentations in individuals with NEXMIF-related disorders. This study underscores the importance of genetic testing in individuals with overlapping ASD and epilepsy phenotypes as early diagnosis may facilitate targeted therapeutic interventions and genetic counseling. Further research is needed to clarify the molecular mechanisms linking NEXMIF dysfunction to epileptic syndromes and neurodevelopmental disorders. Full article

(This article belongs to the Section Medical Research)

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18 pages, 890 KiB

Open AccessArticle

Classification of Heart Failure Using Machine Learning: A Comparative Study

by Bryan Chulde-Fernández, Denisse Enríquez-Ortega, Cesar Guevara, Paulo Navas, Andrés Tirado-Espín, Paulina Vizcaíno-Imacaña, Fernando Villalba-Meneses, Carolina Cadena-Morejon, Diego Almeida-Galarraga and Patricia Acosta-Vargas

Life 2025, 15(3), 496; https://doi.org/10.3390/life15030496 - 19 Mar 2025

Viewed by 1178

Abstract

Several machine learning classification algorithms were evaluated using a dataset focused on heart failure. Results obtained from logistic regression, random forest, decision tree, K-nearest neighbors, and multilayer perceptron (MLP) were compared to obtain the best model. The random forest method obtained specificity = [...] Read more.

Several machine learning classification algorithms were evaluated using a dataset focused on heart failure. Results obtained from logistic regression, random forest, decision tree, K-nearest neighbors, and multilayer perceptron (MLP) were compared to obtain the best model. The random forest method obtained specificity = 0.93, AUC = 0.97, and Matthews correlation coefficient (MCC) = 0.83. The accuracy was high; therefore, it was considered the best model. On the other hand, K-nearest neighbors and MLP (multi-layer perceptron) showed lower accuracy rates. These results confirm the effectiveness of the random forest method in identifying heart failure cases. This study underlines that the number of features, feature selection and quality, model type, and hyperparameter fit are also critical in these studies, as well as the importance of using machine learning techniques. Full article

(This article belongs to the Special Issue Updates in Cardiovascular Medicine: Diagnosis, Treatment and Technical Aspects: 2nd Edition)

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17 pages, 1251 KiB

Open AccessArticle

Can Serum GFAP and UCH-L1 Replace CT in Assessing Acute Ischemic Stroke Severity?

by Ivan Kraljević, Maja Marinović Guić, Danijela Budimir Mršić, Krešimir Dolić, Krešimir Čaljkušić, Benjamin Benzon, Daniela Šupe Domić and Sanja Lovrić Kojundžić

Life 2025, 15(3), 495; https://doi.org/10.3390/life15030495 - 18 Mar 2025

Viewed by 355

Abstract

As acute ischemic stroke (AIS) is still a significant cause of morbidity globally, new methods of rapid diagnostics are continually being researched and improved. Still, the only definite way to diagnose AIS is radiological imaging. Lately, serum biomarkers glial fibrillary acidic protein (GFAP) [...] Read more.

As acute ischemic stroke (AIS) is still a significant cause of morbidity globally, new methods of rapid diagnostics are continually being researched and improved. Still, the only definite way to diagnose AIS is radiological imaging. Lately, serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have shown their usefulness in AIS as potential complementary tools in early recognition. We aimed to investigate if GFAP and UCH-L1 can correlate with comprehensive diagnostic information provided by computed tomography (CT) and several clinical parameters in AIS severity assessment and subsequently with clinical outcomes. Fifty-two patients with AIS and a potential for mechanical thrombectomy (MT) were included in our study. Thirty-seven patients underwent MT. Results showed no correlation of biomarkers with any analyzed CT parameter (thrombus length, volume, and density, clot burden score, collateral score, AIS core and penumbra volume, differences in perfusion between healthy and affected brain tissue). In addition, none of the clinical parameters, such as sex, symptom onset time, or the National Institutes of Health Stroke Scale, correlated with biomarkers. However, lower biomarker levels corresponded with a good clinical outcome, and higher levels to a poor outcome following hospital discharge, irrespective of the performed MT (p = 0.005 for GFAP, p = 0.001 for UCH-L1). In patients with successful MT, there were also differences between patients with a good clinical outcome compared with patients with a poor clinical outcome (p = 0.007 for GFAP, p = 0.004 for UCH-L1). In conclusion, these biomarkers cannot replace imaging modalities but can provide complementary diagnostic information in the setting of AIS. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

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14 pages, 1426 KiB

Open AccessArticle

Predictive Factors of Non-Elevation of Carcinoembryonic Antigen 125 in Acute Heart Failure

by Raquel López-Vilella, Francisco González-Vílchez, Borja Guerrero Cervera, Víctor Donoso Trenado, Zoser Saura Carretero, Julia Martínez-Solé, Sara Huélamo Montoro, Luis Martínez Dolz and Luis Almenar Bonet

Life 2025, 15(3), 494; https://doi.org/10.3390/life15030494 - 18 Mar 2025

Viewed by 1211

Abstract

This study aims to analyze the factors associated with the lack of carbohydrate antigen 125 (CA-125) elevation in cases of acute heart failure (HF) decompensation. This retrospective study was conducted on 3167 consecutive patients admitted for acute HF in the cardiology department of [...] Read more.

