Life

13 pages, 503 KB

Open AccessArticle

Immature Platelet Fraction as a Surrogate Marker of Thrombo-Inflammation in Hospitalized COVID-19 Patients

by Adrian Duek, Alexandra Zimin, Yael Hershkop, Michal Cipok, Amir Cohen and Merav Leiba

Life 2025, 15(12), 1846; https://doi.org/10.3390/life15121846 (registering DOI) - 30 Nov 2025

Although COVID-19 is associated with significant thrombo-inflammatory complications, reliable biomarkers to guide antithrombotic therapy remain limited. Immature platelet fraction (IPF) reflects platelet turnover and may indicate heightened thrombotic risk. We retrospectively analyzed 133 hospitalized COVID-19 patients (median age 68 years) at a single [...] Read more.

Although COVID-19 is associated with significant thrombo-inflammatory complications, reliable biomarkers to guide antithrombotic therapy remain limited. Immature platelet fraction (IPF) reflects platelet turnover and may indicate heightened thrombotic risk. We retrospectively analyzed 133 hospitalized COVID-19 patients (median age 68 years) at a single center. IPF and inflammatory markers (WBC, ANC, D-dimer, LDH, CRP) were measured on admission. Correlations between IPF and these biomarkers were assessed overall and in clinical subgroups (age, sex, disease severity, comorbidities, and treatment). We found that IPF was positively correlated with WBC and ANC in patients less than 70 years old (r = 0.36 and 0.33, respectively; p < 0.05), males, and those with moderate-to-severe disease. Among patients with congestive heart failure, IPF correlated strongly with D-dimer (r = 0.78, p = 0.013). Similar associations were observed in patients requiring enoxaparin or antiplatelet therapy. No significant correlations were found in patients age 70 or older. Based on these findings, we conclude that elevated IPF is associated with increased inflammatory and thrombotic activity in hospitalized COVID-19 patients, especially in younger, male, and more severe cases. These findings suggest IPF may serve as a dynamic marker for thrombo-inflammation and help identify patients who might benefit from more intensive antithrombotic therapy. Larger studies are warranted to validate IPF as a biomarker for personalized management of COVID-19. Full article

(This article belongs to the Section Physiology and Pathology)

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26 pages, 3155 KB

Open AccessArticle

Beyond HOMA-IR: Comparative Evaluation of Insulin Resistance and Anthropometric Indices Across Prediabetes and Type 2 Diabetes Mellitus in Metabolic Syndrome Patients

by Mohamed-Zakaria Assani, Lidia Boldeanu, Anda Lorena Dijmărescu, Daniel Cosmin Caragea, Ionela Mihaela Vladu, Diana Clenciu, Adina Mitrea, Alexandra-Ștefania Stroe-Ionescu, Mariana-Emilia Caragea, Isabela Siloși and Mihail Virgil Boldeanu

Life 2025, 15(12), 1845; https://doi.org/10.3390/life15121845 (registering DOI) - 30 Nov 2025

Abstract

Insulin resistance is central in metabolic syndrome, but indices such as Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) require insulin assays that are costly and not always available. Non-insulin-based indices and refined anthropometric markers may offer simpler risk stratification in prediabetes and diabetes. Our [...] Read more.

Insulin resistance is central in metabolic syndrome, but indices such as Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) require insulin assays that are costly and not always available. Non-insulin-based indices and refined anthropometric markers may offer simpler risk stratification in prediabetes and diabetes. Our objective was to compare insulin and non-insulin-based indices of insulin resistance, together with advanced anthropometric and lipid markers, between prediabetes (PreDM) and type 2 diabetes (T2DM) and across hypertension grades in metabolic syndrome. We conducted a cross-sectional study in 200 adults with metabolic syndrome, 80 with PreDM and 120 with T2DM. Clinical, anthropometric and biochemical parameters were recorded, and HOMA-IR, Homeostasis Model Assessment of Beta-cell function (HOMA%B), Metabolic Score for Insulin Resistance (METS-IR), triglyceride to glucose index (TyG), triglyceride-to-glucose index to high-density lipoprotein cholesterol ratio (TyG/HDL-c) and other derived indices were calculated. Group comparisons, correlations and multiple linear regression were performed. Compared with PreDM, T2DM showed higher glycemic indices and inflammation, but similar body mass index (BMI) and triglycerides. Across glycemic categories and hypertension grades, METS-IR, TyG and TyG/HDL-c increased and correlated strongly with body roundness index (BRI), abdominal volume index (AVI) and weight-adjusted waist index (WWI), while HOMA-IR contributed little independent information. In regression models, lipid adipose product (LAP) and WWI best explained METS-IR in prediabetes, whereas TyG and BRI were the main determinants of METS-IR in diabetes. In metabolic syndrome with PreDM or T2DM, METS-IR and TyG, particularly combined with BRI, AVI and WWI, outperformed traditional lipid ratios and added value beyond HOMA-IR. These composite indices appear useful for insulin resistance assessment when insulin measurement is unavailable or unreliable. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Syndrome: Epidemiology)

23 pages, 3744 KB

Open AccessArticle

Dynamic Gene Network Alterations and Identification of Key Genes in the Spleen During African Swine Fever Virus (ASFV) Infection

by Jae-Beom Go, Vuong Nghia Bui, Duy Tung Dao, Ngoc Anh Bui, Jihye Cha, Hu Suk Lee and Dajeong Lim

Life 2025, 15(12), 1844; https://doi.org/10.3390/life15121844 (registering DOI) - 30 Nov 2025

Abstract

ASFV is responsible for high mortality in domestic pigs and has caused substantial economic impact on the global swine industry due to herd losses, trade restrictions, and disease control measures. We analyzed publicly available spleen RNA-seq data from ASFV-infected pigs (n = [...] Read more.

