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Search Results (31,743)

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15 pages, 1064 KB  
Review
Extracellular Matrix in Human Disease and Therapy: From Pathogenic Remodeling to Biomaterial Platforms and Precision Diagnostics
by Jun-Hyeog Jang
Biomedicines 2026, 14(1), 247; https://doi.org/10.3390/biomedicines14010247 (registering DOI) - 21 Jan 2026
Abstract
The extracellular matrix (ECM) is a dynamic, tissue-specific network that integrates biochemical and mechanical cues to regulate cell behavior and organ homeostasis. Increasing evidence indicates that dysregulated ECM remodeling is an upstream driver of chronic human diseases rather than a passive consequence of [...] Read more.
The extracellular matrix (ECM) is a dynamic, tissue-specific network that integrates biochemical and mechanical cues to regulate cell behavior and organ homeostasis. Increasing evidence indicates that dysregulated ECM remodeling is an upstream driver of chronic human diseases rather than a passive consequence of injury. This review summarizes principles of ECM organization, mechanotransduction, and pathological remodeling and highlights translational opportunities for ECM-targeted therapies, biomaterial platforms, and precision diagnostics. We conducted a narrative synthesis of foundational and recent literature covering ECM composition and turnover, stiffness-dependent signaling, and disease-associated remodeling across fibrosis/cardiovascular disease, cancer, and metabolic disorders, together with advances in ECM-based biomaterials, drug delivery, and ECMderived biomarkers and imaging. Across organs, a self-reinforcing cycle of altered matrix composition, excessive crosslinking, and stiffness-dependent mechanotransduction (including integrin–FAK and YAP/TAZ pathways) sustains fibroinflammation, myofibroblast persistence, and progressive tissue dysfunction. In tumors, aligned and crosslinked ECM promotes invasion, immune evasion, and therapy resistance while also shaping perfusion and drug penetration. Translational strategies increasingly focus on modulating ECM synthesis and crosslinking, normalizing rather than ablating matrix architecture, and targeting ECM–cell signaling axes in combination with anti-fibrotic, cytotoxic, or immunotherapeutic regimens. ECM biology provides a unifying framework linking pathogenesis, therapy, and precision diagnostics across chronic diseases. Clinical translation will benefit from standardized quantitative measures of matrix remodeling, mechanism-based biomarkers of ECM turnover, and integrative imaging–omics approaches for patient stratification and treatment monitoring. Full article
(This article belongs to the Section Cell Biology and Pathology)
11 pages, 1256 KB  
Article
Retromandibular Anteroparotid Versus Transparotid Approach for Subcondylar Mandibular Fractures: A Retrospective Comparative Study of 80 Cases
by Andrea Battisti, Danilo Di Giorgio, Federica Orsina Ferri, Marco Della Monaca, Benedetta Capasso, Paolo Priore, Valentina Terenzi and Valentino Valentini
J. Clin. Med. 2026, 15(2), 887; https://doi.org/10.3390/jcm15020887 (registering DOI) - 21 Jan 2026
Abstract
Background/Objectives: Subcondylar mandibular fractures represent a challenging subset of maxillofacial trauma due to their proximity to the temporomandibular joint and the facial nerve. The retromandibular approach can be performed through either an anteroparotid or a transparotid route, but comparative clinical data remain [...] Read more.
Background/Objectives: Subcondylar mandibular fractures represent a challenging subset of maxillofacial trauma due to their proximity to the temporomandibular joint and the facial nerve. The retromandibular approach can be performed through either an anteroparotid or a transparotid route, but comparative clinical data remain limited. This study aimed to evaluate clinical outcomes, complication profiles, and operative parameters associated with the retromandibular anteroparotid versus transparotid approach for open reduction and internal fixation (ORIF) of subcondylar fractures. Methods: A retrospective analysis was conducted on 80 consecutive patients treated for subcondylar mandibular fractures at the Department of Maxillofacial Surgery, Umberto I General Hospital, Sapienza University of Rome, between 2018 and 2025. All patients underwent ORIF via a retromandibular approach (anteroparotid or transparotid) with a minimum follow-up of 6 months. Demographic data, trauma etiology, fracture morphology (classified as simple or complex), associated fractures, surgical approach, fixation details, operative time, hospital stay, and postoperative complications were collected. Facial nerve function was clinically assessed and graded using the House–Brackmann scale. Associations