Life

17 pages, 1908 KB

Open AccessArticle

Manual Dexterity Rehabilitation in Parkinson’s Disease and Paranoid Schizophrenia: A Controlled Study

by Tatiana Balint, Alina-Mihaela Cristuta, Adina Camelia Slicaru, Ilie Onu, Daniel Andrei Iordan and Ana Onu

Life 2026, 16(2), 196; https://doi.org/10.3390/life16020196 (registering DOI) - 24 Jan 2026

Abstract

Background: Manual dexterity (MD) impairment is a frequent and disabling feature in patients with Parkinson’s disease (PD) and paranoid schizophrenia (PS), significantly affecting functional independence and activities of daily living. However, rehabilitation strategies specifically targeting fine motor control remain insufficiently integrated into routine [...] Read more.

Background: Manual dexterity (MD) impairment is a frequent and disabling feature in patients with Parkinson’s disease (PD) and paranoid schizophrenia (PS), significantly affecting functional independence and activities of daily living. However, rehabilitation strategies specifically targeting fine motor control remain insufficiently integrated into routine physiotherapy (PT). Objective: This study investigated the effects of a structured, progressive PT program incorporating targeted MD training on upper limb function in patients with PD and PS. Methods: A prospective, exploratory, interventional study was conducted in 30 patients, allocated to either an experimental group (EG, n = 20) or a control group (CG, n = 10). Participants had PD (Hoehn and Yahr stages II–III) or chronic, clinically stable PS. MD was assessed using the Purdue Pegboard Test, Coin Rotation Task, and Kapandji opposition score. The EG completed a four-phase, 40-week dexterity-oriented rehabilitation program, while the CG received standard disease-specific PT. Between-group differences in change scores were analyzed using one-way ANOVA. Results: The EG showed significantly greater improvements than the CG in thumb opposition, psychomotor processing speed, and unilateral and bilateral fine motor performance (p < 0.001 for all), with large to very large effect sizes (η² = 0.45–0.76). No significant between-group differences were observed for complex sequential assembly tasks. Conclusions: Integrating targeted MD training into structured PT programs significantly improves fine motor performance in patients with PD and PS, supporting its inclusion in rehabilitation protocols for residential and outpatient care settings. Full article

(This article belongs to the Special Issue Physical Medicine and Rehabilitation: Trends and Applications—4th Edition)

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22 pages, 3191 KB

Open AccessReview

Airway Management in the ICU and Emergency Department in Resource-Limited Settings

by Sahil Kataria, Deven Juneja, Ravi Jain, Tonny Veenith and Prashant Nasa

Life 2026, 16(2), 195; https://doi.org/10.3390/life16020195 - 23 Jan 2026

Abstract

Airway management is central to the care of critically ill patients, yet it remains one of the most challenging interventions in emergency departments and intensive care units. Patients often present with severe physiological instability, limited cardiopulmonary reserve, and high acuity, while clinicians often [...] Read more.

Airway management is central to the care of critically ill patients, yet it remains one of the most challenging interventions in emergency departments and intensive care units. Patients often present with severe physiological instability, limited cardiopulmonary reserve, and high acuity, while clinicians often work under constraints related to time for preparation, equipment availability, trained workforce, monitoring, and access to advanced rescue techniques. These challenges are particularly pronounced in low- and middle-income countries and other resource-limited or austere environments, where the margin for error is narrow and delays or repeated attempts in airway management may rapidly precipitate hypoxemia, hemodynamic collapse, or cardiac arrest. Although contemporary airway guidelines emphasize structured preparation and rescue pathways, many assume resources that are not consistently available in such settings. This narrative review discusses pragmatic, context-adapted strategies for airway management in constrained environments, with emphasis on physiology-first preparation, appropriate oxygenation and induction techniques, simplified rapid-sequence intubation, and the judicious use of basic airway adjuncts, supraglottic devices, and video laryngoscopy, where available. Adapted difficult airway algorithms, front-of-neck access in the absence of surgical backup, human factors, team training, and ethical considerations are also addressed. This review aims to support safer and effective airway management for critically ill patients in resource-limited emergency and intensive care settings. Full article

(This article belongs to the Special Issue Intensive Care Medicine: Current Concepts and Future Perspectives)

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11 pages, 691 KB

Open AccessArticle

The Effects of Comorbidities on Outcomes After Total Hip Replacement

by Hou Hoi Iong, Chih-Hung Chang, Jwo-Luen Pao, Wen-Chih Chen, Shang-Ming Lin and Cheng-Tzu Wang

Life 2026, 16(2), 194; https://doi.org/10.3390/life16020194 - 23 Jan 2026

Abstract

Background: The relationship between comorbidity burden, as measured by the American Society of Anesthesiologists (ASA) classification, and functional recovery after total hip replacement (THR) remains uncertain. This study aimed to clarify whether ASA grade independently predicts postoperative patient-reported outcomes. Methods: We conducted a [...] Read more.