This study aims to analyze the factors associated with the lack of carbohydrate antigen 125 (CA-125) elevation in cases of acute heart failure (HF) decompensation. This retrospective study was conducted on 3167 consecutive patients admitted for acute HF in the cardiology department of a referral hospital (June 2019 to June 2024). Admissions from outpatient clinics (n: 1018) and transfers from other hospitals (n: 752) were excluded. The variables of interest included clinical, echocardiographic, therapeutic, and analytical factors. Low CA-125 levels were defined as values ≤ 50 U/mL. A total of 1397 patients were included, of whom 515 had normal CA-125 levels and 882 had elevated levels. Clinically, independent predictors of low CA-125 were sinus rhythm on electrocardiogram (OR: 1.42, 95% CI: 1.12–1.64; p: 0.003) and sleep apnea–hyponpnea syndrome (OR: 1.76, 95% CI: 1.15–2.70; p: 0.009). Echocardiographically, inferior vena cava collapse greater than 50% with inspiration was associated with low CA-125 (OR: 1.78, 95% CI: 1.19–2.69; p = 0.005), as well as with non-severe right ventricular dysfunction. (OR: 2.42; IC95%: 1.39–4.20; p: 0.002). Analytically, elevated NT-proBNP levels were associated with elevated CA-125 levels (OR: 0.99; IC95%: 0.99–0.99; p: 0.006). Survival was higher in the group with CA-125 ≤ 50 U/mL (p: 0.019). Conversely, as CA-125 values increased, mortality also rose. In conclusion, the absence of CA-125 elevation in patients admitted for acute HF is associated with sinus rhythm, sleep apnea–hyponpnea syndrome, low NT-proBNP levels, and inferior vena cava collapse greater than 50% with inspiration. Full article

(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Diseases: From Pathophysiology to Diagnosis and Treatment: 3rd Edition)

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15 pages, 3194 KiB

Open AccessEditor’s ChoiceReview

Neural Mechanisms of Cognitive Behavioral Therapy Efficacy in Anxiety Disorders: A Scoping Review of fMRI-Based Studies That Tested the Dual Model

by Judith Domínguez-Pérez, Wenceslao Peñate-Castro and Francisco Luis Rivero-Pérez

Life 2025, 15(3), 493; https://doi.org/10.3390/life15030493 - 18 Mar 2025

Viewed by 1049

Abstract

Anxiety disorders are common mental health conditions characterized by excessive fear and anxiety. Cognitive behavioral therapy (CBT) has demonstrated efficacy, yet the possible neurobiological mechanisms underpinning its effects remain debated. The dual-route model offers a potential explanation by suggesting that CBT increases activation [...] Read more.

Anxiety disorders are common mental health conditions characterized by excessive fear and anxiety. Cognitive behavioral therapy (CBT) has demonstrated efficacy, yet the possible neurobiological mechanisms underpinning its effects remain debated. The dual-route model offers a potential explanation by suggesting that CBT increases activation in the brain areas responsible for emotion regulation while decreasing activation in limbic areas. This scoping review examined possible neurobiological mechanisms supporting CBT’s efficacy in anxiety disorders by exclusively reviewing studies that utilized functional magnetic resonance imaging (fMRI). The included studies published since 2018 focused on adult samples that received CBT for anxiety disorders, with pre- or post-treatment fMRI data. The data extraction followed a standardized process, with key variables, such as the study design, population, and neuroimaging findings, systematically charted. While the dual-route model explains key aspects of CBT’s neurobiological effects, the findings suggest the need for expansion to incorporate areas such as the precuneus, particularly in specific phobias and social anxiety disorder. Further research is required to refine this model and explore additional mechanisms underlying CBT’s efficacy. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

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8 pages, 221 KiB

Open AccessArticle

Target-Controlled Sedation with Propofol Infusion for PEG-J Placement in Advanced Parkinson’s Disease: A Prospective Observational Study on Safety and Feasibility

by Janos Szederjesi, Irina Săplăcan, Alexandra Lazăr, Matild Keresztes, Georgiana-Mihaela Muller-Șerban, Jozsef Attila Szasz and Bianca Liana Grigorescu

Life 2025, 15(3), 492; https://doi.org/10.3390/life15030492 - 18 Mar 2025

Viewed by 322

Abstract

Introduction: The management of sedation during percutaneous endoscopic gastrojejunostomy (PEG-J) placement in patients with advanced Parkinson’s disease (PD) is challenging due to the complex interactions between PD treatment, anesthetic agents, and the disease’s motor and non-motor symptoms. This study evaluates the effectiveness and [...] Read more.

Introduction: The management of sedation during percutaneous endoscopic gastrojejunostomy (PEG-J) placement in patients with advanced Parkinson’s disease (PD) is challenging due to the complex interactions between PD treatment, anesthetic agents, and the disease’s motor and non-motor symptoms. This study evaluates the effectiveness and safety of a target-controlled infusion (TCI) propofol protocol in the context of PEG-J placement in advanced PD patients. Materials and Methods: This prospective study included 169 patients diagnosed with advanced Parkinson’s disease (Hoehn and Yahr stages 4 and 5) who underwent PEG-J placement at Târgu Mureș County Emergency Clinical Hospital, Romania. Sedation was induced and maintained using TCI propofol, with additional benzodiazepines and short-acting opioids, while muscle relaxants were not used. Procedural success rates and adverse outcomes were assessed for 30 days post-procedure. Results: The sedation protocol demonstrated a high procedural success rate. No deaths were reported within 30 days post-procedure. Conclusion: This study highlights the feasibility and clinical applicability of a TCI propofol protocol for PEG-J placement in patients with advanced PD (stages 4 and 5). While no deaths were recorded within the 30-day follow-up, the sample size is insufficient to draw definitive conclusions regarding long-term safety. Full article

(This article belongs to the Special Issue Critical Issues in Intensive Care Medicine)

16 pages, 2788 KiB

Open AccessArticle

Tangeretin Unravels Metabolic Dysfunction-Associated Fatty Liver Disease in Rats by Enhancing the IRS/Akt Pathway

by Ittipon Yuenyong, Prapassorn Potue, Putcharawipa Maneesai, Juthamas Khamseekaew, Apiwan Manimmanakorn, Metee Iampanichakul and Poungrat Pakdeechote

Life 2025, 15(3), 491; https://doi.org/10.3390/life15030491 - 18 Mar 2025

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Abstract

Excessive high-fat diet (HFD) intake can precipitate metabolic dysfunction-associated fatty liver disease (MAFLD). Tangeretin is a citrus flavonoid possessing many biological properties. We examined the impact of tangeretin on MAFLD and its underlying mechanism. Rats were given HFD plus 15% fructose solution for [...] Read more.

