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Volume 16
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Life, Volume 16, Issue 1 (January 2026) – 184 articles

Cover Story (view full-size image): Women show a higher prevalence of mood- and stress-related disorders, yet the biological mechanisms underlying this vulnerability remain poorly understood. This review examines neuroinflammation as a sex-specific process shaping emotional regulation across the female lifespan. Integrating evidence from human and animal studies, it highlights how hormonal fluctuations interact with immune signaling, microglial activity, stress systems, and neurotransmission, creating periods of increased vulnerability during puberty, the menstrual cycle, pregnancy, the postpartum period, and perimenopause. By linking endocrine transitions to neuroimmune mechanisms, this review provides an integrated framework for female susceptibility to depression and anxiety and supports the development of sex-informed preventive and therapeutic strategies. View this paper
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10 pages, 1594 KB  
Article
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
Viewed by 227
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  
Review
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
Viewed by 320
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  
Review
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
Viewed by 516
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  
Review
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
Viewed by 328
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  
Case 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
Viewed by 269
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  
Systematic 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
Viewed by 411
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  
Article
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
Viewed by 213
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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21 pages, 2021 KB  
Article
Spatial Cluster of Air Pollutants and Its Association with Life Expectancy, Age-Specific Mortality Risk, and Cause-Specific Mortality Rate: A County-Level Ecological Study Across the USA
by Jing Wang, Qiaochu Xu, Rong Rong, Bingjie Qu, Xiang Shi, Bin Hu, Peng Zhao, Chengxiu Ling and Ying Chen
Life 2026, 16(1), 177; https://doi.org/10.3390/life16010177 - 21 Jan 2026
Viewed by 239
Abstract
Air pollution has been one of the major threats to public health. The study aimed to determine latent patterns of geographical distribution of health-related air pollutants across the USA and to evaluate real-world cumulative effects of these patterns on public health metrics. It [...] Read more.
Air pollution has been one of the major threats to public health. The study aimed to determine latent patterns of geographical distribution of health-related air pollutants across the USA and to evaluate real-world cumulative effects of these patterns on public health metrics. It was an ecological study using county-level data on the concentrations of 12 air pollutants over 20 years. Latent class analysis was used to identify the common clusters of life expectancy-associated air pollutants based on their concentration characteristics in the final counties studied (n = 699). Multivariate linear regression analyses were then applied to assess the relationship between the LCA-derived clusters and health measurements with confounding adjustment. We found that PM2.5 mass, PM10 speciation, and NONOxNOy (the reactive nitrogen species) were associated with life expectancy and thus were included in LCA. Among five identified clusters, the one with a more severe pollutant profile was associated with a decreasing life expectancy, an increasing mortality risk among middle-aged and elderly populations (≥45 years), and an increasing mortality rate caused by chronic respiratory conditions, cardiovascular diseases, and neoplasms. Our study brings new perspectives on real-world geographical patterns of air pollution to explain health disparities across the USA. Full article
(This article belongs to the Section Epidemiology)
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12 pages, 859 KB  
Article
Erythema Protection Efficacy of Plant-Derivative Compounds in Mice Based on Narrow-Band Reflectance Spectroscopy Data
by Diego Armando Villamizar Mantilla, Luis Alberto Nuñez, Elena E. Stashenko, María Pilar Vinardell and Jorge Luis Fuentes
Life 2026, 16(1), 176; https://doi.org/10.3390/life16010176 - 21 Jan 2026
Viewed by 195
Abstract
Background: Plants represent an important source of photoprotective compounds that are capable of protecting human skin from solar-induced damage. In this study we investigated the suitability of a murine model for estimating the Erythema Protection Efficacy (EPE) of natural compound. Methods: [...] Read more.
Background: Plants represent an important source of photoprotective compounds that are capable of protecting human skin from solar-induced damage. In this study we investigated the suitability of a murine model for estimating the Erythema Protection Efficacy (EPE) of natural compound. Methods: UVB-induced skin erythema in albino BALB/c mice was quantified using a Mexameter MX18 MDD colorimeter. The ARRIVE principle was followed. The Minimum Erythema Dose (MED) was determined based on Log10 dose–erythema response curves. EPE values for UV filters (e.g., titanium dioxide or zinc oxide) and selected plant-derived compounds (apigenin, caffeic acid, epigallocatechin gallate, kaempferol, and pinocembrin) were calculated as the ratio between the MED of protected skin and that of unprotected skin. Results: The UVB-induced erythema in both female and male mouse skin followed a linear response. Erythema intensity varied by sex and by the dorsal skin area examined. MED values ranged from 39 to 57 mJ/cm2 in female mice and from 71 to 80 mJ/cm2 in male mice. In both sexes, MED increased linearly with the logarithm of the radiation dose. All tested compounds (apigenin, caffeic acid, epigallocatechin gallate, kaempferol, and pinocembrin) provided protection against UV-radiation-induced erythema in mouse skin. Among them, apigenin, caffeic acid, and kaempferol exhibited the highest EPE values, indicating strong potential for incorporation into sunscreen formulations. Conclusions: The murine EPE metric proved to be a useful tool for identifying plant-derived compounds with potential relevance for the photoprotection of human skin. Full article
(This article belongs to the Section Physiology and Pathology)
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58 pages, 1801 KB  
Review
Medicinal Plants and Phytochemicals in Cardioprotection—Mechanistic Pathways and Translational Roadmap
by Diana Maria Morariu-Briciu, Alex-Robert Jîjie, Sorin Lucian Bolintineanu, Ana-Maria Pah, Sorin Dan Chiriac, Adelina Chevereșan, Victor Dumitrașcu, Cătălin Prodan Bărbulescu and Radu Jipa
Life 2026, 16(1), 175; https://doi.org/10.3390/life16010175 - 21 Jan 2026
Viewed by 537
Abstract
Despite major advances in guideline-directed cardiovascular therapy, residual cardiovascular risk persists, partly driven by oxidative stress, chronic inflammation, endothelial dysfunction, and mitochondrial injury not fully addressed by current drugs. Translation of plant-based cardioprotectants is constrained by preparation-dependent variability in extract chemistry (plant part/cultivar/processing [...] Read more.
