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Life, Volume 16, Issue 3 (March 2026) – 167 articles

Cover Story (view full-size image): This review examines the emerging interplay between the gut microbiome and systemic therapies in psoriasis. The gut microbial ecosystem may contribute to treatment response through immune and metabolic signaling, while systemic therapies may also modify microbial composition and function. By summarizing current evidence on microbiota-related pathways and drug–microbiome interactions, the article presents pharmacomicrobiomics as a promising perspective for understanding treatment heterogeneity and advancing precision medicine in psoriasis. View this paper
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15 pages, 269 KB  
Article
Eccentric Hamstring Strength and Interlimb Asymmetry in Professional Football Players: A NordBord-Based Longitudinal Analysis of Two Professional Teams
by Tolga Altuğ, Mehmet Söyler, Coşkun Yılmaz, Meriç Eraslan, Ahmet Serhat Aydın, Mustafa Nurullah Kadı, Pelin Akyol and Hamza Küçük
Life 2026, 16(3), 532; https://doi.org/10.3390/life16030532 - 23 Mar 2026
Cited by 1 | Viewed by 704
Abstract
The aim of this study was to examine temporal changes in eccentric hamstring strength, impulse-based mechanical outputs, and interlimb asymmetry in professional football players performing a football-specific eccentric hamstring training program. Forty male football players (18–25 years) from two teams competing in the [...] Read more.
The aim of this study was to examine temporal changes in eccentric hamstring strength, impulse-based mechanical outputs, and interlimb asymmetry in professional football players performing a football-specific eccentric hamstring training program. Forty male football players (18–25 years) from two teams competing in the Turkish Second Professional Football League participated in this longitudinal cohort study. Eccentric hamstring performance was assessed at three time points (pre-, mid-, and post-season) using the NordBord Hamstring Testing System. Mixed-design repeated-measures ANOVA revealed significant main effects of time and significant time × Team interactions for left and right maximal impulse values (p < 0.05). In contrast, maximal eccentric force variables showed no significant time effects, although significant time × Team interactions were observed for both limbs (p < 0.05). Interlimb maximal force asymmetry and mean asymmetry demonstrated significant time effects, while Team effects and interaction terms were not significant. Overall, these findings indicate that temporal changes in eccentric hamstring performance in professional football players may be more clearly reflected in force–time–dependent metrics, particularly impulse, rather than peak force outputs. Accordingly, impulse-based measures may provide additional insight into eccentric hamstring performance changes in professional football players. Full article
(This article belongs to the Section Physiology and Pathology)
15 pages, 882 KB  
Article
Integrating Wearable Sensors and Clinical Tools for Assessing Pelvic Gait Symmetry During ACL Recovery
by Atanas Kostadinov Drumev and Danelina Emilova Vacheva
Life 2026, 16(3), 531; https://doi.org/10.3390/life16030531 - 23 Mar 2026
Viewed by 712
Abstract
Anterior cruciate ligament (ACL) injuries frequently lead to persistent gait asymmetries, posing challenges for early rehabilitation and functional status. Comprehensive monitoring of pelvic gait symmetry during rehabilitation remains underexplored. This study evaluated post-operative functional status using an integrated monitoring approach combining pelvic-mounted inertial [...] Read more.
Anterior cruciate ligament (ACL) injuries frequently lead to persistent gait asymmetries, posing challenges for early rehabilitation and functional status. Comprehensive monitoring of pelvic gait symmetry during rehabilitation remains underexplored. This study evaluated post-operative functional status using an integrated monitoring approach combining pelvic-mounted inertial measurement unit (IMU) sensors with standardized clinical assessments in 32 individuals (9 women, 23 men; aged 19–64) following ACL reconstruction with patellar tendon autografts. IMU recordings captured pelvic oscillations in the sagittal, frontal, and transverse planes during standardized 10 m walking tests, providing objective digital biomarkers of gait symmetry. Clinical assessments included knee range of motion, thigh circumference, swelling, and pain using a modified 0–20 visual analogue scale (VAS). Across the early rehabilitation period, VAS scores decreased from 13.6 to 3.0, knee swelling from 2.88 cm to 1.09 cm, knee extension deficit from −9.38° to −2.03°, and knee flexion improved from 61.56° to 98.75°. Thigh hypotrophy increased from 1.13 cm to 2.53 cm. Pelvic oscillations improved in all planes (sagittal: 36.2 to 49.2; frontal: 71.9 to 92.2; transverse: 73.4 to 90.9), reflecting progressive restoration of gait control as patients transitioned from crutch-assisted to independent walking. The integration of wearable sensor data with clinical metrics enabled sensitive tracking of pelvic gait symmetry and functional status, demonstrating the utility of technology-supported monitoring to support individualized clinical assessment and early-phase monitoring following ACL reconstruction. Full article
(This article belongs to the Special Issue Sports Biomechanics, Injury, and Physiotherapy)
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32 pages, 4906 KB  
Article
Integrative Pharmacological and Computational Analysis of Abelmoschus esculentus Phytochemicals: Enzyme Inhibition, Molecular Docking, and Dynamics Simulation Against Key Antidiabetic Targets
by Humera Banu, Eyad Al-Shammari, Fevzi Bardakci, Mitesh Patel, Mohd Adnan, Mohammad Idreesh Khan, Noor AlFahhad and Syed Amir Ashraf
Life 2026, 16(3), 530; https://doi.org/10.3390/life16030530 - 23 Mar 2026
Viewed by 762
Abstract
The present work set out to examine the antidiabetic capacity of Abelmoschus esculentus (okra) fruit extract through a combined experimental and computational framework. Enzyme inhibition assays were carried out against four metabolic targets, and IC50 values stood at 7.66 ± 0.31 mg/mL [...] Read more.
The present work set out to examine the antidiabetic capacity of Abelmoschus esculentus (okra) fruit extract through a combined experimental and computational framework. Enzyme inhibition assays were carried out against four metabolic targets, and IC50 values stood at 7.66 ± 0.31 mg/mL for alpha-glucosidase, 5.21 ± 0.18 mg/mL for alpha-amylase, 2.11 ± 0.15 microg/mL for DPP-4, and 9.17 ± 0.54 mg/mL for pancreatic lipase. The extract showed moderate-to-weak activity relative to standard inhibitors acarbose, sitagliptin, and orlistat. Sixteen drug-like phytochemicals obtained from the IMPPAT 2.0 database were docked against the crystal structures of all four tested enzymes (PDB: 8CB1, 5E0F, 2ONC, 1LPB). Alpha-Carotene, Vitamin E, and Spiraeoside emerged as the top-ranked compounds across all targets, with alpha-Carotene recording the strongest binding affinity of −11.1 kcal/mol against pancreatic lipase, which was 4.2 kcal/mol more negative than the positive control orlistat (−6.9 kcal/mol). PLIP-based interaction profiling mapped out hydrogen bonds, hydrophobic contacts, pi-stacking, and salt bridges at the atomic level. Absorption, distribution, metabolism, and excretion (ADME) and toxicity screening of alpha-Carotene returned a favourable pharmacokinetic profile with predicted LD50 of 1510 mg/kg (Class 4) and inactivity across most toxicity endpoints. A 100 ns molecular dynamics simulation of the pancreatic lipase-alpha–Carotene complex, alongside the orlistat control, showed stable root mean square deviation (RMSD) (0.15–0.22 nm), a consistent Rg (~1.97 nm), and sustained hydrogen bonding throughout the trajectory. Free-energy landscape analysis revealed a well-defined single energy basin for alpha-Carotene, suggesting a thermodynamically stable binding conformation. These findings lay the molecular basis for using okra phytochemicals as adjunctive agents in diabetes management, though in vivo validation remains necessary. Full article
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17 pages, 983 KB  
Article
Dynamics and Predictive Values of Urinary Podocyte Biomarkers Following SGLT2 Inhibition in CKD
by Alexandra Urs, Diana Moldovan, Crina Claudia Rusu, Cosmina Ioana Bondor, Alina Ramona Potra, Dacian Tirinescu, Maria Țicală, Yuriy Maslyennikov, Andrada Alina Bărar, Ioana Dînșoreanu and Ina Maria Kacso
Life 2026, 16(3), 529; https://doi.org/10.3390/life16030529 - 23 Mar 2026
Viewed by 593
Abstract
Podocyte injury is an early hallmark of chronic kidney disease (CKD) and can be influenced by SGLT2 inhibitors (SGLT2i). Early effects of SGLT2i include transient estimated glomerular filtration rate (eGFR) dip and reduced proteinuria; however, the latter may be subtle in patients with [...] Read more.