Excessive high-fat diet (HFD) intake can precipitate metabolic dysfunction-associated fatty liver disease (MAFLD). Tangeretin is a citrus flavonoid possessing many biological properties. We examined the impact of tangeretin on MAFLD and its underlying mechanism. Rats were given HFD plus 15% fructose solution for four months to produce metabolic syndrome. Metabolic syndrome rats were administered 100 mg/kg of metformin or 25 mg/kg of tangeretin for the last four weeks. HFD-induced increased body weight, liver weight, adipose tissue weight, fasting blood glucose, serum insulin, total triglyceride, total cholesterol, and free fatty acids and reduced adiponectin and high-density lipoprotein cholesterol levels in metabolic syndrome, which were alleviated by tangeretin (p < 0.05). Tangeretin stabilized alanine transaminase activity, liver catalase, and inflammatory and oxidative stress markers in HFD rats compared to untreated HFD rats (p < 0.05). Tangeretin reduced hepatic steatosis induced by HFD. Downregulation of hepatic insulin receptor substrate-1 (IRS-1) and protein kinase B (Akt) protein expression in metabolic syndrome rats was recovered by tangeretin (p < 0.05). Metformin, an antihyperglycemic drug, produced comparable effects to tangeretin. In conclusion, tangeretin attenuates metabolic disorders and fatty liver induced by HFD in rats. The underlying mechanisms involve reducing oxidative stress, and inflammation and enhancing insulin sensitivity. Full article

(This article belongs to the Special Issue Implications of Bioactive Compounds in Lifelong Disorders)

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14 pages, 890 KiB

Open AccessArticle

Study of the Arrhythmogenic Profile in Dogs with Acute and Chronic Monocytic Ehrlichiosis

by Carolina Dragone Latini, Angélica Alfonso, Maurício Gianfrancesco Filippi, Mayra de Castro Ferreira Lima, Antônio Carlos Paes, Jaqueline Valença Corrêa, Beatriz Almeida Santos, Miriam Harumi Tsunemi and Maria Lucia Gomes Lourenço

Life 2025, 15(3), 490; https://doi.org/10.3390/life15030490 - 18 Mar 2025

Viewed by 325

Abstract

Canine monocytic ehrlichiosis (CME) is a globally prevalent disease transmitted by the tick Rhipicephalus sanguineus and caused by the Gram-negative bacterium Ehrlichia spp. Following an incubation period, the infection is categorized based on the progression of the disease into acute, subclinical, and chronic [...] Read more.

Canine monocytic ehrlichiosis (CME) is a globally prevalent disease transmitted by the tick Rhipicephalus sanguineus and caused by the Gram-negative bacterium Ehrlichia spp. Following an incubation period, the infection is categorized based on the progression of the disease into acute, subclinical, and chronic stages. Besides hematological alterations, the cardiovascular system is significantly impacted by the hemodynamic effects of the disease, as persistent anemia can lead to myocardial hypoxia and the activation of inflammatory processes, potentially causing myocarditis. It is known that in dogs infected with Ehrlichia canis, there is a higher occurrence of arrhythmias and a predominance of sympathetic activity. This study assessed arrhythmogenic parameters, including P wave dispersion (Pd), QT dispersion (QTd), and QT instability, along with heart rate variability (HRV) analysis from 24 h Holter monitoring in naturally infected dogs during the acute phase (n = 10) and chronic phase (n = 10) compared to a control group (n = 10). The Pd and QTd values were higher in the infect group, confirming the arrhythmogenic character. Instability parameters (TI, LTI, and STI) were higher in sick animals, but no worsening was observed in the chronic phase. All HRV metrics in the time domain were higher in the control group, indicating a balanced sympathovagal activity throughout the day in healthy dogs. Additionally, parameters linked to parasympathetic activity (rMSSD and pNN50) were reduced in the sick groups, confirming the dominance of sympathetic activity. These findings indicate a decrease in HRV in sick individuals and reinforce this useful marker for assessing the influence of the autonomic nervous system on the cardiovascular system. In conclusion, CME exhibits arrhythmogenic activity characterized by the deterioration of predictive parameters for ventricular arrhythmias and increased activity of the sympathetic autonomic nervous system in the heart. This is likely secondary to myocarditis, myocardial hypoxia, and structural damage to cardiomyocytes. Full article

(This article belongs to the Section Animal Science)

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17 pages, 2614 KiB

Open AccessArticle

Bidah Pomegranate Landrace: Chemical Composition, Antioxidant, Antibacterial, and Anticancer Activity

by Abdalrhaman M. Salih, Nada M. Alattas, Qasi D. Alsubaie and Saheed O. Anifowose

Life 2025, 15(3), 489; https://doi.org/10.3390/life15030489 - 18 Mar 2025

Viewed by 692

Abstract

Pomegranate (Punica granatum L.) belongs to the Punicaceae family and is native to Central Asia; yet, it has a wide geographical distribution globally, reflecting its adaptation to different climatic conditions. Pomegranate is among the oldest and most significant cultivated crops, thriving extensively [...] Read more.

