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30 pages, 1152 KB  
Review
Pediatric Mild Traumatic Brain Injury and Concussion: Modern Pathophysiological Insights, Diagnostic Advances, and Active Management Protocols
by Mirjana Raicevic and Srdjan S. Nikolovski
Brain Sci. 2026, 16(9), 998; https://doi.org/10.3390/brainsci16090998 (registering DOI) - 21 Sep 2026
Abstract
Traumatic brain injury and pediatric concussion represent major global public health concerns. This narrative review aims to provide an updated overview of pediatric concussion by integrating current evidence regarding pathophysiology, diagnostic advances, neuroimaging, biomarkers, and evidence-based management strategies. Concussion pathophysiology involves a complex [...] Read more.
Traumatic brain injury and pediatric concussion represent major global public health concerns. This narrative review aims to provide an updated overview of pediatric concussion by integrating current evidence regarding pathophysiology, diagnostic advances, neuroimaging, biomarkers, and evidence-based management strategies. Concussion pathophysiology involves a complex neurometabolic cascade characterized by ionic imbalance, mitochondrial dysfunction, cerebral blood flow alterations, diffuse axonal injury, and neuroinflammation. In pediatric populations, unique neurodevelopmental vulnerabilities (higher head-to-torso ratio, weaker cervical musculature, ongoing myelination) magnify these disturbances. Contemporary management has evolved from prolonged rest to early active recovery, incorporating brief initial rest (24–48 h) followed by sub-symptom threshold aerobic exercise, structured return-to-learn accommodations, and stepped return-to-sport protocols. Emerging diagnostic tools include the Child SCAT6/Child SCOAT6, vestibular/ocular motor screening, and blood biomarkers (GFAP, UCH-L1, NfL). Future research should focus on standardizing pediatric biomarker thresholds and validating multimodal diagnostic algorithms through prospective multicenter studies. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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18 pages, 16023 KB  
Article
Multi-Source Geophysical Data Integration for Underwater Target Detection in Complex Seabed Environments: A Case Study of the Nan’ao I Shipwreck, China
by Yonghang Li, Jiale Chen, Yuanzhao Meng, Dashun Xiao, Hai Lin, Huiqiang Yao, Zepeng Huang, Haoyi Zhou and Shi Zhang
Remote Sens. 2026, 18(16), 2832; https://doi.org/10.3390/rs18162832 - 20 Aug 2026
Viewed by 493
Abstract
The search and discovery of underwater shipwreck sites represent the most arduous and critical phases of underwater archaeology. Wooden shipwrecks, in particular, are characterized by low acoustic impedance contrast and weak magnetic anomalies, coupled with their limited physical dimensions. Consequently, they predominantly exist [...] Read more.
The search and discovery of underwater shipwreck sites represent the most arduous and critical phases of underwater archaeology. Wooden shipwrecks, in particular, are characterized by low acoustic impedance contrast and weak magnetic anomalies, coupled with their limited physical dimensions. Consequently, they predominantly exist as shallow-buried, discontinuous small targets scattered within confined areas, making their detection exceptionally challenging. Furthermore, the complexity of the submarine environment—including rugged topography, turbid water columns, and strong currents—poses formidable obstacles to the effective detection of these archaeological remains. Single geophysical methods are often limited by insufficient imaging resolution, interpretation ambiguity, and geological noise, making precise localization and characterization difficult. Focusing on the Nan’ao I Ming Dynasty shipwreck located in waters approximately 24 m deep off the coast of Nan’ao, Guangdong Province, China, this study proposes and validates an “acoustic-magnetic” multi-source data integration detection method. This approach systematically integrates high-resolution multibeam echo sounding (MBES), side-scan sonar (SSS), sub-bottom profiling (SBP), and marine magnetic data to establish a comprehensive framework for identification and integration analysis. The results indicate that the MBES bathymetric data reveal a regular, elongated structure oriented north–south (approximately 