Background: The relationship between comorbidity burden, as measured by the American Society of Anesthesiologists (ASA) classification, and functional recovery after total hip replacement (THR) remains uncertain. This study aimed to clarify whether ASA grade independently predicts postoperative patient-reported outcomes. Methods: We conducted a retrospective analysis of 218 consecutive patients from a prospectively maintained institutional registry who underwent primary unilateral THR between March 2021 and March 2024 in a single center. Patients were stratified into ASA 1–2 and ASA 3 groups. The Oxford Hip Score (OHS, 0–48) was collected preoperatively and at 1 week, 3 months, and 6 months postoperatively. Between-group differences were assessed, and multivariable linear regression was used to identify predictors of 6-month OHS. Results: Compared with ASA 1–2 patients, ASA 3 patients had lower preoperative OHS and longer hospital stay, but both groups showed substantial improvement over time and achieved excellent mean OHS at 6 months. In the adjusted model, higher ASA grade remained an independent negative predictor of 6-month OHS, whereas higher preoperative OHS and BMI were positive predictors. Conclusions: Despite presenting with worse baseline function and requiring longer hospitalization, ASA 3 patients experienced clinically meaningful recovery and achieved favorable 6-month outcomes after THR. Higher ASA status should therefore inform perioperative optimization rather than preclude surgery. Full article

(This article belongs to the Special Issue Osteoarthritis: New Insights into Mechanisms, Diagnosis, Therapy and Management)

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13 pages, 613 KB

Open AccessArticle

Selective Motor Entropy Modulation and Targeted Augmentation for the Identification of Parkinsonian Gait Patterns Using Multimodal Gait Analysis

by Yacine Benyoucef, Jouhayna Harmouch, Borhan Asadi, Islem Melliti, Antonio del Mastro, Pablo Herrero, Alberto Carcasona-Otal and Diego Lapuente-Hernández

Life 2026, 16(2), 193; https://doi.org/10.3390/life16020193 - 23 Jan 2026

Abstract

Background/Objectives: Parkinsonian gait is characterized by impaired motor adaptability, altered temporal organization, and reduced movement variability. While data augmentation is commonly used to mitigate class imbalance in gait-based machine learning models, conventional strategies often ignore physiological differences between healthy and pathological movements, potentially [...] Read more.

Background/Objectives: Parkinsonian gait is characterized by impaired motor adaptability, altered temporal organization, and reduced movement variability. While data augmentation is commonly used to mitigate class imbalance in gait-based machine learning models, conventional strategies often ignore physiological differences between healthy and pathological movements, potentially distorting meaningful motor dynamics. This study explores whether preserving healthy motor variability while selectively augmenting pathological gait signals can improve the robustness and physiological coherence of gait pattern classification models. Methods: Eight patients with Parkinsonian gait patterns and forty-eight healthy participants performed walking tasks on the Motigravity platform under hypogravity conditions. Full-body kinematic data were acquired using wearable inertial sensors. A selective augmentation strategy based on smooth time-warping was applied exclusively to pathological gait segments (×5, σ = 0.2), while healthy gait signals were left unaltered to preserve natural motor variability. Model performance was evaluated using a hybrid convolutional neural network–long short-term memory (CNN–LSTM) architecture across multiple augmentation configurations. Results: Selective augmentation of pathological gait signals achieved the highest classification performance (94.1% accuracy, AUC = 0.97), with balanced sensitivity (93.8%) and specificity (94.3%). Performance decreased when augmentation exceeded an optimal range of variability, suggesting that beneficial augmentation is constrained by physiologically plausible temporal dynamics. Conclusions: These findings demonstrate that physiology-informed, selective data augmentation can improve gait pattern classification under constrained data conditions. Rather than supporting disease-specific diagnosis, this proof-of-concept study highlights the importance of respecting intrinsic differences in motor variability when designing augmentation strategies for clinical gait analysis. Future studies incorporating disease-control cohorts and subject-independent validation are required to assess specificity and clinical generalizability. Full article

(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)

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17 pages, 2891 KB

Open AccessReview

Sickle Cell Disease and Male Infertility: Pathophysiological Mechanisms, Clinical Manifestations, and Fertility Preservation Strategies—A Narrative Review

by Christos Roidos, Aris Kaltsas, Evangelos N. Symeonidis, Vasileios Tzikoulis, Nikolaos Pantazis, Chara Tsiampali, Natalia Palapela, Athanasios Zachariou, Nikolaos Sofikitis and Fotios Dimitriadis

Life 2026, 16(2), 192; https://doi.org/10.3390/life16020192 - 23 Jan 2026

Abstract

Sickle cell disease (SCD) is an inherited hemoglobinopathy in which hemoglobin S polymerization drives hemolysis and vaso-occlusion with progressive organ morbidity. Male reproductive impairment is increasingly recognized but remains underreported. This narrative review summarizes mechanistic pathways, clinical manifestations, and fertility preservation options relevant [...] Read more.