Pomegranate (Punica granatum L.) belongs to the Punicaceae family and is native to Central Asia; yet, it has a wide geographical distribution globally, reflecting its adaptation to different climatic conditions. Pomegranate is among the oldest and most significant cultivated crops, thriving extensively in tropical and subtropical climates. Besides its nutritional uses, pomegranate has been employed in traditional medicine for treating various diseases, including cancer prevention, antimicrobial activity, male infertility, ulcers, and diarrhea. The Bidah pomegranate cultivar is known for its unique sweet taste and high productivity yield. However, there is limited knowledge about its nutritional composition and medicinal value. Therefore, this study aimed to evaluate the functional potential of Bidah pomegranate in terms of its phytochemicals, antioxidant capacity, antibacterial, and anticancer activity. Different analytical techniques were used to investigate the chemical composition and antioxidant properties of Bidah pomegranate. Moreover, the biological activity of shoot and callus of Bidah pomegranate cultivar was assessed against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and the colorectal cancer cell line (CaCo-2). Gas chromatography/mass spectrometry (GC/MS) analysis of the shoot and callus extracts revealed about 17 and 18 phytochemical compounds, respectively. Phenolic quantification showed that pomegranate materials contained high amounts of phenolic content. Additionally, Bidah pomegranate cultivar possesses high antioxidant activity with a low half-maximal inhibitory concentration (IC50) value. Furthermore, the pomegranate extract showed promising results with human pathogenic bacteria (E. coli and S. aureus), especially against S. aureus and the colorectal cancer cell line (CaCo-2). The findings of this study support the traditional use of pomegranate in folk medicine and highlight its potential for further exploration as a source of therapeutic agents. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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20 pages, 5088 KiB

Open AccessArticle

Exploring Fungal Abundance and WHO Fungal Priority Pathogens in Agricultural Fields: A One Health Perspective in Northeast Thailand

by Chayaporn Lakmuang, Syahriar Nur Maulana Malik Ibrahim, Teeratat Kaewjon, Nattapol Kraisitudomsook, Naraporn Somboonna, Ratmanee Chanabun, Ariya Chindamporn and Nuttapon Pombubpa

Life 2025, 15(3), 488; https://doi.org/10.3390/life15030488 - 18 Mar 2025

Viewed by 472

Abstract

Fungal pathogens prevalent in agricultural areas pose a significant risk to human health, with some exhibiting high fatality rates, as reported by the WHO Fungal Pathogen Priority List (WHO FPPL). This study investigates fungal communities in northeast Thailand’s agricultural areas, focusing on potential [...] Read more.

Fungal pathogens prevalent in agricultural areas pose a significant risk to human health, with some exhibiting high fatality rates, as reported by the WHO Fungal Pathogen Priority List (WHO FPPL). This study investigates fungal communities in northeast Thailand’s agricultural areas, focusing on potential reservoirs of the WHO FPPL. Samples were collected from rice, cassava, rubber trees, and sugarcane fields across 18 provinces with distinct geological features. Metabarcoding of the ITS1 region and taxonomic analysis were conducted, and potential pathogens were selected according to WHO FPPL criteria. The results showed that overall fungal community richness and diversity were influenced by plant fields but not significantly different by geological features. Soil organic matter and water content affected fungal dynamics only in rubber tree fields. Fungal pathogens from the WHO FPPL were found in all four plant fields, with higher abundance in Chaiyaphum province, especially in sugarcane fields, and the lowest in Nong Bua Lam Phu. Candida tropicalis, a high-priority pathogen, was predominantly associated with rock salt features. This study underscores the need for vigilance among farmers and emphasizes the importance of confirming fungal pathogenicity. Full article

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

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20 pages, 839 KiB

Open AccessReview

Immunonutrition in ERAS Protocol for Patients with Gynecologic Cancer: A Narrative Review of the Literature

by Vasilios Lygizos, Dimitrios Haidopoulos, Dimitrios Efthymios Vlachos, Antonia Varthaliti, Maria Fanaki, George Daskalakis, Nikolaos Thomakos and Vasilios Pergialiotis

Life 2025, 15(3), 487; https://doi.org/10.3390/life15030487 - 18 Mar 2025

Viewed by 519

Abstract

In-hospital patients who are in the gynecologic oncology setting often suffer from malnutrition, which is one of the primary problems, the rate of which reportedly ranges from 28% to 70%. Malnutrition is a significant risk factor for immunosuppression, negatively impacting immune response and [...] Read more.