ASFV is responsible for high mortality in domestic pigs and has caused substantial economic impact on the global swine industry due to herd losses, trade restrictions, and disease control measures. We analyzed publicly available spleen RNA-seq data from ASFV-infected pigs (n = 13 total samples), including 7 pre-infection (0 dpi), 4 samples at 2 days post-infection (2 dpi), and 2 samples at 5 dpi (5 dpi). Weighted gene co-expression network analysis (WGCNA) identified 19 modules; module–trait correlations revealed six modules associated with infection time. A co-expression module enriched for innate immune and antiviral response genes was strongly upregulated at 2 dpi, whereas a module enriched for ribosomal, translation, and metabolic process genes was broadly downregulated at 5 dpi. Protein–protein interaction analysis highlighted hub genes, including EPRS1 and USP7 within core cellular/translation programs and CMPK2 and ZBP1 within innate-immune signaling. Collectively, our results provide a network-level view of dynamic host responses and indicate coordinated shifts in immune and metabolic programs over time. These results identify CMPK2, ZBP1, EPRS1, and USP7 as hypothesis-generating hub gene candidates, warranting further validation to establish mechanistic roles and assess potential translational relevance. Full article

(This article belongs to the Special Issue Vetinformatics-Driven Approaches to Animal Health and Disease)

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21 pages, 3985 KB

Open AccessArticle

Genome-Wide Identification and Abiotic Stress-Responsive Expression Analysis of the SOS1 Gene Family in Gossypium hirsutum L.

by Laraib Iqra, Muhammad Naveed Shahid and Gustavo Caetano-Anollés

Life 2025, 15(12), 1843; https://doi.org/10.3390/life15121843 (registering DOI) - 30 Nov 2025

Abstract

The Salt Overly Sensitive 1 (SOS1) gene family encodes plasma membrane Na⁺/H⁺ antiporters essential for ionic homeostasis and salt tolerance in plants. Here, we performed a comprehensive genome-wide characterization of SOS1 genes in allotetraploid cotton (Gossypium hirsutum [...] Read more.

The Salt Overly Sensitive 1 (SOS1) gene family encodes plasma membrane Na⁺/H⁺ antiporters essential for ionic homeostasis and salt tolerance in plants. Here, we performed a comprehensive genome-wide characterization of SOS1 genes in allotetraploid cotton (Gossypium hirsutum L.). Fifteen GhSOS1 genes were identified and found unevenly distributed across the A and D subgenomes, indicating that segmental duplication, rather than tandem duplication, was the major driver of family expansion. Phylogenetic analysis resolved four well-supported clades, revealing deep conservation with dicot homologs from Arabidopsis thaliana, Solanum species, and Vigna trilobata, alongside cotton-specific diversification. Ka/Ks ratios indicated strong purifying selection with limited adaptive divergence. Conserved Na⁺/H⁺ exchanger domains and membrane-spanning architectures were maintained, whereas motif and promoter variation suggested functional specialization. Structural modeling confirmed typical multi-helical antiporter topology but revealed the absence of a cytoplasmic regulatory domain, implying alternative modes of regulation, possibly via oxidative stress–response components such as RCD1. Promoter analysis uncovered multiple stress- and hormone-responsive cis-elements, and expression profiling identified GhSOS1-5 and GhSOS1-11 as strongly induced by salt and drought stress. Collectively, these findings highlight the evolutionary retention, structural conservation, and regulatory diversification of GhSOS1 genes, establishing a foundation for improving abiotic stress resilience in cotton. Full article

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

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18 pages, 1924 KB

Open AccessSystematic Review

Urinary KIM-1 for Early Detection of Acute Kidney Injury in Neonates: A Systematic Review and Meta-Analysis

by Manapat Praditaukrit, Moragot Chatatikun, Aman Tedasen, Suntornwit Praditaukrit, Sirihatai Konwai, Jason C. Huang, Wiyada Kwanhian Klangbud and Atthaphong Phongphithakchai

Life 2025, 15(12), 1842; https://doi.org/10.3390/life15121842 (registering DOI) - 30 Nov 2025

Abstract

Acute kidney injury (AKI) is a significant clinical concern in neonates, threatening optimal outcomes. Early and accurate diagnosis is crucial; however, current methods lack sufficient sensitivity. This meta-analysis aimed to evaluate urinary kidney injury molecule-1 (uKIM-1) for AKI in neonates by quantifying differences [...] Read more.

Acute kidney injury (AKI) is a significant clinical concern in neonates, threatening optimal outcomes. Early and accurate diagnosis is crucial; however, current methods lack sufficient sensitivity. This meta-analysis aimed to evaluate urinary kidney injury molecule-1 (uKIM-1) for AKI in neonates by quantifying differences in uKIM-1 levels between AKI and non-AKI neonates. We systematically searched major databases for comparative studies. Quality assessment was performed using the Newcastle-Ottawa Scale, and the certainty of the evidence was assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. A random-effects meta-analysis estimated the pooled Hedges’ g in uKIM-1 levels, accounting for heterogeneity. Subgroup analyses explored sources of heterogeneity (continent, study design, sampling time, AKI definition). Publication bias was assessed using Egger’s and Begg’s tests, as well as with a funnel plot. Data from 13 studies involving 552 neonates indicated a significant association between elevated uKIM-1 levels and AKI. High heterogeneity was observed (I² = 80.32%). The pooled Hedges’ g was 0.62 (95% CI: 0.16–1.07, p = 0.01). Subgroup analysis showed stronger associations in African studies (Hedges’ g = 2.12), those using KDIGO (Hedges’ g = 0.96), cohort studies, and sampling within 2–4 days (Hedges’ g = 0.76). No publication bias was detected. This meta-analysis synthesizes evidence on uKIM-1 as an AKI biomarker. While uKIM-1 shows promise, high heterogeneity and diagnostic performance warrant further research to improve AKI detection and management in neonates. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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16 pages, 565 KB