Podocyte injury is an early hallmark of chronic kidney disease (CKD) and can be influenced by SGLT2 inhibitors (SGLT2i). Early effects of SGLT2i include transient estimated glomerular filtration rate (eGFR) dip and reduced proteinuria; however, the latter may be subtle in patients with normal or moderately increased albuminuria. In such cases, urinary podocyte-derived biomarkers may provide sensitive early indicators of SGLT2i effect. This study prospectively assessed short-term changes in urinary podocyte biomarkers (nephrin, podocin, podocalyxin) following SGLT2i initiation in diabetic and non-diabetic CKD patients. Our cohort had a low urinary albumin to creatinine ratio (UACR) of 19.09 mg/g (6.28; 164.93) and preserved eGFR 45 mL/min/1.73 m2 (36.85; 53.15). At baseline, podocyte biomarkers were mutually correlated, whereas only podocalyxin was associated with UACR. Baseline podocalyxin independently predicted transient eGFR dip and UACR reduction. Early decreases in both podocin and podocalyxin were associated with eGFR decline and lower UACR at 3 months. ROC analyses identified cutoff values for all three biomarkers that predicted short-term eGFR decline, with baseline podocalyxin demonstrating the highest discriminative accuracy. These findings support pleiotropic nephroprotective effects of SGLT2 inhibitors and identify urinary podocyte biomarkers—particularly podocalyxin, and to a lesser extent podocin—as a sensitive indicator of early renal response. Full article
(This article belongs to the Special Issue CKD and Glomerular Diseases)
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15 pages, 594 KB  
Systematic Review
Treatment Options in Managing Infections Following Calcaneal Fractures: A Systematic Review
by Giacomo Capece, Chiara Comisi, Guido Bocchino, Rocco Maria Comodo, Virginia Cinelli, Federico Moretti, Tommaso Greco, Giulio Maccauro and Carlo Perisano
Life 2026, 16(3), 528; https://doi.org/10.3390/life16030528 - 23 Mar 2026
Viewed by 793
Abstract
Background: Calcaneal fractures are complex injuries frequently associated with significant soft tissue damage and a high risk of post-operative complications, particularly infection. Despite advances in surgical techniques, infectious complications remain a major cause of morbidity and can severely compromise functional outcomes. The aim [...] Read more.
Background: Calcaneal fractures are complex injuries frequently associated with significant soft tissue damage and a high risk of post-operative complications, particularly infection. Despite advances in surgical techniques, infectious complications remain a major cause of morbidity and can severely compromise functional outcomes. The aim of this systematic review was to analyze the incidence, management strategies, and clinical impact of infectious complications following surgical treatment of calcaneal fractures. Methods: A systematic literature search was conducted in MEDLINE, Scopus, and Web of Science in accordance with PRISMA guidelines, including studies published up to May 2025. Randomized controlled trials and prospective and retrospective cohort studies involving adult patients surgically treated for calcaneal fractures and reporting post-operative infectious outcomes were included. Data extraction focused on patient demographics, fracture characteristics, surgical techniques, infection rates, microbiological findings, management strategies, complications, and functional outcomes. Methodological quality and risk of bias were assessed using the MINORS score. Due to substantial heterogeneity, results were synthesized descriptively. Results: Forty studies met the inclusion criteria, encompassing 5343 patients and 4638 surgically treated calcaneal fractures. Displaced intra-articular fractures predominated, with Sanders type II and III accounting for 79.8% of classified fractures, while Sanders type IV fractures represented 20.2% and were associated with higher complication rates. The overall post-operative infection rate was 9.4%, including 6.3% superficial surgical site infections and 3.0% deep infections. Open fractures accounted for 7.5% of reported cases and demonstrated markedly higher infection rates than closed injuries. Deep infections frequently required implant removal (62%), prolonged intravenous antibiotic therapy (100%), and additional surgical procedures (71%). Staphylococcus aureus, including methicillin-resistant strains, was the most commonly isolated pathogen. Functional outcomes were consistently worse in patients who developed infections. Conclusions: Infectious complications remain a clinically significant problem following surgical treatment of calcaneal fractures, particularly in severe fracture patterns, open injuries, and patients with relevant comorbidities. Deep infections are associated with substantial morbidity and inferior functional outcomes. Optimization of patient-related risk factors, careful surgical planning, and the selective use of minimally invasive approaches may help reduce infection risk. Further high-quality prospective studies with standardized outcome measures are needed to define optimal management strategies. Full article
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10 pages, 320 KB  
Article
Management of Hypothyroidism in Pregnancy and Its Impact on Maternal and Perinatal Outcomes: A Single-Center Retrospective Cohort Study
by Chinnu George Samuel, Asma Jamil, Mohamed Bashir, Hala Abdullahi and Ibrahim Ibrahim
Life 2026, 16(3), 527; https://doi.org/10.3390/life16030527 - 22 Mar 2026
Viewed by 1017
Abstract
Background: Hypothyroidism is one of the most common endocrine conditions during pregnancy and has been associated with poor obstetric and perinatal outcomes. There is still a lack of data from Middle Eastern populations, despite its clinical significance. This study aimed to evaluate thyroid [...] Read more.
Background: Hypothyroidism is one of the most common endocrine conditions during pregnancy and has been associated with poor obstetric and perinatal outcomes. There is still a lack of data from Middle Eastern populations, despite its clinical significance. This study aimed to evaluate thyroid management patterns during pregnancy and examine the association between thyroid function control and maternal and perinatal outcomes in women with hypothyroidism at a tertiary care center in Qatar. Methods: A retrospective cohort study including 379 pregnant women with hypothyroidism diagnosed between January 2019 and November 2022 was conducted at Sidra Medicine in Doha, Qatar. Based on trimester-specific Thyroid-stimulating hormone (TSH )reference values, participants were categorized as having adequately or inadequately controlled thyroid function. Data on obstetrics, biochemistry, and demographics were taken from electronic medical records (EMR). Statistical analyses were performed using chi-square tests for categorical variables and t-tests for continuous variables, with a significance threshold of p < 0.05. Results: Participants had a mean Body Mass Index (BMI) of 30.33 ± 6.14 kg/m2 and an average age of 32.65 ± 4.99 years; 54% of them were Qataris. Of the patients, 58.5% had positive thyroid antibodies and 55.7% had pre-gestational hypothyroidism. Women with pre-gestational hypothyroidism required significantly higher levothyroxine doses compared with those with gestational hypothyroidism (93.2 ± 47.5 mcg/day vs. 67.6 ± 30.1 mcg/day; p < 0.001). Treatment adjustment was demonstrated by the improvement in TSH normalization from 51.3% in the first trimester to 64.2% in the third trimester (p = 0.041). No significant associations were observed with pre-eclampsia, preterm delivery, hypertension, or placental abruption. However, women with normal third-trimester TSH had a higher prevalence of gestational diabetes mellitus (GDM) compared with those with elevated TSH (51.6% vs. 36.8%; p = 0.013). Conclusions: Appropriate trimester-specific monitoring and timely levothyroxine titration was associated with improved biochemical control without adverse maternal outcomes. Greater levothyroxine requirements in women with pre-gestational hypothyroidism emphasize the importance of early intervention. These findings highlight the potential benefit of structured thyroid monitoring and multidisciplinary care approaches in pregnancy and may help inform future regional clinical practice guidelines. Full article
(This article belongs to the Section Medical Research)
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18 pages, 1609 KB  
Article
Airborne Ragweed (Ambrosia artemisiifolia) Allergen Exposure and Sensitization Pattern in Western Romania: A 5-Year Retrospective Cross-Sectional Observational Analysis of Sensitization Prevalence, Complemented by a Parallel Temporal Analysis of Aerobiological Data and Symptom-Driven Healthcare Presentation Patterns Study
by Valentin-Cristian Iovin, Carmen Neamtu, Roxana Buzan, Corina Porr, Alina-Daniela Totorean, Ana-Adina Iovin, Andreea-Adriana Neamtu, Diana Luisa Lighezan and Carmen Panaitescu
Life 2026, 16(3), 526; https://doi.org/10.3390/life16030526 - 22 Mar 2026
Viewed by 633
Abstract
Ragweed (Ambrosia artemisiifolia) represents a major and expanding source of aeroallergen exposure in Europe, with rising sensitization rates and substantial clinical impact. However, population-level data integrating airborne pollen exposure with detailed clinical sensitization patterns remain limited. We conducted a 5-year retrospective [...] Read more.
Ragweed (Ambrosia artemisiifolia) represents a major and expanding source of aeroallergen exposure in Europe, with rising sensitization rates and substantial clinical impact. However, population-level data integrating airborne pollen exposure with detailed clinical sensitization patterns remain limited. We conducted a 5-year retrospective cross-sectional observational analysis of sensitization prevalence, complemented by a parallel temporal analysis of aerobiological data and symptom-driven healthcare presentation patterns (2020–2024) in Timisoara, Romania, including all patients undergoing first-time sensitization evaluation at a tertiary referral hospital. Sensitization was assessed using standardized skin prick testing to common aeroallergens and other allergen categories, while airborne ragweed pollen concentrations were monitored through a peri-urban network of real-time bio-particle analyzers. Statistical analyses included descriptive statistics, multivariable logistic regression, χ2 tests for co-sensitization patterns, and comparative analyses of clinical manifestations across sensitization profiles. Among 4404 eligible patients, 50.7% were sensitized to at least one allergen. Ragweed sensitization was identified in 24.1% of patients, with a mean age of 31.1 years at diagnosis and no significant sex-related difference. Most ragweed-sensitized patients were polysensitized (71.5%), predominantly to other aeroallergens. Increasing age was independently associated with lower odds of polysensitization to other aeroallergens (adjusted OR = 0.97 per year, 95% CI: 0.96–0.98), while sex showed no independent association. Patients with ragweed sensitization alone and those cosensitized with aeroallergens exhibited similar prevalence of respiratory manifestations, whereas individuals with additional non-aeroallergen sensitization showed lower prevalence of rhinitis, conjunctivitis, and asthma but slightly higher rates of asthma exacerbations. Weekly diagnoses of ragweed sensitization demonstrated a pronounced seasonal peak between calendar weeks 33 and 38 (mid-August to late September), coinciding with peak airborne ragweed pollen concentrations. Ragweed sensitization therefore represents a substantial and seasonally driven healthcare burden in western Romania, characterized by frequent polysensitization, distinct clinical manifestation patterns across sensitization profiles, and close temporal alignment between airborne pollen exposure and clinical presentation. Integrating aerobiological monitoring with clinical surveillance may support targeted prevention strategies and improved patient management. Full article
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12 pages, 1871 KB  
Article
Quantification of Isoflurane Uptake for Immobilization of Ostrich Embryos for Preclinical In Ovo Imaging
by Thomas Winkens, Wiebke Neuschulz, Hans-Wolfgang Hoppe, Olga Perkas, Philipp Seifert, Falk Gühne, Julia Greiser, Martin Freesmeyer and Christian Kühnel
Life 2026, 16(3), 525; https://doi.org/10.3390/life16030525 - 22 Mar 2026
Viewed by 486
Abstract
Preclinical imaging has recently been expanded through the use of ostrich embryos as an alternative in vivo model. In ovo experiments represent a promising substitute for conventional rodent-based animal testing. For artifact-free dynamic nuclear medicine imaging, reliable immobilization of embryos is essential. Although [...] Read more.