34 m × 12 m), closely matching the main hull and deck configuration. The SSS imagery exhibited high backscatter intensity and parallel linear textures, effectively delineating the hard shipwreck structure and the associated rigid protective frame employed for in situ preservation. SBP data confirmed the semi-buried state of the shipwreck (burial depth of approximately 0.6 m). Spatial variations in sediment thickness around the site suggested ongoing modification by strong hydrodynamic processes. Marine magnetic surveys identified localized negative anomalies (−210 nT relative to the ambient magnetic field), contrasting sharply with the positive anomalies of the surrounding natural reefs, thereby indicating an artificial ferromagnetic source. The spatial registration and feature superposition of multi-source data facilitated the characterization of the shipwreck, demonstrating its potential to mitigate environmental interference and enhance detection reliability in this complex environment. Using the Nan’ao I shipwreck site as a case study, this study provides a detailed characterization of the site’s 3D morphology, burial state, and physical properties. The proposed methodology offers a practical and robust technical solution for underwater shipwreck archaeology in complex nearshore environments, providing significant implications for proactive discovery, efficient investigation, and protection of underwater cultural heritage (UCH). Full article
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19 pages, 15881 KB  
Article
Genome-Wide Identification, Characterization, and Expression Profiling of the UBP Gene Family in Prunus mume Under Chilling and Freezing Stresses
by Wenqing Zheng, Jinyu Fan, Jiakai Zhao, Yajing Duan, Jie Meng and Xi Zhang
Forests 2026, 17(8), 895; https://doi.org/10.3390/f17080895 - 30 Jul 2026
Viewed by 546
Abstract
The UBP gene family plays a key role in various physiological processes, including cell cycle regulation, DNA repair, and stress responses. UBPs have been identified and analyzed in several species, including Moso Bamboo, Arabidopsis thaliana, Oryza sativa L., and Brachypodium distachyon [...] Read more.
The UBP gene family plays a key role in various physiological processes, including cell cycle regulation, DNA repair, and stress responses. UBPs have been identified and analyzed in several species, including Moso Bamboo, Arabidopsis thaliana, Oryza sativa L., and Brachypodium distachyon. However, the UBP family within Prunus mume Siebold & Zucc. remains unexplored. In this study, 30 PmUBPs were identified and characterized, all of which contained the UCH conserved domain. They were grouped into 16 subfamilies via evolutionary analysis, revealing similarities in genome structure and motif distribution. PmUBPs were distributed on seven chromosomes and three scaffolds. Gene duplication events, including tandem duplication and segmental duplication, promoted the expansion of PmUBPs. Collinear analysis demonstrated the close relationship between P. armeniaca, P. persica, P. avium, and P. mume. Transcriptome data revealed distinct relative expression trends in PmUBP genes across different tissues. Promoter cis-acting element analysis revealed an abundance of hormone-, light-, and stress-responsive elements across all genes. Transcriptome and reverse transcription quantitative PCR (RT-qPCR) analysis showed that PmUBP2, PmUBP11, PmUBP13, PmUBP18, PmUBP22, and PmUBP26 exhibited relatively high expressions under low-temperature stress. This study provides a theoretical foundation for the role of PmUBP genes in response to low-temperature stress. Full article
(This article belongs to the Section Genetics and Molecular Biology)
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17 pages, 476 KB  
Review
Serum Biomarkers of Brain Injury in Diagnosis of Patients After Seizure in Emergency Department: A Systematic Review
by Mateusz Antonow and Mariusz Siemiński
Int. J. Mol. Sci. 2026, 27(14), 6432; https://doi.org/10.3390/ijms27146432 - 20 Jul 2026
Viewed by 654
Abstract
Distinguishing seizures from other causes of transient loss of consciousness in the emergency department (ED) is challenging. This PRISMA-guided systematic review evaluated serum brain injury biomarkers for the acute diagnosis of seizures in adults. We searched PubMed and Web of Science for studies [...] Read more.