Open AccessArticle

Transvaginal Uterine Fibroid Radiofrequency Ablation (TV-RFA): Retrospective Analysis and Preliminary Report

by Karolina Chmaj-Wierzchowska, Agnieszka Lach, Kinga Bednarek, Adrian Nowak, Adrian Mruczyński, Alan Bruszewski, Piotr Piekarski, Adam Malinger and Maciej Wilczak

Life 2025, 15(12), 1841; https://doi.org/10.3390/life15121841 (registering DOI) - 30 Nov 2025

Abstract

(1) Background: Transvaginal RFA is a minimally invasive treatment for myomas in women opting for uterus preservation. The present study aimed to evaluate the efficacy and safety of transvaginal RFA to treat myomas, reduce symptoms, decrease myoma volume, and identify prognostic factors for [...] Read more.

(1) Background: Transvaginal RFA is a minimally invasive treatment for myomas in women opting for uterus preservation. The present study aimed to evaluate the efficacy and safety of transvaginal RFA to treat myomas, reduce symptoms, decrease myoma volume, and identify prognostic factors for predicting treatment response. (2) Methods: The study group included 45 women treated for uterine fibroids at the Gynecological and Obstetrics Clinical Hospital in Poznań. From 1 July 2024 to 31 March 2025, a total of 45 transvaginal radiofrequency ablation (TV-RFA) procedures were performed. (3) Results: Ultrasound findings revealed that fibroid dimensions and volume significantly decreased at 1-month follow-up compared to those at pre-procedure (88.7 ± 116.3 vs. 64.6 ± 82.6 cm³; p = 0.003). Ultrasound findings demonstrated that fibroid depth (4.8 ± 2.1 vs. 4.1 ± 2.2; p = 0.01) and fibroid volume (88.7 ± 116.3 vs. 82.4 ± 93.9 cm³; p = 0.02) were significantly decreased at 3-month follow-up compared to their pre-procedure values. Menstrual bleeding duration showed significant differences between the pre-procedure state and 1-month follow-up (N = 23; T = 2; Z = 4.14; p < 0.001) and 3-month follow-up (N = 8; T = 1; Z = 2.38; p = 0.017), with a significant reduction after the RFA procedure. Significant differences were observed in bleeding severity at pre-procedure and at 1-month follow-up (N = 22; T = 11.5; Z = 3.73; p < 0.001); however, no significant differences in bleeding severity were noted at the 3-month follow-up (N = 7; T = 4; Z = 1.69; p = 0.09). These results should be interpreted cautiously due to the small number of patients with complete 3-month follow-up. (4) Conclusions: Transvaginal radiofrequency ablation is an effective, precise, and safe minimally invasive approach for treating uterine fibroids. These preliminary findings are promising but require confirmation in larger cohorts with longer follow-up. Full article

(This article belongs to the Special Issue Advanced Research in Obstetrics and Gynecology)

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16 pages, 786 KB

Open AccessArticle

Electromyographic Patterns of Scapular Muscles During Four Variations of Protraction–Retraction Exercises

by Eui-Young Jung, Su-Yeon Roh and Woo-Lim Mun

Life 2025, 15(12), 1840; https://doi.org/10.3390/life15121840 (registering DOI) - 29 Nov 2025

Abstract

(1) Background: How variations of the push-up plus (PUP)—particularly changes in the base of support and scapular excursion—affect scapular muscle activation remains unclear. This study compared phase-specific electromyographic (EMG) activity of scapular muscles during four protraction–retraction exercises. (2) Methods: Twenty-six healthy male participants [...] Read more.

(1) Background: How variations of the push-up plus (PUP)—particularly changes in the base of support and scapular excursion—affect scapular muscle activation remains unclear. This study compared phase-specific electromyographic (EMG) activity of scapular muscles during four protraction–retraction exercises. (2) Methods: Twenty-six healthy male participants (age: 22.88 ± 1.45 years; height: 1.74 ± 0.05 m; weight: 77.31 ± 8.61 kg; body mass index (BMI): 25.61 ± 2.43 kg/m²) with Pilates experience performed four scapular protraction–retraction exercises under two base-of-support (quadruped vs. single-leg) and two movement-range (PUP vs. STD) conditions. Exercise order was randomized, and sufficient rest intervals were provided to minimize fatigue effects. Surface electromyography was recorded from six scapular muscles and normalized to maximal voluntary isometric contraction. The study was registered on CRIS (KCT0010032). (3) Results: Single-leg PUP showed the greatest serratus anterior (SA) activation, with increases of approximately 30% in protraction, 20–25% in isometric, and 15–20% in retraction. STD variations elicited higher trapezius activation, especially during large scapular excursions. The UT/SA ratio was significantly lower in PUP conditions (η²p = 0.544), reflecting a more favorable stabilization pattern. (4) Conclusions: This experimental repeated-measures study demonstrates that combining single-leg support with traditional PUP meaningfully increases SA recruitment across all phases, whereas increased scapular range enhances trapezius engagement. These findings provide novel phase-specific insights into how PUP variations modulate closed-chain scapular stabilization and may assist clinicians in selecting targeted exercises. Interpretation should be limited to trained healthy males. Full article