Preclinical imaging has recently been expanded through the use of ostrich embryos as an alternative in vivo model. In ovo experiments represent a promising substitute for conventional rodent-based animal testing. For artifact-free dynamic nuclear medicine imaging, reliable immobilization of embryos is essential. Although previous studies have demonstrated the feasibility of isoflurane anesthesia, the kinetics and uptake mechanisms of isoflurane in ostrich embryos remain insufficiently characterized. The aim of this study was to characterize gas exchange dynamics in ostrich eggs and to quantify isoflurane uptake using two complementary approaches: indirect consumption measurements in a closed system and direct quantification by serial blood sampling. Fourteen ostrich eggs, including seven fertilized and seven unfertilized specimens, were analyzed at developmental stages up to day 37 of incubation. Gas exchange was assessed in a sealed container using a clinical anesthesia gas monitoring system to measure oxygen consumption and carbon dioxide excretion. Isoflurane uptake was evaluated during exposure to concentrations of 2%, 4%, or 6%. In a separate experimental series, serial blood samples were collected during and after exposure to the same concentrations to determine systemic uptake. Fertilized embryos showed progressive increases in metabolic activity, with a maximal oxygen consumption and carbon dioxide excretion of 116 mL/h/kg and 93 mL/h/kg on day 37. Indirect measurements demonstrated isoflurane uptake rates of up to 1.1 mL/min at 6%, with proportionally lower values at 4% and 2%. Blood analyses confirmed systemic absorption, peak concentrations of 160 µg/mL, and detectable residual levels for up to 120 min after exposure. These findings refine in ovo imaging. Full article
(This article belongs to the Special Issue Innovations in Nuclear Medicine and Molecular Imaging)
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11 pages, 891 KB  
Article
The Effect of a Novel Achilles Brace on Concentric and Eccentric Achilles Tendon Loading During Tendon Tear Mechanisms
by Roni Gottlieb, Shai Greenberg, Asaf Shalom and Julio Calleja Gonzalez
Life 2026, 16(3), 524; https://doi.org/10.3390/life16030524 - 21 Mar 2026
Viewed by 638
Abstract
(1) Achilles tendon rupture is one of the most severe lower-limb injuries, frequently occurring during movements involving maximal dorsiflexion with the knee at near-full extension. Preventive strategies are crucial, particularly for athletes engaged in high-risk sports such as basketball. (2) In this work, [...] Read more.
(1) Achilles tendon rupture is one of the most severe lower-limb injuries, frequently occurring during movements involving maximal dorsiflexion with the knee at near-full extension. Preventive strategies are crucial, particularly for athletes engaged in high-risk sports such as basketball. (2) In this work, we examined the effect of a novel Achilles brace on Achilles tendon loading during concentric and eccentric mechanisms associated with tendon rupture. (3) Twenty-eight young basketball players performed tests under two conditions: with the adaptive brace and without it (control). Participants were divided into two groups (n = 14 in both). The first group assessed concentric Achilles loading by performing three plantar-flexor strength tests in three different joint configurations: maximal dorsiflexion with the knee flexed (FKF); injury mechanism position—full plantar flexion with the knee extended (FKE); and neutral ankle position with the knee extended (NKE). The number of maximal heel-raise repetitions performed before onset of fatigue was recorded. The second group assessed eccentric tendon loading by performing single-leg forced maximal-velocity dorsiflexion with the knee extended. In all tests, the time between maximal plantar flexion and maximal dorsiflexion, as well as the ankle range of motion, was analyzed using 2D video. Paired t-tests were used to compare braced and control conditions. In all tests, the ankle range of motion (ROM) did not differ significantly between brace and control conditions. Wearing the brace significantly improved plantar-flexor muscle strength only in the FKE test (31 ± 1.3 repetitions with brace vs. 21 ± 1.3 in control, p < 0.05). No significant differences were found for the FKF (27 ± 1.3 vs. 25 ± 1.3) or NKE (25 ± 1.3 vs. 24 ± 1.3) positions. During drop eccentric loading, wearing the brace resulted in a significantly slower transition time from plantar flexion to dorsiflexion (460 ± 60 ms with brace vs. 320 ± 30 ms in control, p < 0.001). (4) In brief, the novel Achilles brace was found to significantly reduces Achilles tendon load during both concentric and eccentric activities, but only in high-risk joint positions. These findings suggest that the brace provides mechanical protection, and may reduce the risk of Achilles tendon rupture, in athletes exposed to high tendon stress. Full article
(This article belongs to the Section Physiology and Pathology)
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13 pages, 1008 KB  
Article
Acute Biochemical Responses to Competitive Tournament Load in Female Handball Players: Hormonal, Inflammatory and Muscle Damage Markers
by Zarife Pancar, Yücel Makaracı, Celal Gençoğlu, Burak Karaca and Hasan Ulusal
Life 2026, 16(3), 523; https://doi.org/10.3390/life16030523 - 21 Mar 2026
Viewed by 593
Abstract
Background: Congested tournament schedules impose substantial physiological stress in team sports; however, the integrated endocrine and inflammatory responses to real competitive match load in female handball players remain insufficiently characterized. Objective: This study aimed to characterize the acute biochemical responses, including hormonal, inflammatory, [...] Read more.
Background: Congested tournament schedules impose substantial physiological stress in team sports; however, the integrated endocrine and inflammatory responses to real competitive match load in female handball players remain insufficiently characterized. Objective: This study aimed to characterize the acute biochemical responses, including hormonal, inflammatory, muscle damage, and bone metabolism markers, elicited by competitive tournament load in female handball players and to provide practical insights for optimizing recovery strategies and load management during short-term competitive periods. Methods: In a pre–post study design, venous blood samples were collected from competitive female athletes (n = 8; age 20.83 ± 2.93 years) before the first match and after the fourth consecutive match of an official university qualification tournament. Biochemical analyses included cortisol, insulin, IL-6, creatine kinase (CK), IGF-1, irisin, lactate dehydrogenase (LDH), osteocalcin, and testosterone. Pre-to-post changes were assessed using paired t-tests and effect sizes. Results: Tournament load induced substantial multisystem physiological perturbations. Significant increases were observed in cortisol (p < 0.001), insulin (p = 0.044), IL-6 (p < 0.001), CK (p < 0.001), and osteocalcin (p = 0.005), indicating activation of the hypothalamic–pituitary–adrenal axis, systemic inflammation, muscle membrane disruption, and enhanced bone turnover. Conversely, IGF-1 (p < 0.001) and testosterone (p = 0.004) significantly decreased, reflecting suppression of anabolic signaling and a shift toward a catabolic hormonal environment under cumulative match stress. LDH significantly decreased (p = 0.002), while irisin showed no significant change (p > 0.05). Conclusions: These findings demonstrate that congested tournament schedules provoke an integrated endocrine–inflammatory stress response in female handball players. Importantly, the observed anabolic–catabolic imbalance highlights the need for individualized recovery strategies, optimized load management, and adequate recovery periods to mitigate maladaptation and reduce injury risk during short-term competitive tournaments. Full article
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13 pages, 649 KB  
Article
Cardiovascular Safety Signals of Oral Versus Topical Minoxidil in FAERS: A Disproportionality Analysis (Analytic Cohort 2012–2025)
by Hima Bindu Makkena and Vikas Kasu
Life 2026, 16(3), 522; https://doi.org/10.3390/life16030522 - 21 Mar 2026
Viewed by 1047
Abstract
Oral minoxidil, including low-dose regimens, is increasingly used off-label for alopecia, but cardiovascular safety remains a clinical concern. We compared cardiovascular adverse event reporting patterns for oral versus topical minoxidil using a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS). FAERS [...] Read more.