Distinguishing seizures from other causes of transient loss of consciousness in the emergency department (ED) is challenging. This PRISMA-guided systematic review evaluated serum brain injury biomarkers for the acute diagnosis of seizures in adults. We searched PubMed and Web of Science for studies published between 2015 and 2025 and included 14 studies in which blood sampling occurred shortly after the event, reflecting the ED diagnostic window. Given the heterogeneity across studies, the overall certainty of the evidence was low. Neuron-specific enolase (NSE) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) were consistently elevated after epileptic seizures compared to healthy controls. NSE effectively differentiated seizures from syncope, while UCH-L1 and glial fibrillary acidic protein (GFAP) distinguished epileptic from psychogenic non-epileptic seizures (PNESs). Neurofilament light chain (NfL) remained stable after a single seizure but increased markedly in status epilepticus (SE). S100B and BDNF results were inconsistent. Although no single biomarker serves as a standalone test, NSE and UCH-L1 are promising complementary diagnostic tools for identifying epileptic seizures in adults. Furthermore, NfL is a strong candidate marker for SE, reflecting neuroaxonal injury. Larger prospective, standardized studies are needed before routine ED implementation. Full article
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5 pages, 168 KB  
Editorial
Advanced Technologies for Maritime and Underwater Archaeology—2nd Edition
by Javier Prieto, Fabio Bruno, Antonio Lagudi, Michela Ricca, Mauro Francesco La Russa, George Papatheodorou and Nikola Mišković
J. Mar. Sci. Eng. 2026, 14(13), 1200; https://doi.org/10.3390/jmse14131200 - 30 Jun 2026
Viewed by 490
Abstract
Underwater cultural heritage (UCH) is one of the richest and most vulnerable records of humankind’s past [...] Full article
21 pages, 9121 KB  
Review
Research Progress of Blood-Based Biomarkers for the Diagnosis and Prognostic Evaluation of Acute Ischemic Stroke
by Yuheng Shu, Yiren Qin and Qi Fang
Biomolecules 2026, 16(7), 937; https://doi.org/10.3390/biom16070937 - 24 Jun 2026
Viewed by 1201
Abstract
Blood-based biomarkers offer a promising “biochemical imaging” approach for acute ischemic stroke (AIS) management, providing objective and accessible tools to complement conventional neuroimaging. This narrative review synthesizes recent advances in biomarkers derived from multiple neurovascular unit (NVU) compartments, including glial fibrillary acidic protein [...] Read more.
Blood-based biomarkers offer a promising “biochemical imaging” approach for acute ischemic stroke (AIS) management, providing objective and accessible tools to complement conventional neuroimaging. This narrative review synthesizes recent advances in biomarkers derived from multiple neurovascular unit (NVU) compartments, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neuron-specific enolase (NSE), neurofilament light chain (NfL), matrix metalloproteinase-9 (MMP-9), Claudin-5, Occludin, brain-derived neurotrophic factor (BDNF), interleukin-33 (IL-33), tumor necrosis factor-alpha (TNF-alpha), PARK7/DJ-1, glycogen phosphorylase BB (GP-BB), and circulating microRNAs. We focus on their stage-specific clinical utility across three scenarios: (1) ultra-early differentiation between ischemic stroke and intracerebral hemorrhage in prehospital and emergency settings; (2) dynamic prediction and monitoring of hemorrhagic transformation after reperfusion therapies; and (3) assessment of infarct burden, neurorepair potential, and long-term functional outcomes. Despite their promise, clinical translation remains hindered by assay platform heterogeneity, lack of standardized cut-off values, limited cost-effectiveness data, and insufficient prospective validation adjusted for key covariates such as age and renal function. We further discuss multi-marker panel construction, including strategies to address biomarker collinearity and overfitting. Future directions emphasize stage-specific panels, point-of-care testing devices, and artificial intelligence algorithms to advance precision medicine in stroke care. Full article
(This article belongs to the Section Molecular Biomarkers)
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18 pages, 3151 KB  
Systematic Review
GFAP and UCH-L1 for Ruling out Intracranial Lesions After Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis
by Lorena San Miguel, Vicky Jespers and Dominique Roberfroid
J. Clin. Med. 2026, 15(13), 4858; https://doi.org/10.3390/jcm15134858 - 23 Jun 2026
Viewed by 584
Abstract
Background: Patients with mild traumatic brain injury (mTBI) have a small but clinically relevant risk of intracranial injury (ICI), requiring timely detection. Computed tomography (CT) remains the diagnostic gold standard but is costly and exposes patients to ionising radiation. Combining blood-based biomarkers, [...] Read more.