In-hospital patients who are in the gynecologic oncology setting often suffer from malnutrition, which is one of the primary problems, the rate of which reportedly ranges from 28% to 70%. Malnutrition is a significant risk factor for immunosuppression, negatively impacting immune response and postoperative recovery capacity. At the time of the surgeries, due to their wide scope and aggressive treatments such as chemotherapy and radiotherapy, the situation becomes more serious. Those micronutrients taking part in immunonutrition, namely, arginine, omega-3 fatty acids, nucleotides, and antioxidants, have the potential to prevent inflammation, protect against infections, and promote healing after the surgery. Research has shown that immunonutrition can lower the risk of postoperative infection, promote the normal healing of wounds, and reduce the hospital stays of patients, as well as support malnutrition status during chemotherapy. This review is based on a literature search conducted in Medline, Scopus, Clinicaltrials.gov, Cochrane CENTRAL, and Google Scholar, with the last search date being November 2024. Some studies. found that perioperative immunonutrition decreases wound infections and affects some immune indexes in gynecologic oncology patients positively. However, factors such as non-compliant patients, high costs, and non-standard formulations can deter its wider use. Patient adherence drops postoperatively mainly due to nausea and decreased appetite, whereas the cost of enriched formulations acts as an economic barrier. Postoperative compliance drops from ~78% prior to surgery to ~28% due to nausea, anorexia, and chemotherapy. Additionally, cost remains a constraining factor since special formulas are 2–4 times that of normal nutrition. While immunonutrition reduces hospital stay (by ~2–3 days) and infection rate (by 25–40%), access is hindered by prohibitive initial costs and lack of insurance coverage. Approaches such as subsidized schemes, enhanced palatability, and cost–benefit analyses are required to increase adoption. In addition, the lack of standardized protocols makes the clinical community hesitant to adopt this approach. Immunonutrition is, despite these problems, still hoped to be the new adjunct to gynecologic oncology patients. In future studies, it is imperative to pay attention to the best formulations that produce the best outcomes and evaluate and implement guidelines that are based on evidence. Together, with these improvements, immunonutrition could very well be an integral part of perioperative care thus completing the process by which patients in intense treatments are benefited not only via treatment but also via quality of life. Full article

(This article belongs to the Section Medical Research)

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14 pages, 2314 KiB

Open AccessArticle

Regulatory Mechanisms of Phytohormones in Thiocyanate-Exposed Rice Plants: Integrating Multi-Omics Profiling with Mathematical Modeling

by Yi Kang, Chengzhi Li and Xiaozhang Yu

Life 2025, 15(3), 486; https://doi.org/10.3390/life15030486 - 18 Mar 2025

Viewed by 430

Abstract

Plants experience various abiotic stresses, among which pollutant stress is one of the most damaging, threatening plant productivity and survival. Thiocyanate (SCN⁻), a recalcitrant byproduct of industrial processes, poses escalating threats to agroecosystems by disrupting plant hormonal homeostasis, which is critical [...] Read more.

Plants experience various abiotic stresses, among which pollutant stress is one of the most damaging, threatening plant productivity and survival. Thiocyanate (SCN⁻), a recalcitrant byproduct of industrial processes, poses escalating threats to agroecosystems by disrupting plant hormonal homeostasis, which is critical for stress adaptation. Here, we dissect the regulatory interplay of phytohormones in rice (Oryza sativa L.) under SCN⁻ stress (4.80–124.0 mg SCN/L) through integrated transcriptomic and metabolomic profiling. Quantitative hormonal assays revealed dose- and tissue-specific perturbations in phytohormone homeostasis, with shoots exhibiting higher sensitivity than roots. Transcriptomic analysis revealed that a number of differentially expressed genes (DEGs) mapped in different phytohormone pathways in SCN⁻-treated rice seedlings, and their transcript abundances are tissue-specific. To identify the phytohormones governing rice’s sensitivity to SCN⁻ stress, we developed a Total Hormonal Sensitivity Index (THSI) through an integrative multivariate framework, which combines Modified Variable Importance in Projection (VIP_(m)) scores to quantify hormonal fluctuations and Total Weighted Contribution Scores (TWCS) at the gene-level from hormonal pathways. This study establishes a system-level understanding of how phytohormonal crosstalk mediates rice’s adaptation to SCN⁻ stress, providing biomarkers for phytoremediation strategies in contaminated paddies. Full article

(This article belongs to the Special Issue Plant Biotic and Abiotic Stresses 2024)

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18 pages, 821 KiB

Open AccessArticle

Psoriasis and Seborrheic Keratoses: Insights from Biologic Therapy and Skin Imaging

by Florin Ciprian Bujoreanu, Diana Sabina Radaschin, Mihail Alexandru Badea, Laura Bujoreanu Bezman, Carmen Pantiș, Carmen Tiutiuca, Liliana Baroiu, Elena Niculeț, Alina Pleșea Condratovici and Alin Laurențiu Tatu

Life 2025, 15(3), 485; https://doi.org/10.3390/life15030485 - 17 Mar 2025

Viewed by 576

Abstract

Psoriasis is one of the most frequent immune-mediated chronic inflammatory cutaneous disease that exerts a considerable psychological impact, including low self-esteem, stigmatization, and depression. In recent years, biologic therapies have substantially transformed the therapeutic landscape for individuals with moderate-to-severe psoriasis, shifting treatment towards [...] Read more.

Psoriasis is one of the most frequent immune-mediated chronic inflammatory cutaneous disease that exerts a considerable psychological impact, including low self-esteem, stigmatization, and depression. In recent years, biologic therapies have substantially transformed the therapeutic landscape for individuals with moderate-to-severe psoriasis, shifting treatment towards a more targeted and personalized approach. Seborrheic keratoses (SKs) are common benign skin lesions, and their association with psoriasis and biologic therapy remains poorly understood. Our retrospective study evaluated a small cohort of patients with moderate-to-severe psoriasis undergoing biologic therapy at a tertiary dermatology center in Southeastern Europe to evaluate potential correlations with SK development. Smokers had fewer SKs, whereas postmenopausal women and osteoporosis patients had significantly higher SK counts, implicating hormonal influences. PUVA therapy was linked to an increased SK count, whereas UVB and methotrexate treatments had a lesser effect. These findings suggest that biologic therapy and systemic factors may influence SK development, emphasizing the need for further prospective research. Full article

(This article belongs to the Special Issue Current Research on Dermatology: Pathology, Clinical Manifestation, Investigation and Therapy—Third Edition)

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25 pages, 1174 KiB

Open AccessReview

Applications of Diquafosol Sodium in Ophthalmology: A Comprehensive Review of Therapeutic Utility

by Chelsea Qiu Lin Tan, Duoduo Wu, Xin Yun Toh, Blanche Xiaohong Lim, Kendrick Co Shih, Louis Tong and Chris Hong Long Lim

Life 2025, 15(3), 484; https://doi.org/10.3390/life15030484 - 17 Mar 2025

Viewed by 1236

Abstract

Diquafosol sodium is a purinergic P2Y₂ receptor agonist that is garnering much interest for its potential therapeutic benefits in ocular surface management. This review provides a comprehensive analysis of diquafosol’s pharmacology, clinical effectiveness, and role in the evolving landscape of ocular surface [...] Read more.