Oral minoxidil, including low-dose regimens, is increasingly used off-label for alopecia, but cardiovascular safety remains a clinical concern. We compared cardiovascular adverse event reporting patterns for oral versus topical minoxidil using a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS). FAERS data (2004Q1–2025Q3) were imported and deduplicated; minoxidil reports were restricted to primary/secondary suspect (PS/SS) drugs and eligible reports from 2012 to 2025. Exposure was classified as ORAL, TOPICAL, BOTH, or UNKNOWN using a standardized route/dose-form dictionary. Signals for Core and Expanded cardiovascular MedDRA Preferred Terms (PTs) were assessed using reporting odds ratios (RORs) with 95% confidence intervals; sensitivity analyses included alopecia-restricted cohorts excluding hypertension indications. In the primary ORAL-versus-TOPICAL cohort (559 oral; 56,947 topical), 23 Core-list PTs and 31 Expanded-list PTs met the signal definition. Strongest primary signals included pericardial effusion (ROR 307; 95% CI 158–597), hypertensive crisis (ROR 1037; 95% CI 133–8117), pulmonary hypertension (ROR 932; 95% CI 118–7368), and pulmonary edema (ROR 1965; 95% CI 114–33,813). In an alopecia-restricted sensitivity cohort excluding hypertension/blood-pressure indications (146 oral; 24,367 topical), hemodynamic and effusion-related PTs (e.g., tachycardia, palpitations, orthostatic hypotension, syncope, and pericardial effusion) remained disproportionately reported, although event counts were smaller and confidence intervals were wider. Oral minoxidil PS/SS reports in FAERS showed disproportionate reporting of several cardiovascular PTs relative to topical minoxidil reports. However, because FAERS is a spontaneous reporting system without exposed-patient denominators and with important limitations including under-reporting, stimulated reporting, incomplete clinical information, and residual confounding, these findings should be interpreted strictly as hypothesis-generating reporting signals rather than evidence of incidence, relative risk, or definitive comparative clinical safety. Full article
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26 pages, 2197 KB  
Review
Next-Generation Genotyping: Innovations Driving Plant Genomic Improvement
by Valeriya Kostyukova, Roza Kenzhebekova, Egor Protsenko, Bakyt Dulat, Marina Khusnitdinova and Dilyara Gritsenko
Life 2026, 16(3), 521; https://doi.org/10.3390/life16030521 - 21 Mar 2026
Viewed by 1013
Abstract
In recent years, plant genotyping has been shifting from the accumulation of whole-genome data toward their effective use in breeding programs This review examines key genotyping platforms, including single-nucleotide polymorphism (SNP) arrays, reduced-representation sequencing methods such as genotyping-by-sequencing (GBS) and restriction site-associated DNA [...] Read more.
In recent years, plant genotyping has been shifting from the accumulation of whole-genome data toward their effective use in breeding programs This review examines key genotyping platforms, including single-nucleotide polymorphism (SNP) arrays, reduced-representation sequencing methods such as genotyping-by-sequencing (GBS) and restriction site-associated DNA sequencing (RAD-seq), targeted genotyping approaches, and whole-genome sequencing (WGS), analyzing their informativeness, cost, and computational limitations. The transition to pangenome-based genotyping and graph genomes is discussed, as these approaches reduce reference bias and increase sensitivity for detecting structural variants, introgressions, and rare alleles that are important for adaptation and breeding. The growing role of AI/ML is highlighted in modeling complex genotype–phenotype relationships, integrating genomic and phenotypic data, and improving the accuracy and interpretability of genomic predictions. Full article
(This article belongs to the Special Issue Advances in Plant Biotechnology and Molecular Breeding)
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23 pages, 923 KB  
Review
From Beat to Risk: How Heart Rate Variability Predicts Arrhythmias in Type 2 Diabetes
by Amelian Madalin Bobu, Ștefania-Teodora Duca, Andrei Ionut Cucu, Diana Alina Avieriței, Cosmina-Georgiana Ponor, Maria-Ruxandra Cepoi, Sandu Cucută, Bianca-Ana Dmour, Claudia Florida Costea, Gina Botnariu and Irina-Iuliana Costache-Enache
Life 2026, 16(3), 520; https://doi.org/10.3390/life16030520 - 21 Mar 2026
Viewed by 1244
Abstract
Type 2 diabetes mellitus is associated with major cardiovascular complications, including cardiac autonomic neuropathy, which contributes to sympathetic–parasympathetic imbalance and increases susceptibility to arrhythmias and sudden cardiac death. Heart rate variability, assessed through R–R intervals on electrocardiography and 24 h Holter monitoring, represents [...] Read more.
Type 2 diabetes mellitus is associated with major cardiovascular complications, including cardiac autonomic neuropathy, which contributes to sympathetic–parasympathetic imbalance and increases susceptibility to arrhythmias and sudden cardiac death. Heart rate variability, assessed through R–R intervals on electrocardiography and 24 h Holter monitoring, represents a sensitive, non-invasive marker of autonomic dysfunction and arrhythmogenic risk. In patients with type 2 diabetes mellitus, chronic hyperglycaemia, oxidative stress, and metabolic inflammation lead to early impairment of the autonomic nervous system, manifested by consistent reductions in SDNN, RMSSD, pNN50, total power, and the high-frequency component, indicating diminished parasympathetic tone and sympathetic predominance. Nonlinear HRV indices demonstrate a loss of complexity and fractal organisation, providing additional prognostic value beyond conventional time- and frequency-domain analyses. Reduced HRV correlates with the severity of cardiac autonomic neuropathy, duration of diabetes, and poor glycaemic control, identifying patients with increased arrhythmogenic vulnerability. HRV analysis enables prediction of arrhythmic risk, facilitating the identification of high-risk individuals and guiding personalised interventions. The integration of HRV assessment into routine clinical practice may improve the early detection of subclinical autonomic neuropathy and optimise cardiovascular risk stratification and management in patients with type 2 diabetes mellitus. Full article
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13 pages, 960 KB  
Article
Perioperative Tranexamic Acid Reduces Bleeding and Wound Complications in Post-Bariatric Abdominoplasty: A Retrospective Cohort Study
by Shaghayegh Gorji, Bettina Zidek, Tobias Hirsch, Philipp Wiebringhaus, Maximilian Jacobi and Sascha Wellenbrock
Life 2026, 16(3), 519; https://doi.org/10.3390/life16030519 - 21 Mar 2026
Viewed by 680
Abstract
Background: Post-bariatric abdominoplasty is associated with a high risk of bleeding and wound complications due to extensive tissue resection and impaired tissue quality. Tranexamic acid (TXA) reduces perioperative bleeding in multiple surgical disciplines, but evidence in massive-weight-loss abdominoplasty is limited. The aim of [...] Read more.
Background: Post-bariatric abdominoplasty is associated with a high risk of bleeding and wound complications due to extensive tissue resection and impaired tissue quality. Tranexamic acid (TXA) reduces perioperative bleeding in multiple surgical disciplines, but evidence in massive-weight-loss abdominoplasty is limited. The aim of our study was to evaluate the association between perioperative TXA use and bleeding-related and surgical outcomes in post-bariatric abdominoplasty. Methods: This retrospective cohort study included 97 patients undergoing post-bariatric abdominoplasty, of whom 49 received perioperative TXA and 48 did not. The primary outcome was a composite of bleeding-related complications within 30 days, including hematoma, clinically relevant bleeding, or reoperation. Secondary outcomes included overall and specific surgical site complications, drain output and duration, length of hospital stay, and perioperative hemoglobin changes. Multivariable regression analyses adjusted for body mass index, abdominoplasty type, and year of surgery. Results: Bleeding-related complications were significantly lower in the TXA group compared with controls (4.1% vs. 33.3%; unadjusted OR 0.09, 95% CI 0.02–0.40; p < 0.001). This association remained significant after adjustment (adjusted OR 0.13, 95% CI 0.03–0.68; p = 0.016). TXA use was associated with lower cumulative drain output (median 200 vs. 382.5 mL; p < 0.001) and shorter drainage duration (median 4 vs. 5 days; p < 0.001). Overall complications were reduced in the TXA group (42.9% vs. 66.7%; p = 0.025), driven by fewer wound healing disturbances. Hemoglobin changes, seroma, and infection rates were similar between groups. Conclusions: Perioperative TXA use in post-bariatric abdominoplasty is associated with significantly fewer bleeding-related and wound complications without increased adverse effects, supporting its use in this high-risk population. Full article
(This article belongs to the Section Medical Research)
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19 pages, 1032 KB  
Review
Assessment of Congestion in Heart Failure Using VExUS: Current Evidence, Limitations and Clinical Perspectives
by Cosmina-Georgiana Ponor, Maria-Ruxandra Cepoi, Marilena Renata Spiridon, Ionuț Tudorancea, Amelian Mădălin Bobu, Minerva Codruta Badescu, Alexandru Dan Costache, Sandu Cucută and Irina-Iuliana Costache-Enache
Life 2026, 16(3), 518; https://doi.org/10.3390/life16030518 - 20 Mar 2026
Viewed by 2399
Abstract
Background: Systemic venous congestion is a key driver of organ dysfunction in heart failure (HF), yet accurate non-invasive quantification remains challenging. Recognizing residual congestion is critical, since it predicts HF readmissions and mortality. Traditional assessments (physical exam, jugular venous pressure, inferior vena [...] Read more.