Sickle cell disease (SCD) is an inherited hemoglobinopathy in which hemoglobin S polymerization drives hemolysis and vaso-occlusion with progressive organ morbidity. Male reproductive impairment is increasingly recognized but remains underreported. This narrative review summarizes mechanistic pathways, clinical manifestations, and fertility preservation options relevant to men with SCD. PubMed, the Cochrane Library, and Medscape were searched through 31 December 2025 for human studies addressing endocrine changes, semen quality, priapism and erectile dysfunction, oxidative stress, and treatment-related gonadotoxicity. Evidence supports converging mechanisms: recurrent vaso-occlusion and chronic hypoxia may injure the seminiferous epithelium and impair Leydig cell steroidogenesis; oxidative stress and inflammation contribute to sperm DNA and membrane damage; and disease-modifying or curative therapies such as hydroxyurea and hematopoietic stem cell transplantation can further compromise spermatogenesis. Clinically, men with SCD may present with oligozoospermia, azoospermia, hypogonadism, and sexual dysfunction, particularly after recurrent ischemic priapism. Fertility preservation should be discussed early, ideally before prolonged hydroxyurea exposure or transplantation, and may include semen cryopreservation and testicular sperm extraction (TESE) with assisted reproduction when needed. Prospective longitudinal studies are required to define reproductive trajectories and optimize counseling and management. Full article

(This article belongs to the Section Medical Research)

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12 pages, 1138 KB

Open AccessArticle

The Role of Homocysteine in Pediatric MASLD: A Bipotential Biomarker of Cardiovascular Risk and Liver Fibrosis

by Antonella Mosca, Nadia Panera, Giulia Andolina, Luca Della Volpe, Anna Pastore, Maria Rita Braghini, Lidia Monti, Paola Francalanci, Giovanna Soglia, Andrea Pietrobattista and Anna Alisi

Life 2026, 16(2), 191; https://doi.org/10.3390/life16020191 - 23 Jan 2026

Abstract

The increasing prevalence of metabolic dysfunction-associated fatty liver disease (MASLD) in children requires robust, non-invasive biomarkers to enable accurate disease staging and risk stratification. Elevated serum levels of homocysteine (Hcy) have emerged as potential risk factors for cardiometabolic disease in adults, including MASLD. [...] Read more.

The increasing prevalence of metabolic dysfunction-associated fatty liver disease (MASLD) in children requires robust, non-invasive biomarkers to enable accurate disease staging and risk stratification. Elevated serum levels of homocysteine (Hcy) have emerged as potential risk factors for cardiometabolic disease in adults, including MASLD. In this observational retrospective study, we investigated the role of serum Hcy levels as a potential biomarker for disease severity and liver fibrosis in a pediatric cohort of 182 children with MASLD. In 89 patients, liver biopsy allowed the classification into metabolic dysfunction-associated steatohepatitis (MASH). Associations between Hcy, metabolic parameters, fibrosis scores, and histological features were examined, and the diagnostic performance of Hcy for liver fibrosis was evaluated using ROC analysis. Multivariate analyses identified elevated Hcy levels as independently associated with HOMA-IR (β = 0.55; p = 0.049), TG/HDL ratio (β = 3.23; p = 0.002), and liver fibrosis (β = 2.59; p = 0.04). Hcy showed a predictive accuracy of 81% for fibrosis. However, the combined diagnostic models of Hcy with non-invasive fibrotic scores (i.e., APRI and FIB-4) or TG/HDL ratio showed only a modest accuracy (AUC = 0.62–0.69). In conclusion, our data suggest that Hcy is associated with fibrosis and cardiometabolic risk. However, these results should be interpreted as exploratory and do not establish homocysteine as a diagnostic biomarker. Full article

(This article belongs to the Special Issue Metabolic Health: The Interplay Between NAFLD, MAFLD, MASLD and Cardiovascular Disease)

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10 pages, 794 KB

Open AccessArticle

Hemoglobin-to-Red Cell Distribution Width Ratio and Vitamin D Status as Early Predictors of Cardiovascular Risk in Primary Sjögren’s Syndrome

by Francesca Coppi, Francesco Sbarra, Aurora Vicenzi, Cecilia Campani, Martina Moretti, Dilia Giuggioli, Caterina Vacchi, Amelia Spinella, Daniela Aschieri, Anna Vittoria Mattioli, Francesco Fedele, Alessio Baccarani, Marcello Pinti, Alessandra Dei Cas, Federica Fantuzzi, Leila Bigdelu, Gianluca Pagnoni and Susan Darroudi

Life 2026, 16(2), 190; https://doi.org/10.3390/life16020190 - 23 Jan 2026

Abstract

Introduction: Primary Sjögren’s (pSS) is an autoimmune disease that affects several organs, especially the heart, and raises cardiovascular risk. Investigating the associations of hemoglobin-to-red cell distribution width (RDW) ratio (HRR), vitamin D status, and cardiac function could provide valuable insights and biomarkers regarding [...] Read more.

Introduction: Primary Sjögren’s (pSS) is an autoimmune disease that affects several organs, especially the heart, and raises cardiovascular risk. Investigating the associations of hemoglobin-to-red cell distribution width (RDW) ratio (HRR), vitamin D status, and cardiac function could provide valuable insights and biomarkers regarding early cardiovascular risk in patients with pSS. Method: This cross-sectional study involved 61 patients diagnosed with pSS based on ACR/EULAR criteria. Data on demographics, hematological (Hb, RDW), echocardiography, and serum vitamin D levels were collected. Echocardiograms were conducted by trained cardiologists following established guidelines, while vitamin D levels were measured using ELISA. Statistical analyses, including univariate linear regression, were performed with SPSS in order to identify whether HRR tertiles were related to cardiac function and vitamin D status. Results: A study of 61 pSS patients (mean age 59.8 years, 89% female) revealed that patients with a lower hemoglobin-to-RDW ratio (HRR ≤ 0.98) had significantly higher pulmonary artery pressures (PAPs) and lower values for the tricuspid annular plane systolic excursion (TAPSE)/PAPs ratio, contributing to poor right heart function. These associations were particularly strong in patients with insufficient levels of vitamin D (<30 ng/mL), while differences in other echocardiographic parameters remained nonsignificant between HRR groups. Conclusions: These findings underscore the clinical value of HRR as a composite biomarker that reflects the interplay between anemia, inflammation, and cardiovascular health in primary Sjögren’s disease. They also suggest that vitamin D status may be an important therapeutic consideration to mitigate cardiopulmonary risks in this population. Full article