between fracture type, surgical approach, number of plates, and complications were evaluated using Chi-square or Fisher’s exact tests, while operative time was compared using one-way ANOVA and Kruskal–Wallis tests (p < 0.05). Results: The cohort had a mean age of 41.9 years and was predominantly male (67.5%). The anteroparotid route was used in 54 patients (67.5%) and the transparotid route in 26 (32.5%). Overall, 10 patients (12.5%) developed postoperative complications, including transient facial nerve weakness, malocclusion, visible scarring, and sialocele. All cases of sialocele occurred in the transparotid subgroup, whereas no salivary complications were observed after the anteroparotid approach. No permanent facial nerve deficits, temporomandibular joint ankylosis, or long-term facial asymmetry were recorded at 6 months. No significant association was found between surgical approach and overall complication rate, but complex fracture patterns were significantly associated with increased operative time. Conclusions: The retromandibular approach is a safe and effective option for ORIF of subcondylar mandibular fractures. Both anteroparotid and transparotid routes provided reliable exposure and stable fixation with low complication rates. The anteroparotid route appears to minimize parotid-related complications, such as sialocele, while maintaining comparable functional outcomes. These findings support the retromandibular anteroparotid approach as a valuable alternative in the surgical management of subcondylar fractures. Full article
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60 pages, 3055 KB  
Review
Advanced 3D/4D Bioprinting of Flexible Conductive Materials for Regenerative Medicine: From Bioinspired Design to Intelligent Regeneration
by Kuikui Zhang, Lezhou Fang, Can Xu, Weiwei Zhou, Xiaoqiu Deng, Chenkun Shan, Quanling Zhang and Lijia Pan
Micro 2026, 6(1), 8; https://doi.org/10.3390/micro6010008 - 21 Jan 2026
Abstract
Regenerative medicine is increasingly leveraging the synergies between bioinspired conductive biomaterials and 3D/4D bioprinting to replicate the native electroactive and hierarchical microenvironments essential for functional tissue restoration. However, a critical gap remains in the intelligent integration of these technologies to achieve dynamic, responsive [...] Read more.
Regenerative medicine is increasingly leveraging the synergies between bioinspired conductive biomaterials and 3D/4D bioprinting to replicate the native electroactive and hierarchical microenvironments essential for functional tissue restoration. However, a critical gap remains in the intelligent integration of these technologies to achieve dynamic, responsive tissue regeneration. This review introduces a “bioinspired material–printing–function” triad framework to systematically synthesize recent advances in: (1) tunable conductive materials (polymers, carbon-based systems, metals, MXenes) designed to mimic the electrophysiological properties of native tissues; (2) advanced 3D/4D printing technologies (vat photopolymerization, extrusion, inkjet, and emerging modalities) enabling the fabrication of biomimetic architectures; and (3) functional applications in neural, cardiac, and musculoskeletal tissue engineering. We highlight how bioinspired conductive scaffolds enhance electrophysiological behaviors—emulating natural processes such as promoting axon regeneration cardiomyocyte synchronization, and osteogenic mineralization. Crucially, we identify multi-material 4D bioprinting as a transformative bioinspired approach to overcome conductivity–degradation trade-offs and enable shape-adaptive, smart scaffolds that dynamically respond to physiological cues, mirroring the adaptive nature of living tissues. This work provides the first roadmap toward intelligent electroactive regeneration, shifting the paradigm from static implants to dynamic, biomimetic bioelectronic microenvironments. Future translation will require leveraging AI-driven bioinspired design and organ-on-a-chip validation to address challenges in vascularization, biosafety, and clinical scalability. Full article
32 pages, 448 KB  
Review
Innovative Assistive Technologies for Tetraplegia: A Narrative Review of Systematic and Emerging Evidence
by Lorenzo Desideri, Regina Gregori Grgič, Antonia Pirrera and Daniele Giansanti
Healthcare 2026, 14(2), 274; https://doi.org/10.3390/healthcare14020274 - 21 Jan 2026
Abstract
Background: Assistive technologies (ATs) for individuals with tetraplegia have evolved from mechanical aids to complex neurotechnological, digital, and psychosocial systems. However, the evidence base remains fragmented, with heterogeneous methodologies and limited integration across domains. This review synthesizes recent review-level evidence to clarify current [...] Read more.