Despite major advances in guideline-directed cardiovascular therapy, residual cardiovascular risk persists, partly driven by oxidative stress, chronic inflammation, endothelial dysfunction, and mitochondrial injury not fully addressed by current drugs. Translation of plant-based cardioprotectants is constrained by preparation-dependent variability in extract chemistry (plant part/cultivar/processing and extraction method), low and variable systemic exposure for key actives (notably curcuminoids and many polyphenols), and clinically relevant safety/interaction considerations (e.g., hepatotoxicity reports with concentrated green tea extracts and antiplatelet-related bleeding-risk considerations for some botanicals). We therefore provide a mechanism- and translation-oriented synthesis of evidence for cardioprotective botanicals, chosen for long-standing traditional use and scientific validation with reproducible experimental data and, where available, human studies, including Crataegus monogyna, Allium sativum, Olea europaea, Ginkgo biloba, Leonurus cardiaca, and Melissa officinalis. Across studies, polyphenols (especially flavonoids and phenolic acids) and organosulfur compounds are most consistently associated with cardioprotection, while terpene-derived constituents and secoiridoids contribute mechanistically in plant-specific settings (e.g., Ginkgo and Olea). Predominantly in experimental models, these agents engage redox-adaptive (Nrf2), mitochondrial (mPTP), endothelial, and inflammatory (NF-κB) pathways, with reported reductions in ischemia–reperfusion injury, oxidative damage, and apoptosis. Clinical evidence remains heterogeneous and is largely confined to short-term studies and surrogate outcomes (blood pressure, lipids, oxidative biomarkers, endothelial function), with scarce data on hard cardiovascular endpoints or event reduction. Priorities include standardized, chemotype-controlled formulations with PK/PD-guided dosing and adequately powered randomized trials that assess safety and herb–drug interactions. Full article
(This article belongs to the Section Pharmaceutical Science)
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27 pages, 1372 KB  
Review
Cutaneous-Tropism Viruses: Unraveling Pathogenetic Mechanisms and Immunoprophylactic Strategies
by Mariana Lupoae, Alina Mihaela Elisei, Ancuța Iacob, Andreea Lupoae, Alin Laurențiu Tatu, Elena Niculeț, Maria Nina Căuș, Denisa Batîr, Aurel Nechita, Mădălina Nicoleta Matei, Claudia Simona Ștefan, Elena Lăcrămioara Lisă, Lungu Irinel and Dana Tutunaru
Life 2026, 16(1), 174; https://doi.org/10.3390/life16010174 - 21 Jan 2026
Viewed by 329
Abstract
Cutaneous viral infections result from the complex interaction between viruses and skin structures, influenced by viral tropism and the host immune response. They can generate lesions ranging from transient rashes to chronic or potentially tumorous formations. Cutaneous manifestations are often the first sign [...] Read more.
Cutaneous viral infections result from the complex interaction between viruses and skin structures, influenced by viral tropism and the host immune response. They can generate lesions ranging from transient rashes to chronic or potentially tumorous formations. Cutaneous manifestations are often the first sign of infection and allow for early recognition. The aim of this review is to analyze the role of viruses in skin pathology, the mechanisms of infection, and the clinical impact. A narrative review of the recent literature was performed, including original articles, systematic reviews, and clinical guidelines on cutaneous viral infections. Data on pathogenic mechanisms, types of lesions, evolution, and therapeutic options were evaluated, covering the main viruses involved in dermatology: herpesviruses, papillomaviruses, poxviruses, and viruses associated with acute rashes. Cutaneous viral infections can be self-limited, recurrent, or chronic, and some can promote malignant transformation of skin cells. The variability of clinical manifestations reflects the virus–host interaction and influences diagnosis and management. Recent advances highlight the development of vaccines and targeted antiviral therapies, which improve prognosis and infection control. Viruses play a major role in the etiology of skin diseases, and their early recognition is essential for preventing complications. Understanding the mechanisms of infection and the cutaneous response contributes to the optimization of therapeutic and preventive strategies, strengthening the modern management of viral cutaneous pathology. Full article
(This article belongs to the Section Physiology and Pathology)
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15 pages, 501 KB  
Article
Static Estimation of Vista-Space Egocentric Distance with Iterative Feedback: A Cognitive–Perceptual Task
by Constantin Ciucurel and Elena Ioana Iconaru
Life 2026, 16(1), 173; https://doi.org/10.3390/life16010173 - 21 Jan 2026
Viewed by 192
Abstract
Accurate egocentric distance estimation in vista space depends on the interaction between perceptual encoding and cognitive recalibration. This study examined how iterative, feedback-based learning modulates spatial accuracy, perceptual bias, and task efficiency in large-scale environments. A total of 133 participants (mean age = [...] Read more.
Accurate egocentric distance estimation in vista space depends on the interaction between perceptual encoding and cognitive recalibration. This study examined how iterative, feedback-based learning modulates spatial accuracy, perceptual bias, and task efficiency in large-scale environments. A total of 133 participants (mean age = 26.3 ± 7.44 years) performed distance estimations on three outdoor targets (134 m, 575 m, 1463 m) using a mobile web application providing immediate corrective feedback (too short/too long). Six variables were analyzed: first estimate (FE), error of first estimate (EFE), mean estimate (ME), error of mean estimate (EME), number of attempts (NAs), and trial duration (TD). Given the non-normal data distribution, nonparametric tests were applied (Friedman and Wilcoxon signed-rank tests with Bonferroni correction). All variables showed significant within-subject effects across distances (p < 0.001). Post hoc analyses indicated that EFE and EME differed significantly between all target pairs (p < 0.0167), revealing a shift from slight overestimation at 134 m to increasing underestimation at 575 m and 1463 m. NA was significantly higher for the farthest target (p < 0.0167), indicating greater cognitive load and iterative correction effort. TD differed significantly only between consecutive distances (p < 0.0167), suggesting non-linear temporal adaptation. These results demonstrate that iterative feedback improves perceptual stability and efficiency but does not remove distance compression. The consistent bias and adaptive response patterns support a feedback-driven, binary search-like recalibration mechanism. The proposed mobile paradigm offers a scalable and valid approach for assessing perceptual–cognitive calibration in both natural and virtual spatial contexts. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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11 pages, 495 KB  
Article
Trends in the Management of Bladder Cancer with Emphasis on Frailty: A Nationwide Analysis of More Than 49,000 Patients from a German Hospital Network
by Tobias Klatte, Frederic Bold, Julius Dengler, Michela de Martino, Sven Hohenstein, Ralf Kuhlen, Andreas Bollmann, Thomas Steiner and Nora F. Dengler
Life 2026, 16(1), 169; https://doi.org/10.3390/life16010169 - 21 Jan 2026
Viewed by 336
Abstract
Background: Bladder cancer (BC) predominantly affects older patients, and their multidisciplinary treatment often includes surgical intervention. Frailty can influence treatment decisions and is associated with poorer outcomes. This study analyses trends in demographics, treatment patterns and frailty in a large, nationwide, real-world inpatient [...] Read more.