(This article belongs to the Special Issue Feature Papers in Medical Research: 4th Edition)

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11 pages, 2846 KB

Open AccessArticle

Musculotendinous Anatomy in Congenital Split Foot: Anatomical Description of a Rare Case and Literature Review

by Vladimir Kenis, Dmitry Starchik, Alexander Kochish, Dmitry Busarin and Nino Abdiba

Life 2026, 16(2), 189; https://doi.org/10.3390/life16020189 - 23 Jan 2026

Abstract

Background: Congenital split foot/hand is a rare limb anomaly. Although various surgical techniques have been described, detailed gross anatomical studies of soft tissue adaptation, particularly in the foot, are extremely rare. This study presents a detailed anatomical description of a case of severe [...] Read more.

Background: Congenital split foot/hand is a rare limb anomaly. Although various surgical techniques have been described, detailed gross anatomical studies of soft tissue adaptation, particularly in the foot, are extremely rare. This study presents a detailed anatomical description of a case of severe bilateral split foot. Methods: A comprehensive dissection was performed on the lower limb of a 64-year-old male donor with bilateral split foot/hand. Results: Radiographic evaluation classified the deformity as Blauth type IV, characterized by the absence of the lateral cuneiform bone and severe hypoplasia/aplasia of the second and third metatarsals. Significant changes were revealed in the musculotendinous apparatus. The key finding was a unique tendon loop passing through the central cleft, formed by the tendon of the extensor digitorum longus and connecting with the tendons of the flexor digitorum longus and flexor hallucis longus. Conclusions: This study presents the first detailed macroscopic anatomical description of split foot, demonstrating that this congenital anomaly involves complex, structured tendon and muscle adaptations that extend beyond skeletal deficiencies alone. The discovery of a persistent tendon loop—previously reported only once in split hand—indicates asynchronous development of skeletal and soft tissue structures. These findings should be taken into account for surgical planning, emphasizing the need to identify and manage such abnormal soft tissue structures during reconstructive procedures. Full article

(This article belongs to the Special Issue Topographical Anatomy and Physiological Mechanics of the Musculoskeletal System)

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17 pages, 1558 KB

Open AccessReview

Beyond Platelet Count: Rethinking Platelet-Rich Plasma Efficacy Through Growth Factor Biology and Functional Quality

by Fábio Ramos Costa, Joseph Purita, Rubens Martins, Luyddy Pires, Ansar Mahmood, Gabriel Silva Santos, André Kruel, João Protásio Netto and José Fábio Lana

Life 2026, 16(2), 188; https://doi.org/10.3390/life16020188 - 23 Jan 2026

Abstract

The efficacy of platelet-rich plasma (PRP) has long been associated with platelet concentration, yet clinical outcomes remain highly variable and frequently inconsistent. This review challenges the assumption that platelet count alone defines PRP efficacy, proposing instead that functional platelet quality and growth-factor bioactivity [...] Read more.

The efficacy of platelet-rich plasma (PRP) has long been associated with platelet concentration, yet clinical outcomes remain highly variable and frequently inconsistent. This review challenges the assumption that platelet count alone defines PRP efficacy, proposing instead that functional platelet quality and growth-factor bioactivity are equally critical determinants of therapeutic outcomes. Platelets act as carriers of bioactive molecules stored within alpha granules, including growth factors such as platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF), which orchestrate the cellular and molecular events of tissue repair. Variations in donor biology, age, metabolic status, and oxidative stress profoundly influence platelet functionality and growth-factor release. Likewise, centrifugation parameters, temperature control, and activation methods dictate whether these mediators are preserved or prematurely exhausted. Collectively, these findings reveal that platelet number alone cannot predict regenerative potency. The future of PRP standardization requires the integration of platelet quality indices, growth-factor quantification, and patient optimization protocols into clinical practice. By shifting focus from platelet enumeration to bioactivity assessment, regenerative medicine can achieve more consistent, personalized, and scientifically accurate outcomes. Full article

(This article belongs to the Section Cell Biology and Tissue Engineering)

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16 pages, 5410 KB

Open AccessArticle

The Number and Habitat Use of Mesopredators Based on the Camera Trapping and Location of Burrows in Hungary

by Zoltán Horváth, András Vajkai and Mihály Márton

Life 2026, 16(2), 187; https://doi.org/10.3390/life16020187 - 23 Jan 2026

Abstract

The increasing population of mesopredators in Central Europe necessitates precise monitoring for effective game management. This study aimed to estimate the minimum population and reproduction of the European badger (Meles meles), red fox (Vulpes vulpes), and golden jackal ( [...] Read more.

