Life

9 pages, 971 KB

Open AccessCase Report

EndoVAC Therapy for Post-TEVAR Secondary Esophageal Fistula: A Rare Case of Delayed Secondary Esophageal Fistula After TEVAR Managed with Endoluminal Vacuum Therapy

by Bogdan-Mihnea Ciuntu, Andreea Ludușanu, Adelina Tanevscki, Rareș Ștefan Costârnache, Mihaela Corlade-Andrei, Petru Radu Soroceanu, Dan Vintilă, Irina Mihaela Abdulan, Mihai-Lucian Zabara and Gheorghe Balan

Life 2026, 16(3), 460; https://doi.org/10.3390/life16030460 - 11 Mar 2026

Abstract

Background: Aorto-esophageal fistula is a rare but life-threatening condition most often linked to thoracic aortic aneurysms and significant upper gastrointestinal bleeding. Thoracic endovascular aortic repair (TEVAR) is a crucial, life-saving procedure, but delayed complications, such as secondary esophageal fistulas caused by endograft erosion, [...] Read more.

Background: Aorto-esophageal fistula is a rare but life-threatening condition most often linked to thoracic aortic aneurysms and significant upper gastrointestinal bleeding. Thoracic endovascular aortic repair (TEVAR) is a crucial, life-saving procedure, but delayed complications, such as secondary esophageal fistulas caused by endograft erosion, can develop. Prompt recognition and multidisciplinary management are vital for survival. Case Presentation: We describe a 57-year-old patient with cardiovascular comorbidities and a saccular thoracic aortic aneurysm, who initially presented with massive hematemesis, melena, and hemodynamic instability. Imaging showed an aorto-esophageal fistula. Emergency treatment included placing a fully covered esophageal stent followed by TEVAR. Three weeks later, he experienced fever, chest pain, and worsening dysphagia. Laboratory tests indicated elevated inflammatory markers and hypoalbuminemia. Computed tomography revealed a new retrocardial esophageal fistula at T9, caused by mechanical erosion from the thoracic endograft. Endoluminal vacuum-assisted closure (EndoVAC) therapy was performed, leading to clinical improvement and the return of esophageal function. Conclusions: This case highlights a rare instance of a delayed secondary esophageal fistula after TEVAR beneath a preexisting stent, likely due to chronic contact between the endograft and esophagus. Despite advancements in endoscopic therapy, secondary fistulas after TEVAR are associated with high morbidity. Early diagnosis, aggressive infection management, structured nutritional support, and a multidisciplinary approach are essential. Extraluminal or intraluminal vacuum-assisted closure offers a promising minimally invasive option for managing complex esophageal defects. Full article

(This article belongs to the Special Issue Organ Predilection of Certain Gastrointestinal Diseases—Pathophysiology, Diagnosis and Management)

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19 pages, 1106 KB

Open AccessArticle

Clinical Prediction of Functional Decline in Multiple Sclerosis Using Volumetry-Based Synthetic Brain Networks

by Alin Ciubotaru, Alexandra Maștaleru, Thomas Gabriel Schreiner, Cristiana Filip, Roxana Covali, Laura Riscanu, Robert-Valentin Bilcu, Laura-Elena Cucu, Sofia Alexandra Socolov-Mihaita, Diana Lăcătușu, Florina Crivoi, Albert Vamanu, Ioana Martu, Lucia Corina Dima-Cozma, Romica Sebastian Cozma and Oana-Roxana Bitere-Popa

Life 2026, 16(3), 459; https://doi.org/10.3390/life16030459 - 11 Mar 2026

Abstract

Background: Disability progression in multiple sclerosis (MS) is increasingly recognized as a consequence of large-scale brain network disruption rather than isolated regional damage. Although diffusion tensor imaging (DTI) is the reference method for assessing structural connectivity, its limited availability restricts widespread clinical application. [...] Read more.

Background: Disability progression in multiple sclerosis (MS) is increasingly recognized as a consequence of large-scale brain network disruption rather than isolated regional damage. Although diffusion tensor imaging (DTI) is the reference method for assessing structural connectivity, its limited availability restricts widespread clinical application. There is therefore a critical need for alternative approaches capable of capturing network-level alterations using routinely acquired MRI data. Objective: This study aimed to determine whether synthetic structural connectivity matrices derived from standard regional volumetric MRI can capture clinically meaningful network alterations in MS and predict subsequent functional progression, particularly upper limb decline. Methods: Regional brain volumetry was obtained from routine T1-weighted MRI using an automated, clinically approved volumetric pipeline. Synthetic structural connectivity matrices were generated by integrating principles of structural covariance, distance-dependent connectivity, and disease-specific vulnerability patterns. Graph-theoretical network metrics were extracted to characterize global and regional topology. Machine learning models including logistic regression, support vector machines, random forests, and gradient boosting were trained to predict clinical progression defined by worsening on the 9-Hole Peg Test. Dimensionality reduction was performed using principal component analysis, and model performance was evaluated using balanced accuracy, AUC-ROC, and resampling-based validation. Feature importance analyses were conducted to identify network vulnerability patterns. Results: Synthetic connectivity networks exhibited biologically plausible properties, including preserved but attenuated small-world organization. Global efficiency showed a strong inverse correlation with disability severity (EDSS). Patients with clinical progression demonstrated marked reductions in network integration and segregation, alongside increased characteristic path length. Machine learning models achieved robust prediction of upper limb functional decline, with ensemble-based methods performing best (balanced accuracy > 80%, AUC-ROC up to 0.85). A limited subset of connections accounted for a disproportionate share of predictive power, predominantly involving frontoparietal associative networks, thalamocortical pathways, and inter-hemispheric connections. In a longitudinal subset, network-level alterations preceded measurable clinical deterioration by several months. Conclusions: Synthetic structural connectivity derived from routine volumetric MRI captures clinically relevant network-level disruption in multiple sclerosis and enables accurate prediction of functional progression. By bridging network neuroscience with widely accessible imaging data, this framework provides a pragmatic alternative for connectomic analysis when diffusion imaging is unavailable and supports a network-based understanding of disease evolution in MS. Full article