Background: Bladder cancer (BC) predominantly affects older patients, and their multidisciplinary treatment often includes surgical intervention. Frailty can influence treatment decisions and is associated with poorer outcomes. This study analyses trends in demographics, treatment patterns and frailty in a large, nationwide, real-world inpatient cohort in Germany. Methods: This retrospective observational study included a total of 49,139 consecutive patients, who received inpatient care for BC at all HELIOS hospitals in Germany between 2016 and 2022. Frailty was assessed using the Hospital Frailty Risk Score (HFRS) and categorised as low (<5), intermediate (5–15), or high (>15). Trends in HFRS, treatment modalities, and demographic variables were analysed using regression models and compared between the periods 2016–2019 and 2020–2022. Results: Of the 49,139 patients, 27,979 were treated between 2016–2019 and 21,160 between 2020–2022. Patients treated in the later period were slightly older but had a lower comorbidity index. The proportion of patients with low frailty increased (73.4% vs. 75.5%, p < 0.01), intermediate frailty decreased (23.5% vs. 21.5%, p < 0.01) and the proportion of highly frail patients remained stable at 3.0% (p = 0.95). Rates of transurethral resection declined over time, whereas rates of RC remained stable (p = 0.12). The use of systemic therapy increased (p = 0.003), particularly among low frailty elderly patients. Early intravesical chemotherapy following transurethral resection declined significantly in 2020–2022 (p < 0.001), particularly among elderly patients with high frailty. Mean length of hospital stay decreased by one day, while ICU admission rates and in-hospital mortality remained stable across time periods. Conclusions: This study shows frailty-specific changes in hospitalisation patterns and inpatient management of BC in Germany, underscoring the value of frailty assessment in population-based research. The proportion of patients classified as having low frailty increased over time. Significant changes in the use of intravesical chemotherapy and systemic therapy were associated with frailty. The decline in early intravesical chemotherapy may have implications for recurrence risk and downstream healthcare utilisation. Full article
(This article belongs to the Special Issue Advances and Challenges in Urothelial and Prostate Cancer: Toward Precision Urologic Oncology)
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18 pages, 450 KB  
Review
Metabolic Dysfunction at the Core: Revisiting the Overlap of Cardiovascular, Renal, Hepatic, and Endocrine Disorders
by Maria-Daniela Tanasescu, Andrei-Mihnea Rosu, Alexandru Minca, Andreea-Liana Rosu, Maria-Mihaela Grigorie, Delia Timofte and Dorin Ionescu
Life 2026, 16(1), 172; https://doi.org/10.3390/life16010172 - 20 Jan 2026
Viewed by 569
Abstract
Metabolic dysfunction has emerged as a central driver of cardiovascular, renal, hepatic, and endocrine disorders, challenging traditional organ-specific disease models. Increasing evidence indicates that conditions such as obesity, type 2 diabetes, chronic kidney disease, heart failure, and metabolic dysfunction–associated steatotic liver disease frequently [...] Read more.
Metabolic dysfunction has emerged as a central driver of cardiovascular, renal, hepatic, and endocrine disorders, challenging traditional organ-specific disease models. Increasing evidence indicates that conditions such as obesity, type 2 diabetes, chronic kidney disease, heart failure, and metabolic dysfunction–associated steatotic liver disease frequently develop in parallel, reflecting shared upstream metabolic abnormalities rather than isolated pathologies. This narrative review synthesizes recent clinical, epidemiologic, biomarker, and therapeutic evidence to examine metabolic dysfunction as a unifying framework for multisystem disease, with particular focus on the cardiovascular–renal–hepatic–metabolic (CRHM) model. A targeted literature search of major biomedical databases was conducted to identify relevant studies published between 2020 and 2025, encompassing observational cohorts, randomized trials, and integrative reviews addressing cross-organ metabolic interactions. The reviewed evidence highlights consistent clinical overlap across organ systems, stage-dependent risk amplification and the utility of shared metabolic and inflammatory biomarkers in capturing multisystem vulnerability. In parallel, contemporary metabolic therapies demonstrate coordinated benefits across cardiovascular, renal, and hepatic domains, supporting the concept of common modifiable disease drivers. The reviewed evidence supports a shift from organ-based toward metabolic-centric frameworks for risk stratification and prevention. Viewing metabolic dysfunction as the organizing principle of cardiometabolic disease may improve recognition of multisystem risk, facilitate earlier intervention, and provide a more coherent foundation for precision and preventive medicine, in an era of growing cardiometabolic multimorbidity. Full article
(This article belongs to the Special Issue Advances in Vascular Health and Metabolism)
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28 pages, 3665 KB  
Article
The Dual Anaplerotic Model (DAM): Integral Roles of Pyruvate Carboxylase and the GABA Shunt in Beta Cell Insulin Secretion
by Vladimir Grubelnik, Jan Zmazek and Marko Marhl
Life 2026, 16(1), 171; https://doi.org/10.3390/life16010171 - 20 Jan 2026
Viewed by 291
Abstract
We present a simplified phenomenological computational framework that integrates the GABA shunt into established metabolic mechanisms underlying pancreatic beta cell insulin secretion. The GABA shunt introduces carbon into the tricarboxylic acid (TCA) cycle via succinate, thereby functioning as an anaplerotic pathway. This anaplerotic [...] Read more.
We present a simplified phenomenological computational framework that integrates the GABA shunt into established metabolic mechanisms underlying pancreatic beta cell insulin secretion. The GABA shunt introduces carbon into the tricarboxylic acid (TCA) cycle via succinate, thereby functioning as an anaplerotic pathway. This anaplerotic input is coupled to oscillatory cataplerotic fluxes, primarily involving α-ketoglutarate, whose effective extrusion requires coordinated counter-fluxes of malate and aspartate. Within the model, these cataplerotic exchanges are facilitated by UCP2-mediated transport processes and necessitate complementary anaplerotic replenishment through pyruvate carboxylase (PC). Based on this functional interdependence, we introduce the Dual Anaplerotic Model (DAM), which conceptually links two anaplerotic routes—the GABA shunt-mediated pathway and the glucose-dependent PC pathway—into a unified metabolic response module. DAM describes a coordinated, breathing-like redistribution of carbon between mitochondrial and cytosolic metabolite pools, while efficient oxidative metabolism of glucose-derived carbon entering the TCA cycle via pyruvate dehydrogenase is maintained. The model is driven by experimentally observed ATP/ADP and Ca2+ dynamics and is not intended to generate autonomous oscillations. Instead, it enables qualitative, phase-dependent visualization of how dual anaplerotic fluxes constrain and shape oscillatory metabolic states in beta cells. DAM provides an integrative conceptual scaffold for interpreting experimental observations and for motivating future quantitative modeling and experimental studies addressing metabolic regulation in physiological and pathophysiological contexts. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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29 pages, 3890 KB  
Review
Selection for Molecularly Complementary Modules (MCMs) Drives the Origins and Evolution of Pleiofunctional, Epistatic Interactomes (PEIs)
by Robert Root-Bernstein
Life 2026, 16(1), 170; https://doi.org/10.3390/life16010170 - 20 Jan 2026
Viewed by 260
Abstract
The huge number of possible permutations of genes, proteins and small molecules make the random emergence of cellular networks problematic. How, therefore, do interactomes come into existence? What selects for their stability and functionality? I hypothesize that interactomes originate from molecularly complementary modules [...] Read more.