The increasing population of mesopredators in Central Europe necessitates precise monitoring for effective game management. This study aimed to estimate the minimum population and reproduction of the European badger (Meles meles), red fox (Vulpes vulpes), and golden jackal (Canis aureus) in two hunting grounds in southwestern Hungary (Drávaszentes and Darány). Methods included a total burrow count conducted in early 2025, followed by the deployment of wildlife cameras at inhabited setts to record adults and cubs. Results indicated an inhabited burrow density of 1.05/100 ha for badgers and 0.38/100 ha for foxes in Drávaszentes, with average litter sizes of 1.13 and 2.33 cubs, respectively. In Darány, badger density was 1.43/100 ha, while jackals were present at 0.2/100 ha. Additionally, habitat composition preference was analysed using QGIS by comparing Corine Land Cover categories within 400 m buffers around burrows against random points. Habitat analysis suggested local preferences for non-irrigated arable land and mixed forests. These findings provide essential baseline data on predator population dynamics to support conscious management decisions. Full article

(This article belongs to the Special Issue Conservation Ecology and Management of Mammalian Predators)

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4 pages, 151 KB

Open AccessEditorial

Messy Chemistry and the Emergence of Life

by Alberto Vázquez-Salazar and Ranajay Saha

Life 2026, 16(2), 186; https://doi.org/10.3390/life16020186 - 23 Jan 2026

Abstract

Chemical complexity is not a nuisance to be minimized in origin of life research, it is an enabling condition. This second edition of the Special Issue on the Origin of Life in Chemically Complex Messy Environments gathers contributions that embrace multicomponent mixtures, dynamic [...] Read more.

Chemical complexity is not a nuisance to be minimized in origin of life research, it is an enabling condition. This second edition of the Special Issue on the Origin of Life in Chemically Complex Messy Environments gathers contributions that embrace multicomponent mixtures, dynamic geochemical settings, and nonequilibrium processes. The papers collected here survey surface hydrothermal routes to reactive nitriles, groundwater evolution of alkaline lakes, and transition metal sulfide-driven amino acid and amide formation without cyanide. They report one pot nucleoside and nucleotide synthesis from formamide over cerium phosphate, review non aqueous organophosphorus pathways, and probe peptide rich mixtures and formose type networks under serpentinization associated minerals. The issue also advances conceptual frameworks, including atmospheric photochemical signatures for biosignature discrimination, the role of chiral mineral surfaces in enantioseparation, and computational simulations of the origin of LUCA. Together, these studies position messy chemistry as a crucible that turns chemical diversity and environmental heterogeneity into routes toward organization and function. Full article

(This article belongs to the Special Issue Origin of Life in Chemically Complex Messy Environments: 2nd Edition)

21 pages, 5177 KB

Open AccessArticle

Identification of FDA-Approved Drugs as Potential Inhibitors of WEE2: Structure-Based Virtual Screening and Molecular Dynamics with Perspectives for Machine Learning-Assisted Prioritization

by Shahid Ali, Abdelbaset Mohamed Elasbali, Wael Alzahrani, Taj Mohammad, Md. Imtaiyaz Hassan and Teng Zhou

Life 2026, 16(2), 185; https://doi.org/10.3390/life16020185 - 23 Jan 2026

Abstract

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific kinase that regulates meiotic arrest and fertilization. Its largely restricted expression in female germ cells and absence in somatic tissues make it a highly selective target for reproductive health interventions. Despite its central role in [...] Read more.

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific kinase that regulates meiotic arrest and fertilization. Its largely restricted expression in female germ cells and absence in somatic tissues make it a highly selective target for reproductive health interventions. Despite its central role in human fertility, no clinically approved WEE2 modulator is available. In this study, we employed an integrated in silico approach that combines structure-based virtual screening, molecular dynamics (MD) simulations, and MM-PBSA free-energy calculations to identify repurposed drug candidates with potential WEE2 inhibitory activity. Screening of ~3800 DrugBank compounds against the WEE2 catalytic domain yielded ten high-affinity hits, from which Midostaurin and Nilotinib emerged as the most mechanistically relevant based on kinase-targeting properties and pharmacological profiles. Docking analyses revealed strong binding affinities (−11.5 and −11.3 kcal/mol) and interaction fingerprints highly similar to the reference inhibitor MK1775, including key contacts with hinge-region residues Val220, Tyr291, and Cys292. All-atom MD simulations for 300 ns demonstrated that both compounds induce stable protein–ligand complexes with minimal conformational drift, decreased residual flexibility, preserved compactness, and stable intramolecular hydrogen-bond networks. Principal component and free-energy landscape analyses further indicate restricted conformational sampling of WEE2 upon ligand binding, supporting ligand-induced stabilization of the catalytic domain. MM-PBSA calculations confirmed favorable binding free energies for Midostaurin (−18.78 ± 2.23 kJ/mol) and Nilotinib (−17.47 ± 2.95 kJ/mol), exceeding that of MK1775. To increase the translational prioritization of candidate hits, we place our structure-based pipeline in the context of modern machine learning (ML) and deep learning (DL)-enabled virtual screening workflows. ML/DL rescoring and graph-based molecular property predictors can rapidly re-rank docking hits and estimate absorption, distribution, metabolism, excretion, and toxicity (ADMET) liabilities before in vitro evaluation. Full article

(This article belongs to the Special Issue Role of Machine and Deep Learning in Drug Screening)

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10 pages, 1594 KB

Open AccessArticle

The Exceptional Solubility of Cyclic Trimetaphosphate in the Presence of Mg²⁺ and Ca²⁺

by Megan G. Bachant and Ulrich F. Müller

Life 2026, 16(1), 184; https://doi.org/10.3390/life16010184 - 22 Jan 2026

Abstract

Studying the origin of life requires identifying chemical and physical processes that could have supported early self-replicating and evolving molecular systems. Besides the requirement of information storage and transfer, an essential aspect is an energy source that could have thermodynamically driven the formation [...] Read more.