Background: Systemic venous congestion is a key driver of organ dysfunction in heart failure (HF), yet accurate non-invasive quantification remains challenging. Recognizing residual congestion is critical, since it predicts HF readmissions and mortality. Traditional assessments (physical exam, jugular venous pressure, inferior vena cava [IVC] size) are imprecise. The Venous Excess Ultrasound Score (VExUS) is a semi-quantitative point-of-care ultrasound (POCUS) protocol that integrates IVC diameter with Doppler flow patterns in the hepatic, portal and intrarenal veins to grade systemic venous overload. Methods: We conducted a narrative review of literature (2018–2025) regarding the usefulness of VExUS in HF, covering congestion pathophysiology, clinical evidence (hemodynamic correlations, organ dysfunction, outcomes), potential applications, integration with lung ultrasound, echocardiography and biomarkers, limitations of its assessment and future directions. Results and Discussions: In HF, elevated right atrial pressure causes venous congestion. VExUS integrates IVC diameter with Doppler waveforms of hepatic, portal, and intrarenal veins to grade congestion. Emerging evidence shows higher VExUS grades correlate with elevated filling pressures, renal dysfunction, and worse outcomes. Its use may guide diuretic therapy, aid discharge planning, and monitor outpatient congestion, especially when combined with lung ultrasound and biomarkers. However, VExUS has limitations: it is technical and operator-dependent. Importantly, large trials validating VExUS-guided management are lacking. Future directions include AI-driven automation of Doppler analysis and integration with multimodal congestion monitoring to provide a comprehensive congestion assessment. Conclusions: VExUS is a promising noninvasive tool for quantifying congestion in HF. Higher grades are associated with organ dysfunction and poor prognosis. Incorporating this technique into HF care may improve congestion-guided therapy, but large-scale validation is required before routine use. Full article
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14 pages, 1391 KB  
Article
Scaling Surface-Guided Radiation Therapy to Larger Lung Cancer Cohorts: Frameless Immobilization and Enhanced Setup Accuracy
by Jang Bo Shim, Jeongeun Hwang, Sun Myung Kim, Yeong Cheol Lee, Eun Hee Jeon and Hakyoung Kim
Life 2026, 16(3), 517; https://doi.org/10.3390/life16030517 - 20 Mar 2026
Viewed by 577
Abstract
Objectives: This study aimed to evaluate the setup accuracy and intrafractional geometric stability of surface-guided radiation therapy (SGRT) under frameless immobilization in lung cancer radiotherapy and to assess its clinical utility in a relatively large patient cohort. Materials and Methods: A total of [...] Read more.
Objectives: This study aimed to evaluate the setup accuracy and intrafractional geometric stability of surface-guided radiation therapy (SGRT) under frameless immobilization in lung cancer radiotherapy and to assess its clinical utility in a relatively large patient cohort. Materials and Methods: A total of 678 treatment fractions from 52 patients with primary non-small cell lung cancer (NSCLC), treated between October 2024 and November 2025, were retrospectively analyzed. Patient setup was performed using SGRT with the Identify system, and cone-beam computed tomography (CBCT) served as the reference for internal target localization Intrafractional setup displacements, center-of-mass (COM) shifts, residual setup errors, and intrafractional clinical target volume (CTV) variations were evaluated. Spatial agreement between planned and intrafractional tumor volumes was quantified using the Dice Similarity Coefficient (DSC). Results: The mean CBCT-based intrafractional shifts were −0.01 mm (vertical), 0.03 mm (longitudinal), and 0.01 mm (lateral), indicating negligible systematic errors. The greatest variability was observed in the longitudinal direction (standard deviation, 1.32 mm), with a maximum displacement of 4.58 mm. COM-based analysis demonstrated near-zero mean displacements in all directions, with standard deviations ranging from 0.01 to 0.02 mm. DSC values ranged from 0.91 to 0.98, with a mean of 0.96, indicating excellent spatial agreement between planned and intrafractional tumor volumes. Residual setup errors were predominantly within ±1 mm, and the mean intrafractional CTV volume change was minimal (0.27 cm3). Conclusions: SGRT-based frameless lung cancer radiotherapy demonstrated high setup accuracy and robust intrafractional geometric stability. Although slightly greater variability was observed in the longitudinal direction, overall positional deviations and volumetric changes remained within clinically acceptable limits. These findings support the feasibility of integrating SGRT with CBCT-guided radiotherapy and suggest potential benefits for workflow efficiency and planning target volume margin optimization. Full article
(This article belongs to the Special Issue Pathology, Diagnosis, and Treatments of Airway Diseases)
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28 pages, 2639 KB  
Article
A Triple-Hit Multi-Omics Framework for Psoriasis: Microbial Metabolic Remodeling and Immune Cell Methylome Signature Associated with an AMP-Dominant Lesional Program
by Yoon Kyeong Lee, Hak Yong Kim and Donghwan Shim
Life 2026, 16(3), 516; https://doi.org/10.3390/life16030516 - 20 Mar 2026
Viewed by 654
Abstract
The gut–skin axis is increasingly implicated in psoriasis pathogenesis, yet the cross-compartment convergence of molecular programs remains incompletely defined. We constructed a conceptual “Triple-Hit” multi-omics framework by integrating five independent public datasets spanning gut microbial functional remodeling (shotgun metagenomics), systemic immune cell methylomes [...] Read more.
The gut–skin axis is increasingly implicated in psoriasis pathogenesis, yet the cross-compartment convergence of molecular programs remains incompletely defined. We constructed a conceptual “Triple-Hit” multi-omics framework by integrating five independent public datasets spanning gut microbial functional remodeling (shotgun metagenomics), systemic immune cell methylomes (PBMC and CD8+ T-cell EPIC 850K), and lesional skin regulatory layers (miRNA and bulk RNA-seq). In the gut compartment, functional profiles exhibited a selective reduction in microbial lipid catabolic potential, including decreased fatty acid degradation and a lowered composite lipid degradation score, alongside heterogeneous shifts across SCFA-associated metabolic pathways. Systemically, PBMC methylomes revealed widespread regional remodeling (45,396 DMRs) enriched for membrane-proximal signaling and cytoskeletal programs, while CD8+ T cells showed specific epigenetic alterations in lipid- and glycosphingolipid-associated loci, suggesting a systemic metabolic–epigenetic alignment. In the skin, we identified a compact miRNA signature (168 DE-miRNAs) and a mechanistically interpretable, directionality-constrained miRNA–mRNA bridge that aligns with an AMP-dominant inflammatory transcriptome, consistent with reduced post-transcriptional restraint. Collectively, these findings support a convergent multi-omics framework linking putative microbial metabolic remodeling, systemic immune priming, and cutaneous effector programs. This study provides a systems-level perspective on psoriasis pathogenesis, highlighting the metabolic–epigenetic–transcriptional convergence as a potential avenue for therapeutic intervention. Full article
(This article belongs to the Special Issue Mechanisms and Novel Biomarkers in Chronic Inflammatory Diseases)
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11 pages, 1897 KB  
Article
An Analysis of Hip and Knee Joint Movement Characteristics in Overweight Individuals During Sit-to-Stand Transfers—Based on Statistical Parametric Mapping: An Exploratory Study
by Guohui Zhao, Feifei Ma and Lei Li
Life 2026, 16(3), 515; https://doi.org/10.3390/life16030515 - 20 Mar 2026
Viewed by 511
Abstract
Objective: The objective of this study was to explore the motion characteristics and movement strategies of the hip and knee joints in overweight individuals during sit-to-stand (STS) transfers using statistical parametric mapping (SPM). Methods: Twenty subjects were divided into an overweight group ( [...] Read more.
Objective: The objective of this study was to explore the motion characteristics and movement strategies of the hip and knee joints in overweight individuals during sit-to-stand (STS) transfers using statistical parametric mapping (SPM). Methods: Twenty subjects were divided into an overweight group (n = 10) and a normal-weight group (n = 10) based on body mass index (BMI). The Qualisys infrared motion capture system and Kistler three-dimensional force platform were used for motion data collection, and Visual 3D and Matlab were used to calculate the angles and torque indicators of the lower limb hip and knee joints. Results: During the STS process, the maximum hip flexion angle of the overweight group was smaller than that of the control group (Z = −1.83, p = 0.043, r = 0.39), while the maximum abduction and external rotation angles were greater than those of the control group (Z = −2.15, p = 0.022, r = 0.46; Z = −2.02, p = 0.028, r = 0.48). SPM analysis showed that during the 0–52% phase of the hip joint in the frontal plane, the abduction amplitude of the overweight population was greater than that of the normal population (p < 0.05). The minimum external rotation angle of the knee joint was less than that of the control group (F(1,18) = 9.135, p = 0.043). The peak internal adduction and abduction torque of the hip joint in the overweight group was greater than that of the control group (Z = 2.37, p = 0.017, r = 0.54). Conclusions: Compared with the normal-weight population, the overweight population exhibited distinct motion characteristics of the hip and knee joints during the STS, with particularly pronounced differences in the hip joint. To maintain stability during STS, the overweight population adopts a compensatory movement strategy featuring a wider base of support via hip abduction and increased muscular torque to control frontal plane stability, which imposes greater functional loads on the hip joint. BMI-related movement characteristics should be studied in young adults under controlled experimental conditions, and future studies are needed to verify whether similar patterns exist in older adults. Full article
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18 pages, 1979 KB  
Review
The Use of Metabolomes in Risk Stratification of Patients with Heart Failure: A Scoping Review
by Umar G. Adamu, Marheb Badianyama, Minenhle Mayisela, Joel Amoni, Dineo Tsabedze, Muzi Maseko and Nqoba Tsabedze
Life 2026, 16(3), 514; https://doi.org/10.3390/life16030514 - 20 Mar 2026
Cited by 1 | Viewed by 697
Abstract
Heart failure (HF) is associated with substantial morbidity and mortality. Metabolic abnormalities are increasingly recognized as integral to HF pathophysiology and may provide incremental value for phenotyping and prediction of outcomes. However, a comprehensive synthesis of metabolic alterations and their prognostic implications remains [...] Read more.