(This article belongs to the Special Issue Effects of Exercise Training on Muscle Function—2nd Edition)

12 pages, 910 KB

Open AccessArticle

Triple-Tracer Sentinel Node Mapping: Maximizing Detection, Minimizing Dissection

by Daniel Alin Cristian, Bogdan Popescu, Cristian Valentin Toma, Sertaç Ata Güler, Adrian Bordea, Emil Popa, Draga-Maria Mandi, Bianca Maria Floarea and Răzvan-Valentin Scăunaşu

Life 2025, 15(12), 1839; https://doi.org/10.3390/life15121839 (registering DOI) - 29 Nov 2025

Abstract

Background: Background: Sentinel lymph node (SLN) biopsy often combines technetium-99m (99mTc), indocyanine green (ICG), and methylene blue (MB), but few contemporary audits quantify the performance of each tracer when used together in routine practice. Methods: We conducted a single-center retrospective audit of 111 [...] Read more.

Background: Background: Sentinel lymph node (SLN) biopsy often combines technetium-99m (99mTc), indocyanine green (ICG), and methylene blue (MB), but few contemporary audits quantify the performance of each tracer when used together in routine practice. Methods: We conducted a single-center retrospective audit of 111 consecutive SLN procedures for breast cancer patients undergoing SLNB using a triple-tracer approach with technetium-99m (99mTc), indocyanine green (ICG), and methylene blue (MB). We evaluated sentinel lymph node detection rates, the number of nodes retrieved, tracer concordance, and subgroup performance (including those with mastectomy and post-neoadjuvant therapy). Results: Identification was 96.4% for 99mTc (107/111), 93.7% for ICG (104/111), and 78.4% for MB (87/111). Performance was heterogeneous (Q = 26.2, p < 0.001); 99mTc and ICG each outperformed MB (Holm-adjusted p < 0.001), while 99mTc and ICG did not differ significantly. Triple-tracer workflows were associated with higher odds of detection; cross-validated AUCs reached 0.98 for 99mTc and 0.82 for ICG. Conclusions: Technetium remains a foundational tracer for SLNB, with ICG serving as a valuable adjunct that enhances nodal visualization and overall detection efficacy, and MB adds redundancy. Triple-tracer mapping achieved the best overall nodal identification and was associated with fewer sentinel nodes excised when complete tracer concordance was observed. Full article

(This article belongs to the Special Issue Advances in the Epidemiology, Physiology, Diagnosis and Treatment of Breast Cancer)

27 pages, 649 KB

Open AccessReview

Pulmonary Manifestations of Inborn Errors of Immunity: Diagnostic and Therapeutic Insights

by Katarzyna Napiorkowska-Baran, Szczepan Cofta, Paweł Treichel, Marta Tykwinska, Kinga Lis, Aleksandra Matyja-Bednarczyk, Bartłomiej Szymczak, Maciej Szota, Jozef Slawatycki, Michal Kulakowski and Zbigniew Bartuzi

Life 2025, 15(12), 1838; https://doi.org/10.3390/life15121838 (registering DOI) - 29 Nov 2025

Abstract

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetically determined disorders that lead to immune dysfunction, recurrent infections, and organ-specific complications. The lungs are among the most commonly affected organs, with both infectious and noninfectious manifestations that significantly contribute to [...] Read more.

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetically determined disorders that lead to immune dysfunction, recurrent infections, and organ-specific complications. The lungs are among the most commonly affected organs, with both infectious and noninfectious manifestations that significantly contribute to morbidity and mortality. This study aimed to provide a comprehensive overview of pulmonary manifestations in IEI, with emphasis on pathophysiological mechanisms, diagnostic approaches, and therapeutic strategies. Methods: A narrative review and synthesis of current literature and clinical guidelines were conducted, focusing on pulmonary involvement in IEI as classified by the International Union of Immunological Societies (IUIS). The analysis included data on infectious and noninfectious complications, imaging findings, immunological assessments, and management strategies, supported by clinical evidence and expert consensus. Results: Pulmonary manifestations in IEI encompass a wide spectrum of conditions. Infectious complications include recurrent bacterial pneumonias, bronchitis, and opportunistic infections, frequently resulting in irreversible lung damage such as bronchiectasis. Noninfectious complications, including granulomatous–lymphocytic interstitial lung disease (GLILD) and interstitial lung disease (ILD), are common in disorders such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). Early diagnosis using high-resolution computed tomography (HRCT) and immunological testing, combined with the timely initiation of immunoglobulin replacement therapy and anti-biotic prophylaxis, significantly improves prognosis. Conclusions: Pulmonary complications are key clinical indicators of IEI and often precede systemic manifestations. Early, integrated, and interdisciplinary diagnostic and therapeutic management are crucial for preventing irreversible lung damage and improving patient outcomes. Regular monitoring and individualized therapy, including immunoglobulin replacement, targeted immunosuppression, and vaccination, are the cornerstones of effective long-term care in IEI. Full article

(This article belongs to the Special Issue Treatment and Prognosis of Thoracic Diseases)

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13 pages, 1209 KB

Open AccessSystematic Review

Ocular Surface Parameters in Glaucoma Patients Treated with Topical Prostaglandin Analogs and the Importance of Switching to Preservative-Free Eye Drops—A Systematic Review

by Jaromir Wasyluk, Grzegorz Rotuski, Marta Dubisz and Radosław Różycki

Life 2025, 15(12), 1837; https://doi.org/10.3390/life15121837 (registering DOI) - 29 Nov 2025

Abstract

Background: The use of preservative agents in eye drop solutions may worsen symptoms of ocular surface disease, which is a highly prevalent syndrome worldwide. Preservatives are often used in pharmacotherapy of glaucoma, another disease concerning tens of millions of people around the globe. [...] Read more.