Background: Assistive technologies (ATs) for individuals with tetraplegia have evolved from mechanical aids to complex neurotechnological, digital, and psychosocial systems. However, the evidence base remains fragmented, with heterogeneous methodologies and limited integration across domains. This review synthesizes recent review-level evidence to clarify current trends, gaps, and directions in ATs for tetraplegia. Methods: A narrative review of reviews was conducted following the ANDJ checklist. PubMed and Scopus were searched for systematic, scoping, and narrative reviews addressing assistive technologies relevant to tetraplegia. After screening, de-duplication, and quality appraisal, 20 reviews were included and synthesized narratively. Results: The included reviews clustered into four main domains: neural and regenerative interfaces, motor and biomechanical assistive systems, digital and adaptive rehabilitation ecosystems, and psychosocial and integrative frameworks. Across domains, evidence highlights a shift toward personalized, adaptive, and interoperable systems, supported by neurotechnologies, robotics, mobile health, and virtual reality. Common limitations include heterogeneous outcome measures, scarcity of longitudinal evidence, limited system interoperability, and persistent inequities in access and adoption. Emerging applications of artificial intelligence support adaptive control, monitoring, and personalization, though robust clinical validation remains limited. Conclusions: This synthesis provides a structured overview of review-level evidence on assistive technologies for tetraplegia. The findings underscore the need for coordinated, multidisciplinary approaches and more rigorous, longitudinal evaluation to support the development of inclusive, human-centered, and interoperable assistive ecosystems. Full article
19 pages, 979 KB  
Systematic Review
Diagnostic Assessment of Periodontal and Dentoalveolar Complications Following Mini-Screw-Assisted Rapid Palatal Expansion in Adults and Late Adolescents: A Systematic Review
by Barbara Frenna, Raffaella Grimaldi, Salvatore Fiandaca, Renisa Basha, Monica Caprio, Giacomo Emanuele Maria Rizzo, Alessio Verdecchia and Enrico Spinas
Diagnostics 2026, 16(2), 352; https://doi.org/10.3390/diagnostics16020352 - 21 Jan 2026
Abstract
Objectives: This systematic review aimed to evaluate the effectiveness of currently available methods for the diagnosis and monitoring of skeletal, dental, and soft tissue changes, as well as the adequacy of follow-up protocols, in adolescents and adults treated with miniscrew-assisted rapid palatal [...] Read more.
Objectives: This systematic review aimed to evaluate the effectiveness of currently available methods for the diagnosis and monitoring of skeletal, dental, and soft tissue changes, as well as the adequacy of follow-up protocols, in adolescents and adults treated with miniscrew-assisted rapid palatal expansion (MARPE). Materials and Methods: This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive electronic literature search was performed across five databases (PubMed, Scopus, Embase, Cochrane, and Web of Science) to identify prospective and retrospective clinical studies evaluating dental, periodontal, and alveolar bone outcomes associated with MARPE in late adolescent and adult patients. Study selection, data extraction, and risk of bias assessment were independently performed by two reviewers. Risk of bias was assessed using the ROBINS-I tool for non-randomized studies and the RoB 2 tool for randomized studies. The certainty of the evidence was evaluated using the GRADE approach. Owing to substantial methodological heterogeneity and limited follow-up duration, a structured qualitative (narrative) synthesis of the results was performed. Results: A total of 20 studies were included in the systematic review. The reported adverse events primarily involved hard and soft tissues and were identified using cone-beam computed tomography (CBCT), clinical and periodontal examination, panoramic and cephalometric radiography, and digital dental casts. Dental effects, including dental tipping, were frequently reported across the included studies. Alveolar bone loss was reported in 11 studies, buccal alveolar bone dehiscence in 3 studies, and failure of palatal suture opening in 6 studies. In most of the included studies, follow-up was either not reported or limited. Conclusions: The MARPE technique appears to be potentially effective in achieving transverse maxillary expansion in late adolescent and adult patients. However, the included studies report possible adverse events affecting periodontal and alveolar bone tissues, such as alveolar bone thinning and gingival hypertrophy, the assessment of which requires an integrated diagnostic approach combining CBCT imaging with clinical and periodontal examination. Overall, the certainty of the available evidence was low to very low, mainly due to a high risk of bias, methodological heterogeneity, and limited or absent follow-up in most studies. Therefore, the results should be interpreted with caution. Well-designed prospective controlled studies with standardized protocols and long-term follow-up are needed to conclusively evaluate the safety and long-term clinical stability of the MARPE technique. Full article
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11 pages, 385 KB  
Communication
Complement Activation as a Predictor of Postoperative Delirium in Elderly Spine Surgery Patients
by Antje Vogelgesang, Hannah Wolf, Sarah Strack, Agnes Flöel, Henry W. S. Schroeder, Jonas Müller, Jan-Uwe Müller, Angelika Fleischmann, Robert Fleischmann, Diana Pauly and Johanna Ruhnau
Int. J. Mol. Sci. 2026, 27(2), 1077; https://doi.org/10.3390/ijms27021077 - 21 Jan 2026
Abstract
Postoperative delirium (POD) is a frequent and serious complication among elderly surgical patients. Despite its clinical relevance, reliable biomarkers for early identification and pathophysiological insight remain limited. Recent evidence implicates systemic immune activation and complements dysregulation as contributors to cognitive decline after surgery. [...] Read more.