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

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19 pages, 2817 KB

Open AccessArticle

Short-Term Fascial Circulation Exercise Modulates Task-Related Prefrontal Oxygenation During Executive Tasks in Older Women: An fNIRS Pilot Study

by Suyoung Hwang, Yae-Hyun Leem, Moon Hee Kim and Eun-Surk Yi

Life 2026, 16(3), 458; https://doi.org/10.3390/life16030458 - 11 Mar 2026

Abstract

Background: Evidence linking fascia-oriented rhythmic movement to executive function and prefrontal hemodynamics in older adults remains limited. This pilot study examined the feasibility and preliminary within-subject associations of a four-week Fascial Circulation Exercise (FCE) program in older Korean women. Methods: Twelve [...] Read more.

Background: Evidence linking fascia-oriented rhythmic movement to executive function and prefrontal hemodynamics in older adults remains limited. This pilot study examined the feasibility and preliminary within-subject associations of a four-week Fascial Circulation Exercise (FCE) program in older Korean women. Methods: Twelve cognitively screened women (74.3 ± 6.7 years) completed supervised FCE for four weeks. Pre–post assessments included body composition, grip strength, isokinetic knee performance, executive tasks (TMT-A/B, CDT), and task-evoked prefrontal activation measured via functional near-infrared spectroscopy (ΔHbO). Paired t-tests with effect sizes were reported. Results: Fat mass decreased (−0.71 kg, p = 0.016; dz = −0.74), whereas body weight and BMI were unchanged. Selective improvements were observed in knee flexor peak torque and extensor endurance (p < 0.05), with no change in grip strength. ΔHbO increased in the orbitofrontal, ventrolateral, and frontopolar regions during executive tasks. Behavioral performance improved in CDT and showed a trend toward improvement in TMT-B. Conclusions: Short-term FCE was feasible and was associated with reduced fat mass, selective neuromuscular gains, and increased task-evoked prefrontal oxygenation. The findings are exploratory and support future randomized controlled trials to determine clinical efficacy. Full article

(This article belongs to the Special Issue Advanced Research in Exercise Medicine)

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22 pages, 540 KB

Open AccessPerspective

Modulating Vimentin: A Systems-Level Therapeutic Strategy for Sepsis and Complex Diseases

by Ruihuan Chen, Jianping Wu, Daniel Jafari and Annica K. B. Gad

Life 2026, 16(3), 457; https://doi.org/10.3390/life16030457 - 11 Mar 2026

Abstract

Sepsis remains a leading global health challenge, characterized by high mortality and a persistent lack of disease-modifying therapies. Despite decades of investment, therapeutic progress has been constrained by reductionist strategies that target isolated pathogenic components. This perspective argues that these failures reflect a [...] Read more.

Sepsis remains a leading global health challenge, characterized by high mortality and a persistent lack of disease-modifying therapies. Despite decades of investment, therapeutic progress has been constrained by reductionist strategies that target isolated pathogenic components. This perspective argues that these failures reflect a fundamental mischaracterization of sepsis—not as a disorder of discrete pathways, but as the collapse of complex biological systems in which normally coordinated processes become desynchronized. We identify the intermediate filament protein vimentin as a determinant of system fate governing the transition from adaptive host defense to pathological breakdown. Acting as a context-dependent network integrator and signal amplifier, vimentin coordinates antagonistic cellular programs by integrating biochemical and biophysical cues across immune, vascular, and metabolic systems. Under physiological stress, this coordination enables the orderly activation and resolution of inflammatory and suppressive responses required for pathogen control and restoration of homeostasis. In sepsis, persistent or excessive insults drive vimentin-mediated overactivation, uncoupling these programs and propagating systems-level instability that culminates in organ dysfunction. By integrating mechanistic, preclinical, and emerging clinical evidence, this perspective proposes vimentin modulation as a clinically translatable, systems-oriented strategy aimed at realigning host response networks to address the dynamic, opposing pathologies of sepsis that have eluded current therapies. Full article

(This article belongs to the Special Issue Current Advances in Diagnosis and Treatment of Sepsis)

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19 pages, 1422 KB

Open AccessArticle

Baseline DISE Anatomy Predicts Jaw-Thrust Responsiveness in Obstructive Sleep Apnea

by Wei-Hung Chang, Kuan-Pen Yu, Li-Kuo Kuo and Chung Lee

Life 2026, 16(3), 456; https://doi.org/10.3390/life16030456 - 11 Mar 2026

Abstract

Background: Drug-induced sleep endoscopy (DISE) with a jaw-thrust maneuver is used to simulate mandibular advancement in obstructive sleep apnea (OSA), yet determinants of functional airway improvement remain incompletely defined. Objective: To identify clinical, polysomnographic, and baseline DISE anatomic factors associated with jaw-thrust responsiveness. [...] Read more.