Heart failure (HF) is associated with substantial morbidity and mortality. Metabolic abnormalities are increasingly recognized as integral to HF pathophysiology and may provide incremental value for phenotyping and prediction of outcomes. However, a comprehensive synthesis of metabolic alterations and their prognostic implications remains limited. This scoping review aimed to map metabolic changes in HF, describe analytical methods, and evaluate their diagnostic and prognostic relevance for clinical risk assessment. Methods: We systematically searched PubMed, Scopus, Web of Science, Cochrane Central, and grey literature from January 2010 to December 2024 to identify studies evaluating metabolic profiling in patients with HF. Two independent reviewers screened studies using predefined inclusion criteria and data were extracted using a customized charting form. Discrepancies were resolved by consensus or a third reviewer. We reported and synthesized findings narratively in accordance with scoping review methodology. Results: Seventy-two studies (66 observational and 6 randomized) were included, encompassing HF phenotypes including HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The analytical approaches included mass spectrometry and nuclear magnetic resonance (1H-NMR) platforms. The main metabolite classes that demonstrated prognostic significance were amino acids, acylcarnitines, and lipids, and gut-derived metabolites, which were associated with mortality, HF hospitalization, or disease progression. Several studies reported incremental prognostic value beyond conventional biomarker; however, most were exploratory, with modest sample sizes, limited external validation, and heterogeneous methodologies. Conclusions: Metabolomic profiling identifies biologically relevant alterations predicted worse clinical outcomes in HF and may complement existing risk assessment strategies. Nevertheless, standardized workflows and large prospective validation studies are required before clinical implementation can be considered. Full article
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17 pages, 2966 KB  
Article
The Formose Reaction with SO2: A Computational Study
by Emily M. Sisson and Jeremy Kua
Life 2026, 16(3), 513; https://doi.org/10.3390/life16030513 - 20 Mar 2026
Viewed by 759
Abstract
This study examines the influence of SO2 and its hydrate H2SO3 on the free energies of the core autocatalytic cycle of the formose reaction. We find that SO2 and H2SO3 readily condense with aldehyde and [...] Read more.
This study examines the influence of SO2 and its hydrate H2SO3 on the free energies of the core autocatalytic cycle of the formose reaction. We find that SO2 and H2SO3 readily condense with aldehyde and alcohol functional groups to form bisulfite analogs of formose proto-metabolites under modeled conditions. The bisulfite functional group can provide intramolecular catalytic enhancement in specific isomers towards aldol additions and the retroaldol step that regenerates two equivalents of glycolaldehyde from tetrose. The bisulfite moiety reduces the favorability of the parasitic Cannizzaro side-reaction both thermodynamically and kinetically, thus potentially furnishing more throughput towards forming sugars. As a prebiotic analog to phosphate, we find that bisulfite slightly stabilizes ribose over its C5 aldose diastereomers thermodynamically, although the effect is modest and may be influenced by solution dynamics. Full article
(This article belongs to the Special Issue Chemical Evolutionary Pathways to Origins of Life)
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12 pages, 1624 KB  
Article
Association Between Serum Vitamin D Levels and Colorectal Carcinoma: Insights from a Case Control Study in Northern Saudi Arabia
by Anass M. Abbas, Ashok Kumar Sah, Reef A. Alodhayd, Shahad A. Alblehed, Aryaf M. Almaeen, Saja T. Almadhor, Hala E. Sabaa, Rania Z. Alghafil, Nasir A. Nour, Abdulkhakov Ikhtiyor Umarovich, Ranjay Kumar Choudhary, Rabab H. Elshaikh and Manar G. Shalabi
Life 2026, 16(3), 512; https://doi.org/10.3390/life16030512 - 20 Mar 2026
Viewed by 925
Abstract
Background: Colorectal cancer (CRC) is a major global health concern and a leading cause of cancer-related mortality. In Saudi Arabia, it is the most common cancer among men and the third most common among women. The disease affects predominantly older adults, with an [...] Read more.
Background: Colorectal cancer (CRC) is a major global health concern and a leading cause of cancer-related mortality. In Saudi Arabia, it is the most common cancer among men and the third most common among women. The disease affects predominantly older adults, with an increasing number of cases reported in younger populations. Emerging evidence suggests a potential association between Vitamin D deficiency and CRC risk and progression. Aim: This study aimed to investigate the relationship between serum Vitamin D levels and colorectal cancer, and to evaluate its association with clinicopathological characteristics. Methodology: A retrospective case–control study was conducted on newly diagnosed CRC patients between January 2021 and August 2024 at King Abdul-Aziz Specialist Hospital, Prince Muteb Hospital, and the Oncology Center in Al Jouf, Saudi Arabia. A total of 100 CRC cases and 50 healthy controls were included. Serum 25-hydroxyvitamin D levels were measured and categorized as deficient (<20 ng/mL), insufficient (21–29 ng/mL), and normal (≥30 ng/mL). Histopathological features and tumor characteristics were analyzed. Statistical analyses included independent t-test, one-way ANOVA, and chi-square tests. Results: During the four-year period, 5399 gastrointestinal specimens were analyzed, of which 2111 (39.1%) were colorectal specimens. CRC was diagnosed in 107 cases (5.1%), and 100 patients met the inclusion criteria. The mean age of patients was 53.07 ± 13.3 years, and 69% were older than 50 years. Males represented 58% of cases (male-to-female ratio 1.4:1). Invasive adenocarcinoma was the predominant histological subtype (81%), with the sigmoid colon being the most common tumor site (39%). Vitamin D deficiency was significantly more prevalent in CRC patients (59%) compared to controls (22%). The mean serum Vitamin D level was significantly lower in cases (18.7 ± 11.3 ng/mL) than in controls (34.9 ± 15.6 ng/mL) (p < 0.001). No significant difference in Vitamin D levels was observed between males and females. Lower Vitamin D levels were significantly associated with advanced tumor grade (p = 0.004), lymphovascular invasion (p < 0.001), lymph node involvement (p = 0.001), and distant metastasis (p < 0.001). Representative histopathological images confirmed invasive moderately differentiated adenocarcinoma with characteristic malignant glandular architecture. Conclusions: Vitamin D deficiency was highly prevalent among colorectal cancer patients and was significantly associated with advanced tumor characteristics, including higher grade and metastatic features. These findings suggest a strong inverse relationship between serum Vitamin D levels and CRC development and progression. Further large-scale prospective and interventional studies are warranted to clarify the causal role of Vitamin D and its potential therapeutic implications in colorectal cancer prevention and management. Full article
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16 pages, 5461 KB  
Article
A Quantitative Comparison of Medial and Coronal Dentate Gyrus Microdissection Strategies and a Softening-Based Workflow for Reproducible Tissue Procurement
by Turan Koç and Nail Can Öztürk
Life 2026, 16(3), 511; https://doi.org/10.3390/life16030511 - 20 Mar 2026
Viewed by 1529
Abstract
A reliable isolation of the dentate gyrus (DG) is a critical pre-analytical step for region-specific neurobiological assays, yet DG microdissection practices vary widely and are rarely compared quantitatively under standardized conditions. In addition, long-term paraformaldehyde-fixed archival brain tissue is commonly regarded as unsuitable [...] Read more.
A reliable isolation of the dentate gyrus (DG) is a critical pre-analytical step for region-specific neurobiological assays, yet DG microdissection practices vary widely and are rarely compared quantitatively under standardized conditions. In addition, long-term paraformaldehyde-fixed archival brain tissue is commonly regarded as unsuitable for microdissection because of reduced pliability and poor anatomical contrast, limiting its use for training and protocol development. Here, we quantitatively compare two commonly used DG microdissection strategies, a medial (intact-block) approach and a coronal (slice-guided) approach across fresh, fixed, and softened-fixed rat brain hemispheres under matched conditions. To enable the use of archival material, fixed hemispheres were subjected to a simple 15-day slow-running tap water softening protocol to improve tissue handling and landmark visibility. Dissection duration and anatomical specificity were evaluated, the latter quantified by measuring residual cornu ammonis (CA)1–3 area on hematoxylin–eosin-stained coronal sections following DG removal. In fresh tissue, the medial approach enabled significantly faster DG isolation than the coronal approach, while both strategies achieved comparable anatomical specificity. In softened-fixed tissue, dissection times increased for both approaches, but the same relative performance ranking was preserved. Softening markedly improved tissue pliability and boundary visualization, particularly benefiting the coronal, stepwise dissection strategy. Residual CA1–3 areas did not differ significantly between approaches or tissue states. This study provides a validated, training-oriented DG microdissection workflow that supports methodological standardization, reproducibility, and 3R-aligned use of archival tissue, strengthening the pre-analytical foundation for downstream region-specific neuroscience assays. Full article
(This article belongs to the Section Physiology and Pathology)
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25 pages, 712 KB  
Review
Smart Drug-Delivery Approaches for Enhanced Management of Comorbid Conditions in Alzheimer’s Disease
by Gabriela-Dumitrita Stanciu, Ivona Costachescu, Camelia Dascalu and Bogdan-Ionel Tamba
Life 2026, 16(3), 510; https://doi.org/10.3390/life16030510 - 19 Mar 2026
Viewed by 778
Abstract
Alzheimer’s disease (AD) remains a major unmet medical challenge due to its complex pathology, high interpatient heterogeneity and frequent association with systemic comorbidities. Conventional pharmacotherapy is limited by poor blood–brain barrier permeability, off-target effects and reduced efficacy in polymedicated elderly populations. Smart drug-delivery [...] Read more.