Postoperative delirium (POD) is a frequent and serious complication among elderly surgical patients. Despite its clinical relevance, reliable biomarkers for early identification and pathophysiological insight remain limited. Recent evidence implicates systemic immune activation and complements dysregulation as contributors to cognitive decline after surgery. This study investigated the association between perioperative levels of selected complement pathway proteins and both the incidence and severity of POD. Methods: We performed a secondary analysis of 22 patients aged ≥ 60 years from the prospective CONFESS cohort undergoing elective spine surgery. Complement proteins (C1q, C2, C4), mannose-binding lectin (MBL), Factor D [FD], Factor B [FB], Factor I [FI] were quantified from blood samples collected at baseline, preoperatively, and on postoperative days 1 and 2. POD was assessed using the Nursing Delirium Screening Scale (Nu-DESC) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Delirium severity was rated with the Confusion Assessment Method–Severity (CAM-S) scale. Associations were tested using univariate and multivariate regression analyses. Preoperative levels of FD and C2 were significantly elevated in patients who developed POD (FD: p = 0.023; C2: p = 0.044), while C4 levels trended lower. FD remained an independent predictor of POD in multivariate regression (p = 0.049), although cognitive performance was the only significant predictor when adjusted for surgery duration. Delirium severity was associated with perioperative reductions in C1q, FI, and FB and with increased MBL levels, explaining up to 43% of CAM-S score variance. These findings highlight the role of complement activation—particularly FD, C2, MBL—in the development and clinical expression of POD. Complement profiling may offer a novel approach for risk stratification and therapeutic targeting in perioperative neurocognitive disorders. Full article
40 pages, 3249 KB  
Review
Fibrous Biomaterial Scaffold for Tympanic Membrane Repair: Microarchitectural Engineering and Structure Function Performance
by Lea Jiang, Chokri Cherif and Michael Wöltje
J. Funct. Biomater. 2026, 17(1), 53; https://doi.org/10.3390/jfb17010053 - 21 Jan 2026
Abstract
Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they [...] Read more.
Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they come with well-known limitations. Beyond the need for additional harvesting procedures, these grafts rarely reproduce the intricate, fibrous layering of the native TM, which can compromise sound transmission after healing. In search of alternatives, fibre-based scaffolds have attracted considerable interest. The primary advantage of this material is the level of structural control it affords. The fibre orientation, porosity, and overall microarchitecture can be adjusted to replicate the organisation and mechanical behaviour of the natural membrane. A range of biocompatible polymers—among them silk fibroin, poly(ε-caprolactone), poly(lactic acid), and poly(vinyl alcohol) and their composites—provide options for tuning stiffness, degradation rates, and interactions with cells, making them suitable building blocks for TM repair constructs. This review provides a comprehensive overview of contemporary fabrication methodologies, namely electrospinning, additive manufacturing, melt electrowriting, and hybrid strategies. In addition, it offers a detailed discussion of the evaluation procedures employed for these scaffolds and discusses how scaffold structure affects later performance. Mechanical testing, microstructural imaging, and in vitro biocompatibility assays help to determine how closely a construct can approach the performance of the native tissue. Bringing these elements together may support the gradual translation of fibre-based TM scaffolds into clinical practice. Full article
(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)
18 pages, 581 KB  
Review
AI-Enhanced POCUS in Emergency Care
by Monica Puticiu, Diana Cimpoesu, Florica Pop, Irina Ciumanghel, Luciana Teodora Rotaru, Bogdan Oprita, Mihai Alexandru Butoi, Vlad Ionut Belghiru, Raluca Mihaela Tat and Adela Golea
Diagnostics 2026, 16(2), 353; https://doi.org/10.3390/diagnostics16020353 - 21 Jan 2026
Abstract
Point-of-care ultrasound (POCUS) is an essential component of emergency medicine, enabling rapid bedside assessment across a wide spectrum of acute conditions. Its effectiveness, however, remains constrained by operator dependency, variable image quality, and time-critical decision-making. Recent advances in artificial intelligence (AI) offer opportunities [...] Read more.