The huge number of possible permutations of genes, proteins and small molecules make the random emergence of cellular networks problematic. How, therefore, do interactomes come into existence? What selects for their stability and functionality? I hypothesize that interactomes originate from molecularly complementary modules (MCMs) that are selected for stability and retain their interactivity when mixed and matched with other such modules to create novel molecules and complexes displaying emergent properties not present in the individual components of the network. Because evolution can only proceed by working upon existing variants, and these variants emerge from selection of MCMs, the resulting systems must exhibit the characteristics of pleiofunctional, epistatic interactomes (PEIs). The resulting systems should display “molecular paleontology”, providing clues as to the historical process by which these MCMs were incorporated into the system. The MCM mechanism of PEI evolution is illustrated here by two case studies. The first concerns the prebiotic emergence of the glutathione–ascorbate anti-oxidant system and its later incorporation into regulation of glucose transport and catecholamine receptor activity. The second concerns the MCM evolution of the ribosome as, perhaps, the first PEI, and its role as a module for the later construction of the first cellular genomes. Full article
(This article belongs to the Special Issue 2nd Edition—Featured Papers on the Origins of Life)
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17 pages, 1180 KB  
Review
Research Progress on the Application of Mass Spectrometry Imaging Technology in Cerebral Disease
by Yao Qiao, Jie Yin, Shuyu Lu and Lihui Yin
Life 2026, 16(1), 168; https://doi.org/10.3390/life16010168 - 20 Jan 2026
Viewed by 368
Abstract
Mass spectrometry imaging (MSI) is an innovative analytical technique that integrates chemical analysis with spatial localization, enabling label-free, in situ detection and visualization of diverse biomolecules within tissue sections. This review summarizes the recent advances in the application of MSI to neurological disorders, [...] Read more.
Mass spectrometry imaging (MSI) is an innovative analytical technique that integrates chemical analysis with spatial localization, enabling label-free, in situ detection and visualization of diverse biomolecules within tissue sections. This review summarizes the recent advances in the application of MSI to neurological disorders, with a focus on Parkinson’s disease, Alzheimer’s disease, schizophrenia, and traumatic brain injury. Studies have demonstrated that MSI can delineate the spatial heterogeneity of disease-related molecules—such as neurotransmitters, lipids, and metabolites—thereby providing new perspectives for understanding the pathological mechanisms of neurodegenerative and psychiatric diseases. Platforms including MALDI-MSI and DESI-MSI have been effectively employed for visualizing drug distribution, characterizing lipid metabolic pathways, and identifying spatial biomarkers. Although challenges remain in quantitative accuracy, spatial resolution, and the detection of low-abundance molecules, advances in high-resolution mass spectrometry, single-cell-level imaging, and multi-omics integration are expected to further enhance the utility of MSI in the investigation of brain diseases. Full article
(This article belongs to the Section Radiobiology and Nuclear Medicine)
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22 pages, 2221 KB  
Article
Cytokines Adsorption During Ex Situ Machine Perfusion of Liver Grafts from Elderly Donors: A Pilot, Prospective, Randomized Study
by Giulia Cirillo, Lorenzo Bernardi, Daniele Pezzati, Maria Franzini, Emanuele Balzano, Giovanni Tincani, Jessica Bronzoni, Caterina Martinelli, Arianna Trizzino, Lorenzo Petagna, Paola Carrai, Stefania Petruccelli, Ranka Vukotic, Erlis Uruci, Matilde Masini, Serena Babboni, Serena Del Turco, Riccardo Morganti, Vincenzo De Tata, Aldo Paolicchi, Giandomenico Biancofiore, Adriano Peris, Chiara Lazzeri, Giuseppina Basta and Davide Ghinolfiadd Show full author list remove Hide full author list
Life 2026, 16(1), 167; https://doi.org/10.3390/life16010167 - 20 Jan 2026
Viewed by 325
Abstract
Ischemia–reperfusion injury (IRI) is a mechanism based on inflammatory mediators’ release and activation of effectors of damage. Studies showed a correlation between cytokine, severity of damage, and post-operative outcomes. Ex situ perfusion may work as a platform for the treatment of IRI mechanisms, [...] Read more.
Ischemia–reperfusion injury (IRI) is a mechanism based on inflammatory mediators’ release and activation of effectors of damage. Studies showed a correlation between cytokine, severity of damage, and post-operative outcomes. Ex situ perfusion may work as a platform for the treatment of IRI mechanisms, such as the removal of cytokines using cytokine adsorption (CA). We assessed the safety and benefits of an integrated CA during ex situ dual-oxygenated hypothermic (D-HOPE) and normothermic perfusion (NMP). During the period of July 2021–December 2023, 84 octogenarian liver grafts, suitable for transplantation, were considered: 12 were randomized to D-HOPE or NMP with or without CA (D-HOPE + CA, D-HOPE, NMP + CA, NMP groups, n = 3 each) and compared to 72 performed using grafts preserved in static cold storage (SCS). IL-1, IL-6, IL-10, and TNF-a perfusate concentrations were evaluated together with perfusion parameters and post-operative outcomes. Perfusion procedures were unaffected by CA integration. In NMP, cytokine levels were 10–40 times higher than in healthy subjects and 20–50 times higher than D-HOPE. Cytokines were removed both in D-HOPE and NMP, but the concentration-dependent mechanisms of action of CA led to more remarkable removal in NMP. IL-10 and TNF-a concentrations were significantly lower in NMP + CA than in NMP. The application of CA was associated with significantly higher arterial flows both in D-HOPE and NMP, and reduced neutrophil infiltration in NMP. No differences in post-operative outcomes were found among groups. In conclusion, cytokine adsorption during ex situ machine perfusion of liver grafts from elderly donors is safe and feasible and is associated with modulation of inflammatory mediators and perfusion dynamics. These findings are hypothesis-generating, and larger studies are required to determine the clinical impact of this strategy. Full article
(This article belongs to the Special Issue Transformative Technologies in Liver Transplantation)
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10 pages, 382 KB  
Article
Hemifacial Spasms with Unusual Neurovascular Compression Type: Arterial Cisternal Segment Offender
by Hyun Seok Lee, Soung Wook Park, Sang-Ku Park and Kwan Park
Life 2026, 16(1), 166; https://doi.org/10.3390/life16010166 - 19 Jan 2026
Viewed by 282
Abstract
(1) Background: Hemifacial spasm (HFS) is most commonly caused by neurovascular compression at the root exit zone (REZ) of the facial nerve; however, isolated compression along the distal cisternal segment is uncommon and remains poorly characterized. This study aimed to analyze the clinical [...] Read more.