Background: Patients with mild traumatic brain injury (mTBI) have a small but clinically relevant risk of intracranial injury (ICI), requiring timely detection. Computed tomography (CT) remains the diagnostic gold standard but is costly and exposes patients to ionising radiation. Combining blood-based biomarkers, glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), with clinical decision rules may allow safe exclusion of ICI without CT, reducing unnecessary imaging, radiation exposure, and resource use. Methods: A systematic review of clinical and economic studies in patients with mTBI was registered in PROSPERO (CRD420251051158). Searches were conducted in January 2025 and updated in May 2025 in MEDLINE, Embase, and the Cochrane Library. The aim was to assess the diagnostic accuracy and economic value of the combination of GFAP and UCH-L1 compared with CT scanning to rule out ICI in both adults and children with mTBI. Where available, studies directly comparing GFAP and UCH-L1 with S100β were also analysed descriptively. The quality of the clinical evidence was assessed with QUADAS-2 and GRADE. Meta-analyses used a bivariate random-effects model, with heterogeneity and sensitivity analyses explored. Results: Overall, 21 studies were considered in our review. Moderate- to high-quality evidence indicates that GFAP and UCH-L1, when used together with clinical assessment, have very high sensitivity and can reliably rule out ICI in adults with mTBI presenting within 12 h to the emergency department. Evidence for paediatric populations shows promise but remains very limited. Specificity is low, particularly in older adults, which limits the ability to reduce CT use in this high-risk group. Research on age-adjusted cut-offs is ongoing and may help to reduce the proportion of false positive tests without compromising sensitivity. Few studies directly compared GFAP and UCH-L1 with S100β, with slightly higher to equivalent sensitivity for GFAP and UCH-L1. Economic evaluations suggest possible cost savings and reduced CT utilisation, but these analyses rely on assumptions unsupported by robust data and are highly context-dependent. There is a lack of clarity in the included studies regarding whether existing clinical head rules were used to define the study populations (i.e., to determine which patients would be recommended for CT scanning) and, if so, which specific rules were applied. Conclusions: Evidence shows that GFAP and UCH-L1 can safely exclude ICI in adults with mTBI in whom a CT scan would otherwise be considered based on clinical assessment or decision rules. Nevertheless, real-world evidence and cost-effectiveness data are scarce. Further prospective studies, including paediatric and elderly populations, and integration with clinical decision rules will be informative to ensure optimal use in clinical practice. Full article
(This article belongs to the Section Brain Injury)
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13 pages, 937 KB  
Article
Validation of Blood-Based Biomarkers After Mild Traumatic Brain Injury with GCS 15 in a Singapore Emergency Department: An Observational Study
by Win Sen Kuan, Ying Wei Yau, Desiree Xin Ying Lim, Chew Kiat Yeoh, Nicole Mun Teng Cheung, Hannah Xin Yi Lim and Mui Teng Chua
Medicina 2026, 62(6), 1095; https://doi.org/10.3390/medicina62061095 - 5 Jun 2026
Viewed by 828
Abstract
Background and Objectives: Traumatic brain injury (TBI) affects millions of people worldwide. The Glasgow Coma Scale (GCS) is commonly used to characterize its severity. Head computed tomography (CT) is frequently the diagnostic imaging modality of choice. Recently, blood-based biomarkers such as ubiquitin [...] Read more.
Background and Objectives: Traumatic brain injury (TBI) affects millions of people worldwide. The Glasgow Coma Scale (GCS) is commonly used to characterize its severity. Head computed tomography (CT) is frequently the diagnostic imaging modality of choice. Recently, blood-based biomarkers such as ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) have emerged as possible adjuncts to head CT in evaluating mild TBI (mTBI). We aim to validate the performance of the Abbott Alinity i TBI test (UCH-L1 and GFAP) compared to head CT in an Asian cohort with mTBI and GCS 15. Materials and Methods: This prospective observational study was conducted at a tertiary academic medical center from 2 December 2024 to 19 March 2025. Patients aged 21 years and above who sustained head injury within 12 h of ED attendance had GCS of 15 and required head CT as per attending physician were eligible. Plasma was separated from whole blood within 10 min of collection and immediately stored at −20 °C. UCH-L1 and GFAP levels were analyzed in batches within 28 days of recruitment at the hospital central laboratory using the Alinity i