Point-of-care ultrasound (POCUS) is an essential component of emergency medicine, enabling rapid bedside assessment across a wide spectrum of acute conditions. Its effectiveness, however, remains constrained by operator dependency, variable image quality, and time-critical decision-making. Recent advances in artificial intelligence (AI) offer opportunities to augment POCUS by supporting image acquisition, interpretation, and quantitative analysis. This narrative review synthesizes current evidence on AI-enhanced POCUS applications in emergency care, encompassing trauma, non-traumatic emergencies, integrated workflows, resource-limited settings, and education and training. Across trauma settings, AI-assisted POCUS has demonstrated promising performance for automated detection of pneumothorax, hemothorax, and free intraperitoneal fluid, supporting standardized eFAST examinations and rapid triage. In non-traumatic emergencies, AI-enabled cardiovascular, pulmonary, and abdominal applications provide automated measurements and pattern recognition that can approach expert-level performance when image quality is adequate. Integrated AI–POCUS systems and educational tools further highlight the potential to expand ultrasound access, support non-expert users, and standardize training. Nevertheless, important limitations persist, including limited generalizability, dataset bias, device heterogeneity, and uncertain impact on clinical decision-making and patient outcomes. In conclusion, AI-enhanced POCUS is transitioning from proof-of-concept toward early clinical integration in emergency medicine. While current evidence supports its role as a decision-support tool that may enhance consistency and efficiency, widespread adoption will require prospective multicentre validation, development of representative POCUS-specific datasets, vendor-agnostic solutions, and alignment with clinical, ethical, and regulatory frameworks. Full article
(This article belongs to the Special Issue Application of Ultrasound Imaging in Clinical Diagnosis)
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15 pages, 801 KB  
Systematic Review
Artificial Intelligence in Pediatric Dentistry: A Systematic Review and Meta-Analysis
by Nevra Karamüftüoğlu, Büşra Yavuz Üçpunar, İrem Birben, Asya Eda Altundağ, Kübra Örnek Mullaoğlu and Cenkhan Bal
Children 2026, 13(1), 152; https://doi.org/10.3390/children13010152 - 21 Jan 2026
Abstract
Background/Objectives: Artificial intelligence (AI) has gained substantial prominence in pediatric dentistry, offering new opportunities to enhance diagnostic precision and clinical decision-making. AI-based systems are increasingly applied in caries detection, early childhood caries (ECC) risk prediction, tooth development assessment, mesiodens identification, and other key [...] Read more.
Background/Objectives: Artificial intelligence (AI) has gained substantial prominence in pediatric dentistry, offering new opportunities to enhance diagnostic precision and clinical decision-making. AI-based systems are increasingly applied in caries detection, early childhood caries (ECC) risk prediction, tooth development assessment, mesiodens identification, and other key diagnostic tasks. This systematic review and meta-analysis aimed to synthesize evidence on the diagnostic performance of AI models developed specifically for pediatric dental applications. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase following PRISMA-DTA guidelines. Studies evaluating AI-based diagnostic or predictive models in pediatric populations (≤18 years) were included. Reference screening, data extraction, and quality assessment were performed independently by two reviewers. Pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using random-effects models. Sources of heterogeneity related to imaging modality, annotation strategy, and dataset characteristics were examined. Results: Thirty-two studies met the inclusion criteria for qualitative synthesis, and fifteen were eligible for quantitative analysis. For radiographic caries detection, pooled sensitivity, specificity, and AUC were 0.91, 0.97, and 0.98, respectively. Prediction models demonstrated good diagnostic performance, with pooled sensitivity of 0.86, specificity of 0.82, and AUC of 0.89. Deep learning architectures, particularly convolutional neural networks, consistently outperformed traditional machine learning approaches. Considerable heterogeneity was identified across studies, primarily driven by differences in imaging protocols, dataset balance, and annotation procedures. Beyond quantitative accuracy estimates, this review critically evaluates whether current evidence supports meaningful clinical translation and identifies pediatric domains that remain underrepresented in AI-driven diagnostic innovation. Conclusions: AI technologies exhibit strong potential to improve diagnostic accuracy in pediatric dentistry. However, limited external validation, methodological variability, and the scarcity of prospective real-world studies restrict immediate clinical implementation. Future research should prioritize the development of multicenter pediatric datasets, harmonized annotation workflows, and transparent, explainable AI (XAI) models to support safe and effective clinical translation. Full article
(This article belongs to the Section Pediatric Dentistry & Oral Medicine)
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17 pages, 1927 KB  
Perspective
The Interplay Between Neuromodulation and Stem Cell Therapy for Sensory-Motor Neuroplasticity After Spinal Cord Injury: A Perspective View
by Anthony Yousak, Kaci Ann Jose and Ashraf S. Gorgey
J. Clin. Med. 2026, 15(2), 879; https://doi.org/10.3390/jcm15020879 - 21 Jan 2026
Abstract
Spinal Cord Injury (SCI) rehabilitation is undergoing a transformative shift with the emergence of new treatment strategies. Historically, treatment options were limited, and few offered meaningful recovery. Recent work in human models has shown that neuromodulation specifically with spinal cord epidural stimulation (SCES) [...] Read more.