(1) Background: Hemifacial spasm (HFS) is most commonly caused by neurovascular compression at the root exit zone (REZ) of the facial nerve; however, isolated compression along the distal cisternal segment is uncommon and remains poorly characterized. This study aimed to analyze the clinical features, intraoperative neurophysiological patterns, and surgical outcomes of patients with HFS caused by cisternal segment arterial compression. (2) Methods: Among 874 patients who underwent microvascular decompression (MVD) for HFS, 18 (2.1%) were identified as having isolated neurovascular conflict at the cisternal segment, all involving the anterior inferior cerebellar artery (AICA). Clinical characteristics, offender location, intraoperative monitoring results including lateral spread response (LSR), brainstem auditory evoked potentials, and postoperative outcomes were retrospectively evaluated. A standardized Teflon interposition technique was used in all cases. (3) Results: Postoperatively, 83.3% of patients experienced immediate spasm relief, and at the latest available follow-up, 94.4% achieved significant improvement without severe complications. (4) Conclusions: Although rare, cisternal segment arterial compression can produce typical HFS and should be considered when REZ compression is unclear or when intraoperative neuromonitoring does not respond as expected. Microvascular decompression using Teflon interposition is a safe and effective treatment option for this anatomically challenging offender location. Full article
(This article belongs to the Section Medical Research)
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11 pages, 1105 KB  
Article
Biofeedback Fixation Training in the Rehabilitation of Patients with Geographic Atrophy
by Kristóf Vörös, Illés Kovács, Gréta Kézdy, Ágnes Élő, Zsuzsa Szilágyi, Mirella Barboni, Zsuzsa Récsán, Zoltán Zsolt Nagy and Monika Ecsedy
Life 2026, 16(1), 165; https://doi.org/10.3390/life16010165 - 19 Jan 2026
Viewed by 311
Abstract
Geographic atrophy (GA) is a progressive cause of central vision loss with limited rehabilitation options. This prospective case series aimed to evaluate the effects of biofeedback fixation training (BFT) on visual function and vision-related quality of life (QoL) in patients with GA. Eighteen [...] Read more.
Geographic atrophy (GA) is a progressive cause of central vision loss with limited rehabilitation options. This prospective case series aimed to evaluate the effects of biofeedback fixation training (BFT) on visual function and vision-related quality of life (QoL) in patients with GA. Eighteen patients with total central vision loss in one eye underwent BFT on the fellow eye (study eye) using the Macular Integrity Assessment (MAIA) system, which was used to select a new, previously chosen preferred retinal locus (PRL) to stabilize fixation or adopt a new fixation locus. Patients were followed for an average of 13.2 months (range 3–26 months). Functional outcomes included best corrected visual acuity (ETDRS chart), reading performance (Radner test), and contrast sensitivity (Spot Checks test). MAIA parameters comprised average retinal sensitivity, fixation distance and stability (P1, P2), and changes in the bivariate contour ellipse area (BCEA). Vision-related quality of life was assessed using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). Following BFT, visual acuity, reading ability and contrast sensitivity improved significantly (p value: p < 0.02), and fixation stability and NEI-VFQ-25 scores showed a positive trend. These findings indicate that BFT is a feasible and promising rehabilitation approach for patients with GA. Full article
(This article belongs to the Special Issue Novel Diagnostics and Therapeutics for Ophthalmic Diseases)
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19 pages, 2204 KB  
Article
Machine Learning Approach for Differentiation of Pheochromocytoma from Adrenocortical Cancer and Non-Functioning Adrenal Adenomas
by Timur Nurkhabinov, Irena Ilovayskaya, Anna Lugovskaya, Victor Popov and Lidia Nefedova
Life 2026, 16(1), 164; https://doi.org/10.3390/life16010164 - 19 Jan 2026
Viewed by 341
Abstract
Background: The differentiation of pheochromocytoma (PCC) from other adrenal lesions, particularly in incidentalomas with non-benign radiological characteristics (size > 4 cm or density > 10 HU), remains a clinical challenge. The study aimed to develop and validate an interpretable machine learning (ML) model [...] Read more.
Background: The differentiation of pheochromocytoma (PCC) from other adrenal lesions, particularly in incidentalomas with non-benign radiological characteristics (size > 4 cm or density > 10 HU), remains a clinical challenge. The study aimed to develop and validate an interpretable machine learning (ML) model for pairwise differentiation of PCC from adrenocortical carcinomas (ACCs) and non-functioning adrenal adenomas (NAAs) and to identify the most important clinical features. Methods: We analyzed a dataset of 50 clinical, laboratory, and radiological parameters from 123 patients with histologically verified adrenal tumors (63 PCC, 30 ACC, 30 NAA). Four classifiers—Logistic Regression (LR), Random Forest (RF), Linear Discriminant Analysis (LDA), and Extreme Gradient Boosting (XGBoost)—were trained for binary classification tasks (PCC vs. ACC, PCC vs. NAA, ACC vs. NAA) using a robust nested stratified cross-validation pipeline to ensure generalizability and avoid overfitting. Results: All four models showed strong predictive performance, with discrimination (AUC) more than 0.8. Our analysis, based on the interpretable LR model, identified the key discriminators differentiated PCC from both ACC and NAA: maximum systolic blood pressure, grade 3 hypertension, headache, palpitation, tachycardia, male sex, and concomitant gastric and duodenal ulcers. In contrast, lower back pain and general weakness were strong signs of lower probability of PCC. The tumor density specifically differentiated PCC from NAA, whereas tumor size was an important marker for distinguishing PCC and ACC. Conclusions: We developed robust ML models capable of accurately differentiating PCC from other adrenal tumors in complex cases. The models provide a clinically actionable tool for pre-surgical decision support. Furthermore, the identification of key discriminative features enhances the clinical understanding of PCC and facilitates its differential diagnosis prior to histological verification. Full article
(This article belongs to the Special Issue Advanced Machine Learning for Disease Prediction and Prevention)
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53 pages, 11565 KB  
Review
Recent Advances in Dual COX/LOX Inhibitor Design (2020–2024): Establishing “The Rule of Four for Inflammation”
by Filippos Panteleimon Chatzipieris, Errikos Petsas, George Lambrinidis, Stamatia Vassiliou and Christos T. Chasapis
Life 2026, 16(1), 163; https://doi.org/10.3390/life16010163 - 19 Jan 2026
Viewed by 580
Abstract
The arachidonic acid pathway plays a pivotal role in the biosynthesis of important inflammatory and signal transducing agents such as prostaglandins, leukotrienes and thromboxanes. When this pathway is deregulated, it leads to pathological conditions such as cardiovascular diseases, metabolic diseases, and cancer. Two [...] Read more.