TBI test. Results: Among 120 patients enrolled, there was predominance of males (55.8%, 67/120) and Chinese ethnicity (75.8%, 91/120). The median age was 73 (interquartile range [IQR] 56 to 79) years. Overall incidence of positive head CT was 9.2% (11/120); all 11 patients had positive Alinity i TBI tests. The sensitivity and negative predictive value of the biomarkers in our cohort were both 100% (95% confidence intervals [CIs] 71.5% to 100% and 78.2% to 100%, respectively), specificity 13.8% (95% CI 7.9% to 21.7%) and positive predictive value 10.5% (95%CI 5.4% to 18%). Exploratory post hoc analysis suggested that GFAP alone, at the prespecified assay threshold, was associated with modestly higher specificity [21.1% (95% CI 13.9% to 30.0%)] in this cohort. Conclusions: The Alinity i TBI test can safely rule out intracranial injury in patients with mTBI and GCS 15 presenting within 12 h of injury. However, specificity was low, limiting its ability to reduce head CT use in its current form. Exploratory post hoc analyses of the individual biomarkers, particularly GFAP alone, should be interpreted cautiously. Future studies should focus on optimizing specificity while maintaining a high degree of sensitivity. Full article
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18 pages, 1255 KB  
Article
Age- and Sex-Related Differences in GFAP and UCH-L1 Levels in Mild Traumatic Brain Injury
by Celia Espinar-Barranco, Gemma Álvarez-Corral, María del Rio-Rico, María Isabel Romero Manjón, Eva Gutiérrez, Francisco Ruiz-Cabello and Juan Francisco Gutiérrez-Bautista
Int. J. Mol. Sci. 2026, 27(11), 4944; https://doi.org/10.3390/ijms27114944 - 29 May 2026
Viewed by 543
Abstract
Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) are increasingly used to rule out intracranial injury in patients with mild traumatic brain injury (mTBI); however, their circulating levels may be influenced by demographic factors. This study [...] Read more.
Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) are increasingly used to rule out intracranial injury in patients with mild traumatic brain injury (mTBI); however, their circulating levels may be influenced by demographic factors. This study evaluated the effects of age and sex on GFAP and UCH-L1 concentrations and assessed whether adjusted cut-off values improve the diagnostic performance of head computed tomography (CT). In this retrospective observational study, 820 consecutive patients with mTBI presenting within 12 h of injury underwent CT imaging and biomarker measurements using a chemiluminescent immunoassay. CT-positive findings were identified in 11.8% of patients (n = 97). Biomarker levels were analyzed according to age and sex, and optimized cut-off values were derived and evaluated. GFAP concentrations varied significantly according to both age and sex, whereas UCH-L1 demonstrated mainly sex-related differences. The use of manufacturer-recommended fixed cut-offs resulted in markedly reduced specificity in older patients, particularly for GFAP. Age-adjusted cut-offs improved specificity while maintaining high negative predictive values across all age groups, although this was accompanied by a reduction in sensitivity and an increase in false-negative results. For the combined GFAP/UCH-L1 assay, sensitivity ranged from 90.9% to 100%, specificity from 42.6% to 57.0%, and negative predictive values from 97.7% to 100%. Age-adjusted cut-off values for GFAP ranged from 82.1 to 112.2 pg/mL across adult age groups, whereas age-adjusted UCH-L1 cut-off values ranged from 469.6 to 1072.5 pg/mL. In conclusion, age and sex significantly influence GFAP and UCH-L1 concentrations in mTBI patients. Demographic-adjusted cut-offs improve diagnostic calibration and reduce false-positive classifications while maintaining high negative predictive values despite a moderate reduction in sensitivity. Full article
(This article belongs to the Section Molecular Neurobiology)
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18 pages, 7077 KB  
Article
Sub-Bottom Profiler in Underwater Archaeology: Comparative Analysis for Non-Intrusive Surveying and Documentation of Underwater Cultural Heritage in Spain
by Soledad Estrella Solana Rubio, Felipe Cerezo Andreo, Sebastián Federico Ramallo Asensio, Francisco López-Castejón, Darío Bernal-Casasola, Miguel Ángel Cau Ontiveros, Rafael Sabio González and Emilio Gamo Pazos
J. Mar. Sci. Eng. 2026, 14(10), 943; https://doi.org/10.3390/jmse14100943 - 19 May 2026
Viewed by 1053
Abstract
In this paper, the results of several geophysical surveys developed with a Sub-Bottom Profiler in different regions of Spain are presented. This research forms part of a broader project aimed at developing innovative non-invasive methodologies for documenting Underwater Cultural Heritage (UCH). The 2001 [...] Read more.