Spinal Cord Injury (SCI) rehabilitation is undergoing a transformative shift with the emergence of new treatment strategies. Historically, treatment options were limited, and few offered meaningful recovery. Recent work in human models has shown that neuromodulation specifically with spinal cord epidural stimulation (SCES) paired with task-specific training (TsT) can partially restore motor function such as the ability to stand, step, and perform volitional movements. Despite these advances, the recovery has been shown to plateau even with the combination of therapies. The recovery process typically leads to partial rather than complete restoration of function. This limitation arises because current approaches primarily reactivate existing circuits rather than repair the disrupted pathways. Scar tissue and loss of descending and ascending connections remain major barriers to full recovery, restricting the transmission of neural signals. We argue that the next phase of research should be a synergistic strategy building upon the successes of neuromodulation and TsT while incorporating a regenerative therapy such as stem-cell-based interventions. Whereas neuromodulation and task-specific training increases excitability and reorganizes existing networks, stem cells have the potential to repair structural damage and re-establish communication across injured regions or facilitating the establishment of dormant pathways. The future of SCI recovery relies on multi-modal synergistic interventions that are likely to maximize long-term functional outcomes. In the current perspective, we summarized the basic findings on applications of SCES on restoration of sensory-motor functions. We then projected on current interventions on utilizing stem cell therapy intervention. We highlighted the outcomes of randomized clinical trials, and the major barriers for considering the synergistic approach between SCES and stem cell intervention. We are hopeful that this perspective may lead to roundtable scientific discussion to bridge the gap on how to conduct numerous clinical trials in the field. Full article
(This article belongs to the Section Clinical Neurology)
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21 pages, 1083 KB  
Review
Pathogen Evasion of Humoral Innate Immunity: Coping with C-Reactive Protein and Serum Amyloid A
by Weichen Gong, Xuefei Cheng, Julio Villena and Haruki Kitazawa
Int. J. Mol. Sci. 2026, 27(2), 1072; https://doi.org/10.3390/ijms27021072 - 21 Jan 2026
Abstract
C-reactive protein (CRP) and serum amyloid A (SAA) are classical acute-phase proteins that exemplify humoral innate immunity, the soluble arm of the host’s first-line defense. Beyond their traditional use as biomarkers of inflammation, both proteins function as active effectors against pathogens by binding [...] Read more.
C-reactive protein (CRP) and serum amyloid A (SAA) are classical acute-phase proteins that exemplify humoral innate immunity, the soluble arm of the host’s first-line defense. Beyond their traditional use as biomarkers of inflammation, both proteins function as active effectors against pathogens by binding microbial components, activating complements, and modulating inflammation. However, bacteria, viruses, and fungi have co-evolved diverse mechanisms to cope with or evade these host defenses. This review aims to summarize the current understanding of CRP and SAA as soluble innate immune effectors and to highlight pathogen strategies to counteract their antimicrobial pressure. We systematically surveyed and summarized evidence from experimental and clinical studies describing “function of CRP and SAA during infection”, “CRP and SAA in innate immune defense”, and “evasion mechanisms across bacterial, viral, and fungal pathogens”. CRP and SAA are rapidly upregulated in response to infection and contribute to pathogen recognition, opsonization, and inflammation. Pathogens, however, employ multiple coping strategies, including surface modification to block CRP binding, proteolytic degradation of acute-phase proteins, shielding within biofilms, and subversion of host signaling. These countermeasures enable microbes to reduce immune clearance and promote persistence. CRP and SAA represent central elements of humoral innate immunity, shaping the outcome of host–pathogen interactions. Pathogen adaptations to these proteins illustrate an ongoing evolutionary arms race between host defense and microbial survival. A deeper understanding of these processes may open avenues for novel therapeutic approaches, such as targeting microbial evasion factors or enhancing host acute-phase responses. Full article
(This article belongs to the Section Molecular Microbiology)
26 pages, 1466 KB  
Systematic Review
Systolic Versus Diastolic Echocardiographic Assessment of Epicardial Adipose Tissue for the Detection of Obstructive Coronary Artery Disease: A Systematic Review and Meta-Analysis
by Andrea Sonaglioni, Giulio Francesco Gramaglia, Gian Luigi Nicolosi, Massimo Baravelli and Michele Lombardo
J. Clin. Med. 2026, 15(2), 878; https://doi.org/10.3390/jcm15020878 - 21 Jan 2026
Abstract
Background: Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot increasingly associated with the development and progression of coronary artery disease (CAD). Transthoracic echocardiography is the most widely used modality for EAT assessment; however, substantial heterogeneity exists regarding the timing [...] Read more.