Alzheimer’s disease (AD) remains a major unmet medical challenge due to its complex pathology, high interpatient heterogeneity and frequent association with systemic comorbidities. Conventional pharmacotherapy is limited by poor blood–brain barrier permeability, off-target effects and reduced efficacy in polymedicated elderly populations. Smart drug-delivery systems (DDS), particularly nanotechnology-based platforms, have emerged as promising strategies to enhance brain targeting, optimize controlled drug release and mitigate systemic toxicity. This review examines recent advances in intelligent DDS for AD, with a focus on nanocarriers designed to modulate amyloid aggregation, neuroinflammation, oxidative stress and cholinergic dysfunction. Special attention is given to the impact of the most common comorbid conditions on DDS pharmacokinetics, safety and clinical performance. Furthermore, the challenges associated with clinical translation, such as long-term safety, immunogenicity, manufacturing scalability and regulatory harmonization, are critically discussed. In this context, versatile controlled release platforms that integrate rational design, predictive modeling and Quality by Design-driven manufacturing are highlighted as key enablers of translational success. By bridging intelligent formulation design with scalable production and regulatory readiness, advanced controlled release systems offer a pathway toward precision and patient-centered therapies. Such platforms hold significant potential to accelerate the safe integration of smart DDS into Alzheimer’s disease management and broader neurotherapeutic applications. Full article
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13 pages, 281 KB  
Article
Integrating Focused Shockwave Therapy into Rehabilitation for Groin Pain Syndrome: A Prospective Study in Soccer Players
by Gabriele Santilli, Flavia Santoboni, Elisa Checchi, Antonio Franchitto, Antonello Ciccarelli, Samanta Taurone, Eleonora Latini, Valter Santilli, Giorgio Felzani, Sveva Maria Nusca, Donatella Trischitta, Maria Chiara Vulpiani and Mario Vetrano
Life 2026, 16(3), 509; https://doi.org/10.3390/life16030509 - 19 Mar 2026
Viewed by 795
Abstract
Background/Objectives: Groin pain syndrome (GPS) is a frequent and heterogeneous condition in athletes, often associated with persistent pain and functional limitation. Both focused extracorporeal shockwave therapy (f-ESWT) and exercise-based rehabilitation have been proposed as conservative treatment options, but evidence for their combined [...] Read more.
Background/Objectives: Groin pain syndrome (GPS) is a frequent and heterogeneous condition in athletes, often associated with persistent pain and functional limitation. Both focused extracorporeal shockwave therapy (f-ESWT) and exercise-based rehabilitation have been proposed as conservative treatment options, but evidence for their combined use in GPS remains limited. This prospective single-arm pilot study aimed to describe temporal changes in pain and function following a multimodal conservative program combining f-ESWT and structured rehabilitation in athletes with GPS, using validated groin-specific outcome measures. Methods: Thirty-one consecutive adult soccer players (mean age 28.4 ± 5.8 years; 77.4% male) with clinically and MRI-confirmed GPS underwent three weekly f-ESWT sessions (Duolith; 2400 pulses/session; 4 Hz; energy flux density 0.20 mJ/mm2) integrated within a supervised 16-week rehabilitation program (progressive adductor strengthening, core stabilization, and stretching). Outcomes were assessed at baseline (T0), 1 month (T1), and 4 months (T2): HAGOS (primary), VAS pain, and Roles and Maudsley (RM). Within-subject changes were analyzed using repeated-measures ANOVA with Bonferroni correction. Results: Statistically significant temporal changes were observed across all outcomes (all p < 0.001). HAGOSs changed from 47.23 ± 7.79 at T0 to 77.94 ± 16.18 at T1 and 90.00 ± 14.26 at T2 (partial η2 = 0.89). VAS decreased from 6.81 ± 1.25 to 3.68 ± 1.11 and 1.90 ± 1.45 (partial η2 = 0.91). RM decreased from 2.39 ± 0.50 to 1.52 ± 0.57 and 1.26 ± 0.63 (partial η2 = 0.72). No adverse events were reported. Conclusions: In this single-arm pilot study, the multimodal program combining f-ESWT and structured rehabilitation was associated with temporal changes in groin-specific function and pain that exceeded established MCID thresholds. However, in the absence of a control group, these findings are purely descriptive and hypothesis-generating. The observed changes cannot be attributed to f-ESWT specifically, as the 16-week rehabilitation program likely contributed substantially to the outcomes. These preliminary observations require confirmation through adequately powered randomized controlled trials comparing the combined intervention to rehabilitation alone. Full article
(This article belongs to the Section Medical Research)
11 pages, 1843 KB  
Article
Diagonal Earlobe Crease and the Risk of New-Onset Atrial Fibrillation After Cavotricuspid Isthmus Ablation in Patients with Typical Atrial Flutter
by Moo-Nyun Jin, Young Ju Kim and Changho Song
Life 2026, 16(3), 508; https://doi.org/10.3390/life16030508 - 19 Mar 2026
Viewed by 573
Abstract
Background: Atrial fibrillation (AF) frequently develops in patients with atrial flutter (AFL), even after successful cavotricuspid isthmus (CTI) ablation. Identifying simple clinical markers for early detection is crucial. Diagonal earlobe crease (ELC), also known as Frank’s sign, has been proposed as a [...] Read more.
Background: Atrial fibrillation (AF) frequently develops in patients with atrial flutter (AFL), even after successful cavotricuspid isthmus (CTI) ablation. Identifying simple clinical markers for early detection is crucial. Diagonal earlobe crease (ELC), also known as Frank’s sign, has been proposed as a marker of aging and cardiovascular risk. This study investigates the association between ELC and the risk of new-onset AF following CTI ablation in patients with AFL. Methods: We conducted a retrospective cohort study of 292 patients without a prior history of AF who underwent CTI ablation for typical AFL between 2015 and 2024. The presence of ELC was assessed at baseline CTI ablation. The primary outcome was the occurrence of new-onset AF during follow-up, stratified according to the presence of ELC. The median follow-up duration was 49 months, with a minimum follow-up of 6 months. Results: Among the 292 patients, 72 (24.7%) exhibited ELC. Patients with ELC were older (59 ± 11 years vs. 55 ± 14 years, p = 0.05). During the follow-up period, new-onset AF occurred in 31 patients with ELC (43.1%) and 65 patients without ELC (29.5%) (p = 0.03). Kaplan–Meier analysis demonstrated that the occurrence of AF was significantly higher in the ELC group than in the non-ELC group (log-rank test, p = 0.013). Multivariate analysis revealed that ELC was independently associated with an increased risk of AF (hazard ratio 1.67, 95% confidence interval 1.03–2.72, p = 0.039). Conclusions: The presence of ELC is associated with a higher risk of new-onset AF following CTI ablation in patients with AFL. ELC may serve as a simple, non-invasive clinical marker to identify patients who may benefit from closer rhythm surveillance after AFL ablation. Full article
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41 pages, 1037 KB  
Review
Clinical Applications of Artificial Intelligence in Cardiovascular Imaging: Where Do We Stand?
by Archit A. Singhal, Tiffany Bowyer-Howell, Nikant Sabharwal, Andrew Lewis, Andrew R. J. Mitchell, Oliver Rider and John A. Henry
Life 2026, 16(3), 507; https://doi.org/10.3390/life16030507 - 19 Mar 2026
Viewed by 1288
Abstract
Cardiovascular imaging is essential in the diagnosis, phenotyping and prognostic assessment of cardiovascular disease. However, longstanding limitations constrain the accuracy, throughput, and scalability of cardiovascular imaging techniques. Artificial intelligence (AI) has demonstrated a diverse range of potential benefits across modalities, including echocardiography, computerised [...] Read more.