Diquafosol sodium is a purinergic P2Y₂ receptor agonist that is garnering much interest for its potential therapeutic benefits in ocular surface management. This review provides a comprehensive analysis of diquafosol’s pharmacology, clinical effectiveness, and role in the evolving landscape of ocular surface management. Future research should focus on optimising formulations, treatment duration, and exploring potential combination therapies to maximise therapeutic outcomes. By targeting underlying pathophysiological mechanisms, diquafosol represents a significant advancement in ocular surface management and a valuable addition to existing therapies. Full article

(This article belongs to the Special Issue Prognosis and Management of Dry Eye Disease)

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17 pages, 1045 KiB

Open AccessArticle

Evaluation of Product Yield and Fatty Acid Composition of Three Flax (Linum usititassimum L.) Varieties Depending on Different Sowing Dates

by Nazlı Aybar Yalınkılıç, Şilan Çiçek Bayram and Sema Başbağ

Life 2025, 15(3), 483; https://doi.org/10.3390/life15030483 - 17 Mar 2025

Viewed by 381

Abstract

The flax (Linum usititassimum L.) plant can grow in various agroecological environments. However, there are some factors that affect the production and quality of flax. Sowing date is one of the important factors determining crop productivity. In this study, four different sowing [...] Read more.

The flax (Linum usititassimum L.) plant can grow in various agroecological environments. However, there are some factors that affect the production and quality of flax. Sowing date is one of the important factors determining crop productivity. In this study, four different sowing dates (20–22 March, 1–3 April, 15–18 April and 30 April, respectively) were applied to determine the appropriate sowing date in terms of yield and oil quality in three flax varieties (Sarı Dane, Kara Kız, Beyaz Gelin). The study results showed that by delaying sowing, the seed filling period of the plant was exposed to high temperatures, and this caused decreases in seed yield. In other words, the most positive results in terms of agronomic characteristics were obtained from the first sowing date. In this respect, the highest oil yield of 760 kg ha⁻¹ and the highest oil content of 34% were obtained from the Sarı Dane variety. Similarly, flaxseed showed high values in terms of alphalinolenic acid (54.25%), palmitic acid (6.36%), stearic acid (7%), oleic acid (22.54%) and linoleic acid (14%) at the first and second planting times, while these rates decreased relatively as the planting time was delayed. According to the results of the two-year study, it was determined that the ecological conditions of the region were suitable for flax cultivation. However, it is clear that delaying the sowing date causes significant decreases in both the agronomic traits of flax and the oil quality for industrial purposes. In this respect, considering the ecology of the region, sowing flax in the last week of March or the first week of April is suitable for optimum yield and oil quality. Full article

(This article belongs to the Section Plant Science)

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27 pages, 4424 KiB

Open AccessReview

DNA Methylation in Urine and Feces Indicative of Eight Major Human Cancer Types Globally

by Melanie Engstrom Newell, Ayesha Babbrah, Anumitha Aravindan, Raj Rathnam and Rolf U. Halden

Life 2025, 15(3), 482; https://doi.org/10.3390/life15030482 - 17 Mar 2025

Viewed by 662

Abstract

Toxic chemicals and epigenetic biomarkers associated with cancer have been used successfully in clinical diagnostic screening of feces and urine from individuals, but they have been underutilized in a global setting. We analyzed peer-reviewed literature to achieve the following: (i) compile epigenetic biomarkers [...] Read more.

Toxic chemicals and epigenetic biomarkers associated with cancer have been used successfully in clinical diagnostic screening of feces and urine from individuals, but they have been underutilized in a global setting. We analyzed peer-reviewed literature to achieve the following: (i) compile epigenetic biomarkers of disease, (ii) explore whether research locations are geographically aligned with disease hotspots, and (iii) determine the potential for tracking disease-associated epigenetic biomarkers. Studies (n = 1145) of epigenetic biomarkers (n = 146) in urine and feces from individuals have established notable diagnostic potential for detecting and tracking primarily gastric and urinary cancers. Panels with the highest sensitivity and specificity reported more than once were SEPT9 (78% and 93%, respectively) and the binary biomarker combinations GDF15, TMEFF2, and VIM (93% and 95%), NDRG4 and BMP3 (98% and 90%), and TWIST1 and NID2 (76% and 79%). Screening for epigenetic biomarkers has focused on biospecimens from the U.S., Europe, and East Asia, whereas data are limited in regions with similar/higher disease incidence rates (i.e., data for New Zealand, Japan, and Australia for colorectal cancer). The epigenetic markers discussed here may aid in the future monitoring of multiple cancers from individual- to population-level scales by leveraging the emerging science of wastewater-based epidemiology (WBE). Full article

(This article belongs to the Special Issue Revolutionizing Neuroregeneration)

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15 pages, 1280 KiB

Open AccessReview

New World Primates and Their Human Counterparts Share Diseases That Abound with CEACAM and Other Effector Molecules

by Martin Tobi, Daniel Ezekwudo, Benita McVicker, Harvinder Talwar, Laura Kresty, Elizabeth Curran, Ronald Veazey, Peter J. Didier, James Hatfield, Mike Lawson and Sonia M. Najjar

Life 2025, 15(3), 481; https://doi.org/10.3390/life15030481 - 17 Mar 2025

Viewed by 501

Abstract

Background: Herein, we review the Cotton Top Tamarin (CTT), Saguinus oedipus, a unique spontaneous model for colorectal cancer (CRC). Despite its predisposition to inflammatory bowel disease (IBD) and frequent development of CRC, the CTT is adept at avoiding colorectal metastasis in the [...] Read more.