In this paper, the results of several geophysical surveys developed with a Sub-Bottom Profiler in different regions of Spain are presented. This research forms part of a broader project aimed at developing innovative non-invasive methodologies for documenting Underwater Cultural Heritage (UCH). The 2001 UNESCO Convention on the Protection of the Underwater Heritage recommends the use of non-destructive techniques, in situ conservation, and prioritising exploration over recovery. Geophysical techniques allow the non-invasive documentation of UCH without altering archaeological remains. The Sub-Bottom Profiler was tested in several underwater archaeological surveys under different objectives, depths, and environmental conditions. The research questions addressed the amount of information obtainable without intrusion and the optimal use of the equipment for methodological innovation. Based on the results, methodological conclusions are drawn regarding the influence of seabed composition on acoustic performance, the importance of controlling navigation speed and vessel stability, and the strong impact of sea state on data quality. The need for frequency and motion-correction optimisation to balance resolution and penetration is also highlighted, as well as the usefulness of SBP for anomaly detection, site monitoring, and palaeolandscape reconstruction. These findings contribute to establishing a transferable methodological framework applicable to other case studies. Full article
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9 pages, 691 KB  
Article
A Randomized Placebo-Controlled Trial of Mild Hyperbaric Oxygen on Serum Biomarkers in Persistent Post-Concussive Symptoms: Analysis at 13-Week Follow-Up
by Emilie E. Vomhof-DeKrey and Olayinka David Ajayi
Trauma Care 2026, 6(2), 9; https://doi.org/10.3390/traumacare6020009 - 7 May 2026
Viewed by 895
Abstract
Background: The management of persistent post-concussive symptoms (PPCS) is limited by the absence of objective biomarkers to guide treatment. We examined the early effects of a mild hyperbaric oxygen protocol on serum biomarkers of neuronal injury (neurofilament light chain, NfL), astrogliosis (glial fibrillary [...] Read more.
Background: The management of persistent post-concussive symptoms (PPCS) is limited by the absence of objective biomarkers to guide treatment. We examined the early effects of a mild hyperbaric oxygen protocol on serum biomarkers of neuronal injury (neurofilament light chain, NfL), astrogliosis (glial fibrillary acidic protein, GFAP), acute neuronal injury (ubiquitin C-terminal hydrolase L1, UCH-L1), and axonal stability (total tau) in patients with PPCS. Methods: In this single-center, randomized, placebo-controlled trial, we enrolled adults with PPCS lasting from 3 months to 5 years after mild traumatic brain injury. Participants received 40 sessions of either active treatment (≥99% O2 at 1.5 atmospheres absolute, ATA) or a true chamber placebo (21% O2 with simulated pressure changes). Serum samples were collected at baseline and 13 weeks after treatment. The primary outcome was the difference between groups in serum NfL levels. Analysis was performed on an intention-to-treat basis using a two-way ANOVA with Šídák’s multiple comparison test. Findings: Of 84 individuals assessed, 20 were randomized (Placebo, n = 9; Intervention, n = 11). Eight from each group received their respective interventions. At 13 weeks, one participant from each group was lost to follow-up, leaving seven per group for analysis. We found no significant differences in serum levels of GFAP, NfL, total tau, or UCH-L1 between the intervention and placebo groups from baseline to 13 weeks. Conclusions: A 40-session mild hyperbaric oxygen protocol at 1.5 ATA did not significantly change serum biomarkers of neuronal injury, astrogliosis, or acute neuronal damage at 13 weeks post-treatment in individuals with PPCS. This early-phase analysis, at the highest point of participant retention, provides no evidence of a treatment effect on these pathophysiological markers. Full article
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16 pages, 2089 KB  
Article
The Activation of Aldehyde Dehydrogenase 2 (ALDH2) by Alda-1 and Flurbiprofen as a Common Mechanism to Reduce Alcohol Intake in Rats
by Juan Manuel Torres, Carolina Ponce, Vicente Pérez, Ignacio Gutiérrez-Vega, María Elena Quintanilla, David Vásquez and Mario Rivera-Meza
Int. J. Mol. Sci. 2026, 27(7), 3248; https://doi.org/10.3390/ijms27073248 - 3 Apr 2026
Viewed by 1604
Abstract
Excessive alcohol consumption causes millions of deaths annually, yet current pharmacological treatments for alcohol use disorders show limited efficacy and poor adherence, creating an urgent need for new therapeutic alternatives. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde, a key mediator of the rewarding effects [...] Read more.