Background: The use of preservative agents in eye drop solutions may worsen symptoms of ocular surface disease, which is a highly prevalent syndrome worldwide. Preservatives are often used in pharmacotherapy of glaucoma, another disease concerning tens of millions of people around the globe. These numbers are predicted by the World Health Organization and are predicted to increase with time due to constant aging of populations. Methods: PubMed and Scopus databases were searched for articles investigating the topic of ocular surface disease in relation with glaucoma pharmacotherapy, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The aim of this review is to summarize the effect of various solvents used in drug formulations and ways to quantify their impact on the ocular surface. Discussion and Conclusions: Topical ophthalmic preservative-free formulations are better tolerated and less burdensome for all patients. They should be considered especially for glaucoma patients, who are expected to take medications for years, up to decades or a lifetime in many cases. Due to the chronicity of dry eye disease and the lack of reliable ways for lacrimal and meibomian gland renewal, primary prophylaxis is of uttermost importance. Unfortunately, despite the development of many measuring devices, the standardization of diagnostic methods poses a challenge due to high variability of results which are influenced by a myriad of factors—local, internal, and external. Full article

(This article belongs to the Special Issue New Diagnostic and Therapeutic Developments in Eye and Systemic Diseases)

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18 pages, 534 KB

Open AccessArticle

Dopaminergic Genetic Variation and Trait Impulsivity: The Role of COMT rs4680 in Mixed Behavioral and Substance Addictions

by Gabriela Zdunek, Remigiusz Recław, Aleksandra Suchanecka, Krzysztof Chmielowiec, Dariusz Larysz, Marta Kuczak-Wójtowicz, Kinga Łosińska, Jolanta Chmielowiec and Anna Grzywacz

Life 2025, 15(12), 1836; https://doi.org/10.3390/life15121836 (registering DOI) - 29 Nov 2025

Abstract

Background: Impulsivity is a multidimensional trait associated with the development and maintenance of behavioral and substance addictions. Genetic polymorphisms, particularly within the dopaminergic system, are thought to modulate individual differences in impulsivity. The COMT rs4680 (Val158Met) polymorphism influences enzymatic activity of catechol-O-methyltransferase [...] Read more.

Background: Impulsivity is a multidimensional trait associated with the development and maintenance of behavioral and substance addictions. Genetic polymorphisms, particularly within the dopaminergic system, are thought to modulate individual differences in impulsivity. The COMT rs4680 (Val158Met) polymorphism influences enzymatic activity of catechol-O-methyltransferase and may alter dopaminergic tone in the prefrontal cortex. This study investigated whether COMT rs4680 genotype interacts with addiction status (behavioral and substance addictions) to influence trait impulsivity. Methods: The study included 309 Polish men: 128 with mixed behavioral and substance addictions and 181 healthy controls. All participants completed the Barratt Impulsiveness Scale (BIS-11) and were genotyped for COMT rs4680. A two-way ANOVA was used to assess main and interaction effects of genotype and group on total and subscale BIS-11 scores. Results: Individuals with mixed addictions scored significantly higher on all BIS-11 subscales (p < 0.01). A significant interaction effect was observed for the Non-Planning (F_2,303 = 4.40, p = 0.0131, η² = 0.028) and Total BIS-11 scale (F_2,303 = 5.77, p = 0.0035, η² = 0.037), with the A/A genotype associated with increased impulsivity, especially among the clinical group. Conclusions: These findings support a gene-by-environment interaction in impulsivity, where COMT rs4680 Met/Met homozygotes may be more susceptible to heightened impulsivity in addiction contexts. The results highlight the potential utility of COMT genotyping in personalizing therapeutic strategies for impulse-related disorders such as addictive disorders. This study extends evidence on dopaminergic modulation of impulsivity to behavioral and substance addictions. Full article

(This article belongs to the Section Genetics and Genomics)

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6 pages, 2523 KB

Open AccessCase Report

First-in-Human Application of Very High-Power Short-Duration RF Ablation for Refractory AVNRT: A Case Report

by Milos Babic, Milosav Tomovic, Dejan Vukajlovic, Vasko Zugic, Aleksandra Grbovic, Masa Petrovic, Milovan Bojic and Aleksandra Nikolic

Life 2025, 15(12), 1834; https://doi.org/10.3390/life15121834 (registering DOI) - 29 Nov 2025

Abstract

Background: Refractory atrioventricular nodal reentrant tachycardia (AVNRT) is a rare condition, but poses a clinical challenge after failed standard ablation. Very high-power, short-duration (vHPSD) radiofrequency (RF) ablation has not yet been explored in slow pathway ablation/modification. Case Summary: A 61-year-old woman with recurrent [...] Read more.