The arachidonic acid pathway plays a pivotal role in the biosynthesis of important inflammatory and signal transducing agents such as prostaglandins, leukotrienes and thromboxanes. When this pathway is deregulated, it leads to pathological conditions such as cardiovascular diseases, metabolic diseases, and cancer. Two key enzymes of the pathway are cyclooxygenases (COXs) and lipoxygenases (LOXs), which are responsible for the production of prostaglandins and leukotrienes, respectively. Consequently, these enzymes have long been recognized as key therapeutic targets for the treatment and management of inflammatory disorders and other pathological conditions associated with inflammation. In this review, we describe the new evidence over the last 4 years regarding the arachidonic acid pathway. Moreover, we will pay attention to the structure and function of the COX-2 and 5-LOX enzymes and their role in inflammation, as well as define their active sites. Later, we will discuss the most potent, dual inhibitors of COX-2 and 5-LOX enzymes, based on in vitro and in vivo experiments, from 2020–2024. Structure–activity relationship (SAR) analysis of these compounds revealed four key structural features required for potent dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). We refer to these criteria as “The Rule of Four for Inflammation”. Full article
(This article belongs to the Section Pharmaceutical Science)
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13 pages, 898 KB  
Article
AI-Powered Lateral DEXA Morphometry for Integrated Evaluation of Thoracic Kyphosis and Bone Density Assessment in Patients with Axial Spondyloarthritis
by Elena Bischoff, Stoyanka Vladeva, Xenofon Baraliakos and Nikola Kirilov
Life 2026, 16(1), 162; https://doi.org/10.3390/life16010162 - 19 Jan 2026
Viewed by 265
Abstract
Axial spondyloarthritis (axSpA) is a chronic inflammatory disorder causing structural spinal damage and pathological thoracic kyphosis. Accurate quantification of spinal curvature is crucial for monitoring disease progression and guiding treatment. Conventional Cobb angle measurement on radiographs or DEXA images is widely used but [...] Read more.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disorder causing structural spinal damage and pathological thoracic kyphosis. Accurate quantification of spinal curvature is crucial for monitoring disease progression and guiding treatment. Conventional Cobb angle measurement on radiographs or DEXA images is widely used but is time-consuming and prone to inter-observer variability. This study evaluates an automated deep learning-based approach using a You Only Look Once (YOLO) model for vertebral detection on lateral morphometric DEXA scans and estimation of thoracic kyphosis angles. A dataset of 512 annotated DEXA images, including 182 from axSpA patients, was used to train and test the model. Kyphosis angles were computed by fitting a circle through detected vertebral centroids (Th4–Th12) and calculating the corresponding curvature angle. Model-predicted angles demonstrated strong agreement with physician-measured Cobb angles (r = 0.92, p < 0.001), low mean squared error (4.2°) and high sensitivity and specificity for detecting clinically significant kyphosis. Automated lateral DEXA morphometry provides a rapid, reproducible and clinically interpretable method for assessing thoracic kyphosis and bone density in axSpA, representing a practical tool for integrated structural and metabolic evaluation. Full article
(This article belongs to the Section Medical Research)
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26 pages, 1203 KB  
Review
Learning from an Emerging Infection: How the COVID-19 Pandemic Reshaped Gastric Cancer Care
by Alexandru Marian Vieru, Dumitru Radulescu, Liliana Streba, Emil Tiberius Trasca, Sergiu Marian Cazacu, Razvan-Cristian Statie, Petrica Popa and Tudorel Ciurea
Life 2026, 16(1), 161; https://doi.org/10.3390/life16010161 - 19 Jan 2026
Viewed by 353
Abstract
Background/Objectives: The COVID-19 pandemic profoundly disrupted gastric cancer care, reducing access to screening, delaying diagnosis, and altering therapeutic pathways worldwide. Beyond clinical challenges, it exposed structural weaknesses in healthcare systems but also accelerated innovation. Methods: We conducted a narrative review supported by a [...] Read more.
Background/Objectives: The COVID-19 pandemic profoundly disrupted gastric cancer care, reducing access to screening, delaying diagnosis, and altering therapeutic pathways worldwide. Beyond clinical challenges, it exposed structural weaknesses in healthcare systems but also accelerated innovation. Methods: We conducted a narrative review supported by a structured literature search (PubMed/MEDLINE, Scopus, Web of Science; 1 January 2014–30 November 2025), with a narrative synthesis of observational studies, registry analyses, and meta-analyses addressing COVID-19–related changes in gastric cancer epidemiology, diagnosis, treatment, vaccination, and telemedicine. A PRISMA-style flow diagram was used to illustrate study selection. Results: Elective endoscopy volumes fell by up to 80%, leading to diagnostic backlogs and increased proportions of advanced-stage gastric cancer. Surgical postponements, modified chemotherapy and radiotherapy schedules, and reduced molecular/genetic testing further compromised outcomes. Conversely, vaccination, telemedicine, capsule endoscopy, and adaptive triage frameworks enabled partial recovery of services. Geographical variations were observed in the recovery of gastric cancer care services, with regions that had established screening infrastructure generally resuming activity more rapidly, whereas others experienced ongoing delays and diagnostic backlogs. Conclusions: This review integrates epidemiological, diagnostic, and therapeutic evidence to demonstrate how COVID-19 redefined gastric cancer care. By highlighting regional disparities and outlining a conceptual model for oncologic resilience, it provides an innovative framework for future crisis preparedness. The lessons of the pandemic—digital health integration, flexible treatment protocols, and international collaboration—represent a foundation for more robust, equitable gastric cancer management in the post-pandemic era. Full article
(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations)
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13 pages, 1773 KB  
Article
Speed and Distance Redistribution—Lower Limb Power Strategy in Single-Leg-Approach Jumps
by Wei-Hsun Tai, Hsien-Te Peng, Jian-Zhi Lin, Hai-Bin Yu and Po-Ang Li
Life 2026, 16(1), 160; https://doi.org/10.3390/life16010160 - 18 Jan 2026
Viewed by 293
Abstract
This study systematically investigated the influence of approach kinematics on the subsequent kinetics and power production strategies during the approach to running jumps with a single leg (ARJSL). Twenty-five physically active male university students performed ARJSL trials under two prescribed approach speeds (fast [...] Read more.