Excessive alcohol consumption causes millions of deaths annually, yet current pharmacological treatments for alcohol use disorders show limited efficacy and poor adherence, creating an urgent need for new therapeutic alternatives. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde, a key mediator of the rewarding effects of alcohol in the brain, making ALDH2 activation a promising therapeutic target. This study investigated whether flurbiprofen, an FDA-approved nonsteroidal anti-inflammatory drug that activates ALDH2, reduces alcohol intake compared to the experimental ALDH2 activator Alda-1 and the structurally similar NSAID ibuprofen. Male alcohol-preferring UChB rats received oral flurbiprofen (2.5–10 mg/kg), Alda-1 (5 mg/kg), or ibuprofen (5 mg/kg) during acquisition and chronic phases of voluntary alcohol consumption under a two-bottle free-choice paradigm. Both flurbiprofen and Alda-1 reduced alcohol intake by approximately 60% and similarly increased ALDH2 activity 3–4-fold in brain and liver tissues. Ibuprofen showed modest effects (25% alcohol intake reduction). In vitro assays confirmed that flurbiprofen and Alda-1, but not ibuprofen, activated ALDH2 in PC-12 cells. Enzymatic assays and molecular docking revealed that Alda-1 lacks cyclooxygenase-inhibitory activity, unlike flurbiprofen, suggesting that ALDH2 activation is the primary mechanism underlying reduced alcohol consumption. These findings identify flurbiprofen as a clinically available ALDH2 activator with significant translational potential for treating alcohol use disorders. Full article
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15 pages, 1742 KB  
Article
CHI3L1 Expression in Chordoma: Implications for Immunotherapeutic Intervention
by Beatrice Campilan, Christian Godinez, Jonathan Arditi, Jessica Ding, Kaylee Gallagher, Andrew Fogarty, Christian Schroeder, Madison J. Michles, Weston de Lomba, Joselynn Wallace, John Santiago, Michael Punsoni, Suchitra Kamle, Jack A. Elias, Christine Lee, Ziya L. Gokaslan, Margot Martinez-Moreno and Patricia L. Zadnik Sullivan
Cells 2026, 15(4), 377; https://doi.org/10.3390/cells15040377 - 22 Feb 2026
Cited by 1 | Viewed by 1326
Abstract
Chordomas are rare, highly morbid tumors arising from notochordal progenitor cells along the spinal axis, associated with severe neurological complications and high recurrence rates. Their resistance to conventional therapies and limited options beyond surgical resection and high-dose radiation underscore the urgent need for [...] Read more.
Chordomas are rare, highly morbid tumors arising from notochordal progenitor cells along the spinal axis, associated with severe neurological complications and high recurrence rates. Their resistance to conventional therapies and limited options beyond surgical resection and high-dose radiation underscore the urgent need for novel therapeutic targets. Publicly available preliminary RNA sequencing data from the Chordoma Foundation identified chitinase-3-like 1 (CHI3L1), a secreted glycoprotein implicated in immune checkpoint regulation and epithelial–mesenchymal transition (EMT), as a promising candidate for chordoma immunotherapy. Yet, the comprehensive function of CHI3L1 in chordoma immune response remains unclear. To evaluate its presence in chordoma, we employed RNA-based analyses alongside enzyme-linked immunosorbent assays (ELISA) on commercially available chordoma cell lines (JHC7, U-CH12, U-CH1, U-CH1-N) and human chordoma tumor specimens. Our results demonstrate elevated CHI3L1 expression in chordoma cells relative to notochordal precursors, with comparative analyses revealing higher CHI3L1 expression in the primary tumor relative to recurrent samples. These findings suggest the potential role of CHI3L1 in chordoma tumorigenesis, emphasizing its relevance as a biomarker and therapeutic target for primary tumors. Future studies are necessary to elucidate the mechanistic role of CHI3L1 in chordoma immune evasion and to explore targeted interventions that may improve patient outcomes in this aggressive cancer. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Novel Therapeutic Strategies in Chordoma)
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25 pages, 11974 KB  
Article
Restoring Ambiguous Boundaries: An Efficient and Robust Framework for Underwater Camouflaged Object Detection
by Zihan Wei, Yucheng Zheng, Yaohua Shen and Xiaofei Yang
Sensors 2026, 26(3), 872; https://doi.org/10.3390/s26030872 - 28 Jan 2026
Cited by 2 | Viewed by 1090
Abstract
The efficacy of Underwater Camouflaged Object Detection (UCOD) is fundamentally constrained by severe boundary ambiguity, where biological mimicry blends targets into complex backgrounds and aquatic optical degradation erodes edge details. We propose a lightweight boundary perception detector named CAR-YOLO (Camouflage Ambiguity Resolution YOLO). [...] Read more.