Studying the origin of life requires identifying chemical and physical processes that could have supported early self-replicating and evolving molecular systems. Besides the requirement of information storage and transfer, an essential aspect is an energy source that could have thermodynamically driven the formation and replication of these molecular assemblies. Chemical energy sources such as cyclic trimetaphosphate are attractive because they could drive replication with relatively simple catalysts. Here, we focus on cyclic trimetaphosphate (cTmp), and compare its solubility in water to linear triphosphate, pyrophosphate, and phosphite when Mg²⁺ or Ca²⁺ are present. These solubilities are important for facilitating the reactions under prebiotically plausible conditions. The results showed that cTmp was soluble even at molar concentrations of Mg²⁺ and little precipitation with 200 mM Ca²⁺. In contrast, pyrophosphate and linear triphosphate precipitated efficiently even at low divalent metal ion concentrations. The precipitation of phosphate was pH-dependent, showing similar precipitation with Mg²⁺ and Ca²⁺ at a prebiotically plausible pH of 6.5. Phosphite was soluble at high Mg²⁺ concentrations but started precipitating with increasing Ca²⁺ concentration. At conditions that model Archaean seawater, cTmp was the most soluble of these compounds. Together, this experimental overview may help to identify promising conditions for lab-based investigations of phosphate-based energy metabolisms in early life forms. Full article

(This article belongs to the Special Issue Prebiotic Chemistry: The Molecular Origins of Life)

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25 pages, 1564 KB

Open AccessReview

Seric Molecular Markers Correlated with Stroke Rehabilitation Outcomes: A Narrative Review

by Bianca-Gabriela Ene, Brindusa Ilinca Mitoiu, Mariana Catalina Ciornei, Madalina Coman-Stanemir, Angelo Voicu, Floris Petru Iliuta and Ioana Raluca Papacocea

Life 2026, 16(1), 183; https://doi.org/10.3390/life16010183 - 22 Jan 2026

Abstract

An increasing number of stroke survivors are burdened by persistent disabilities, requiring long-term rehabilitation. However, the extent of functional gain is highly variable, severely impairing patients’ quality of life. This variability highlights a critical gap in current prognostic tools, which rely primarily on [...] Read more.

An increasing number of stroke survivors are burdened by persistent disabilities, requiring long-term rehabilitation. However, the extent of functional gain is highly variable, severely impairing patients’ quality of life. This variability highlights a critical gap in current prognostic tools, which rely primarily on clinical and neuroimaging data. The aim of this review is to synthesize the current literature on serum biomarkers in stroke survivors and to evaluate their prognostic value for rehabilitation outcomes. Our synthesis indicates that biomarkers reflecting distinct pathophysiological processes are emerging as key prognostic indicators. Markers of inflammation such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Interleukin-1 beta (IL-1β), and neuro-glial injury, including S100 Calcium-Binding Protein B (S100B), Neuron-Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), and Neurofilament Light Chain (NfL), are consistently associated with poorer functional outcomes. Conversely, markers of neuroplasticity, such as Brain-Derived Neurotrophic Factor (BDNF) and Insulin-like Growth Factor-1 (IGF-1), serve as potential indicators of recovery potential, although their predictive accuracy remains inconsistent across studies. Furthermore, emerging biomarkers of synaptic activity, such as Syntaxin-1a (STX1A) and Synaptosomal-Associated Protein, 25kDa (SNAP-25), and neuromuscular junction integrity, such as C-terminal Agrin Fragment (CAF), offer novel insights into brain–periphery communication, though their clinical utility is still under investigation. While promising, the translation of these biomarkers into clinical practice is hindered by methodological limitations, including assay heterogeneity and lack of large-scale validation. Future standardization of these molecular signatures is a critical step toward implementing precision medicine in stroke rehabilitation. Full article

(This article belongs to the Section Medical Research)

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23 pages, 1029 KB

Open AccessReview

Perianal Crohn’s Disease in Inflammatory Bowel Disease: Diagnosis, Assessment and Treatment

by Ilaria Faggiani, Isabel Lagos Villaseca, Ferdinando D’Amico, Federica Furfaro, Alessandra Zilli, Sara Massironi, Tommaso Lorenzo Parigi, Virginia Solitano, Clelia Cicerone, Laurent Peyrin-Biroulet, Silvio Danese and Mariangela Allocca

Life 2026, 16(1), 182; https://doi.org/10.3390/life16010182 - 22 Jan 2026

Abstract

Perianal fistulizing Crohn’s disease (pfCD) represents one of the most challenging manifestations of CD, often associated with severe phenotypes, refractory luminal inflammation, and a substantial reduction in quality of life. Its pathogenesis is multifactorial and incompletely understood, involving genetic susceptibility, epithelial and stromal [...] Read more.