Background: Refractory atrioventricular nodal reentrant tachycardia (AVNRT) is a rare condition, but poses a clinical challenge after failed standard ablation. Very high-power, short-duration (vHPSD) radiofrequency (RF) ablation has not yet been explored in slow pathway ablation/modification. Case Summary: A 61-year-old woman with recurrent AVNRT despite two prior ablations and multiple antiarrhythmics underwent successful slow pathway ablation using a 90-watt, 4-s vHPSD protocol. CARTO-guided mapping localized the presumed slow pathway, followed by several 90 W applications. Transient second-degree AV block (Wenckebach type) occurred and resolved spontaneously. The patient remained arrhythmia-free at 6-month follow-up. Conclusions: This is the first reported clinical use of 90 W/4 s RF energy for AVNRT. The vHPSD approach may offer an effective alternative for patients with refractory AVNRT. Full article

(This article belongs to the Section Medical Research)

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15 pages, 3651 KB

Open AccessArticle

Distinct Profiles of Patient-Reported Outcomes Across Allergen Signatures in Chronic Rhinosinusitis

by Dachan Kim, Chan Min Jung, Hyung-Ju Cho, Chang-Hoon Kim and Min-Seok Rha

Life 2025, 15(12), 1835; https://doi.org/10.3390/life15121835 (registering DOI) - 28 Nov 2025

Abstract

Background: Chronic rhinosinusitis (CRS) exhibits marked symptom heterogeneity that is not fully explained by anatomy or endotypes. Although allergen types shape symptom patterns in allergic rhinitis, largescale systematic analyses linking allergen sensitization profiles to patient-reported outcome measures in patients with CRS are [...] Read more.

Background: Chronic rhinosinusitis (CRS) exhibits marked symptom heterogeneity that is not fully explained by anatomy or endotypes. Although allergen types shape symptom patterns in allergic rhinitis, largescale systematic analyses linking allergen sensitization profiles to patient-reported outcome measures in patients with CRS are limited. Methods: We conducted a multicenter, retrospective surgical cohort study (n = 1880) including patients with CRS who underwent preoperative specific IgE testing for 35 inhalant allergens and completed the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire within 1 year. Using a previously validated nonnegative matrix factorization model, we deconvolved each patient’s IgE profile into four allergen signatures (Mite, Grass/Weed, Pet, and Tree) and defined a dominant group. Associations between signature contributions and SNOT-22 items, domain subscores, and total score were estimated by ordinary least squares, adjusting for age, sex, nasal polyps, and asthma, with coefficients scaled per 10-percentage-point increase. Item-level multiplicity was controlled for using the false discovery rate. Seasonality was assessed using monthly means and the coefficient of variation of the dominant group. Results: Dominant groups were nonallergic (50%), mite (26%), grass/weed (9%), pet (9%), and tree (5%). Symptoms varied by age and sex, characterized by notably low nasal scores with aging and a high female burden for several items, motivating covariate adjustment. Signature–symptom associations were domain-specific: the pet signature showed the strongest and most consistent associations with nasal domain (such as rhinorrhea and nasal obstruction) and emotion domain (feelings of embarrassment); mite and grass/weed signatures were linked to the function domain (daytime fatigue/productivity); whereas the tree signature showed no significant associations. Seasonal patterns aligned with exposure ecology: grass/weed and tree groups had the largest relative variation (high coefficient of variations), the pet group showed the highest absolute burden year-round, and the mite group varied modestly with winter–spring predominance. Conclusions: Allergen signatures distilled from routine IgE panels explained meaningful variations in CRS patient-reported outcome measures, mapping to distinct symptom domains and seasonal profiles. Incorporating signature information into clinical assessments may support personalized counseling, anticipatory management around exposure windows, and targeted evaluation of environmental or immunologic interventions. Full article

(This article belongs to the Special Issue Cutting-Edge Research in Rhinology and Allergy: Unraveling Disease Mechanisms and Treatment Innovations)

16 pages, 576 KB

Open AccessReview

Complete Pathological Response to Neoadjuvant Treatment in Pancreatic Ductal Adenocarcinoma—Can We Achieve a Long-Term Survival? A Narrative Review

by Magdalena Gajda, Ewa Grudzińska, Łukasz Liszka, Joanna Pilch-Kowalczyk and Sławomir Mrowiec

Life 2025, 15(12), 1833; https://doi.org/10.3390/life15121833 (registering DOI) - 28 Nov 2025

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality in Europe, with a 5-year survival rate of approximately 10%. Surgical intervention is the only curative method of treatment in PDAC. However, especially in the case of patients with borderline [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality in Europe, with a 5-year survival rate of approximately 10%. Surgical intervention is the only curative method of treatment in PDAC. However, especially in the case of patients with borderline or locally advanced cancer, neoadjuvant treatment is often administered in an attempt to downstage the tumor. Uncommonly, after neoadjuvant treatment, no viable tumor in the specimen after surgical resection is found- this is defined as a complete pathological response (pCR). Our paper presents a narrative review of this rare phenomenon and its possible association with patient’s survival. Conclusions: Achieving pCR may be associated with a significant improvement in the prognosis of patients with PDAC. However, it remains unknown why pCR is achievable in only a few patients. Further studies on large groups of patients are needed to identify the factors that increase the chance of pCR. Full article

(This article belongs to the Special Issue Pancreatic Cancer: Long Survivals)

17 pages, 1212 KB

Open AccessArticle

Association Between the Serum Creatinine to Cystatin C Ratio, Physical Activity, and Frailty in Middle-Aged and Older Adults in China: A Nationwide Cohort Study

by Kai Song, Chuanwen Yu and Yanwei You

Life 2025, 15(12), 1832; https://doi.org/10.3390/life15121832 (registering DOI) - 28 Nov 2025

Abstract

Background: Frailty is a major barrier to healthy ageing, yet early identification strategies remain limited. The serum creatinine-to-cystatin C ratio (sarcopenia index, SI) has emerged as a cost-effective biomarker of muscle mass and function, while physical activity (PA) is a key protective factor. [...] Read more.