Background: Herein, we review the Cotton Top Tamarin (CTT), Saguinus oedipus, a unique spontaneous model for colorectal cancer (CRC). Despite its predisposition to inflammatory bowel disease (IBD) and frequent development of CRC, the CTT is adept at avoiding colorectal metastasis in the liver. In contrast, the common marmoset (CM), Callithrix jacchus, is a natural negative control, in that it also contracts IBD, but usually not CRC. We review our findings in these New World monkeys in terms of the expression of CEACAM adhesion models and their related molecules to contrast them with human disease. Methods: Specimens were collected from aforementioned monkey colorectal and other tissues, colonic washings, serum for analysis of tissue extraction, and colonic washings via ELISA, using a battery of antibodies. Fixed tissues were analyzed using immunohistochemistry and CEACAMs were extracted via Western blotting. Serum CEA levels were analyzed using ELISA, and DNA was extracted via a Bigblast genomics sequencing kit. Results: Serum CEA was significantly elevated in CTTs, and one-third of them die from CRC. Unlike others, we were unable to stain for CEA in tissues. The sialylated carbohydrate antigen recognized by monoclonal antibody (MAb) SPAN-1 does stain in 16.7% of CTT tissues, but the anti-aminoproteoglycan MAb, CaCo.3/61, stained 93.3% (OR70·00[CI6.5–754.5] p < 0.0001). The common CEA kits from Abbott and Roche were non-conclusive for CEA. We later adopted a CEA AIA-PACK from Tosoh Medics, which identified a 50 Kda band via Western blotting in humans and CTTs. The CEA levels were higher using the CEA AIA-PACK than the Pharmatrope kit (932 ± 690 versus 432 ± 407 ng/mL (p < 0.05)) in human patient colonic effluent, not statistically significant (NSS) for CTT extracts or effluent (733 ± 325 and 739 ± 401 ng/mL, respectively). It was suggested that the smaller CTT CEA moiety might lack components that facilitate the spread of liver metastasis. Later, using more specific CEA assays and increased numbers of specimens, we were able to show higher CEA serum expression in CTTs than in CMs (632.1 ± 306.1 vs. 81.6 ± 183.6, p < 0.005), with similar differences in the serum samples. Western blotting with the anti-CEA T84.66 MAb showed bands above 100 KDa in CTTs. The profiles in CTTs were similar to human patients with inflammatory bowel disease. We established that the CEA anchorage to the cell was a GPI-linkage, advantageous for the inhibition of differentiation and anoikis. With further CEA DNA analysis, we were able to determine at least five different mechanisms that may inhibit liver metastasis, mostly related to CEA, but later expanded this to seven, and increased the relationships to CEACAM1 and other related molecules. Recently, we obtained CTT liver mRNA transcriptomes that implicated several pathways of interest. Conclusions: With efforts spanning over three decades, we were able to characterize CEA and other changes that allow us to better understand the CTT phenomenon of liver metastasis inhibition. We are in the process of characterizing the CTT liver mRNA transcriptome to compare it with that of the common marmoset. Currently, liver CTT gene expression patterns suggest that ribosomes, lipoproteins, and antioxidant defense are related to differences between CTTs and CMs. Full article

(This article belongs to the Special Issue Veterinary Pathology and Veterinary Anatomy: 3rd Edition)

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14 pages, 1961 KiB

Open AccessArticle

Radiation Diagnostics of the Maxillofacial Region and Skeleton Bone Density in the Case of Vitamin D Insufficiency: A Pilot Study

by Ekaterina Diachkova, Svetlana Tarasenko, Marina Skachkova, Yury Zhilkov, Natalia Serova, Anna Babkova, Beatrice Volel, Ekaterina Blinova, Elizaveta Kytko, Renata Meylanova, Victoria Zaborova and Olesya Kytko

Life 2025, 15(3), 480; https://doi.org/10.3390/life15030480 - 17 Mar 2025

Viewed by 359

Abstract

(1) Background: A decrease in bone mineral density has been noted not only in at-risk patients (e.g., postmenopausal women) but also in young and middle-aged individuals due to changes in lifestyle. The aim of the study was to find a possible correlation for [...] Read more.

(1) Background: A decrease in bone mineral density has been noted not only in at-risk patients (e.g., postmenopausal women) but also in young and middle-aged individuals due to changes in lifestyle. The aim of the study was to find a possible correlation for dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) with cone beam computed tomography (CBCT) of the jaws. (2) Methods: A total of 24 patients (14 women and 10 men aged 25 to 50 years) with partial secondary tooth loss and vitamin D insufficiency underwent cone beam computed tomography of the jaws and skeletal mineral density assessment using DXA (n = 12) and QCT (n = 12). (3) Results: When conducting CBCT of the jaws, a predominance of bone tissue type D3 (350–850 Hu) on the upper jaw (p > 0.05 (F = 0.68) and D2 (850–1350 Hu) on the lower jaw (p > 0.05 (F = 1) was revealed. According to the results of QCT densitometry of the skeleton, signs of osteopenia were found in four patients (with vitamin D3 deficiency) (33%) according to DXA; signs of osteopenia were found in six patients (with severe deficiency and deficiency of vitamin D3) (50%). The difference between QCT and DXA was not significant (p > 0.05) for each group. The significant strong correlation between CBCT and DXA or QCT was not found (p > 0.05). (4) Conclusions: Primary changes in bone density can be detected earlier in the dental system using cone beam computed tomography of the jaws. At the same time, the question of using a specific densitometry method—DXA or QCT—remains open, as their results correlating with CBCT optical density was not approved. Full article