Perianal fistulizing Crohn’s disease (pfCD) represents one of the most challenging manifestations of CD, often associated with severe phenotypes, refractory luminal inflammation, and a substantial reduction in quality of life. Its pathogenesis is multifactorial and incompletely understood, involving genetic susceptibility, epithelial and stromal dysfunction, and microbiome-related mechanisms. Diagnosis and monitoring rely on advanced imaging, while management requires coordinated medical–surgical strategies. Significant unmet needs persist regarding standardized treatment targets, optimal imaging follow-up, and personalized therapeutic pathways. In this review, we aim to summarise and provide a comprehensive overview of the most recent evidence across pathogenesis, diagnosis, classification systems, and therapeutic approaches in pfCD. We highlight key advances in understanding epithelial–mesenchymal transition, immune–microbiome interactions, and genetic determinants of disease behaviour. Improvements in diagnostic modalities—including MRI-based scores, ultrasound technologies, volumetric assessment, and AI-enhanced imaging—are discussed alongside modern classification systems such as TOPClass. Evidence guiding medical therapy, seton management, and surgical decision-making is reviewed, emphasising integrated, goal-oriented care. Despite substantial progress, pfCD remains a difficult-to-treat condition with persistent gaps in early diagnosis, objective monitoring, and individualized management. Emerging imaging technologies, standardized treatment targets, and structured classification frameworks offer promising strategies to overcome current limitations and improve long-term outcomes. Full article

(This article belongs to the Section Medical Research)

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18 pages, 1475 KB

Open AccessReview

Impact of Cadmium Toxicity on Testicular Function: Risk of Male Infertility

by Iva Arato, Elena Eugeni, Giuseppe Basta, Tiziano Baroni, Riccardo Calafiore, Francesca Mancuso and Giovanni Luca

Life 2026, 16(1), 181; https://doi.org/10.3390/life16010181 - 22 Jan 2026

Abstract

The World Health Organization estimates that about 15% of couples in their adult years in industrialized countries experience infertility, which is described as the inability of a sexually active and non-contraceptive couple to achieve spontaneous pregnancy within a year. Environmental pollution is a [...] Read more.

The World Health Organization estimates that about 15% of couples in their adult years in industrialized countries experience infertility, which is described as the inability of a sexually active and non-contraceptive couple to achieve spontaneous pregnancy within a year. Environmental pollution is a significant health concern worldwide and one of the possible risk factors leading to male infertility. Cadmium is a common heavy toxin derived from industrial activities, a ubiquitous environmental pollutant, and can cause severe harm to various organs including the testis. Cadmium toxicity can lead to severe impairment of male germ cells in both rodents and humans, which can result in azoospermia. The negative effects of cadmium on the testicles are caused by its induction of oxidative stress, spermatogenic apoptosis, and testicular inflammation or its detriment to androgenic and sperm cell functions, which damages the vascular endothelium and blood–testis barrier. Overall, this review describes the detrimental impact of cadmium on the testicles and its effect on male infertility. Therefore, by considering recent research findings and identifying future research directions, this review underlines the need to develop new treatments for male infertility related to heavy metal exposure. Full article

(This article belongs to the Special Issue Human Infertility and Reproductive Endocrinology: 2nd Edition)

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13 pages, 1916 KB

Open AccessCase Report

Herb-Induced Liver Injury by Laurus nobilis: A Case Assessed for Causality Using the Updated RUCAM

by Mihnea Soare, Sabina-Florina Călugăr-Șolea, Ciprian Brisc, Marius Rus, Teodora-Maria Bodog, Gabriel Becheanu, Ciprian Mihai Brisc and Mihaela-Cristina Brisc

Life 2026, 16(1), 180; https://doi.org/10.3390/life16010180 - 22 Jan 2026

Abstract

Hepatocellular injury syndrome represents a pathological process with a broad etiological spectrum, including viral infections, autoimmune diseases, or intoxications. Clinicians must identify the potential cause using both anamnestic data and available paraclinical examinations. We present the case of a 55-year-old female patient, admitted [...] Read more.

Hepatocellular injury syndrome represents a pathological process with a broad etiological spectrum, including viral infections, autoimmune diseases, or intoxications. Clinicians must identify the potential cause using both anamnestic data and available paraclinical examinations. We present the case of a 55-year-old female patient, admitted to the Internal Medicine 1 Department at the Clinical County Emergency Hospital Bihor, Oradea, Romania. The patient exhibited nonspecific complaints and insignificant pathological antecedents, but from a biochemical perspective, substantial changes in liver transaminase levels were evident. To establish differential diagnoses, a series of biochemical and immunological tests were performed, along with a thorough medical history. It was concluded that the patient regularly consumes herbal infusions, specifically Laurus nobilis leaves, commonly known as Bay Laurel. Although this might be easily overlooked at first glance, a closer examination could explain the current clinical picture. In April 2024, a 55-year-old female patient with no history of liver pathology was admitted. She complained of asthenia fatigue, anorexia, mixed dyspeptic symptoms, diffuse abdominal pain, and a weight loss of 12 kg. The pathology had insidiously started approximately 3 months prior. On examination, the patient had altered general status, anorexia, and was overweight. Biochemically, the patient had elevated liver transaminase values (AST = 196 U/L and ALT = 357 U/L) that continued to rise during hospitalization, despite hepatoprotective treatment. Various paraclinical examinations were performed to exclude other potential causes of hepatic aggression, having excluded ordinary causes. Consequently, a liver biopsy was performed, and the histopathological examination leaned toward a toxic hepatitis etiology. Application of the updated RUCAM scale yielded a score of eight points (“probable” HILI—Herb-Induced Liver Injury). Clinical and biochemical improvement was observed after complete cessation of bay leaf tea consumption. This case highlights the potential hepatotoxicity of commonly used culinary herbs when consumed in large quantities or as concentrated infusions and emphasizes the importance of detailed anamnesis regarding herbal product use. Full article