The efficacy of Underwater Camouflaged Object Detection (UCOD) is fundamentally constrained by severe boundary ambiguity, where biological mimicry blends targets into complex backgrounds and aquatic optical degradation erodes edge details. We propose a lightweight boundary perception detector named CAR-YOLO (Camouflage Ambiguity Resolution YOLO). Specifically, a frequency-domain dual-path mechanism (FRM-DWT/EG-IWT) leverages selective wavelet aggregation and dynamic injection to recover high-frequency edges. Subsequently, these high-frequency cues are synergized with low-frequency semantic information via the Low-level Adaptive Fusion (LAF) module. To further address noisy samples, an Uncertainty Calibration Head (UCH) refines supervision via prediction consistency. Finally, we constructed specialized datasets based on public data for training and evaluation, including UCOD10K and UWB-COT220. On UCOD10K, CAR-YOLO achieves 27.1% mAP50–95, surpassing several state-of-the-art (SOTA) methods while reducing parameters from 2.58 M to 2.43 M and GFLOPs from 6.3 to 5.9. On the challenging UWB-COT220 benchmark, the model attains 30.7% mAP50–95, marking a 7.7-point improvement over YOLOv11. Furthermore, cross-domain experiments on UODD demonstrate strong generalization. These results indicate that CAR-YOLO effectively mitigates boundary ambiguity, achieving an optimal balance between accuracy, robustness, and efficiency. Full article
(This article belongs to the Section Intelligent Sensors)
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21 pages, 331 KB  
Review
Blood-Based Biomarkers for Traumatic Brain Injury: A New Era in Diagnosis and Prognosis
by Giulia Pignataro, Marta Sacco Fernandez, Marcello Candelli, Gloria Rozzi, Andrea Piccioni, Evelina Forte and Francesco Franceschi
Int. J. Mol. Sci. 2025, 26(24), 12158; https://doi.org/10.3390/ijms262412158 - 18 Dec 2025
Cited by 10 | Viewed by 4411
Abstract
Traumatic brain injury (TBI) is a major global health concern and a leading cause of mortality and disability. Head computed tomography (CT) remains indispensable for the detection of intracranial hemorrhage; however, its indiscriminate use in mild trauma increases radiation exposure, cumulative oncogenic risk, [...] Read more.
Traumatic brain injury (TBI) is a major global health concern and a leading cause of mortality and disability. Head computed tomography (CT) remains indispensable for the detection of intracranial hemorrhage; however, its indiscriminate use in mild trauma increases radiation exposure, cumulative oncogenic risk, and healthcare costs. Consequently, there is growing interest in tools capable of improving sensitivity in mild or early-stage TBI. Protein-based biomarkers are promising complements to conventional assessment. Molecules such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), and neurofilament light chain (NfL) reflect astroglial activation, neuronal injury, and axonal damage, enabling objective evaluation of neurotrauma. Beyond protein biomarkers, metabolomic and lipidomic approaches capture alterations associated with early metabolic distress, oxidative stress, mitochondrial dysfunction, and membrane disruption following TBI. High-resolution mass spectrometry studies have identified reproducible metabolite and lipid signatures correlating with injury severity and functional outcomes. Longitudinal profiling further reveals dynamic metabolic trajectories that distinguish secondary injury progression from stabilization, supporting predictive modeling and risk stratification. Together, these advances pave the way toward precision medicine in neurotrauma. Nevertheless, variability in assay performance and sampling timing continues to limit widespread clinical adoption. Future research should prioritize methodological standardization, analytical validation, and the integration of multi-omic data with machine learning–based predictive models. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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