Background: Drug-induced sleep endoscopy (DISE) with a jaw-thrust maneuver is used to simulate mandibular advancement in obstructive sleep apnea (OSA), yet determinants of functional airway improvement remain incompletely defined. Objective: To identify clinical, polysomnographic, and baseline DISE anatomic factors associated with jaw-thrust responsiveness. Methods: We conducted a single-center retrospective observational study of adults with polysomnography-confirmed OSA who underwent DISE with paired baseline and jaw-thrust VOTE assessments between 1 January 2015 and 31 December 2025 (n = 355). Jaw-thrust responsiveness was defined a priori as a within-subject reduction in the number of obstructed VOTE sites (grade ≥ 1). Multivariable logistic regression was used to identify independent correlates within a prespecified explanatory modeling framework. The study was approved by the Institutional Review Board of Taipei Tzu Chi Hospital (protocol 14-IRB079), with the need for informed consent being waived. Results: Jaw thrust reduced overall obstruction burden from two (two to three) to one (one to two) sites (Wilcoxon p < 0.001). Hypopharyngeal levels demonstrated the greatest improvement, particularly at the tongue base (39.2% to 7.6%) and epiglottis (23.9% to 5.4%) (both p < 0.001). Overall, 62.8% met responder criteria and 18.9% achieved complete normalization. In multivariable analysis (n = 272), baseline tongue-base collapse (adjusted odds ratio [aOR] 2.46, 95% CI 1.20–5.04) and greater baseline multilevel obstruction burden (aOR 1.85 per SD, 95% CI 1.19–2.85) were independently associated with responsiveness, whereas conventional PSG severity metrics were not. Conclusions: In adults with OSA, jaw-thrust responsiveness during DISE is more strongly associated with baseline anatomic phenotype than with global PSG severity. Standardized DISE functional assessment may provide complementary information to support phenotype-informed selection of non-CPAP therapies, pending prospective validation. Full article

(This article belongs to the Special Issue Otolaryngology and Sleep Medicine: From Precision Diagnosis to Advanced Therapeutics)

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21 pages, 1206 KB

Open AccessArticle

Integrating Performance Records and Genetic Evaluations in Spanish Horse Populations Competing in Olympic Disciplines

by María Dolores Gómez, María José Sánchez-Guerrero, Davinia Isabel Perdomo-González, María Ripollés-Lobo, Ester Bartolomé and Mercedes Valera

Life 2026, 16(3), 455; https://doi.org/10.3390/life16030455 - 10 Mar 2026

Abstract

This study evaluates performance data and genetic merit of the main horse populations competing in Olympic disciplines in Spain and examines their implications for the optimization of official Breeding Programs. Performance records from 2004–2023 were analyzed, including 101,093 participations in Dressage, 319,000 in [...] Read more.

This study evaluates performance data and genetic merit of the main horse populations competing in Olympic disciplines in Spain and examines their implications for the optimization of official Breeding Programs. Performance records from 2004–2023 were analyzed, including 101,093 participations in Dressage, 319,000 in Show Jumping, and 17,535 in Eventing. These records were combined with pedigree information from 35,589 horses in Dressage, 33,935 in Show Jumping, and 12,102 in Eventing and evaluated using BLUP animal models to obtain standardized Estimated Breeding Values (EBV; mean 100 ± 20) and a Genetic Global Index (GGI). A single unified evaluation model was implemented for all studbooks, enabling a direct comparison of genetic quality across different breeds. Results revealed marked differences in genetic merit and genetic progress among breeds. Similar mean EBVs were obtained for the three analyzed breeds in Dressage in both the complete and the top 10% populations, with positive genetic trends in Caballo de Deporte Español (CDE) and Pura Raza Española (PRE), while the slope of EBV on birth year was not significantly different from zero in Spanish Anglo-Árabe (AA). CDE showed the highest mean EBVs and accuracies in Show Jumping (EBV up to 109.27; R up to 0.72), with a clear positive genetic trend. In Eventing, CDE and AA showed similar EBVs, while PRE consistently exhibited lower ones, although with a comparatively more favorable genetic trend. Analysis of selection intensity indicated that PRE breeders applied the most consistent genetic criteria, preferentially using animals with GGI > 100, whereas CDE and AA showed discrepancies between genetic merit and reproductive use. Overall, the unified Spanish genetic evaluation system provides reliable comparative information across breeds and has enabled measurable genetic progress, although improvements in breeders’ decision-making and in the use of genetic information are needed to maximize selection response. Full article

(This article belongs to the Special Issue Current Updates on Equidae Breeding and Genetics)

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24 pages, 1288 KB

Open AccessArticle

Transcriptomic Profiling Identifies a Distinct Molecular Signature in OSMF-Derived Oral Squamous Cell Carcinoma

by Kavitha Prasad, Sowmya Samudrala Venkatesiah, Dominic Augustine, Ananya Anurag Anand, Prashanthi Karyala, Sukeerthi Dasharathy, Roopa S. Rao and Soma Chaki

Life 2026, 16(3), 454; https://doi.org/10.3390/life16030454 - 10 Mar 2026

Abstract

Background: Oral Submucous Fibrosis (OSMF) is a significant global oral health problem, particularly prevalent in India, with a high risk of progression to Oral Squamous Cell Carcinoma (OSCC). This study investigates the molecular mechanisms involved in the transformation of OSMF to OSCC using [...] Read more.