This study systematically investigated the influence of approach kinematics on the subsequent kinetics and power production strategies during the approach to running jumps with a single leg (ARJSL). Twenty-five physically active male university students performed ARJSL trials under two prescribed approach speeds (fast and slow) and three approach distances (3, 6, and 9 m) in a 2 × 3 within-subjects design. Three-dimensional motion capture synchronized with force platform data was used to quantify jump height (JH), vertical touchdown velocity (TDv), reactive strength index (RSI), peak joint power (hip, knee, and ankle), and joint stiffness. Significant approach speed × distance interactions were observed for JH (p = 0.006), TDv (p < 0.001), RSI (p = 0.014), ankle stiffness (p = 0.006), and peak power generation at all lower-limb joints (all p < 0.034). The results demonstrate that changes in approach strategy systematically alter the distribution of mechanical power among the hip, knee, and ankle joints, thereby influencing the effectiveness of horizontal-to-vertical momentum conversion during take-off. Notably, RSI and ankle stiffness were particularly sensitive to combined manipulations of speed and distance, highlighting their value as neuromechanical indicators of stretch–shortening cycle intensity and joint loading demands. In conclusion, ARJSL performance depends on finely tuned, speed- and distance-specific biomechanical adaptations within the lower extremity. These findings provide a constrained, joint-level mechanical characterization of how approach speed and distance interact to influence power redistribution and stiffness behavior during ARJSL, without implying optimal or performance-maximizing strategies. Full article
(This article belongs to the Special Issue Sports Biomechanics, Injury, and Physiotherapy)
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18 pages, 1024 KB  
Systematic Review
Anxiety-Related Functional Dizziness: A Systematic Review of the Recent Evidence on Vestibular, Cognitive Behavioral, and Integrative Therapies
by Rosario Ferlito, Francesco Cannistrà, Salvatore Giunta, Manuela Pennisi, Carmen Concerto, Maria S. Signorelli, Rita Bella, Maria P. Mogavero, Raffaele Ferri and Giuseppe Lanza
Life 2026, 16(1), 159; https://doi.org/10.3390/life16010159 - 18 Jan 2026
Viewed by 496
Abstract
Background: Functional dizziness and persistent postural-perceptual dizziness (PPPD) involve mutually reinforcing vestibular symptoms and anxiety. Non-pharmacological interventions, such as vestibular rehabilitation therapy (VRT) and cognitive behavioral therapy (CBT), aim to address both mechanisms, yet their overall effectiveness remains unclear. Methods: We [...] Read more.
Background: Functional dizziness and persistent postural-perceptual dizziness (PPPD) involve mutually reinforcing vestibular symptoms and anxiety. Non-pharmacological interventions, such as vestibular rehabilitation therapy (VRT) and cognitive behavioral therapy (CBT), aim to address both mechanisms, yet their overall effectiveness remains unclear. Methods: We systematically examined randomized controlled trials (RCTs) published between 2000 and 2025 that evaluated VRT, CBT, or multimodal approaches for adults with functional or chronic dizziness (including PPPD and related functional dizziness constructs) accompanied by significant anxiety. Twelve RCTs (513 participants) met the criteria, involving individuals with PPPD, chronic subjective dizziness, chronic vestibular disorders with prominent anxiety, and residual dizziness after benign paroxysmal positional vertigo. Results: Conventional VRT delivered in clinic or as structured home-based programs produced small-to-moderate improvements in dizziness-related disability versus usual care. Combining VRT with CBT or psychologically informed components yielded larger and more consistent reductions in disability and maladaptive dizziness-related beliefs. CBT-based interventions reduced anxiety and dizziness-related distress compared with supportive controls. Emerging modalities, including virtual-reality-based VRT, non-invasive neuromodulation, and heart-rate-variability biofeedback, showed potential, although they were limited by small samples and methodological issues. Most trials had some risk-of-bias concerns and evidence certainty ranged from very low to moderate. Conclusions: Integrated multimodal rehabilitation shows promise, although larger, high-quality RCTs using standardized procedures and outcome measures are required. Full article
(This article belongs to the Special Issue Advances on Physiotherapy and Functional Rehabilitation in Chronic Conditions)
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23 pages, 2463 KB  
Article
Global Comparative Genomics of Stenotrophomonas maltophilia Reveals Cryptic Species Diversity, Resistome Variation, and Population Structure
by Ei Phway Thant, Chollachai Klaysubun, Sirikan Suwannasin, Thitaporn Dechathai, Kamonnut Singkhamanan, Thunchanok Yaikhan, Nattarika Chaichana, Rattanaruji Pomwised, Monwadee Wonglapsuwan, Sarunyou Chusri and Komwit Surachat
Life 2026, 16(1), 158; https://doi.org/10.3390/life16010158 - 17 Jan 2026
Viewed by 351
Abstract
Background: Stenotrophomonas maltophilia is an increasingly important multidrug-resistant opportunistic pathogen frequently isolated from clinical, environmental, and plant-associated niches. Despite its medical relevance, the global population structure, species-complex boundaries, and genomic determinants of antimicrobial resistance (AMR) and ecological adaptation remain poorly resolved, partly [...] Read more.
Background: Stenotrophomonas maltophilia is an increasingly important multidrug-resistant opportunistic pathogen frequently isolated from clinical, environmental, and plant-associated niches. Despite its medical relevance, the global population structure, species-complex boundaries, and genomic determinants of antimicrobial resistance (AMR) and ecological adaptation remain poorly resolved, partly due to inconsistent annotations and fragmented genomic datasets. Methods: Approximately 2400 genome assemblies annotated as Stenotrophomonas maltophilia were available in the NCBI Assembly database at the time of query. After pre-download filtering to exclude metagenome-assembled genomes and atypical lineages, 1750 isolate genomes were retrieved and subjected to stringent quality control (completeness ≥ 90%, contamination ≤ 5%, ≤500 contigs, N50 ≥ 10 kb, and ≤1% ambiguous bases), yielding a final curated dataset of 1518 high-quality genomes used for downstream analyses. Genomes were assessed using CheckM, annotated with Prokka, and compared using average nucleotide identity (ANI), pan-genome analysis, core-genome phylogenomics, and functional annotation. AMR genes, mobile genetic elements (MGEs), and metadata (source, host, and geographic origin) were integrated to assess lineage-specific genomic features and ecological distributions. Results: ANI-based clustering resolved the S. maltophilia complex into multiple distinct genomospecies and revealed extensive misidentification of publicly deposited genomes. The pan-genome was highly open, reflecting strong genomic plasticity driven by accessory gene acquisition. Core-genome phylogeny resolved well-supported clades associated with clinical, environmental, and plant-related niches. Resistome profiling showed widespread intrinsic MDR determinants, with certain lineages enriched for efflux pumps, β-lactamases, and trimethoprim–sulfamethoxazole resistance markers. MGE analysis identified lineage-specific integrative conjugative elements, prophages, and transposases that correlated with source and geographic distribution. Conclusions: This large-scale analysis provides the most comprehensive genomic overview of the S. maltophilia complex to date. Our findings clarify species boundaries, highlight substantial taxonomic misannotation in public databases, and reveal lineage-specific AMR and mobilome patterns linked to ecological and clinical origins. The curated dataset and evolutionary insights generated here establish a foundation for global genomic surveillance, epidemiological tracking, and future studies on the evolution of antimicrobial resistance in S. maltophilia. Full article
(This article belongs to the Section Genetics and Genomics)
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20 pages, 1798 KB  
Article
Genetic Diversity of Prolamin Loci Related to Grain Quality in Durum Wheat (Triticum durum Desf.) in Kazakhstan
by Maral Utebayev, Svetlana Dashkevich, Oksana Kradetskaya, Irina Chilimova, Ruslan Zhylkybaev, Tatyana Zhigula, Tatyana Shelayeva, Gulmira Khassanova, Kulpash Bulatova, Vladimir Tsygankov, Marat Amangeldin and Yuri Shavrukov
Life 2026, 16(1), 157; https://doi.org/10.3390/life16010157 - 17 Jan 2026
Viewed by 289
Abstract
The technological properties of durum wheat grain are determined by prolamins (gliadins and glutenins). Information on the allelic composition of key loci remains incomplete despite existing global studies examining prolamin variability. This highlighted the need to study these traits in durum wheat in [...] Read more.