Background: Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot increasingly associated with the development and progression of coronary artery disease (CAD). Transthoracic echocardiography is the most widely used modality for EAT assessment; however, substantial heterogeneity exists regarding the timing of measurement within the cardiac cycle, with EAT thickness variably assessed during systole or diastole. Whether these measurements provide equivalent information for identifying obstructive CAD remains unclear. This systematic review and meta-analysis evaluated the association between echocardiographically measured EAT thickness and angiographically confirmed obstructive CAD, with specific focus on systolic versus diastolic assessments. Methods: PubMed, Scopus, and EMBASE were systematically searched through December 2025 for observational studies comparing EAT thickness in patients with and without obstructive CAD confirmed by invasive coronary angiography. Random-effects models were used to pool standardized mean differences (SMDs) for systolic and diastolic EAT thickness. Heterogeneity was assessed using the I2 statistic, publication bias by funnel plots and Egger’s regression test, and robustness by meta-regression and leave-one-out sensitivity analyses. Results: Twenty-two studies including more than 6500 patients were analyzed. Both systolic and diastolic EAT thickness were significantly greater in patients with obstructive CAD than in non-CAD controls. Systolic EAT showed a large, pooled effect size (SMD 1.27; 95% CI 0.96–1.59; p < 0.001), while diastolic EAT demonstrated a similarly strong association (SMD 1.59; 95% CI 1.10–2.07; p < 0.001). Heterogeneity was substantial (I2 > 90%), but the direction of effect was consistent across all studies. Meta-regression analyses indicated that demographic, clinical, metabolic, geographic, and methodological characteristics, including ultrasound software/vendor category and timing of EAT measurement, did not significantly moderate the association between EAT thickness and obstructive CAD. No significant publication bias was detected, and sensitivity analyses confirmed the robustness of the results. Conclusions: Echocardiographically measured EAT thickness is strongly and consistently associated with obstructive CAD, irrespective of whether measurements are obtained during systole or diastole. Although both approaches show robust discriminatory capacity at the population level, differences in effect magnitude suggest that they may not be fully interchangeable. Moreover, in the absence of standardized and broadly applicable cut-off values, the interpretation and clinical management of EAT measurements as individual risk predictors require further investigation. Full article
25 pages, 1232 KB  
Review
Oxidative Stress and Its Role in Vascular Damage and Atherosclerosis
by Adela Pozo Giráldez, Adrián Bravo Gómez, Pilar Calmarza, Paula Sienes Bailo, Anita Dayaldasani Khialani, Silvia Montolio Breva, Nerea Sainz-Pastor and Isabel Fort Gallifa
Int. J. Mol. Sci. 2026, 27(2), 1075; https://doi.org/10.3390/ijms27021075 - 21 Jan 2026
Abstract
Oxidative stress (OS) resulting from an imbalance between reactive oxygen species (ROS) generation and antioxidant defenses plays a pivotal role in vascular diseases such as atherosclerosis and hypertension. ROS derived from NADPH oxidase, mitochondria, and xanthine oxidase promote endothelial dysfunction by inducing lipid [...] Read more.
Oxidative stress (OS) resulting from an imbalance between reactive oxygen species (ROS) generation and antioxidant defenses plays a pivotal role in vascular diseases such as atherosclerosis and hypertension. ROS derived from NADPH oxidase, mitochondria, and xanthine oxidase promote endothelial dysfunction by inducing lipid and protein oxidation, apoptosis, and pro-inflammatory signaling, thereby enhancing smooth muscle proliferation and atherogenesis. This review summarizes the molecular mechanisms linking OS to vascular injury and aims to systematically elucidate the role of OS in vascular diseases, with a specific focus on critiquing the current challenges in translating biomarkers to clinical practice and the emerging trends in personalized antioxidant therapy. Particular attention is given to biomarkers of oxidative stress, including those assessing antioxidant enzyme activity and oxidative damage products, which possess potential for clinical use. Therapeutic strategies targeting OS, including dietary and pharmacological antioxidants, show promise in improving vascular health, although clinical outcomes have been inconsistent and it is necessary to resolve the standardization and validation of these biomarkers, develop precise targeted therapies against specific ROS sources (e.g., NOX inhibitors, mitochondrial antioxidants), and explore personalized clinical trials based on redox stratification. Overall, OS is a central mediator in vascular pathology, and progress in biomarker validation and targeted therapies will be essential to translate current knowledge into effective prevention, diagnosis, and treatment of cardiovascular diseases. Personalized approaches based on accurate redox profiling may enhance efficacy. Full article
(This article belongs to the Special Issue Oxidation in Human Health and Disease)
18 pages, 775 KB  
Article
Treatment Efficacy of Semantic Feature Analysis in Logopenic and Semantic Variants of Primary Progressive Aphasia
by İbrahim Can Yaşa, İlknur Maviş and Tuğba Kaya
Healthcare 2026, 14(2), 272; https://doi.org/10.3390/healthcare14020272 - 21 Jan 2026
Abstract
Background/Objectives: Primary Progressive Aphasia (PPA) is a neurodegenerative disorder characterized by gradual and progressive deterioration of speech and language abilities. Speech and language therapy is considered an important intervention to slow decline and support the recovery of linguistic functions in individuals with [...] Read more.