Background: Oral Submucous Fibrosis (OSMF) is a significant global oral health problem, particularly prevalent in India, with a high risk of progression to Oral Squamous Cell Carcinoma (OSCC). This study investigates the molecular mechanisms involved in the transformation of OSMF to OSCC using transcriptomic profiling. Methods: High-throughput RNA sequencing was performed on fresh de novo OSCC samples (n = 8) and OSMF derived OSCC using Illumina-compatible NEXTflex Rapid Directional RNA Sequencing. Normalization and differential gene expression analysis were conducted, and genes exhibiting an absolute log2 fold change of ≥2 with a co-variate-adjusted p-value ≤ 0.05 were identified as significant. Results: Upregulated genes were associated with cytokine and immune responses (ABRA, TTTY14, EIF1AY), cellular proliferation and apoptosis (LINC00314, RPS4Y1, SERPINA5, TRIM63, FABP7), and energy metabolism, indicating metabolic adaptations during malignant progression. Pathway analysis showed increased expression of TNNT1, TNNI1, MYL4, and ACTN3, implicating muscle development and embryonic pathways in OSMF transformation. Conversely, genes related to epithelial differentiation and keratinization (FLG, FLG2, HRNR, TCHH, KRT73), immune regulation and tumor suppression (HLA-G, UNC5D), and metabolic signaling were downregulated, reflecting loss of tissue integrity and immune control. Conclusions: OSMF-derived OSCC exhibits a distinct transcriptomic landscape compared with de novo OSCC, characterized by altered epithelial differentiation, immune modulation, and activation of developmental pathways. The observed gene dysregulation findings establish that OSCC developing in the background of OSMF is molecularly distinct from de novo OSCC, underscoring the biological impact of the pre-existing fibrotic milieu on tumor transcriptional architecture. Full article

(This article belongs to the Section Genetics and Genomics)

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14 pages, 992 KB

Open AccessArticle

Age- and Severity-Stratified Associations Among Polysomnographic Parameters, Lower Urinary Tract Symptoms, and Hormonal Markers in Men with Obstructive Sleep Apnea: A Cross-Sectional Study

by Yu-Hui Huang, Yun-Sheng Chen, Min-Hsin Yang, Kai-Siang Chen, Chieh-Jui Chen, Cheng-Ju Ho and Sung-Lang Chen

Life 2026, 16(3), 453; https://doi.org/10.3390/life16030453 - 10 Mar 2026

Abstract

Background: Obstructive sleep apnea (OSA) is associated with lower urinary tract symptoms (LUTS), particularly nocturia, though mechanisms including hypoxia, intrathoracic pressure changes, and hormonal alterations. While age and severity may influence these associations, stratified analyses remain limited. This study examined polysomnographic (PSG) parameters, [...] Read more.

Background: Obstructive sleep apnea (OSA) is associated with lower urinary tract symptoms (LUTS), particularly nocturia, though mechanisms including hypoxia, intrathoracic pressure changes, and hormonal alterations. While age and severity may influence these associations, stratified analyses remain limited. This study examined polysomnographic (PSG) parameters, International Prostate Symptom Score (IPSS) components, and hormonal/electrolyte markers in age- and severity-stratified men with suspected OSA. Methods: In this cross-sectional study, 104 men (mean age 60.8 ± 9.8 years) underwent PSG. Analyses were stratified by age (<60 vs. ≥60 years) and respiratory disturbance index (RDI) severity. Correlations were used to assess PSG indices, IPSS subdomains (irritative, obstructive, quality of life [QoL]), and markers including antidiuretic hormone [ADH], aldosterone, plasma renin activity [PRA], sodium, potassium. Nocturnal polyuria index (NPI ≥ 33%) was calculated in a subset of participants. Pearson correlations, ANOVA, and Kruskal–Wallis tests were used (p < 0.05), with adjustments for multiple comparisons. Results: Moderate OSA predominated (RDI 27.2 ± 20.4 events/h); nocturia affected 61.5% of the cohort. In those <60 years (n = 48), mild RDI correlated with nocturia (r = 0.42, p = 0.028), while severe RDI correlated strongly with the obstructive subscore (r = 0.96, p = 0.009). In those ≥60 years (n = 56), QoL correlated with sleep efficiency (r = 0.48, p = 0.012) and total sleep time (r = 0.46, p = 0.015). Severe RDI was associated with higher IPSS (14.5 ± 6.2 vs. 10.5 ± 4.8, p = 0.028) and nocturia (3.5 ± 1.7 vs. 2.4 ± 1.1, p = 0.02). ADH was significantly lower in severe OSA (1.4 ± 0.8 vs. 2.7 ± 1.1 pg/mL, p = 0.03). Conclusions: Age and OSA severity modulate PSG–LUTS–hormonal associations. Younger men exhibit hypoxia-linked obstructive symptoms, whereas older men experience sleep fragmentation that impacts QoL. ADH suppression is associated with severe OSA. Full article

(This article belongs to the Special Issue Current Trends in Obstructive Sleep Apnea)

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30 pages, 1752 KB

Open AccessReview

Traditional Uses of Thymus Species in the Balkans: Ethnopharmacology, Food, and Cultural Heritage

by Ina Aneva, Marija Marković, Katarina Husnjak Malovec, Zheko Naychov, Irena Mincheva, Vesna Stankov-Jovanović and Ekaterina Kozuharova

Life 2026, 16(3), 452; https://doi.org/10.3390/life16030452 - 10 Mar 2026

Abstract

Thymus species play an important role in traditional medicine, food practices, and cultural heritage across the Balkan Peninsula, a region characterized by high floristic diversity and long-standing ethnobotanical traditions. This review provides a comprehensive synthesis of published ethnobotanical and ethnopharmacological data on the [...] Read more.