The technological properties of durum wheat grain are determined by prolamins (gliadins and glutenins). Information on the allelic composition of key loci remains incomplete despite existing global studies examining prolamin variability. This highlighted the need to study these traits in durum wheat in Kazakhstan. The effects of specific gliadin components with high- and low-molecular-weight glutenin fractions on gluten quality are also not fully clarified. This study aimed to characterise allelic diversity at prolamin-coding loci and evaluate associated grain quality traits. Using native and denaturing SDS-electrophoresis, 181 tetraploid wheat accessions from Kazakhstan, an International germplasm collection, and 26 breeding lines were analysed for allelic variation and associations with protein content, gluten content, gluten index, and SDS-sedimentation. The γ45 gliadin component and Glu-A3a allele were positively associated with SDS-sedimentation and gluten index, while Glu-B3b had a negative effect. Distinct prolamin profiles were observed among accessions from different ecological and geographical locations. These results support the selection of superior durum wheat genotypes and enable the identification of favourable allele combinations at the Gli-1, Gli-2, Glu-1, and Glu-3 loci in cultivars from Kazakhstan. Comparison with global tetraploid wheat germplasm collections demonstrates unique genetic diversity in genotypes, providing a valuable basis for breeding programs aimed at improving grain and gluten quality in durum wheat in Kazakhstan and Central Asian countries. Full article
(This article belongs to the Special Issue Advances in Plant Biotechnology and Molecular Breeding)
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15 pages, 1890 KB  
Case Report
Liver Lipodystrophy in Barraquer–Simons Syndrome: How Much Should We Worry About?
by Doina Georgescu, Daniel Florin Lighezan, Roxana Buzas, Paul Gabriel Ciubotaru, Oana Elena Țunea, Ioana Suceava, Teodora Anca Albu, Aura Jurescu, Mihai Ioniță and Daniela Reisz
Life 2026, 16(1), 156; https://doi.org/10.3390/life16010156 - 17 Jan 2026
Viewed by 367
Abstract
Lipodystrophy is a rare group of metabolic disorders characterized by the abnormal distribution of body fat, which can lead to various metabolic complications due to the body’s inability to adequately process carbohydrates and fat. We report the case of a female, aged 53 [...] Read more.
Lipodystrophy is a rare group of metabolic disorders characterized by the abnormal distribution of body fat, which can lead to various metabolic complications due to the body’s inability to adequately process carbohydrates and fat. We report the case of a female, aged 53 years, who was admitted as an outpatient for progressive weight loss of the upper part of the body (face, neck, arms, and chest), dyspeptic complaints, fatigue, mild insomnia, and anxious behavior. Her medical history was characterized by the presence of dyslipidemia, hypertension, and a minor stroke episode. However, she denied any family-relevant medical history. Although the clinical perspective suggested a possible late onset of partial acquired lipodystrophy, due to the imaging exam that revealed an enlarged liver with inhomogeneous structure with multiple nodular lesions, scattered over both lobes, a lot of lab work-ups and complementary studies were performed. Eventually, a liver biopsy was performed by a laparoscopic approach during cholecystectomy, the histology consistent with metabolic disease-associated steatohepatitis (MASH). In conclusion, given their heterogeneity and rarity, lipodystrophies may be either overlooked or misdiagnosed for other entities. Barraquer–Simons syndrome (BSS) may be associated with liver disease, including cirrhosis and liver failure. Liver lipodystrophy in BSS may sometimes feature steatosis with a focal, multi-nodular aspect, multiplying the diagnostic burden. Liver lipodystrophy may manifest as asymptomatic fat accumulation but may progress to severe conditions, representing one of the major causes of mortality in BSS, apart from the cardio-vascular comorbidities. Given the potential of severe outcomes, it is mandatory to correctly assess the stage of liver disease since the first diagnosis. Full article
(This article belongs to the Special Issue From Physiology and Pathology Research to Clinical Insights in Gastrointestinal Disorders)
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9 pages, 716 KB  
Article
Evaluation of Factors Impacting Shelter Cats’ Personalities
by Mihai Borzan, Christelle Digonnet, Emoke Pall, Anamaria Ioana Paștiu and Alexandra Tabaran
Life 2026, 16(1), 155; https://doi.org/10.3390/life16010155 - 17 Jan 2026
Viewed by 298
Abstract
Behavior-related factors represent a major cause of cat relinquishment to shelters, highlighting the need for reliable tools to support appropriate matching between cats and adopters. The present study applied the ASPCA® Meet Your Match® Feline-ality™ assessment to evaluate personality profiles of [...] Read more.
Behavior-related factors represent a major cause of cat relinquishment to shelters, highlighting the need for reliable tools to support appropriate matching between cats and adopters. The present study applied the ASPCA® Meet Your Match® Feline-ality™ assessment to evaluate personality profiles of shelter cats and to examine factors associated with variation in personality expression across shelters. A total of 113 cats housed in six shelters in the south of France were assessed using a standardized behavioral protocol. Differences between shelters were evaluated using one-way ANOVA for behavioral scale scores, while associations between personality type and shelter affiliation, sex, coat color, and age were analyzed using χ2 tests of independence. Significant differences between shelters were observed for the majority of behavioral assessment items, as well as for composite valiance and independent–gregarious scale scores. Shelter affiliation was significantly associated with the distribution of Feline-ality™ personality types, indicating that personality profiles were not uniformly distributed across shelters. No statistically detectable association was found between personality type and sex. In contrast, significant associations were observed between personality type and both coat color category and age category, suggesting non-random variation in personality distribution across these factors. These findings indicate that shelter-related and individual factors are associated with variation in feline personality expression. While causal relationships cannot be inferred, the results underscore the importance of considering environmental context and population characteristics when interpreting shelter-based behavioral assessments. The Feline-ality™ framework appears to be a useful tool for characterizing personality variation in shelter cats and may support improved adoption matching when applied with appropriate caution. Full article
(This article belongs to the Section Animal Science)
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