(This article belongs to the Special Issue Feature Papers in Medical Research: 3rd Edition)

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5 pages, 196 KiB

Open AccessEditorial

Bridging Disciplines: Comprehensive Approaches to Cardiovascular Disease Treatment

by Daniela Maria Tanase, Anca Victorita Trifan and Mariana Floria

Life 2025, 15(3), 479; https://doi.org/10.3390/life15030479 - 17 Mar 2025

Viewed by 301

Abstract

Cardiovascular disease (CVD) remains one of the leading causes of death worldwide [...] Full article

(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Diseases: From Pathophysiology to Diagnosis and Treatment)

15 pages, 3447 KiB

Open AccessArticle

Effects of Different Doses of Caffeine on Endurance Exercise Performance in the Heat

by Weiliang Wu, Xifeng Tao, Huiyu Dong, Juan Yang, Yin Liang, Yuanyuan Lv and Laikang Yu

Life 2025, 15(3), 478; https://doi.org/10.3390/life15030478 - 16 Mar 2025

Viewed by 1173

Abstract

This study investigated the effects of different doses of caffeine (3 mg/kg BW and 6 mg/kg BW) on endurance exercise performance in the heat. Seventeen participants completed four randomized, double-blind trials: one in a normal environment (24.6 ± 1.2 °C) and three in [...] Read more.

This study investigated the effects of different doses of caffeine (3 mg/kg BW and 6 mg/kg BW) on endurance exercise performance in the heat. Seventeen participants completed four randomized, double-blind trials: one in a normal environment (24.6 ± 1.2 °C) and three in a hot environment (33.2 ± 1.4 °C), with placebo, 3 mg/kg BW, and 6 mg/kg BW caffeine interventions. Endurance exercise time, cardiorespiratory function, and subjective fatigue perception were measured during incremental cycling tests. The results showed that high temperatures significantly reduced endurance exercise performance in the placebo (p < 0.001) and 3 mg/kg BW (p = 0.003) groups compared to the normal environment, but not in the 6 mg/kg BW group (p = 1.000). Both caffeine doses improved exercise time compared to placebo (3 mg/kg BW, p = 0.005; 6 mg/kg BW, p < 0.001). Caffeine ingestion enhanced pulmonary ventilation (VE), with significant increases in VE_peak (3 mg/kg BW, p = 0.032; 6 mg/kg BW, p = 0.006). Aerobic capacity improved, as evidenced by elevated VO₂peak (3 mg/kg BW, p = 0.010; 6 mg/kg BW, p = 0.001) and PetO₂ (3 mg/kg BW, p = 0.000; 6 mg/kg BW, p = 0.001). Subjective fatigue perception was significantly reduced only with 6 mg/kg BW caffeine (p = 0.020). In conclusion, caffeine ingestion at 3 mg/kg BW and 6 mg/kg BW effectively counteracts the negative effects of heat stress on endurance exercise performance by improving respiratory function, enhancing aerobic capacity, and reducing subjective fatigue. The 6 mg/kg BW dose demonstrated superior effects, making it a potential ergogenic aid for athletes training or competing in the heat. Full article

(This article belongs to the Section Physiology and Pathology)

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Open AccessArticle

Polymorphisms of PPARα and ACTN3 Among Adolescent Egyptian Athletes: A Case–Control Study

by Wael Ramadan, Rehan Monir, Ola El-Emam, Mohamed Diab and Dalia Shaheen

Life 2025, 15(3), 477; https://doi.org/10.3390/life15030477 - 16 Mar 2025

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Abstract

Background: Athletic performance is a complex phenotype affected by individual traits, environmental conditions, training, and genetics. The peroxisome proliferator-activated receptor-alpha (PPARα) and alpha-actinin-3 (ACTN3) are two genes with the potential to influence human performance. The objective of the present study was to assess [...] Read more.

Background: Athletic performance is a complex phenotype affected by individual traits, environmental conditions, training, and genetics. The peroxisome proliferator-activated receptor-alpha (PPARα) and alpha-actinin-3 (ACTN3) are two genes with the potential to influence human performance. The objective of the present study was to assess the genotype frequencies of ACTN3 (R/X) and PPARα (G/C) and to conduct a comparison of these frequencies among Egyptian adolescent athletes. Methods: This case–control study involved 228 individuals (118 elite-level athletes and 110 sedentary controls). Results: This study identified a statistically significant increase in the frequencies of the ACTN3 ‘R’ allele (77.5% compared to 55.9%; p < 0.001) and the PPARα ‘C’ allele (86.4% compared to 14.1%; p < 0.001) among athletes relative to the control groups. A similar pattern was noted for adolescent athletes in comparison to the control group in terms of both the R/R genotype (61.9% compared to 27.3%; p < 0.001) and the C/C genotype (80.5% compared to 2.7%; p < 0.001). In conclusion, these results imply that polymorphisms in ACTN3 and PPARα could be significant predictors for assessing the performance of adolescent Egyptian athletes. Full article

(This article belongs to the Special Issue Focus on Exercise Physiology and Sports Performance: 2nd Edition)

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Life, Volume 15, Issue 3 (March 2025) – 181 articles

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