Thymus species play an important role in traditional medicine, food practices, and cultural heritage across the Balkan Peninsula, a region characterized by high floristic diversity and long-standing ethnobotanical traditions. This review provides a comprehensive synthesis of published ethnobotanical and ethnopharmacological data on the traditional uses of Thymus species in the Balkans. A systematic survey of literature published between 1900 and 2022 was conducted using major scientific databases and classical ethnobotanical sources, covering Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Kosovo, Montenegro, North Macedonia, Romania, Serbia, Slovenia, and the European part of Turkey. In total, 553 records of traditional use were documented. The results reveal that Thymus taxa are most frequently employed for the treatment of respiratory and gastrointestinal disorders, followed by applications related to the nervous, urinary, cardiovascular, and integumentary systems. Culinary uses such as spices, herbal teas, beverages, and food preservatives are widely reported, highlighting the close connection between medicinal and dietary traditions. The analysis also identifies significant taxonomic inconsistencies in the ethnobotanical literature, particularly the frequent misapplication of names such as T. serpyllum and T. vulgaris, which complicates the interpretation of traditional knowledge. Overall, the strong cross-cultural consistency of uses across Balkan countries supports the pharmacological relevance of Thymus species and aligns well with modern phytotherapeutic evaluations. This review underscores the importance of critically integrating ethnobotanical data, taxonomic accuracy, and contemporary phytotherapy to better understand and utilize the therapeutic potential of Thymus species. Full article

(This article belongs to the Section Plant Science)

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16 pages, 1277 KB

Open AccessArticle

Limitations of MMSE in Cognitive Assessment: Revealing Latent Risk via Structural Brain Atrophy

by Moonhyeok Choi, Jaehyun Jo and Jinhyoung Jeong

Life 2026, 16(3), 451; https://doi.org/10.3390/life16030451 - 10 Mar 2026

Abstract

The primary objective of this study was to evaluate the relative contributions of the MMSE and nWBV in three-class cognitive stage classification, with a secondary objective of conducting a subgroup analysis to investigate latent risk within the MMSE-normal population. To achieve this, we [...] Read more.

The primary objective of this study was to evaluate the relative contributions of the MMSE and nWBV in three-class cognitive stage classification, with a secondary objective of conducting a subgroup analysis to investigate latent risk within the MMSE-normal population. To achieve this, we proposed an explainable deep-learning-based analytical framework integrating the MMSE with nWBV, a structural brain atrophy indicator, and systematically assessed the relative contributions of each variable in cognitive impairment stage classification and potential risk screening. Although the MMSE is widely used in clinical practice as a cognitive screening tool, it has limited sensitivity to early or subtle cognitive decline and may not adequately reflect structural brain changes due to the ceiling effect. To address this limitation, we compared four tabular deep learning models—MLP, Tab ResNet, Tab Transformer, and FT Transformer—under identical fivefold cross-validation conditions. Age and sex were fixed as covariates, and feature ablation analysis was conducted to examine the independent and combined effects of the MMSE and nWBV. The results showed no statistically significant differences in classification performance among model architectures, indicating that predictive performance was primarily determined by the informational content of the input variables rather than model complexity. In the feature ablation analysis, the MMSE alone demonstrated strong discriminative power, whereas nWBV alone showed relatively limited performance; however, when combined with the MMSE, nWBV consistently improved classification performance. Furthermore, for interpretability analysis, both Integrated Gradients (IG) and SHAP were applied to validate variable contributions from complementary perspectives. Across both methods, the MMSE and nWBV were repeatedly identified as key contributing features, and interpretability stability was maintained throughout cross-validation folds, supporting the robustness and reliability of the explanatory results. Beyond simple model performance comparisons, this study provides evidence supporting the complementary integration of structural brain atrophy information into MMSE-centered traditional cognitive assessment by jointly considering variable contribution and interpretability stability. This approach is expected to contribute to precision risk screening and clinical decision support in the early stages of cognitive decline. Although the MMSE exhibited strong discriminative performance, nWBV provided complementary structural risk signals within the MMSE-normal subgroup, suggesting that integrating cognitive assessment with structural biomarkers may enhance early risk identification. Full article

(This article belongs to the Section Physiology and Pathology)

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27 pages, 1051 KB

Open AccessReview

Pathogenic Mechanisms in Cervical Cancer: Energy Metabolism, Hypoxia and Therapy

by Valentina Giorgio, Valentina Del Dotto, Martina Grandi, Silvia Grillini, Giancarlo Solaini and Alessandra Baracca

Life 2026, 16(3), 450; https://doi.org/10.3390/life16030450 - 10 Mar 2026

Abstract

Cervical cancer has a high incidence and mortality, and is one of the leading causes of cancer-related deaths among women worldwide. The infection with high-risk subtypes of the human papillomavirus (HPV) represents a crucial factor in the development of precancerous lesions. HPV oncoproteins [...] Read more.