Background: Frailty is a major barrier to healthy ageing, yet early identification strategies remain limited. The serum creatinine-to-cystatin C ratio (sarcopenia index, SI) has emerged as a cost-effective biomarker of muscle mass and function, while physical activity (PA) is a key protective factor. However, their combined role in predicting frailty is unclear. This study aimed to investigate the independent and joint associations of SI and PA with incident frailty in middle-aged and older adults. Methods: We analyzed 5307 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018). SI was calculated from serum creatinine and cystatin C levels, and PA was assessed using standardized questionnaires. Frailty was defined using a 32-item Frailty Index (FI ≥ 0.25). Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SI and PA with incident frailty, adjusting for sociodemographic and health-related factors. Effect modification by PA was formally tested. Results: Over the follow-up period, 1483 participants developed frailty (27.9%). Higher SI was inversely associated with frailty in a dose–response manner: compared with the lowest quartile, HRs (95% CIs) were 0.84 (0.73–0.97) for Q2, 0.83 (0.72–0.96) for Q3, and 0.69 (0.59–0.82) for Q4 (p-trend < 0.001). Each 10-unit increase in SI corresponded to a 6% lower frailty risk (HR = 0.94, 95% CI: 0.91–0.97). PA significantly modified this relationship (interaction p < 0.05), with the strongest protective effect of SI observed among individuals with low PA, and attenuation at higher PA levels. Conclusions: SI is independently associated with a lower risk of incident frailty, particularly among less physically active individuals. These findings support the potential use of SI as a feasible biomarker for early frailty risk stratification and highlight the importance of integrating biomarker-based screening with lifestyle interventions to prevent frailty. Full article

(This article belongs to the Topic Exercise and Human Aging: Physiological and Psychological Functions)

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36 pages, 1579 KB

Open AccessReview

Molecular Regulation of Growth in Aquaculture: From Genes to Sustainable Production

by Dana Andreea Șerban, Cristian-Alin Barbacariu, Mihaela Ivancia and Șteofil Creangă

Life 2025, 15(12), 1831; https://doi.org/10.3390/life15121831 (registering DOI) - 28 Nov 2025

Abstract

The global aquaculture industry produces 91 million tons annually, yet achieving sustainable growth optimization remains constrained by incomplete understanding of regulatory system integration, polyploid genomic complexity, and disconnected molecular-environmental approaches. This systematic review synthesizes 180 peer-reviewed articles (1992–2025) from four databases, revealing that [...] Read more.

The global aquaculture industry produces 91 million tons annually, yet achieving sustainable growth optimization remains constrained by incomplete understanding of regulatory system integration, polyploid genomic complexity, and disconnected molecular-environmental approaches. This systematic review synthesizes 180 peer-reviewed articles (1992–2025) from four databases, revealing that growth regulation operates through integrated multi-level networks: the GH-IGF axis, TGF-β/myostatin signaling, and epigenetic mechanisms responding dynamically to environmental inputs. Research acceleration is evident, with 52.2% of studies published during 2020–2025. Whole-genome duplication events created expanded gene repertoires enabling sophisticated regulatory control while presenting breeding challenges in polyploid species. CRISPR-Cas9 myostatin knockout achieves 15–30% growth enhancement, though practical implementation faces regulatory and economic barriers. DNA methylation and microRNAs enable environmental adaptation and transgenerational trait inheritance, offering complementary approaches to conventional breeding. Climate-resilient strain development requires integrating polyploid breeding methodologies, multi-omics phenotyping platforms, and validated epigenetic markers. Sustainable aquaculture intensification through precision genetics demands coordinated infrastructure development, harmonized regulatory frameworks, and international collaboration to address food security while adapting to climate change. This synthesis establishes research priorities bridging molecular mechanisms with practical applications for sustainable production enhancement. Full article

(This article belongs to the Section Genetics and Genomics)

12 pages, 283 KB

Open AccessArticle

Reliability of Vertical Jump Force-Time Metrics in Collegiate Athletes Compared to Recreationally Active Individuals

by Dimitrije Cabarkapa, Robert Smith, Luke Chowning, Tyler Neltner, Quincy R. Johnson, Yang Yang and Thayne A. Munce

Life 2025, 15(12), 1830; https://doi.org/10.3390/life15121830 (registering DOI) - 28 Nov 2025

Abstract

As neuromuscular performance assessment has become a fundamental component of athlete monitoring, ensuring strong measurement reliability is essential for supporting accurate data-driven decision-making. Thus, the purpose of this study was twofold: (i) to examine the reliability of countermovement vertical jump (CMJ) force-time metrics [...] Read more.

As neuromuscular performance assessment has become a fundamental component of athlete monitoring, ensuring strong measurement reliability is essential for supporting accurate data-driven decision-making. Thus, the purpose of this study was twofold: (i) to examine the reliability of countermovement vertical jump (CMJ) force-time metrics obtained using a portable force plate system (Hawkin Dynamics) and (ii) to determine whether absolute and relative reliability scores differ between well-trained individuals (i.e., athletes) and those less familiar with CMJ force-plate testing (i.e., non-athletes). Seventy-four participants volunteered to take part in this investigation, of whom thirty-nine were NCAA Division-I baseball and track-and-field athletes and thirty-five age-matched non-athletes with no prior CMJ testing experience on force plates. After performing a standardized dynamic warm-up, participants performed three CMJs without arm swing while standing on a dual uniaxial force plate system sampling at 1000 Hz. Each jump trial was separated by a 30 s rest interval. Absolute and relative reliability were assessed using the coefficient of variation (CV) and intraclass correlation coefficient (ICC), respectively. The results revealed that 75% of the variables demonstrated excellent reliability. Specifically, absolute (CV < 10%) and relative (ICC > 0.750) reliability values were good to excellent for most force-time metrics of interest, including braking and propulsive phase duration, peak braking force, average propulsive power, reactive strength index-modified, countermovement depth, and jump height. In contrast, average and peak landing force and inter-limb asymmetry measures during the braking and propulsive phases displayed moderate to good reliability, whereas asymmetry-related variables during the landing phase exhibited poor reliability. In addition, athletes demonstrated lower CV and greater ICC across most metrics compared to non-athletes. Full article