Background/Objectives: Primary Progressive Aphasia (PPA) is a neurodegenerative disorder characterized by gradual and progressive deterioration of speech and language abilities. Speech and language therapy is considered an important intervention to slow decline and support the recovery of linguistic functions in individuals with PPA. This study aims to examine the effectiveness of an elaborated Semantic Feature Analysis (SFA) approach in enhancing naming abilities and semantic networks in individuals with the logopenic and semantic variants of PPA. Methods: Fourteen participants were recruited, including seven individuals with logopenic PPA and seven with semantic PPA. All participants received an elaborated SFA intervention twice weekly for four weeks. The Aphasia Language Assessment Test (ADD), the Turkish Picture Naming Test (T-RAT), and the SAQOL-39 were conducted at the following three time points: prior to treatment (pre-test), immediately after treatment (post-test), and one month post-treatment (follow-up). Results: Significant improvements were observed in ADD, T-RAT, and SAQOL-39 scores in both logopenic and semantic PPA groups following treatment (p < 0.05). Although follow-up scores declined compared to posttest performance (p < 0.05), several follow-up scores remained higher than pretest levels. Between-group comparisons indicated no significant difference in ADD scores; however, logopenic PPA participants demonstrated higher T-RAT scores (p < 0.05), while semantic PPA participants showed higher SAQOL-39 scores, except at follow-up (p < 0.05). Conclusions: Preliminary results suggest that the elaborated SFA intervention is effective in improving naming skills, language functioning, and quality of life in both logopenic and semantic variants of PPA. Although treatment gains partially decreased after one month, many improvements were maintained above baseline, supporting the clinical value of SFA in managing language decline in PPA. Full article
31 pages, 1700 KB  
Review
Prospective of Colorectal Cancer Screening, Diagnosis, and Treatment Management Using Bowel Sounds Leveraging Artificial Intelligence
by Divyanshi Sood, Surbhi Dadwal, Samiksha Jain, Iqra Jabeen Mazhar, Bipasha Goyal, Chris Garapati, Sagar Patel, Zenab Muhammad Riaz, Noor Buzaboon, Ayushi Mendiratta, Avneet Kaur, Anmol Mohan, Gayathri Yerrapragada, Poonguzhali Elangovan, Mohammed Naveed Shariff, Thangeswaran Natarajan, Jayarajasekaran Janarthanan, Shreshta Agarwal, Sancia Mary Jerold Wilson, Atishya Ghosh, Shiva Sankari Karuppiah, Joshika Agarwal, Keerthy Gopalakrishnan, Swetha Rapolu, Venkata S. Akshintala and Shivaram P. Arunachalamadd Show full author list remove Hide full author list
Cancers 2026, 18(2), 340; https://doi.org/10.3390/cancers18020340 - 21 Jan 2026
Abstract
Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for approximately 10% of all cancer cases. Despite the proven effectiveness of conventional screening modalities such as colonoscopy and fecal immunochemical testing (FIT), their invasive nature, high cost, and [...] Read more.
Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for approximately 10% of all cancer cases. Despite the proven effectiveness of conventional screening modalities such as colonoscopy and fecal immunochemical testing (FIT), their invasive nature, high cost, and limited patient compliance hinder widespread adoption. Recent advancements in artificial intelligence (AI) and bowel sound-based signal processing have enabled non-invasive approaches for gastrointestinal diagnostics. Among these, bowel sound analysis—historically considered subjective—has reemerged as a promising biomarker using digital auscultation and machine learning. Objective: This review explores the potential of AI-powered bowel sound analytics for early detection, screening, and characterization of colorectal cancer. It aims to assess current methodologies, summarize reported performance metrics, and highlight translational opportunities and challenges in clinical implementation. Methods: A narrative review was conducted across PubMed, Scopus, Embase, and Cochrane databases using the terms colorectal cancer, bowel sounds, phonoenterography, artificial intelligence, and non-invasive diagnosis. Eligible studies involving human bowel sound-based recordings, AI-based sound analysis, or machine learning applications in gastrointestinal pathology were reviewed for study design, signal acquisition methods, AI model architecture, and diagnostic accuracy. Results: Across studies using convolutional neural networks (CNNs), gradient boosting, and transformer-based models, reported diagnostic accuracies ranged from 88% to 96%. Area under the curve (AUC) values were ≥0.83, with F1 scores between 0.71 and 0.85 for bowel sound classification. In CRC-specific frameworks such as BowelRCNN, AI models successfully differentiate abnormal bowel sound intervals and spectral patterns associated with tumor-related motility disturbances and partial obstruction. Distinct bowel sound-based signatures—such as prolonged sound-to-sound intervals and high-pitched “tinkling” proximal to lesions—demonstrate the physiological basis for CRC detection through bowel sound-based biomarkers. Conclusions: AI-driven bowel sound analysis represents an emerging, exploratory research direction rather than a validated colorectal cancer screening modality. While early studies demonstrate physiological plausibility and technical feasibility, no large-scale, CRC-specific validation studies currently establish sensitivity, specificity, PPV, or NPV for cancer detection. Accordingly, bowel sound analytics should be viewed as hypothesis-generating and potentially complementary to established screening tools, rather than a near-term alternative to validated modalities such as FIT, multitarget stool DNA testing, or colonoscopy. Full article
(This article belongs to the Section Methods and Technologies Development)
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