Cervical cancer has a high incidence and mortality, and is one of the leading causes of cancer-related deaths among women worldwide. The infection with high-risk subtypes of the human papillomavirus (HPV) represents a crucial factor in the development of precancerous lesions. HPV oncoproteins target multiple host factors to promote uncontrolled cellular proliferation, genomic instability, profound metabolic reprogramming, resistance to apoptosis and immune evasion. Thus, cervical carcinogenesis involves metabolic reprogramming in patient cells, such as enhanced aerobic glycolysis, and altered glutamine, lipid and mitochondrial metabolism, which collectively support the bioenergetic and biosynthetic demands of cancer cells. Cancer cells also activate several mechanisms to adapt and survive under hypoxic/anoxic conditions. The mechanisms underlying cervical carcinogenesis often involve non-coding RNAs. This review aims at summarizing the mechanisms and factors involved in the development and progression of cervical cancer following HPV infection, and offers an overview of the available therapies that have been developed for this disease. Full article

(This article belongs to the Special Issue The Role of Mitochondrial Function in Cancer and Diseases and Therapeutic Explorations)

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18 pages, 1011 KB

Open AccessReview

Bright Light Therapy in Psychiatric Disorders: Mechanisms, Clinical Procedures and Evidence

by Simone Pardossi, Letizia Bossini, Veronica Milani, Maria Beatrice Rescalli and Alessandro Cuomo

Life 2026, 16(3), 449; https://doi.org/10.3390/life16030449 - 10 Mar 2026

Abstract

Light is the primary zeitgeber for circadian rhythms, and also through these mechanisms, is closely related to mood regulation. Bright light therapy (BLT) is a therapeutic intervention that specifically exploits this physiological mechanism. This review summarizes the clinical procedures of BLT, the mechanisms [...] Read more.

Light is the primary zeitgeber for circadian rhythms, and also through these mechanisms, is closely related to mood regulation. Bright light therapy (BLT) is a therapeutic intervention that specifically exploits this physiological mechanism. This review summarizes the clinical procedures of BLT, the mechanisms through which light influences circadian rhythms and mood, and the evidence supporting BLT in psychiatric disorders. BLT is administered by considering device distance, treatment duration, and light intensity. Through pathways originating in the retina and projecting to the Suprachiasmatic Nucleus (SCN), light might generate signals within the central nervous system that influence not only circadian regulation but also mood, via connections involving the limbic system, the lateral habenula, and interactions with the hormonal system. At the clinical level, the strongest evidence for BLT concerns seasonal affective disorder, but data also indicate antidepressant efficacy in major depressive disorder and bipolar disorder, with an excellent tolerability profile. Emerging evidence further suggests benefits for insomnia, and sporadic and heterogeneous findings have explored its potential role in other conditions. Future studies are needed to better define the role of BLT in additional psychiatric disorders and in specific symptom domains that may not adequately respond to standard treatments, such as sexual dysfunction. Full article

(This article belongs to the Section Medical Research)

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18 pages, 1838 KB

Open AccessReview

Carob Tree: A Review of Traditional Uses, Medicinal Properties, and Future Perspectives in Sustainable Forestry

by Abdelkader Gadoum, Abdelkader Difallah, Ahmed Adda and Othmane Merah

Life 2026, 16(3), 448; https://doi.org/10.3390/life16030448 - 10 Mar 2026

Abstract

The carob tree (Ceratonia siliqua L.) is indigenous to the Mediterranean basin, noted for its adaptability to biotic and abiotic stresses and its long history of use in traditional agroforestry systems. This review critically analyzes the phytochemical composition of carob, its traditional [...] Read more.

The carob tree (Ceratonia siliqua L.) is indigenous to the Mediterranean basin, noted for its adaptability to biotic and abiotic stresses and its long history of use in traditional agroforestry systems. This review critically analyzes the phytochemical composition of carob, its traditional medicinal uses, and its contemporary applications in the cosmetic, pharmaceutical, and agri-food sectors. Particular attention is placed on the valorization of carob pods, seeds, and leaves, which are transformed into high-value products, including locust bean gum and polyphenol-rich extracts. Recent studies indicate that carob is a rich source of bioactive compounds, particularly phenolic acids and flavonoids such as gallic acid, chlorogenic acid, ellagic acid, catechins, quercetin, and luteolin. These compounds have primarily been investigated in vitro and in vivo, where they exhibited antioxidant, antimicrobial, and potential cardioprotective and gastrointestinal-related effects. This chemical diversity underscores their potential as a prime substitute for future nutraceutical and pharmaceutical applications. The review further addresses the ecological and socio-economic relevance of carob cultivation, particularly in countries such as Algeria, where reforestation and agro-industrial valorization remain underexploited despite their significant economic potential. Overall, this work highlights the need for a comprehensive and critical evaluation of carob-derived bioactive compounds and encourages further well-designed studies, especially clinical investigations, to better substantiate their health-related benefits while supporting sustainable use of this multipurpose species. Full article

(This article belongs to the Section Plant Science)

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4 pages, 1130 KB

Open AccessCorrection

Correction: Hernández-Fuentes et al. Moringa oleifera Leaf Infusion as a Functional Beverage: Polyphenol Content, Antioxidant Capacity, and Its Potential Role in the Prevention of Metabolopathies. Life 2025, 15, 636

by Gustavo A. Hernández-Fuentes, Carmen A. Sanchez-Ramirez, Salma I. Cortes-Alvarez, Alejandrina Rodriguez-Hernández, Ana O. Cabrera-Medina, Norma A. Moy-López, Jorge Guzman-Muñiz, Idalia Garza-Veloz, Iram P. Rodriguez-Sanchez, Margarita L. Martinez-Fierro, Jorge J. Álvarez-Barajas, Nadia Y. Cortes-Alvarez, Silvia G. Ceballos-Magaña, Carmen Meza-Robles and Iván Delgado-Enciso