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

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20 pages, 401 KB

Open AccessSystematic Review

Cervical Spinal Cord Stimulation for Functional Rehabilitation After Spinal Cord Injury: A Systematic Review of Preclinical and Clinical Studies

by Maximilian C. Wankner, Veerle Visser-Vandewalle, Pablo Andrade and Petra Heiden

Life 2026, 16(1), 179; https://doi.org/10.3390/life16010179 - 22 Jan 2026

Abstract

Cervical spinal cord injury causes severe functional impairment with limited spontaneous recovery, and while spinal cord stimulation has emerged as a promising neuromodulatory strategy, evidence for cervical applications remains fragmented. To address this gap, we conducted a systematic review synthesizing preclinical and clinical [...] Read more.

Cervical spinal cord injury causes severe functional impairment with limited spontaneous recovery, and while spinal cord stimulation has emerged as a promising neuromodulatory strategy, evidence for cervical applications remains fragmented. To address this gap, we conducted a systematic review synthesizing preclinical and clinical evidence on cervical spinal cord stimulation for functional rehabilitation following spinal cord injury. The review was registered on PROSPERO (CRD420251088804) and conducted in accordance with PRISMA guidelines, with PubMed, Embase, IEEE Xplore, and Web of Science searched from inception to July 2025 for animal and human studies of cervical spinal cord stimulation, including epidural, intraspinal, and transcutaneous approaches, reporting functional neurological outcomes. Risk of bias was assessed using the Cochrane RoB 2 and ROBINS-I tools, and due to substantial heterogeneity, results were synthesized narratively. Thirty-one studies comprising 119 animals and 156 human participants, met inclusion criteria. Across studies, outcome measures such as GRASSP, ISNCSCI, and dynamometry consistently demonstrated improvements in hand strength, dexterity, and voluntary motor activation. Several studies also reported gains in sensory and autonomic function, whereas respiratory outcomes were infrequently assessed. Adjunctive interventions, including cortical stimulation, brain–computer interface priming, and task-specific training frequently augmented recovery. Adverse events were generally mild, although overall risk of bias was predominantly serious. Overall, cervical spinal cord stimulation demonstrates preliminary assistive and therapeutic effects on motor recovery, with additional sensory, autonomic, and potential respiratory benefits. Full article

(This article belongs to the Special Issue Spinal Neuromodulation: From Basic and Translational Research to Clinical Practice)

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12 pages, 1223 KB

Open AccessArticle

Monocyte Distribution Width as a Biomarker for Predicting Bacteremia: A Retrospective Study in the Emergency Department

by Tse-Hao Chen, Yu-Jang Su, Wei-Hsiang Liao, Weide Tsai, Ding-Kuo Chien, Wen-Han Chang and Chyi-Huey Bai

Life 2026, 16(1), 178; https://doi.org/10.3390/life16010178 - 22 Jan 2026

Abstract

Blood culture is the diagnostic gold standard for bacteremia in the emergency department (ED), but its turnaround time can delay appropriate antimicrobial therapy, highlighting the need for rapid, accessible biomarkers. We retrospectively analyzed adult ED patients from July 2023 to June 2024 who [...] Read more.

Blood culture is the diagnostic gold standard for bacteremia in the emergency department (ED), but its turnaround time can delay appropriate antimicrobial therapy, highlighting the need for rapid, accessible biomarkers. We retrospectively analyzed adult ED patients from July 2023 to June 2024 who underwent blood culture testing and had complete data for monocyte distribution width (MDW), white blood cell count (WBC), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR). Discrimination was assessed using area under the receiver operating characteristic curve (AUROC) and diagnostic accuracy using sensitivity, specificity, and diagnostic odds ratio (DOR); combined models were compared with net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Among 19,325 patients, 2011 (10.4%) had positive blood cultures. MDW had the highest AUROC (0.760) versus CRP (0.730), NLR (0.695), and WBC (0.642); at a cut-off of 22, MDW showed 0.72 sensitivity, 0.68 specificity, and DOR 5.46. The best combined model was MDW+NLR (AUROC 0.785; DOR 6.39; NRI 0.428; IDI 0.770). MDW is a rapid and effective marker for identifying bacteremia in the ED, and performance improves when combined with NLR. Full article

(This article belongs to the Special Issue Advances in Emergency and Critical Care Medicine)

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