Cardiovascular imaging is essential in the diagnosis, phenotyping and prognostic assessment of cardiovascular disease. However, longstanding limitations constrain the accuracy, throughput, and scalability of cardiovascular imaging techniques. Artificial intelligence (AI) has demonstrated a diverse range of potential benefits across modalities, including echocardiography, computerised tomography, nuclear imaging, and magnetic resonance imaging. These benefits include automated quantification of key heart parameters, ability to improve traditional disease detection and phenotyping, and image reconstruction. While the use of AI in clinical workflows is still largely emerging, its significance is becoming established through numerous promising studies. The evidence reviewed indicates that AI can meaningfully enhance disease management, clinical operations and patient experience when used alongside physician expertise. However, several challenges restrict the widespread clinical implementation of AI, including a lack of robust prospective evidence, regulatory hurdles, bias in training datasets, and ethical drawbacks such as data privacy and accountability. Future developments should prioritise large-scale prospective and multicentre validation and address practical and ethical barriers to ensure AI can be utilised safely and effectively in clinical settings. This narrative review comprehensively analyses advances in AI-driven cardiovascular imaging with a focus on clinical implementation. Full article
(This article belongs to the Special Issue Precision Medicine in Cardiovascular Diseases)
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17 pages, 4618 KB  
Review
Reopening Motor Learning Windows: Targeted Re-Engagement of Latent Pathways via Non-Invasive Neuromodulation
by Diego Mac-Auliffe, Akhil Surapaneni and José del R. Millán
Life 2026, 16(3), 506; https://doi.org/10.3390/life16030506 - 19 Mar 2026
Viewed by 769
Abstract
Motor recovery after stroke, spinal cord injury, or traumatic brain injury reflects relearning rather than simple restitution, as surviving circuits retain plastic potential that can be re-engaged through temporally precise stimulation. This review synthesizes convergent findings demonstrating that Hebbian and spike-timing-dependent mechanisms govern [...] Read more.
Motor recovery after stroke, spinal cord injury, or traumatic brain injury reflects relearning rather than simple restitution, as surviving circuits retain plastic potential that can be re-engaged through temporally precise stimulation. This review synthesizes convergent findings demonstrating that Hebbian and spike-timing-dependent mechanisms govern reorganization across cortical, striatal, and spinal levels. Leveraging these timing rules to shape excitability during receptive network states enables durable changes in connectivity and behavior. This effect depends on temporal precision, physiological state, and reinforcement—not stimulus intensity alone—within plasticity windows regulated by metaplastic mechanisms that determine whether Hebbian processes are expressed. Together, these principles define a translational framework for neurorehabilitation, emphasizing biomarker-guided, adaptive, and scalable strategies aligned with intrinsic rules of experience-dependent reorganization. Full article
(This article belongs to the Special Issue Neuromodulation and Motor Skill Enhancement: Prospective Applications)
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26 pages, 1353 KB  
Review
Processed Diets and Food Additives Shape the Gut Microbiota and Chronic Disease Risk Across the Life Course—A Three-Layer Ecosystem Disruption Model (TLED) Model
by Monica Manciulea (Profir), Luciana Alexandra Pavelescu, Gabriel Florin Răzvan Mogoş, Alin Constantin Stancu, Sanda Maria Cretoiu and Ileana Marinescu
Life 2026, 16(3), 505; https://doi.org/10.3390/life16030505 - 19 Mar 2026
Cited by 1 | Viewed by 976
Abstract
Ultra-processed foods (UPFs) represent a distinct dietary paradigm characterized by structurally simplified food matrices and chronic exposure to multiple additives, including emulsifiers, artificial sweeteners, and preservatives. Rather than acting in isolation, these compounds operate within a multi-additive environment that reshapes the gut ecosystem [...] Read more.
Ultra-processed foods (UPFs) represent a distinct dietary paradigm characterized by structurally simplified food matrices and chronic exposure to multiple additives, including emulsifiers, artificial sweeteners, and preservatives. Rather than acting in isolation, these compounds operate within a multi-additive environment that reshapes the gut ecosystem through convergent mechanisms. Emerging evidence suggests that additive-rich ultra-processed dietary environments may disrupt the gut ecosystem through three interconnected layers: (1) structural impairment of the intestinal barrier, including mucus erosion and tight-junction destabilization; (2) microbial metabolic shifts marked by short-chain fatty acid depletion, altered bile acid signaling, and enrichment of lipopolysaccharide-producing taxa; and (3) immune and inflammatory reprogramming promoting low-grade systemic inflammation. These processes collectively reduce ecosystem resilience—the capacity of the gut microbiota to resist and recover from perturbation. Vulnerability to additive-driven dysbiosis varies across the life course. During infancy, incomplete ecosystem stabilization may increase susceptibility to long-term ecological imprinting, whereas in older age, reduced microbial diversity and immune remodeling may impair recovery capacity following dietary stressors. In contrast, fiber-rich, minimally processed dietary patterns appear to enhance microbial resilience by reinforcing functional redundancy, metabolic buffering, and barrier integrity. Although much mechanistic evidence has been derived from experimental models, accumulating human data support the biological plausibility of additive-associated microbiota alterations. By integrating multi-additive exposure, ecosystem disruption, life-course modulation, and resilience within a unified framework, this review provides a mechanistically coherent model linking ultra-processed dietary environments to microbiota-mediated chronic disease risk. Here, we formalize this integrative perspective as the Three-Layer Ecosystem Disruption (TLED) Model. Full article
(This article belongs to the Special Issue The Emerging Role of Microbiota in Health and Diseases)
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10 pages, 789 KB  
Article
Correlation of Early Vascular Aging Ambulatory Score with Kidney Damage in a Hypertensive Population: A Pilot Study
by Georgios Samprokatsidis, Christina Antza, Ioannis Partheniadis, Smaro Palaska, Panagiota Anyfanti and Vasilios Kotsis
Life 2026, 16(3), 504; https://doi.org/10.3390/life16030504 - 19 Mar 2026
Viewed by 465
Abstract
Background: Early vascular aging (EVA) reflects accelerated arterial stiffening and is closely linked to cardiovascular and renal target organ damage. The Early Vascular Aging Ambulatory score (EVAAs) estimates EVA using ambulatory blood pressure monitoring (ABPM) and routinely available clinical parameters. We aim to [...] Read more.
Background: Early vascular aging (EVA) reflects accelerated arterial stiffening and is closely linked to cardiovascular and renal target organ damage. The Early Vascular Aging Ambulatory score (EVAAs) estimates EVA using ambulatory blood pressure monitoring (ABPM) and routinely available clinical parameters. We aim to investigate the association between EVAAs-defined early vascular aging and markers of kidney involvement—particularly albumin-to-creatinine ratio (ACR)—in a hypertensive population. Methods: Fifty treated hypertensive adults undergoing 24 h ABPM were enrolled. All participants underwent laboratory evaluation, including serum electrolytes and 24 h urine collection for albumin, creatinine, sodium, and potassium. EVAAs was calculated using ABPM-derived parameters and established cardiovascular risk factors. Results: EVAAs was positively correlated with ACR (r = 0.276, p = 0.049). In addition, inverse correlations were observed between EVAAs and serum potassium (r = −0.290, p = 0.038) and serum sodium (r = −0.284, p = 0.046). Participants with moderately increased albuminuria tended to exhibit higher EVAAs values, although this difference did not reach statistical significance. Conclusions: EVAAs is associated with early markers of renal involvement in hypertensive patients, supporting its potential role as a non-invasive indicator of subclinical target organ damage. Larger studies are warranted to confirm these findings and to further validate EVAAs as a clinically useful marker of EVA. Full article
(This article belongs to the Special Issue Microvascular Research: Advances and Perspectives)
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20 pages, 1259 KB  
Article
Integrating GDF-15 into Multimarker Assessment of Acute Heart Failure: Diagnostic and Prognostic Implications
by Bianca-Ana Dmour, Minerva Codruta Badescu, Daniela Constantinescu, Cristina Tuchiluș, Corina Maria Cianga, Gina Eosefina Botnariu, Ionela Lăcrămioara Șerban, Awad Dmour, Amelian Madalin Bobu, Alexandru Dan Costache, Maria-Ruxandra Cepoi, Sandu Cucută and Irina Iuliana Costache-Enache
Life 2026, 16(3), 503; https://doi.org/10.3390/life16030503 - 19 Mar 2026
Viewed by 653
Abstract
Acute heart failure (AHF) is a leading cause of hospitalization and mortality worldwide. Despite advances in biomarker-based evaluation, accurate diagnostic and prognostic stratification remains challenging in everyday clinical practice. Growth differentiation factor-15 (GDF-15) has emerged as a biomarker associated with advanced disease profiles, [...] Read more.
Acute heart failure (AHF) is a leading cause of hospitalization and mortality worldwide. Despite advances in biomarker-based evaluation, accurate diagnostic and prognostic stratification remains challenging in everyday clinical practice. Growth differentiation factor-15 (GDF-15) has emerged as a biomarker associated with advanced disease profiles, poor outcomes and complex underlying pathophysiological processes in heart failure (HF). This study aimed to investigate the diagnostic and prognostic value of GDF-15 in the acute setting and to evaluate its incremental role within multimarker assessment strategies. In this prospective cohort study, 60 patients hospitalized with AHF and 42 control subjects were enrolled. Circulating levels of GDF-15, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin I (hs-cTnI) were measured at admission. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and multivariable logistic regression. Prognostic value was evaluated for in-hospital, short-term, and one-year mortality, including multimarker models. GDF-15 levels were significantly elevated in AHF and demonstrated a favorable diagnostic profile, with high specificity and acceptable sensitivity. When integrated into multivariable diagnostic models, GDF-15 added significant value beyond established cardiac biomarkers. For prognosis, standalone biomarkers showed limited long-term discrimination, whereas multimarker approaches incorporating GDF-15 improved short-term mortality prediction and enhanced one-year risk stratification in patients with markedly elevated NT-proBNP levels. GDF-15 provides independent diagnostic and prognostic information in AHF and enhances multimarker strategies for comprehensive patient assessment, supporting its integration as a complementary biomarker in contemporary AHF evaluation. Full article
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