Life 2026, 16(3), 447; https://doi.org/10.3390/life16030447 - 10 Mar 2026

Abstract

In the original publication [...] Full article

(This article belongs to the Section Pharmaceutical Science)

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12 pages, 1423 KB

Open AccessReview

Metabolic Concepts of Sodium-Glucose Cotransporter 2 Inhibitors-Based Therapies Against Hepatocarcinogenesis and Therapy Resistance in Hepatocellular Carcinoma

by Hsien-Hui Chung

Life 2026, 16(3), 446; https://doi.org/10.3390/life16030446 - 10 Mar 2026

Abstract

The prevalence of hepatocellular carcinoma (HCC) has increased in recent years and resulted in many deaths, which necessitates new therapeutic solutions. The pathogenesis of HCC is associated with uncontrolled metabolic modulation and resistance to therapy. As diabetic carcinogenesis accelerates HCC progression, proper evaluation [...] Read more.

The prevalence of hepatocellular carcinoma (HCC) has increased in recent years and resulted in many deaths, which necessitates new therapeutic solutions. The pathogenesis of HCC is associated with uncontrolled metabolic modulation and resistance to therapy. As diabetic carcinogenesis accelerates HCC progression, proper evaluation of anti-diabetic drugs to attenuate HCC is important. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors that suppress renal SGLT2 are beneficial for treating diabetes, chronic kidney diseases, and heart failure, the use of SGLT2 inhibitors for treating HCC remains unclear. In this review article, some oncotargets involved in metabolic reprogramming, including glucose metabolism, Wnt/β-catenin, and hypoxia-inducible factor-1 alpha signaling, and the tumor microenvironment of HCC are briefly highlighted. Moreover, upregulated SGLT2 expression may be associated with hepatocarcinogenesis and therapy resistance, whereas the incorporation of SGLT2 inhibitors into combination therapies effectively attenuates HCC progression, metastasis, and therapy resistance through multiple mechanisms. Notably, how SGLT2 inhibitors modulate immune responses to cancer vaccines against HCC is highly appreciated and requires further evaluation. Thus, the clinical application of SGLT2 inhibitors in HCC and therapy resistance provides a promising direction for therapeutic strategies. Full article

(This article belongs to the Special Issue Liver Disease: Pathogenesis, Diagnosis, and Treatments)

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18 pages, 2233 KB

Open AccessReview

The Protein Histidine Methyltransferase METTL9—From Mechanism to Biological Function

by Pål Ø. Falnes and Erna Davydova

Life 2026, 16(3), 445; https://doi.org/10.3390/life16030445 - 9 Mar 2026

Abstract

Proteins can be methylated at either of the two N atoms of the imidazole ring of histidine, yielding 1-methylhistidine (or pi-methylhistidine) or 3-methylhistidine (tau-methylhistidine). While protein histidine methylation in mammals was discovered more than 50 years ago, the first histidine methyltransferases were identified [...] Read more.

Proteins can be methylated at either of the two N atoms of the imidazole ring of histidine, yielding 1-methylhistidine (or pi-methylhistidine) or 3-methylhistidine (tau-methylhistidine). While protein histidine methylation in mammals was discovered more than 50 years ago, the first histidine methyltransferases were identified only recently. So far, four different human protein histidine methyltransferases have been uncovered, and one of these is METTL9, which is responsible for introducing 1-methylhistidine in a number of proteins. The minimal sequence motif that is required, though not always sufficient, for METTL9-mediated methylation is His-X-His (HxH), where X is preferentially a small uncharged residue. Many METTL9 substrates are methylated at stretches of alternating histidines, i.e., several adjoining HxH motifs, such as HxHxH. Histidines are frequently involved in binding metal ions, such as zinc. Accordingly, it has been shown for several sequences targeted by METTL9, for example, in the immunomodulatory and antibacterial protein S100A9 and the zinc transporter SLC39A7, that histidine methylation diminishes zinc binding and thereby modulates protein function. In this review, we present a detailed account of METTL9-mediated histidine methylation, regarding its discovery, biochemical mechanism, structural features, and biological significance. Full article

(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases: 2nd Edition)

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18 pages, 1081 KB

Open AccessReview

Artificial Intelligence-Enhanced Telerehabilitation in Post-Acute Coronary Syndrome: A Narrative Review of Opportunities, Evidence, and Future Directions

by Alina Gherghin, Mircea Ioan Alexandru Bistriceanu, Ilie Onu, Daniel Andrei Iordan, Florentin Dimofte, Adriana Neofit, Dan Eugen Costin and Alexandru Scafa-Udriste

Life 2026, 16(3), 444; https://doi.org/10.3390/life16030444 - 9 Mar 2026

Abstract

Cardiac telerehabilitation has become a promising alternative to traditional programmes for preventing acute coronary syndrome (ACS) in the secondary phase. However, current implementations are still reactive and standardised, lacking personalisation and flexibility in clinical settings. By integrating artificial intelligence (AI), it may be [...] Read more.