(This article belongs to the Special Issue Musculoskeletal Function and Exercise Physiology: Integrative Approaches and Emerging Insights)

18 pages, 1603 KB

Open AccessArticle

Biofabrication of Terminalia ferdinandiana-Conjugated Gold Nanoparticles and Their Anticancer Properties

by Weerakkodige Hansi Sachintha Alwis, Vinuthaa Murthy, Hao Wang, Roshanak Khandanlou and Richard Weir

Life 2025, 15(12), 1829; https://doi.org/10.3390/life15121829 (registering DOI) - 28 Nov 2025

Abstract

Harnessing nature’s chemistry, this study explores the enhanced biomedical potential of Terminalia ferdinandiana Exell (Kakadu Plum) by transforming its aqueous leaf and fruit extracts into bio-inspired gold nanoparticles (AuNPs). The synthesis process was optimized by varying the Au³⁺/extract ratio and pH, [...] Read more.

Harnessing nature’s chemistry, this study explores the enhanced biomedical potential of Terminalia ferdinandiana Exell (Kakadu Plum) by transforming its aqueous leaf and fruit extracts into bio-inspired gold nanoparticles (AuNPs). The synthesis process was optimized by varying the Au³⁺/extract ratio and pH, with nanoparticle formation verified through UV–visible spectrophotometry, TEM, and DLS analyzes. Kakadu Leaf extract–conjugated AuNPs (AuKLs), synthesized at pH 8 with a 1:25 Au³⁺/extract ratio, produced the smallest and most uniform particles (21.1 nm; PDI 0.17). In contrast, fruit extract alone failed to generate stable nanoparticles, highlighting the pivotal role of leaf phytochemicals as natural reducing and stabilizing agents. Biological evaluations revealed that both the crude leaf extract and AuKLs possessed strong antioxidant capacity, while the AuKLs further exhibited selective anticancer activity effectively inhibiting breast cancer (MCF-7) and human cervical carcinoma (HeLa) cell proliferation without harming normal mammalian breast (MCF10A) cells. A combined 2:1 leaf-to-fruit extract formulation yielded well-stabilized AuNPs (AuKPLs) with biomedical properties comparable to AuKLs, though the fruit extract alone contributed minimally to both nanoparticle formation and biological performance. Overall, this study demonstrates that the phytochemical richness of T. ferdinandiana leaves enables the green synthesis of small, stable, and bioactive gold nanoparticles. The resulting nanoconjugates, AuKLs and AuKPLs, hold considerable promise for future pharmacological and therapeutic applications, bridging traditional plant-based medicine with modern nanotechnology. Full article

(This article belongs to the Special Issue Emerging Applications of Nanobiotechnology in Medicine and Health)

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23 pages, 4991 KB

Open AccessArticle

Computational Investigation Identifies mTOR as a Primary Binding Target of Medicarpin in Cholangiocarcinoma: Insights from Network Pharmacology and Molecular Docking

by Sirinya Sitthirak, Aman Tedasen, Yanisa Rattanapan, Thitinat Duangchan, Hasaya Dokduang, Nawanwat C. Pattaranggoon, Krittamate Saisuwan, Watcharin Loilome and Nisana Namwat

Life 2025, 15(12), 1828; https://doi.org/10.3390/life15121828 - 28 Nov 2025

Abstract

Background: Cholangiocarcinoma (CCA) is an aggressive cancer of biliary tract with poor prognosis and limited therapeutic alternatives. While targeted medicines only benefit a small subset of patients with specific genetic modifications, conventional chemotherapy offers negligible survival advantages. There is an urgent need for [...] Read more.

Background: Cholangiocarcinoma (CCA) is an aggressive cancer of biliary tract with poor prognosis and limited therapeutic alternatives. While targeted medicines only benefit a small subset of patients with specific genetic modifications, conventional chemotherapy offers negligible survival advantages. There is an urgent need for novel medicines with multi-target action to combat the diverse and treatment-resistant characteristics of CCA. Methods: An integrative computational strategy combining drug-likeness evaluation, target prediction, network pharmacology, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses, and molecular docking was employed to elucidate the pharmacological profile of medicarpin, a natural pterocarpan derived from Dalbergia species. Overlapping targets between medicarpin and CCA-related genes were analysed to construct a protein–protein interaction (PPI) network and identify hub genes. Results: Forty-four overlapping targets were identified, with mTOR, SRC, PIK3CA, and CCND1 emerging as central nodes within the network. Enrichment analyses revealed significant involvement in carcinogenic pathways, including PI3K–Akt/mTOR, ErbB signalling, apoptosis regulation, and drug resistance. Molecular docking demonstrated a stable binding of medicarpin within the catalytic pocket of mTOR (binding energy −9.6 kcal/mol), supported by multiple hydrogen bonds and hydrophobic interactions with key residues essential for kinase activation. Conclusions: This study provides systems-level evidence that medicarpin exerts polypharmacological activity against CCA, with mTOR indicated as a possible mechanistic hub. These findings highlight medicarpin’s potential as a promising multi-target therapeutic candidate and underscore the value of natural compounds in expanding treatment strategies for cholangiocarcinoma. Full article

(This article belongs to the Section Pharmaceutical Science)

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