Cardiac telerehabilitation has become a promising alternative to traditional programmes for preventing acute coronary syndrome (ACS) in the secondary phase. However, current implementations are still reactive and standardised, lacking personalisation and flexibility in clinical settings. By integrating artificial intelligence (AI), it may be possible to overcome these limitations and provide intelligent, scalable, and patient-centred care. Methods: We conducted a structured literature review across PubMed, Scopus, the Cochrane Library, and Web of Science, targeting English-language studies published from January 2015 to May 2025. Inclusion criteria included adult populations with a history of ACS or high cardiovascular risk, assessing interventions based on AI, telerehabilitation, or their combination. Studies are needed to report clinical, functional, behavioural, or technological outcomes. A thematic narrative synthesis was utilised. Results: AI-enhanced telerehabilitation demonstrates potential advantages over conventional digital care in selected domains, including adaptive risk prediction, personalised exercise modulation, and adherence support. Several systems report real-time adjustment of exercise protocols, early dropout detection, and predictive analytics for rehospitalisation. AI integration may also contribute to personalised behavioural feedback and psychosocial monitoring. Nevertheless, the overall level of evidence remains preliminary and heterogeneous, with most AI-based interventions evaluated in pilot, feasibility, or modelling studies rather than large-scale randomized trials. Conclusions: The integration of AI into telerehabilitation represents a promising evolution in post-ACS care, shifting from predominantly reactive monitoring toward more adaptive and data-driven support models. While early-phase studies suggest feasibility and potential clinical benefit, robust multicentre randomized controlled trials and cost-effectiveness analyses are required before definitive conclusions regarding superiority or widespread implementation can be drawn. Full article

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

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11 pages, 343 KB

Open AccessArticle

Effects of Two Nights of Severe vs. Mild Sleep Restriction on Vertical Jump Performance in Physically Active Female Students

by Andrija Miksa, Antonio Martinko, Luka Milanovic, Marin Dadic and Ivan Belcic

Life 2026, 16(3), 443; https://doi.org/10.3390/life16030443 - 9 Mar 2026

Abstract

Partial sleep deprivation is common in sports, particularly before competitions. This study examined whether two nights of severe sleep restriction (<4 h/night), compared with mild sleep restriction (control), are associated with changes in SJ and CMJ in physically active female students. Twenty-three female [...] Read more.

Partial sleep deprivation is common in sports, particularly before competitions. This study examined whether two nights of severe sleep restriction (<4 h/night), compared with mild sleep restriction (control), are associated with changes in SJ and CMJ in physically active female students. Twenty-three female students (n = 12 experimental; n = 11 control) were randomly assigned to their respective groups. The experimental group underwent two nights of severe sleep restriction (<4 h/night), while the control group experienced mild sleep restriction. Differences between groups were analyzed using Quade’s nonparametric ANCOVA (sleep duration as covariate), and within-group pre–post changes were evaluated using paired-samples t-tests. No significant differences were found between groups after two nights in CMJ (p = 0.92) or SJ (p = 0.73) performance. Within the experimental group, SJ performance significantly decreased from the initial to the final assessment (p = 0.02), with a large effect size (d = −0.81). CMJ performance in the experimental group showed a non-significant decrease with a moderate effect size (d = −0.45). No significant differences or notable effect sizes were found in the control group (d = 0.01 to 0.23). Within-group results suggest that SJ decreased after severe sleep restriction, while CMJ changes were smaller and not statistically significant; between-group comparisons were not significant, and results appear sensitive to the analytical approach. These exploratory findings suggest that monitoring sleep before power-related tasks may be warranted. Coaches may consider monitoring sleep duration before high-intensity power training, as two nights of severe sleep restriction may be associated with reduced SJ performance. Full article

(This article belongs to the Special Issue Advances and Applications of Sport Physiology: 2nd Edition)

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12 pages, 2144 KB

Open AccessArticle

Sinonasal Inverted Papillomas: Predictors of Recurrence and Malignant Transformation

by Ionut Tanase, Mircea-Sorin Ciolofan, Codrut-Caius Sarafoleanu, Carmen Aurelia Mogoantă, Florentina-Carmen Badea, Constantin-Ioan Busuioc, Shirley Tarabichi, Alex Milea, Ilona Mihaela Liliac, Dan Iovanescu, Gheorghe Iovanescu and Gabriela-Cornelia Musat

Life 2026, 16(3), 442; https://doi.org/10.3390/life16030442 - 9 Mar 2026

Abstract

Sinonasal inverted papillomas (IPs) are rare benign tumors with ~15% postoperative recurrence and a ~8% risk of malignant transformation, with human papillomavirus (HPV) reported as a risk factor in IP malignant transformation. To evaluate clinical, molecular and immunohistochemical factors associated with recurrence and [...] Read more.

Sinonasal inverted papillomas (IPs) are rare benign tumors with ~15% postoperative recurrence and a ~8% risk of malignant transformation, with human papillomavirus (HPV) reported as a risk factor in IP malignant transformation. To evaluate clinical, molecular and immunohistochemical factors associated with recurrence and malignant transformation in IPs. We retrospectively analyzed 73 patients with histologically confirmed IPs that were treated at three tertiary ENT centers, including radiologic data, HPV DNA detection and p16 immunohistochemistry. Univariate analysis was used to identify factors associated with recurrence and malignant transformation, and restricted exploratory multivariable logistic regression models were used to assess recurrence while minimizing overfitting. Fourteen recurrences (19%) were associated with longer symptom duration (p = 0.003), smoking (p = 0.03), advanced Krouse stage (III–IV) (p < 0.001), frontal sinus origin (p = 0.02), HPV+ DNA (50% vs. 22%, p = 0.048), and p16 loss/reduced expression (p = 0.006). Nine recurrences transformed into carcinoma (12%) and were associated with smoking (p = 0.01). HPV+ was not associated with malignancy (p = 1.00). Recurrence was associated with the advanced stage of the IP, tobacco use, longer symptom duration, frontal sinus origin, HPV+, and p16 loss/reduced expression. Full article

(This article belongs to the Section Medical Research)

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